Madeline Version 0.935 Documentation

by Edward H. Trager <ehtrager@umich.edu> (June 2004)

© 2003, 2004 by the Regents of the University of Michigan ALL RIGHTS RESERVED

This software program is released under the GNU General Public License .

Section 1 Overview and Features

What is Madeline?

Madeline is a program for preparing, visualizing, and exploring human pedigree data used in genetic linkage studies. In addition to converting pedigree and marker data into various formats required by linkage analysis software, including Crimap, Genehunter, Allegro, Mendel, Merlin, PedCheck, and Simwalk2, Madeline also provides functionality for querying pedigree data sets and drawing pedigrees.

By combining a database engine with a software engine that understands the relationships between people in pedigrees, Madeline provides functions for investigating data on individuals and pedigrees in genetic linkage studies (Fig. 1).

Note that this release of the program, version 0.935, has numerous changes compared to the previous release (version 0.933). Even if you are thoroughly versed with the workings of version 0.933, you are advised to take a careful look at the numerous changes and new features in the program described in the documentation here.

A Brief History of the Program

As the old adage says, necessity is the mother of invention. When I first started this project a number of years ago, I had never written a recursive descent parser, never implemented balanced binary sorted trees, and I think at that time I had not even heard of the Postscript graphics language! There certainly was no master plan for this program, only the desire to get work done more easily with fewer data conversion headaches. Nor did I or my colleagues sit down and specify a coding standard for the program, much less a documentation standard. Whatever I could write in a reasonable amount of time that happened to work well enough to get the job done was just that, good enough.

Fortunately, a few early decisions were fundamentally correct, even if my implementations were less than perfect. The program began to take shape back in the days when all I knew was DOS and one of my first decisions was to use a DOS 32-bit protected mode library for the Borland compiler. Since the program used a 32-bit flat memory model from day one, it proved easy to port it over to Solaris and HP-UX when I finally got around to learning Unix.

Another early decision was to add an interactive command interface to the program. Early versions of the program required arguments passed from the command line, and it quickly became evident that hundreds of command-line arguments would be difficult to remember and would impair program flexibility. After reading a book on programming in C by Herbert Schildt which showed how to write a BASIC interpreter, as an experiment I decided to create a version of the program with an interactive command parser. That of course proved to be much nicer than the earlier non-interactive versions.

A third pivotal decision was to add pedigree drawing. When I initially suggested doing this, I remember being told that this was a hard problem which I should not waste my time on since other programs existed which already provided that functionality. In retrospect, I'm exceedingly glad I didn't listen to that advice, since the ability to display pedigree data graphically is probably one of the program's greatest strengths. The graphics were originally created using HP's PCL printer language; Postscript was introduced in a later revision of the program.

The program --and the programmer!-- have now begun to mature, but maturation has occurred, and continues to occur, as a slow process. A number of people in the labs where I have worked and elsewhere have found Madeline useful and a timesaver. As a result, I am encouraged to move the program closer to the ideal that I imagine it could be. Although the program and its code still have numerous shortcomings, you can still use these intermediate releases to help you complete your work more quickly, with less hassle, and fewer errors.

Finally, please note that this version of Madeline is released under the GNU General Public License which grants authors and users certain rights. I encourage you to read the license if you are not already familiar with it. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.

Credits

A lot of work goes into a program like this and I am indebted to many people for their help and suggestions. I would especially like to thank the following people:

• For supporting the development of the program while employed under their auspices, as well as for their valuable suggestions: Dr. Julia Richards, Dr. Michael Boenhke.
• For valuable suggestions at various times over the development lifetime of the program: Dr. Elizabeth Hauser, Dr. Carl Langefeld, Kimmo Kohtamaki, Dr. Timo Valle, Dr. Julie Douglas, Dr. Heather Stringham, Bill Duren, Dr. Michael Epstein, Charles Krafchak, Dr. Nobuo Fuse, Dr. Noor Ghiasvand, Dr. Gonçalo Abecasis.
• For writing the LASi Postscript printing engine for future support of Unicode printing in Madeline: Larry Siden.

Supported Platforms

Madeline v. 0.935 has been successfully compiled using at least the following hardware and compiler combinations:

Madeline now uses the GNU Autoconf system for automatic configuration. In light of this, we expect that the program can be built successfully on virtually all modern UNIX-like platforms.

Please review Notes on Installing Madeline Version 0.935 for more information about compiling and installing Madeline on specific platforms.

FUSION Study Support

Madeline was originally designed to meet the needs of the Finland-United States Investigation of NIDDM Genetics (FUSION) study. Because of this, Madeline has specific knowledge about FUSION study IDs. A narrow subset of Madeline's functionality makes use of this knowledge. Click here if you are interested in learning more about Madeline's FUSION-specific functionality. Paragraphs or headings preceded by "FUSION:" describe FUSION-specific functionality. This functionality is only available when FusionSupport is set on. FusionSupport is off by default.

Note: All current development on Madeline focuses on providing general support for genetic linkage studies. FUSION-specific development ceased long ago.

Tutorial

Included with the distribution of the program is an extensive tutorial that will guide you through the entire linkage analysis process using Madeline interactively. The tutorial is located in the tutorial/Documentation subdirectory under the name MadelineTutorial.html. The tutorial subdirectory also contains all of the data files needed to complete the tutorial.

The tutorial can serve as quick introduction to the program and give you a feel to how the program works. After completing the tutorial, you can return to reading the main documentation for an in-depth treatment of the program's features.

Running the Program Interactively and in Batch Mode

Instructions to Madeline are entered at a command prompt. Madeline's command interpreter is not sensitive to capitalization. However, capitalization is often used in this document for clarity of presentation.

Madeline can be run interactively or in batch mode (Fig 2). To run Madeline interactively, type "madeline" at your system prompt and press return. Madeline's "M>" prompt will appear.

Batch files contain a sequence of Madeline commands that have been saved in a text file in ASCII or UTF-8 format. There are two ways to run batch files. The first way is to provide the name of a batch file as a command line parameter after the name of the program. The second way is to start Madeline interactively and then use the run command to execute the batch file. Madeline returns to interactive mode if an error occurs, or when a batch file terminates without a goodbye or quit command.

edtrager@retina:~> madeline starting Madeline in interactive mode
 ______________________________________________________________________________
 ______________________________________________________________________________
  __    __       _       ______     _______   _          _   __    _   _______
 |  \  /  |     / \     |  ___  \  |  _____| | |        | | |  \  | | |  _____|
 |   \/   |    / ^ \    | |   \  \ | |___    | |        | | |   \ | | | |___
 | |\  /| |   / /_\ \   | |    | | |  ___|   | |        | | | |\ \| | |  ___|
 | | \/ | |  /  ___  \  | |___/  / | |_____  | |______  | | | | \   | | |_____
 |_|    |_| /__/   \__\ |_______/  |_______| |________| |_| |_|  \__| |_______|
 ______________________________________________________________________________
 ______________________________________________________________________________

                                 Version  0.935
                           Written by Edward H. Trager
                              <ehtrager@umich.edu>

COPYRIGHT  2003
THE REGENTS OF THE UNIVERSITY OF MICHIGAN
PORTIONS COPYRIGHT  1995 EDWARD H. TRAGER
ALL RIGHTS RESERVED

Madeline comes with ABSOLUTELY NO WARRANTY.  This is free software and
you are welcome to redistribute it under certain conditions.  For details,
type "license"

+-----------------------+-----------+-----------------------------------------+
| Variable or State Flag| Setting   | Description                             |
+-----------------------+-----------+-----------------------------------------+
| EXTERNAL PROGRAMS     |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| Editor                | edith     | Program used to edit files              |
| PostscriptViewer      | gv        | Program used to view Postscript drawings|
| PrintCommand          | lpr       | System program used to print files      |
| WebBrowser            | mozilla   | Program used to view HTML documentation |
+-----------------------+-----------+-----------------------------------------+
| EVALUATION SETTINGS   |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| EvaluationInterval    |   0.50 cM | Value to write to control file.         |
| OffEndDistance        |  10.00 cM | Value to write to control file          |
+-----------------------+-----------+-----------------------------------------+
| DRAWING SETTINGS      |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| Color                 | ON        | Draw pedigrees in color                 |
| ReverseShading        | OFF       | Black is first icon shade               |
| DividedDrawings       | ON        | Paginate drawings by founding group     |
| HighlightRows         | ON        | Alternately highlight data on drawings  |
| LabelCreatedIndividual| ON        | Label virtuals created by Madeline      |
| Orientation           | AUTOMATIC | Automatic based on drawing dimensions   |
| PaperMargin           | 1.00 cm   | Margin (in cm) on all four sides        |
| PaperSize             | USLETTER  | 8.5 x 11.0 inches                       |
+-----------------------+-----------+-----------------------------------------+
| OTHER SETTINGS        |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| AutoExclude           | ON        | Exclude pedigrees automatically         |
| AutoCheckInheritance  | ON        | Check inheritance on OPEN               |
| ConsoleHighlights     | ON        | Use bold/color highlights on console    |
| Delimiter             | TAB       | Delimiter for tables and other output.  |
| FusionSupport         | OFF       | FUSION customizations disabled          |
| HaplotypeDisplay      | OFF       | Display genotypes delimited with "/"    |
| Language              | American E| Language convention used for date, time |
| MapDetails            | OFF       | LIST MAP summary display                |
| SaveAlleleFrequencies | OFF       | Calculate new frequencies on next OPEN  |
| Time                  |           | Friday, December 5, 2003                |
| Verbosity             | VERBOSE   | All messages are printed to the console |
+-----------------------+-----------+-----------------------------------------+
M>
M>quit entering a command in interactive mode
Releasing resources ...
Goodbye!
edtrager@retina:~>madeline chromosome20.script starting Madeline in batch mode
  open 'linkage/chr20.data.mfh' executing first batch command 
  Calculating allele frequencies for 7. D20S173... 
  Calculating allele frequencies for 10. D20S889... 
  Calculating allele frequencies for 13. D20S898... 
  ...

Start Up File -- initial.script

You can set parameters and run commonly needed commands automatically each time Madeline is started by providing a script file called "initial.script". Madeline will first look for a local version of initial.script in the current working directory from which Madeline is invoked. Failing to find initial.script there, Madeline will look in the share/madeline/ subdirectory under the directory prefix where Madeline was installed. For example, if Madeline was installed in /usr/local, then the program will look for /usr/local/share/madeline/initial.script.

Any commands that can normally be invoked on the command line or in a batch file can be placed into initial.script. Assignments to specify default field names or environmental settings are typically placed in initial.script (Fig. 4).

//
// Typical initial.script file:
//

//
// Environment settings:
//
quiet
set language to English
Editor="emacs"
PostscriptViewer="gv"
//
// Pedigree drawing-specific settings:
//
set color off
set PaperSize to A4
// margin in centimeters:
set PaperMargin to 1.5
set orientation to automatic
//
// Pedigree database-specific settings:
//
GenderField='GENDER'
FamilyIDField='FAMILY'
IndividualIDField='INDIVIDUAL'
//
// Map standard missing value indicators:
//
NumericMissingValue[1]=-1
NumericMissingValue[2]=-9
//
// Map database-specific settings:
//
PositionField="POSTN"
OrdinalField ="ORDNL"

Note: Starting with Madeline v. 0.933, it is recommended that site-wide defaults be compiled directly into Madeline by customizing the config.h source file generated by the configure script run by you or your system administrator when Madeline is installed. Many (but not all) parameters can be configured in config.h. Remaining settings can be specified in the initial.script as necessary. If you don't require any site-specific customizations, you can just leave the global default initial.script as is.

Tables

Tables Overview

Madeline processes data stored in tables. A database table is a rectangular array of data. A record is a row in the array. A field is a column in the array. Each record contains one or more identifiers or keys which identify the entity, and the data -- all the measured variables -- for the entity. The measured entity may be an individual in a pedigree, a genetic marker, a position along a genetic map, or something else.

Tables Supported Formats

The program currently supports the following table formats:

1. Madeline column-aligned, space-delimited ASCII and UTF-8 flat files. This is the recommended format.
2. FoxPro and other generic xbase databases (such as dBaseIII, IV).
3. Visual FoxPro which is a variant on the xbase structure.
4. SAS transport file format (theoretically regardless of platform of origin).

Note: Of these four formats, we now recommend using only the Madeline native format because it is open, non-proprietary, human-readable, and editable in any text editor (in the case of UTF-8 files, in any UTF-8 capable text editor: see this link). Although supported in versions 0.933 and 0.935, the legacy xbase and SAS transport formats are deprecated and we may not support them at all in future versions of the program.

The structure of the Madeline format is described below. Sample PHP code for creating Madeline files from database tables is also provided.

Tables Madeline Format

A Madeline-formatted table is a human-readable flat file containing ASCII or UTF-8 characters having the following structure:

• Zero or more blank lines may precede the header.
• The file proper begins with a header block containing column labels.
• One or more blank lines must separate the header block from the data block.
• A rectangular data block follows the header.
• Zero or more blank lines may follow after the last line of the data.

The following figure illustrates how the example "relationships.dat" data file included in the software distribution conforms to this structure:

Madeline Table Format. Tables in the Madeline format are flat files divided into a header block consisting of one or more lines containing column labels and optional type designators, and a data block consisting of even-length records divided into space-delimited data columns. (The vertical blue arrow illustrates how data in a single column can, if necessary, contain embedded white space, as long as that white space does not stretch uninterrupted from the first to the last record: vertically uninterrupted white space delimits columns).

The header contains:

• Column (field) labels.
• Optional column type designators.

Column labels should be CAPITALIZED. Column labels are separated by any amount of white space and can span as many lines as necessary. Each line in the header can contain one or more column labels (This is illustrated above where seventeen column labels span fifteen header lines).

The order of the column labels from left-to-right and top-to-bottom indicates the order of the columns in the data block. Lines in the header can be of varying lengths.

A column type designator consists of single capital letter following after a column label. Any amount of white space can be used between a column label and type designator. The following column type designators are recognized:

Column Type Designators in Madeline Tables

Column Type Designator	Description	Example
C	Designates: that a column contains character (string) data   or that a column containing numeric data be treated as string data (individual and pedigree identifiers, even if they are completely numeric, must be treated as string identifiers in Madeline).	STUDYID C
X	Designates the gender (sex) column. The gender column may alternatively be designated with a "C" for character codes or with an "N" for numeric gender codes.	SEX X
N	Designates that a column containing numeric values be treated as numeric data.	AGE_DX N
D	Designates that a column contains date data in ISO-8601 format (four-digit year followed by a two-digit month and finally a two-digit day). Note that Madeline permits use of any of the usual date delimiters: YYYY . - / MM . - / DD	DOB D
G	Designates that a column contains genotypes as numeric allele labels separated by a forward slash "/" character. Genotype columns can alternatively be designated with a "C": the program will automatically recognize character columns containing genotypes.	D12S4321 G
A	Designates that a column contains one of the two alleles that constitutes a genotype. Allele columns must exist as identically-named pairs.	D12S4321 A D12S4321 A

At least one blank line must follow after the header in order to separate the header block from the data block.

The data block consists of:

• records which form the rows of the data block.

Each record (or row) contains the identifiers and data measured for one entity. For example, a pedigree table contains one row for each individual in a family, where as a map table contains one row for each marker in a genetic map.

The identifiers and data for each record are formatted in:

• columns

Note #1: Column type designators are technically optional in most (but not all) cases. The program contains code to automatically detect column types. Certain type promotions, such as from "C" to "G" and from "C" to "X" are permitted and performed automatically when required. The primary exception occurs when completely numeric individual and pedigree identifiers are used: the program automatically detects the columns as being "N" numeric, but you MUST cast them as "C" because the program requires string identifiers for individuals and pedigrees. The best practice is to include column type designators since this increases file readability for humans and prevents surprises.

Note #2: A problem that can occur with hand-edited data files (as opposed to those generated by a script, program, or database system), is embedded tabs or extra spaces or tabs appended to the end of various lines of the data -- but quite invisible when viewed in a typical editor! These make the data block non-rectangular, which is not allowed.

Madeline's recognize command now specifically looks for embedded tabs and inconsistent data row lengths caused by extra tabs or space characters at the ends of rows. The rectify command will fix both types of problems in most cases. You should also open the data file using a good file editor such as Edith and use the column-highlighting feature (i.e., CTRL+<Left Mouse Button>) to select white space after the last data column. This quickly reveals whether the lines are all the same length or -- as is quite likely going to be the case in problematic files -- not (See figure below). If they are not, a simple CTRL-X in Edith trims off all of the selected segments.

Having trouble getting Madeline to recognize your data file? Often the culprit is hidden spaces and/or tab characters trailing after the last column of data, making it non-rectangular. Another culprit could be tab characters embedded within rows (not illustrated). The rectify command will handle both types of problems. Alternatively, you can use Edith or a similar file editor to display embedded tabs and terminal tabs and spaces. Hold down the CTRL key while pressing the left mouse button to select the trailing white space and remove it (CTRL-X).

Tables Storing Data Containing Accented Latin Letters or Non-Latin Characters

If your data contain strings in non-English languages that use accented Latin letters (such as "ç" and "é" in French, "ñ" in Spanish, and "ü" in German) or non-Latin scripts (Cyrillic, Japanese, Chinese, etc.), then your data must be encoded in the Unicode UTF-8 format and stored using the Madeline table format. You will also need to run Madeline in a Unicode-capable terminal emulator under a UTF-8 locale.

What does this mean? For European users, it means that the Madeline does not support any of the legacy ISO-8859-x character sets, not even ISO-8859-1. For other users, it means that your country's legacy character sets, whether it be KOI-8, JIS, GB18030, or something else, are not supported. The primary issue is that many people's computers are still set to use some legacy encoding system. Fortunately, major Linux distributions are now enabling UTF-8 locales by default. If you are using a recent release of SuSE or Redhat in North America or Europe, your system will be set to use UTF-8 by default. However, if you are using a recent Linux distribution in East Asia (China, Japan, etc.), you should check your locale settings. This document should provide you with most of the information you need to switch over to Unicode under Linux or a similar *nix-based system.

The rules for formatting a UTF-8 table in Madeline format are the same as those for ASCII. In particular, note that columns in the data block must be aligned on byte boundaries with white space (ASCII 0x0020) separating columns. Trying to format such a file manually is not recommended. Instead, store your data in a database and use a scripting language like Perl or PHP to extract the data into the correct format.

See the examples/utf8/utf8.data file as an example of a properly formatted UTF-8 file:

Data files in the Madeline flat file format can contain data in any of the world's scripts encoded in Unicode UTF-8. The last column in the file appears unaligned, but is actually aligned on byte boundaries, not on displayed character boundaries.

Tables Opening Madeline-formatted Tables

Before you can use a flat-file table, you must first run the recognize command which creates a small, complementary binary file with a ".mfh" ( Madeline File Header ) extension. This complementary file stores meta information about the table (names and number of columns, number of rows, etc.) in a binary format which the program uses to optimize table access. To open the table, specify the complementary ".mfh" file name in place of the original data file.

Tables Recognizing Unannotated Tables

An unannotated data file contains no header describing the fields. What do you do if you receive an unannotated data file from a colleague or client? Let Madeline do some of the work for you!

The recognize command contains code to automatically detect columns in unmarked files. The program can even often identify the core gender, individual, father, and mother fields required for pedigree reconstruction. This can save time and tedium. Consider the following excerpt from the "unannotated.data" file included in the examples subdirectory of the software distribution:

NT5641 M AB0115 FM_012 A A AB0116 190/202 166/169 0/0     172/175 154/154 65 89.94 
NT5661 F AB0147 FM_012 A A AB0148 208/211 153/157 201/207 160/175 154/160 50 81.03 
NT5675 F AB0119 FM_012 A A AB0120 205/211 153/166 204/207 166/175 157/157 73 82.06 
NT5676 F AB0123 FM_012 A A AB0124 190/208 156/166 201/207 175/177 154/157 63 88.76 
NT5678 F AB0140 FM_012 A I NT5676 190/208 157/166 201/207 175/177 154/157 60 65.86 
NT5679 F AB0115 FM_012 A I AB0116 202/211 157/169 207/207 172/175 154/154 78 82.92 
NT5724 F AB0135 FM_012 A I AB0136 205/205 166/169 204/210 166/172 154/157 69 71.82 
NT5728 F AB0113 FM_012 A A AB0114 190/190 156/169 204/207 160/175 148/157 64 84.55 
NT5749 F AB0121 FM_012 A A AB0122 205/211 157/157 0/0     166/175 154/160 .  87.46 
NT5752 F AB0121 FM_012 A I AB0122 205/211 153/157 204/207 166/175 148/154 83 88.57 
NT5753 F NT5641 FM_012 U I AB0132 .       .       .       .       .       .  62.94 
NT5757 F AB0130 FM_012 A A AB0131 202/211 157/169 201/207 166/172 154/160 55 70.16 
NT5790 F AB0138 FM_012 U I AB0139 208/208 157/160 207/207 172/172 154/154 .  71.18 
  . . .

Unannotated Table. Having trouble deciphering which column is which? Let Madeline help you!

Running the recognize command on this file produces the following:

M>recognize 'unannotated.data'
Recognizing file "unannotated.dat" to "unannotated.dat.mfh" ...
Skipping a total of 1 line at top.
There are 0 non-empty header lines and 54 data lines.
Data records are 83 bytes long.
The gender field has been identified and will appear in the ".run" file
The individual, father, and mother ID fields have been identified
and will appear in the ".run" command file

 # . Field Name  Start End   Length Prec. Space Type
---- ----------- ----- ----- ------ ----- ----- -----
  1. INDIVIDUAL      1     6     6     0     1 C
  2. GENDER          8     8     1     0     1 X
  3. FATHER         10    15     6     0     1 C
  4. CHAR_003       17    22     6     0     1 C
  5. CHAR_004       24    24     1     0     1 C
  6. CHAR_005       26    26     1     0     1 C
  7. MOTHER         28    33     6     0     1 C
  8. GENO_001       35    41     7     0     1 G
  9. GENO_002       43    49     7     0     1 G
 10. GENO_003       51    57     7     0     1 G
 11. GENO_004       59    65     7     0     1 G
 12. GENO_005       67    73     7     0     1 G
 13. NUME_001       75    76     2     0     1 N
 14. NUME_002       78    82     5     2     1 N
Binary recognition header file (".mfh") written.
   --> If this is a pedigree file,    type 'open "unannotated.dat.mfh" '.
   --> If this is a genetic map file, type 'load "unannotated.dat.mfh"'

The template batch file unannotated.dat.run has been created.

NOTE: The ".run" file contains commands and parameters to assist
      you in opening a flat file database, but generally requires
      editing before use.
M>

Clearly the program cannot perform magic. For example, the program was not able to determine the FamilyIDField (the fourth column in the table) and there are other limitations to what the program can do. Nevertheless, being able to correctly identify the core pedigree structure and genotype columns in an unannotated data file can save you from a tedious manual investigation of the data.

Tables Tables in Legacy Formats

When using xbase or SAS transport formats, Madeline column type designators like X,G, and A do not exist. For legacy formats, only use character, numeric, and date column types. For example, the gender attribute can be stored in a character field coded using "M" and "F". Genotypes can also be stored in character fields. Floating-point and integer fields are cast to Madeline's double-precision numeric floating-point type. Also avoid the logical and date-time field types found in dBase and FoxPro as Madeline won't understand these.

Tables Commands To Open Tables

The command used to open or manipulate a table depends on the type of table being processed:

• Pedigree tables are opened using the open command.
• Genetic map tables are opened using the load or graph load command.
• Each row in a decomposed table contains the alleles for one marker measured on one individual. Decomposed and composed tables can be cross-converted using the compose and decompose commands, respectively. Composed tables can also be merged both row-wise and column-wise using the merge command.
• Tables of allele frequencies can be read in using the read command. They can be saved out using the save command.
• Analysis results tables containing LOD scores are opened using the graph open command.

Madeline's database engine detects operating system and file byte-ordering at run time, permitting tables from PCs to be opened on UNIX workstations, and vice versa.

The different types of tables are described below in turn.

Tables Pedigree Tables

In a pedigree table, each row (record) contains the data for one individual. In Madeline, the names of the family and individual ID fields are stored in variables called FamilyIDField and IndividualIDField, respectively. Basic pedigree reconstruction additionally requires knowledge of the father (FatherIDField), mother (MotherIDField), and gender (GenderField) of each individual. Together, these field variables comprise the five core fields that must be present in every pedigree table:

1. FamilyIDField -- key identifier
2. IndividualIDField -- key identifier
3. FatherIDField -- required for pedigree reconstruction
4. MotherIDField -- required for pedigree reconstruction
5. GenderField -- required for pedigree reconstruction

The remaining identifiable data fields in a pedigree table are classified by Madeline into two groups: (1) phenotype and (2) genotype. Madeline automatically classifies all identifiable fields in a pedigree table into one of these three categories. Each identifiable field is tagged with a single-letter identifier shown below:

1. C -- Core fields
2. P -- Phenotype fields
3. G -- Genotype fields

Core fields are identified by matching field names against the names stored in the field name variables (i.e., FamilyIDField, StudyIDField, GenderField, etc.). Genotype fields are identified by scanning the data. Remaining fields are classified as phenotype fields.

Field classifications are shown in the figure below, illustrating a portion of a typical pedigree table:

Pedigree Tables. All identifiable fields in a pedigree table are classified into one of three categories in Madeline: "C" for core fields, "P" for phenotype fields, and "G" for genotype fields.

Note: The complete set of core fields consists of the five required core fields shown above, plus optional core fields such as AffectionStatusField, MZTwinField, and DateOfBirthField. See Core Data Fields for a complete listing.

Fields containing only missing value indicators that cannot be categorized as "C", "P", or "G" will be marked with an asterisk, "*". Phenotype "P" fields can be tagged by the user as being covariate "V" fields using the toggle command. Phenotype fields are never automatically classified as covariate "V" fields.

Tables Pedigree Tables Containing Allele Columns

When a pedigree table containing allele "A" columns instead of genotype columns, such as a Linkage file, is opened in Madeline, the paired and identically-named allele columns automatically appear as single genotype "G" fields.

Below is an excerpt from the "linkage.ped" data set distributed with the program. Note that while the data block is in the unchanged Linkage format, Madeline still requires that you provide a conformant header in Madeline format to identify the columns:

FAMID    C
STUDYID  C
FATHER   C
MOTHER   C
SEX      N
AFFECTED N
MARKER1  A
MARKER1  A
MARKER2  A
MARKER2  A
MARKER3  A
MARKER3  A
MARKER4  A
MARKER4  A
MARKER5  A
MARKER5  A
MARKER6  A
MARKER6  A


F0021 K0001A 0      0      1 0      0   0    0   0    0   0    0   0    0   0    0   0  
F0021 K0001B 0      0      2 0      0   0    0   0    0   0    0   0    0   0    0   0  
F0021 K00158 K0001A K0001B 1 1      1   4    1   3    1   1    3   4    1   3    1   3  
F0021 K00159 K0001A K0001B 1 0      1   3    1   2    1   1    1   2    1   2    1   2
. . .

Here are the commands to recognize and open this file. Note how the pairs of allele columns are recognized as genotype columns:

M>recognize "linkage.ped"
Recognizing file "linkage.ped" to "linkage.ped.mfh" ...
  ...
 # . Field Name  Start End   Length Prec. Space Type
---- ----------- ----- ----- ------ ----- ----- -----
  1. FAMID           1     5     5     0     1 C
  2. STUDYID         7    12     6     0     1 C
  3. FATHER         14    19     6     0     1 C
  4. MOTHER         21    26     6     0     1 C
  5. SEX            28    28     1     0     1 N
  6. AFFECTED       30    30     1     0     6 N
  7. MARKER1        37    41     5     0     4 G
  8. MARKER2        46    50     5     0     4 G
  9. MARKER3        55    59     5     0     4 G
 10. MARKER4        64    68     5     0     4 G
 11. MARKER5        73    77     5     0     4 G
 12. MARKER6        82    86     5     0     2 G
  ...
M>// Because the LINKAGE file uses zeros to represent
M>// missing parents, we need to add zero to the 
M>// CharacterMissingValue[] array:
M>list CharacterMissingValue
CharacterMissingValue has 5 elements:
CharacterMissingValue[ 1]="."
CharacterMissingValue[ 2]="/"
CharacterMissingValue[ 3]="0/0"
CharacterMissingValue[ 4]="0/ 0"
CharacterMissingValue[ 5]="0/  0"
M>cmv[6]="0"
M>// Madeline's GenderStatus[] and AffectionStatus[]
M>// arrays now contain LINKAGE code mappings by default, so 
M>// we can immediately open the file:
M>open "linkage.ped.mfh"
  6. AFFECTED has 3 levels.
Calculating allele frequencies for   7. MARKER1...
Calculating allele frequencies for   8. MARKER2...
Calculating allele frequencies for   9. MARKER3...
Calculating allele frequencies for  10. MARKER4...
Calculating allele frequencies for  11. MARKER5...
Calculating allele frequencies for  12. MARKER6...
Pedigree table "linkage.ped.mfh" opened with        13 records
  ...
  1.FAMID      Co__1    5.SEX        Co__5    9.MARKER3    Go__3
  2.STUDYID    Co__2    6.AFFECTED   Co__6+  10.MARKER4    Go__4
  3.FATHER     Co__3    7.MARKER1    Go__1   11.MARKER5    Go__5
  4.MOTHER     Co__4    8.MARKER2    Go__2   12.MARKER6    Go__6
M>

Tables Genetic Map Tables

A map table contains map information related to markers on one or more chromosomes. The key fields in a map table are:

1. MapChromosomeField -- chromosome on which marker appears
2. MapMarkerField -- name of the marker

The data fields in a map table are:

1. MapPositionField -- map position from p terminus in centiMorgans
2. MapOrdinalField -- ordinal ranking of the marker in the map from 1 to n where n is the number of markers mapped for the given chromosome

The following optional fields may also be present:

1. MapFemalePositionField -- map position for a female-specific map
2. MapMalePositionField -- map position for a male-specific map
3. MapPositionBPField -- physical map position in base pairs. This is defined but not currently used in the program.

An example of a map table is shown below:

MARKERNAME
CHROMOSOME
ORDINAL
POSITION

D17S944  17  1   82.6
D17S949  17  2   93.3
D17S1304 17  3   94.0
D17S1351 17  4   96.0
D17S1352 17  5   98.1
D17S1807 17  6   99.2
D17S929  17  7   99.2
D17S1301 17  8  100.0
D17S785  17  9  103.5
D17S674  17 10  105.7

A marker map table.

Note: A single map table can contain marker map data for multiple chromosomes. A single table is easier to maintain than multiple tables.

Tables Decomposed and Composed Tables

In traditional metal typography, metal casts of individual letters are "composed" into rows of type for printing on a printing press. In Madeline, we have borrowed the idea of "composing" text to refer to the operation of rearranging a table in which each row contains the alleles for one marker measured on one individual:

FAMID STUDYID MARKERNAME ALLELE1 ALLELE2
----- ------- ---------- ------- -------
P0001 I00001  D12S1304     121     127
P0001 I00001  D12S127       98     104
P0001 I00001  D12S341      134     142
P0001 I00002  D12S1304     117     119
P0001 I00002  D12S127      102     102
P0001 I00002  D12S341      136     138
.     .       .            .       .

Excerpt from a decomposed table. One row contains the alleles for one marker measured on one individual.

... into a table in which each row contains the genotypes for all of the markers measured on one individual ...

FAMID STUDYID  D12S1304  D12S127  D12S341
----- -------  --------  -------  -------
P0001 I00001    121/127   98/104  134/142
P0001 I00001    117/119  102/102  136/138
  . . .

Excerpt of the same data after composition. One row contains the genotypes for all markers measured on one individual.

A marker table contains the alleles for a specific marker measured on a specific individual. Output from the ABI Genotyper software is in this table format. This type of table has three key fields:

1. FamilyIDField -- family of the individual
2. IndividualIDField -- ID of the individual
3. MarkerField -- name of the marker

There are only two essential data fields in a marker table:

1. Allele1Field -- positive integer label assigned to first allele
2. Allele2Field -- positive integer label assigned to second allele

Madeline provides support for integrating the information in a marker table into a pedigree table via the compose and merge commands. The compose command takes care of converting the paired allele fields into the single genotype fields expected in a pedigree table. The merge command allows you to integrate family structure, phenotype, or genotype data from separate tables into a combined table for use in Madeline.

Tables Analysis Results Tables

Output files containing logarithm of odds (LOD) results from certain analysis programs such as Simwalk2 can be converted by Madeline directly into a table format which the program can then use for graphing the results. Output from other analysis programs may require a small amount of manual formatting which is usually not difficult to do.

The convert command may used to produce a table in the right format:

M>convert simwalk file 'sw_chr10.out' to 'chr10.results'
Converting input file "sw_chr10.out" to Madeline-formatted output files ...
        ...
M>

Converting an analysis result file directly into a Madeline table format.

An analysis results table must contain at least a POSITION and a SCORE column. Other columns may also be present. Here is a table of results from a non-parametric Simwalk2 analysis already formatted for use by Madeline. For graphing this data in Madeline, you would have to specify which of the score columns to use by setting Madeline's GraphScoreField to one of the "STAT" columns:

POSITION
STAT_A
STAT_B
STAT_C
STAT_D
STAT_E

 0.0000  0.073   0.046   0.072   0.069   0.077
 4.1691  0.182   0.076   0.180   0.167   0.181
 7.9053  0.163   0.076   0.162   0.156   0.183
10.0506  0.298   0.156   0.311   0.300   0.325
18.0591  0.578   0.409   0.614   0.633   0.665
21.3661  0.633   0.527   0.675   0.726   0.779
36.2864  1.526   0.690   1.478   1.445   1.359
39.7003  1.222   0.529   1.201   1.150   1.056

An analysis results table from Simwalk2 formatted for graphing in Madeline.

For more information on how to graph tables of LOD results, see the graph command.

Supported Data Types

Madeline's database engine supports: character string, numeric (floating point and integer), and date data types.

A logical data type (such as the "L" field type of xbase) or boolean data type is not distinguished from the numeric data type. Use appropriately coded numeric columns for boolean attributes (for example, 1=true, 0=false). Other derived types, such as date-time or monetary types are not supported.

Data Character Data

Character data are read from tables by trimming leading and trailing space characters. Thus, blank entries in a database appear as the empty string, "", which Madeline interprets as a missing value indicator. When entered on the command line, literal character data must be delimited by a pair of matching single or double quotes, e.g., "0001-230" or '0980A'.

Madeline's interpretation of character data is affected by the values stored in the CharacterMissingValue (aliased as CMV) array. Each value stored in this array is interpreted as an additional value to treat as a missing value indicator. The CharacterMissingValue array contains a set of default values that are appropriate for most data sets. Users can reassign current values, or assign additional values as needed.

Users planning on using Linkage files with Madeline in particular should note that the character string "0" (zero, used to represent missing parent IDs in Linkage files) is not considered a missing value by default in Madeline. Recall that Madeline treats individual and pedigree identifiers as character strings.

Data Numeric Data

All numeric data types are converted to double-precision floating point numbers. Literal numeric values are entered on the command line without delimiters. Interpretation of numeric data is affected by the values stored in the NumericMissingValue (aliased as NMV) array. Each value stored in this array is interpreted as an additional value to treat as a missing value indicator. Users should verify whether Madeline's default numeric missing values are appropriate for their data and reassign or add values to this array as necessary.

Data Logical or Boolean Data

Madeline does not recognize a logical or boolean data type separate from the numeric data type. In contexts where a value is to be interpreted as a logical value, Madeline treats zero (0) as #false, and any non-zero, non-missing value as #true. True/false data should thus be coded using a numeric field type with values of 0, 1, and a numeric missing value indicator if required.

Data Date Data

Dates are converted internally into Julian day integers. When entered at the command line, dates must be delimited between curly braces, { }.

Dates in tables or entered on the command line should be in ISO-8601 format (a four-digit year followed by a two-digit month and finally a two-digit day). In tables and on the command line, Madeline permits use of any of the following date delimiters:

YYYY

. - /

MM

. - /

DD

In addition, on the command line you can also use single spaces as delimiters:

M>? {2003 05 17}
{Saturday, May 17, 2003}
M>? ( {2003 05 17} - {1965 07 28} ) / 365.2425
37.8023
M>

M> set language to Japanese
 ...
M>? {2003 05 17}
{2003年5月17日 (土曜日)}

Pope Gregory XIII instituted the calendar that is now used internationally in October of 1582. (However, only the Catholic countries in Europe adopted the Gregorian calendar immediately. Other countries adopted it much later. For example, both England and the American colonies did not adopt it until the middle of the 18th century. Countries such as Thailand did not adopt the international calendar until the late 19th century). Madeline reports all dates since October of 1582 using the Gregorian calendar. In order to have Easter fall at the right time of the year once again, ten days were skipped in October of 1582. Madeline handles this correctly:

M>?{1582.10.04}
{Thursday, October 4, 1582}
M>?{1582.10.04} + 1
{Friday, October 15, 1582}
M>

Ten days were skipped in October of 1582 by Pope Gregory XIII.

Dates prior to October of 1582 are reported using a proleptic calendar that projects the Gregorian-Julian calendar back in time.

Data Display of Dates

By default, Madeline displays dates based on your computer's locale setting. If your computer is set to the "C" or "POSIX" locale or any other non-UTF-8 locale, Madeline defaults to AmericanEnglish conventions for displaying dates.

When you run Madeline under a UTF-8 locale, Madeline displays dates in the selected locale if possible. The program evaluates the following environment variables in order of precedence: LC_ALL, LC_DATE, LC_CTYPE, and LANG to determine how to display dates. Note that Madeline needs to be run in a Unicode-enabled terminal emulator, such as mlterm, for proper display of many languages.

You can also change the conventions used to display dates interactively using the set language command.

Examples are shown below:

edtrager@eyegene:~>LANG=fr_FR.UTF-8 madeline
...
+-----------------------+-----------+-----------------------------------------+
| OTHER SETTINGS        |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| AutoExclude           | ON        |Exclude pedigrees automatically          |
| AutoCheckInheritance  | ON        |Check inheritance on OPEN                |
| ConsoleHighlights     | ON        |Use bold/color highlights on console     |
| Delimiter             | TAB       |Delimiter for tables and other output.   |
| FusionSupport         | OFF       |FUSION customizations disabled           |
| HaplotypeDisplay      | OFF       |Display genotypes delimited with "/"     |
| Language              | French    |Language convention used for date, time  |
| MapDetails            | OFF       |LIST MAP summary display                 |
| SaveAlleleFrequencies | OFF       |Calculate new frequencies on next OPEN   |
| Date                  |           |le lundi 22 décembre 2003                |
| Verbosity             | VERBOSE   |All messages are printed to the console  |
+-----------------------+-----------+-----------------------------------------+
M>? {1983.12.03}
{le samedi  3 décembre 1983}
M>set language to japanese
...
M>? {1983.12.03}
{1983年12月3日 (土曜日)}
M>

UTF-8-based locale settings read from environment variables are used for determining how to display dates. You can also change the language settings interactively using the set language command.

Data Extent of Date Support

Dates may be added and subtracted from one another, with the results being expressed in days. Date data may be displayed on pedigree drawings. Dates may also be used in an expression passed to a view command, a draw command, or to a subsetting command such as exclude, or to the sort command (which sorts the order in which siblings appear on a pedigree drawing).

Most statistical genetics programs for which Madeline provides formatted files as output do not support date data. However, dates can be written to output files in Madeline's generic formats. You will need to toggle date fields on for output since they are toggled off by default.

Data Missing Value Support

Madeline supports entry of missing values from the command line, and also provides a simple mechanism for the user to define sets of values that should be mapped as missing values when a data are read from files.

On the command line, Madeline provides the following ways to represent missing values:

• "" quoted empty string for missing character data
• The token word #missing for missing numeric data
• Empty curly braces { } for missing date data

Protocols in scientific studies often require that missing values be coded to specify reasons for missingness. For example, a set of negative integers outside the range of a measured phenotype may be chosen to represent missing conditions, such as assay pending, no assay, no tube, or similar conditions that result in missing data.

To accomodate such conventions, Madeline permits the user to specify lists of values that are to be treated as missing values. These lists of missing value indicators are stored in two arrays. CharacterMissingValue[] is used whenever character fields, including genotype fields, are referenced. NumericMissingValue[] is used whenever numeric fields are referenced (see table below). For expediency, these arrays can be referenced using abbreviated names, cmv[] and nmv[], respectively. There is currently no missing value array for dates.

Character and numeric missing value arrays in Madeline.

In ASCII and UTF-8 data files, a space-padded blank entry or a single dot (i.e., a period) in a character or numeric column is treated as a "native" missing value. (Therefore, the empty string "" and single dot "." need not be included in the missing value arrays). A typical Madeline-ready data file using single dots as missing value placeholders is shown below:

FAMID C  
STUDYID C 
SEX X  
FATHER C  
MOTHER C  
MZTWIN C  
DZTWIN C  
AFFECTED C
AGE_DX N
D9S247 G 
D9S325 G 
D9S462 G 
D9S1017 G 
D9S1321 G 

L0012  M02448   F N00332   N00333  . . A  68  0/0      349/349  0/0      .        0/0     
L0012  M05605   F N00334   N00335  . . A  63  244/252  349/353  157/167  240/244  234/238 
L0012  M06039   F N00334   N00335  . . A  68  252/254  0/353    157/157  228/240  234/238 
L0012  N00332   M .        .       . . I  .   .        .        .        .        .       
L0012  N00333   F N00336   N00337  . . I  .   .        .        .        .        .       
L0012  N00334   M N00336   N00337  . . I  .   .        .        .        .        .       
L0012  N00335   F .        .       . . I  .   .        .        .        .        .       
L0012  N00336   M .        .       . . I  .   .        .        .        .        .       
L0012  N00337   F .        .       . . I  .   .        .        .        .        .       
L0034  M02453   M N00167   M05758  . . A  48  242/244  0/0      .        232/244  234/242 
L0034  M05758   F N00165   N00166  . . U  89  242/248  0/0      .        232/0    242/246 
L0034  M05759   M N00167   M05758  . . A  45  0/256    0/0      .        232/240  238/242 
L0034  M05856   M N00167   M05758  . . U  53  242/256  0/0      .        232/232  238/246 
L0034  M05876   F N00167   M05758  . . U  59  244/248  0/0      .        240/244  234/242 
L0034  N00165   M .        .       . . I  .   .        .        .        .        .       
L0034  N00166   F .        .       . . I  .   .        .        .        .        .       
L0034  N00167   M .        .       . . I  .   .        .        .        .        .       
L0075  M02454   F N00207   N00208  . . A  61  252/254  355/357  157/169  .        234/236 
L0075  M05526   F N00205   N00206  . . A  83  0/0      339/359  0/0      .        0/0     
...

A typical Madeline-ready data file with single dots (periods) as missing value placeholders. Madeline automatically recognizes single dots and blank entries as missing values in ASCII and UTF-8 data files.

Note: To increase human and machine readability, we highly recommend using dots (periods) as missing-value column placeholders in data files, as shown in the example above.

When data are read from a file, all "native" missing values (blank and single dot entries) and any values that match the values specified in Madeline's CharacterMissingValue[] or NumericMissingValue[] arrays are treated as missing values by Madeline. When data are written back out to files, missing values are automatically translated according to the conventions required by each file format (For example, when Madeline is used to create a file in the Linkage format, the digit zero (0) is used to represent missing values).

At startup, CharacterMissingValue[], contains a set of default missing value indicators appropriate for most character and genotype data. NumericMissingValue[] contains the single missing value of -9999 by default. It is the user's responsibility to recognize whether these defaults are appropriate for your data and make adjustments as required before attempting to open or load data files.

New values can be assigned to existing cells or appended to the end of these lists as required:

M>list cmv view CharacterMissingValue array
CMV has 5 elements:
CMV[ 1]="."
CMV[ 2]="/"
CMV[ 3]="0/0"
CMV[ 4]="0/ 0"
CMV[ 5]="0/  0"
M>cmv[6]="./."        append new value to the end of the list
M>list cmv
CMV has 6 elements:
CMV[ 1]="."
CMV[ 2]="/"
CMV[ 3]="0/0"
CMV[ 4]="0/ 0"
CMV[ 5]="0/  0"
CMV[ 6]="./."
M>list nmv            view NumericMissingValue array
NMV has 1 element:
NMV[ 1]=         -9999
M>nmv[1]=-1           overwrite one value
M>nmv[2]=-9           and append another value
M>list nmv
NMV has 2 elements:
NMV[ 1]=            -1
NMV[ 2]=            -9
M>

Assigning missing value indicators. Missing value indicators may be assigned to existing cells or appended to the ends of Madeline's character and numeric missing value lists.

Assignments should be done before a data table is opened so that the values will be recognized appropriately. The initial.script script file is an appropriate place to set character and numeric missing value indicator defaults.

Data Categorization of Data

Upon opening a pedigree table, Madeline categorizes each field into one of three categories:

• C: Core data
• G: Genotype data
• P: Phenotype data

When a field is completely empty or contains only missing values, Madeline assigns the field to a null category represented by an asterisk, "*".

When required, Madeline allows the user to designate a subset of "P" phenotype fields as "V" covariate fields using the toggle command. Madeline does not automatically assign fields to the "V" covariate category. Field categories are summarized in the table below and described in greater depth below.

Field Categories in Madeline.

Data Core Data Fields

Core "C" data fields provide key information about an individual (see table below). Madeline identifies core fields by their names (in contrast, "G" and "P" fields are distinguished by scanning the data in the table). These names are stored in variables whose values may be reassigned by the user.

In conformance with the requirements of the supported legacy database types, field names must be capitalized, and cannot exceed 10 letters in length. When assigning names to the field variables, Madeline will automatically capitalize and truncate non-conforming names, and will issue warning messages to the user.

Note: Limitations on field name length will likely be relaxed in the next release of the program when support for SAS and dBase/xBase file formats is removed.

Core data fields are either required or optional. The absence of one or more of the five required core fields will generate an error when a pedigree table is opened.

Optional core fields may be required for some operations, but are not required by default. Madeline makes use of the additional information provided in optional core fields whenever they are present. In particular, Madeline's pedigree drawing functionality is greatly enhanced by the presence of optional core fields such as AffectionStatusField and MZTwinField, among others.

Core fields representing categorical attributes of an individual, such as the GenderField and AffectionStatusField have corresponding associative arrays for mapping user data codes to Madeline internal codes.

Core Data Fields in Madeline.

Data Interpretation of Core Data

It is extremely easy to tell Madeline how to translate coded information stored in your data files into values that the program knows about and can process.

Coded values in the GenderField, AffectionStatusField, DeathStatusField, ProbandField, and LiabilityClassField are mapped to Madeline constants using the set of associative arrays shown in the table in the preceding section. Madeline provides default mappings that are appropriate for reading many character-coded and Linkage-coded data tables. For example, the GenderStatus[] array contains the following values by default:

M>list GenderStatus
GenderStatus has 6 elements:
GENDERSTATUS[ 1 ]=0  zero is defined as male in Madeline
GENDERSTATUS[ 2 ]=1 one is defined as female in Madeline
GENDERSTATUS["F"]=1
GENDERSTATUS["M"]=0
GENDERSTATUS["♀"]=1 For animal studies; requires UTF-8 data files in a UTF-8 locale.
GENDERSTATUS["♂"]=0 For animal studies; requires UTF-8 data files in a UTF-8 locale.

These defaults are equivalent to issuing the following sequence of map commands. Note that Madeline constants are prefixed by the hash sign (#):

M>map GenderStatus  1  as #male
M>map GenderStatus  2  as #female
M>map GenderStatus "F" as #female
M>map GenderStatus "M" as #male
M>map GenderStatus "♀" as #female
M>map GenderStatus "♂" as #male

Note how the mapping of 1 as #male and 2 as #female is appropriate for reading data coded according to Linkage file format conventions. The mapping of ♀ (Unicode u+2640) and ♂ (Unicode u+2642) are appropriate for animal studies.

Assignments can be made to the associative arrays directly without using the map command. The following assignment statements replicate the default mappings for the AffectionStatus[] array. The first three assignments allow Madeline to process files coded using the Linkage format conventions. The remaining three assignments support the processing of a substantially more intuitive coding convention that we prefer:

M>// Assignments to support the Linkage/Genehunter format:
M>AffectionStatus[ 0 ]=#missing
M>AffectionStatus[ 1 ]=#unaffected
M>AffectionStatus[ 2 ]=#affected
M>// Assignments to support a substantially more intuitive coding convention:
M>AffectionStatus["A"]=#affected
M>AffectionStatus["I"]=#missing
M>AffectionStatus["U"]=#unaffected

The mappings shown above for GenderStatus[] and AffectionStatus[] are the default mappings present when you start a Madeline session. Codes not present in these associative arrays will be mapped to #missing by default. If your codes match these codes, then you don't need to do anything. If your codes differ from the defaults, then you will need to provide the correct mappings in the initial.script, in a batch file, or on the command line. For example, if your pedigree table used the capitalized words "MALE" and "FEMALE" to indicate males and females respectively, then you would want to execute the following:

M>map GenderStatus "FEMALE" as #female
M>map GenderStatus "MALE" as #male

For the default values in all associative arrays, see Table 4.4.

Note: To insure that Madeline recognizes values in core fields correctly, assignment of values in associative arrays that affect the interpretation of core fields must be made before any open or load command.

Data Database Field Naming Conventions

Different databases impose different restrictions on the length and format of field names. Up to 10 characters can be used for field names in an xbase file, but only up to 8 characters in a SAS transport file. Although Madeline now supports several different file formats, the program originally only supported the xbase file format. As a result of this legacy, Madeline restricts field name identifiers as follows:

• Field names cannot exceed 10 characters in length. If you enter more than 10 characters for a core field identifier, Madeline will truncate the name to the first 10 characters. Madeline will inform you if truncation was required.
• Letters in field names must be capitalized. If you enter a core field identifier in lower case, Madeline will capitalize it for you. Madeline will inform you of a change in capitalization.

Here is an example:

M>AffectionStatusField="AffectionStatus"
Field name assignment has been truncated and capitalized to "AFFECTIONS".
M>

Field names are restricted to capitalized labels of 10 or fewer characters in length.

Note: Madeline will warn you if you try to assign a name with embedded spaces or control characters to a field name variable. However, the program does not actively check for all possible errors in field identifiers. This is the user's responsibility. Madeline also has no way of knowing in advance what type of database file will be opened. For example, the program will not notice if you enter a ten-letter name for use with a SAS transport file that permits only 8-letter field identifiers.

Note: Support for legacy xbase and SAS transport formats may removed in the next version of the program. Field name limitations would then become less restrictive.

Data Family Identifier

The value in FamilyIDField tells Madeline the name of the family ID field to look for in a pedigree table. The default value is "FAMID".

Data Individual and Parental Identifiers

The values in IndividualIDField, FatherIDField, and MotherIDField identify the individual and parent identifier fields for Madeline to look for in a pedigree table. The default values are "STUDYID", "FATHER", and "MOTHER", respectively.

Note: We recognize that the default value of IndividualIDField as STUDYID is not a good choice. The default will very likely become INDIVIDUALID in the next version of the program.

Parent IDs should be present in both the FatherIDField and MotherIDField of all non-founder individuals. The program interprets any individual with missing value indicators for both parents as a founder.

In the event that one of the two parent identifiers is missing for an individual or individuals in a sibship, Madeline automatically generates a random eight-letter identifier to represent the missing parent. The randomly-generated IDs begin and end with exclamation marks to distinguish them from regular IDs. Using the generated ID, Madeline constructs a virtual parent in memory who will appear on pedigree drawings (figure below) and in output generated by the write command. Madeline assumes that all the sibs with the one identified parent are full sibs sharing the one identified and other assumed parent.

Virtual constructed parent in Madeline. A virtual parent with a randomly-generated ID (male on the right) is constructed when the ID of one parent is missing among a sibship of individuals (not shown). Sibs are assumed to be full sibs.

Note: Lack of one parent usually indicates that a data set has not yet been thoroughly examined for errors or missing data. Unlike other programs, Madeline tolerates certain types of missingness and errors. This enhances the program's utility as a proofing tool. However, in the end you still have to fix your errors ;-).

Data Gender Data

The default value for GenderField is "SEX". The GenderField can be either numeric or character. Madeline detects the field type when the pedigree table is opened. Madeline defines two symbolic constants for gender:

• #female which has a value of 1
• #male which has a value of 0

The GenderStatus[] array is used to map external gender codes to Madeline's internal gender constants, #male and #female, as described above under Interpretation of Core Data.

Only terminal individuals without offspring may retain a gender attribute of #missing. During pedigree reconstruction, if Madeline detects any father or mother with a missing gender attribute, the program will automatically change the gender of the individual in memory to be consistent with the reconstruction, and will warn the user of the change (example below). The database file on disk will not be changed.

Madeline will also automatically correct the gender attribute of mislabeled individuals in memory, for example, of a male listed as a mother, or of a female listed as a father (example below), to the extent that these changes still result in logical consistency. Madeline always warns the user of these types of data errors. Again, the data file on disk will not be changed; that is the user's responsibility.

M>open "family.mfh"
   ...
   
ConnectIndividual(): Gender in database is incomplete:
        Gender of G-10-162's mother, G-10-159, changed from MISSING to FEMALE
ConnectIndividual(): Gender in database is incorrect:
        Gender of G-15-012's father, G-15-003, changed from FEMALE to MALE
13 WARNINGS, 11 SEVERE WARNINGS M>

Inconsistencies in Gender. During pedigree reconstruction, Madeline automatically corrects inconsistencies in gender in the data set (as long as such changes do not violate the logical consistency of the reconstruction) and warns the user.

Madeline will warn the user and terminate if conflicting and unresolvable gender roles exist for an individual (for example if an individual is listed as both a mother and a father in the data set).

Note: We recommend coding the GenderField as a character field using conventional codes such as "M" and "F", or "male" and "female". Not only does this enhance human interpretability of the raw data files, but also enhances Madeline's ability to automatically identify columns when the recognize command is used. Numerically-coded fields, such as those in Linkage/Genehunter files, generally cause unecessary confusion and introduce a greater potential for errors.

Data Monozygotic and Dizygotic Twin Data

The MZTwinField should remain blank (or use a single dot) for non-twins, and should contain a single-letter identifier for each twin pair or group of monozygotic siblings. For example, "A" can be used to designate the first twin pair in a family, "B" the second pair, and so on. Since version 0.90 of the program, the MZTwinField has been considered an optional core field.

The optional DZTwinField, used to show dizygotic twins on pedigree drawings, should be coded in the same manner to designate dizygotic twins.

Data Affection Status Data

The AffectionStatusField may be either character or numeric. Madeline defines two symbolic constants for describing the affection status of sampled individuals:

• #unaffected which has a value of 0
• #affected which has a value of 1

Madeline provides the AffectionStatus[] associative array for mapping affection status codes.

Note: Coding the AffectionStatusField as a character field using mnemonic codes is recommended to enhance interpretability of the data in the absence of additional metadata. Numeric fields tend to cause confusion and may increase the potential for human error.

Data Death Status Field

The optional DeathStatusField may be either character or numeric. The default value of DeathStatusField is "DECEASED". Madeline defines the constants #alive, with a value of 0, and #dead, with a value of 1. The DeathStatus[] associative array contains a set of defaults for mapping the DeathStatusField. This is shown below:

M>
M>?DeathStatusField
"DECEASED"
M>?#alive
0
M>?#dead
1
M>list DeathStatus
DeathStatus has 4 elements:
DeathStatus[0]=0
DeathStatus[1]=1
DeathStatus["N"]=0
DeathStatus["Y"]=1
M>

The DeathStatusField, DeathStatus array, and #alive and #dead constants.

Note: Coding the DeathStatusField as a character field using mnemonic codes is recommended to enhance interpretability of the data in the absence of additional meta data. Consider how coding a column using "L" for "living" and "D" for "deceased" is more meaningful than using "1" for "living" and "0" for deceased -- especially when you realize that Madeline's default encoding is exactly the opposite, with "1" being "deceased" and "0" being "living"!

Data Proband Field

The optional ProbandField must be numeric. Madeline assumes that the probands or index cases will be coded using a value of 1, and all other individuals with a value of 0.

Data Liability Class Field

Some output formats, such as Genehunter, have the option of including liability class information. The LiabilityClassField may be numeric or character. Madeline does not interpret the values in this field, but simply passes the values on directly. This means that if a program like Genehunter requires a numeric encoding of liability classes, you must insure that the source data are encoded numerically in a conformant manner.

Data Date of Birth and Death Data

The DateOfBirthField and DateOfDeathField are optional core date fields. When present, Madeline performs checks to insure that dates in these fields are reasonable, and looks for twins based on date of birth who have not been designated as such in the MZTwinField or DZTwinField.

Data Genotype Data

Genotype "G" data are character fields that contain allelic marker data separated by the forward slash "/" character. The allele labels themselves must be numeric, non-alphabetic labels, e.g. "1/2" or "141/142".

The names of genotype fields should be the capitalized names of the markers themselves. This allows Madeline to automatically place the genotype fields into map order whenever a map database for the markers is loaded using the load command. Make sure that marker names in the map table are capitalized to correspond with the required capitalization of field names.

Data Estimation of Allele Frequencies from Genotype Data

When a database is opened, Madeline automatically estimates allele frequencies for all genotype fields using gene counting ignoring family relationships. Allele frequencies are estimated from all records in a database.

Allele frequencies calculated from one pedigree table may be saved out using the save command. A table of allele frequency information can subsequently be read into Madeline using the read command. The format of the allele frequencies table is nearly identical to the format used by Mendel v. 4.1. You need only modify the header at the top of an allele frequency table to conform with the Mendel program convention.

Data Phenotype Data

Phenotype "P" fields are any remaining fields that are not core "C" or genotype "G" fields. Phenotype fields may be character, numeric, or date fields, and are assumed to contain categorical or continuous phenotype information. Because date fields cannot be written to output from the write command, date fields are the only type of phenotype field not flagged for output when a pedigree table is opened.

For some types of output, it may be necessary to designate certain phenotype fields as representing covariates. Madeline therefore maintains a separate covariate or "V" field category which is a subset of the "P" category. Covariate fields are automatically recognized as phenotype fields when writing any format that does not distinguish between phenotype and covariate fields. "P" fields can be marked as "V" fields using the toggle command.

Data Marking and Ordering Data Fields for Output

When a pedigree table is opened, most core "C" fields, all genotype "G" fields, and all phenotype "P" fields (except date fields), are flagged, or toggled on, for output by default. Madeline indicates which fields in a database are toggled for output by placing the letter "o" after the category indicator "C","G", or "P" (example below). A number after the "o" indicates the order in which fields will appear in pedigree drawings and in output from the write command. Fields may be manually reordered using the set field order command.

M>list fields
  1.FAMID      Co__1   20.D20S482    Go__6   39.D20S96     Go_25
  2.STUDYID    Co__2   21.D20S849    Go__7   40.D20S119    Go_26
  3.SEX        Co__3   22.D20S905    Go__8   41.D20S481    Go_27
  4.FATHER     Co__4   23.D20S846    Go__9   42.D20S836    Go_28
  5.MOTHER     Co__5   24.D20S892    Go_10   43.D20S888    Go_29
  6.TWIN       Co__6   25.D20S115    Go_11   44.D20S886    Go_30
  7.AFFECTED   Co__7+  26.D20S851    Go_12   45.D20S197    Go_31
  8.BMI        Po__1   27.D20S917    Go_13   46.D20S178N   Go_32
  9.INS_FAST   Po__2   28.D20S894    Go_14   47.D20S866    Go_33
 10.INS_2H     Po__3   29.D20S189    Go_15   48.D20S196    Go_34
 11.BW_REAL    Po__4   30.D20S898    Go_16   49.D20S857    Go_35
 12.GLU_FAST   Po__5   31.D20S114    Go_17   50.D20S480    Go_36
 13.GLU_2H     Po__6   32.D20S912    Go_18   51.D20S211    Go_37
 14.GAD_DUP    Po__7   33.D20S477    Go_19   52.D20S840    Go_38
 15.D20S103    Go__1   34.D20S874    Go_20   53.D20S120    Go_39
 16.D20S117    Go__2   35.D20S195    Go_21   54.D20S100    Go_40
 17.D20S906    Go__3   36.D20S909    Go_22   55.D20S102    Go_41
 18.D20S193    Go__4   37.D20S107    Go_23   56.D20S171    Go_42
 19.D20S889    Go__5   38.D20S170    Go_24   57.D20S173    Go_43
M>

Fields Categorization and Ordering in Madeline. Core "C" fields are detected by name. Genotype "G" are detected by scanning the data: all remaining fields are assumed to be phenotype "P" fields. Fields are ordered for output respectively within the three groups, "C", "G", and "P". The plus "+" sign after AFFECTED indicates that Madeline has detected this field as the AffectionStatusField: categorical levels of this field will be used to color icon symbols on pedigree drawings.

A field listing is shown when a pedigree table is first opened or at any other time using the list fields command.

The order of genotype fields is automatically set to map order when a marker map database is loaded using the load command. Load can be issued either before (the preferred method) or after an open command. Genotype fields whose names match the names of markers in the map database will be set to the map order.

Fields toggled on for output are displayed in pedigree drawings created with the draw command.

When a write command is executed, the set of core "C" fields required by the specific format being produced will generally be output regardless of the on/off output flag status. For example, Madeline will output the GenderField even if you toggle it off because it is required for almost all output formats. This behavior is required to insure proper file construction. Genotype "Go" fields toggled for output will be written, along with phenotype "Po" (and possibly covariate "Vo") fields toggled for output if the analysis format supports phenotype fields. Some analysis programs, such as Genehunter and Siblink, do not use phenotype data beyond affection status (which is a core field).

Fields may be toggled on or off for output using the toggle command.

Data Genetic Map Data

Madeline makes use of marker map information to:

• Automatically order genotype "Go" fields for output.
• Write marker position and intermarker distance information in locus and control files.

The load command is used to load a table containing genetic maps for one or more chromosomes. A genetic map table may contain only one map for each chromosome. At a minimum, the map table must have columns specifying the chromosome, rank or ordinal position of the marker within the map for a given chromosome, name of the marker, and the position of the marker in centiMorgans:

Minimum Required Fields in a Map Table

Additional columns for sex-specific maps may also be present: see the load command for details.

A map may be viewed using the list map command:

M>load 'marshfield.map.mfh'
Marker maps based on marshfield.map.mfh are now installed.
M>list map for chromosome 7

                    Map Position (Kosambi cM)
                  -----------------------------
Ch Or Marker Name Sex-avg.   Female     Male
-- -- ----------- --------- --------- ---------
 7  1 035XB9         0.0000     .         .
 7  2 GATA24F03      0.0001     .         .
 7  3 GATA61G06      3.7001     .         .
 7  4 TATC010        6.4001     .         .
 7  5 GATA119B03    10.0001     .         .
 7  6 TATT019       17.3001     .         .
 7  7 GATA137H02N   22.0001     .         .
 7  8 GATA41G07     26.0001     .         .
 7  9 GATA137A12    30.5001     .         .
 7 10 GGAA3F06      35.0001     .         .
 7 11 AGAT103       37.7001     .         .
 7 12 GATA13G11     43.0001     .         .
 7 13 GATA026       48.8001     .         .
 7 14 GATA31A10     51.0001     .         .
 7 15 ATA31F09      55.1001     .         .
 7 16 TAT028        57.3001     .         .
 7 17 GATA24D12     63.0001     .         .
 7 18 GATA4E04      65.8001     .         .
 7 19 GATA118G10    72.0001     .         .
 7 20 GATA21D12     77.0001     .         .
 7 21 GATA73D10N    84.0001     .         .
 7 22 GATA87D11     88.4001     .         .
 7 23 GATA3F01      91.0001     .         .
 7 24 ATA78C09NZ    96.6001     .         .
 7 25 GATA5D08     102.0001     .         .
 7 26 GATA23F05    107.0001     .         .
 7 27 ATAC037      112.9001     .         .
 7 28 TTTA001      118.1001     .         .
 7 29 AGAT133      119.1001     .         .
 7 30 GGAA6D03N    121.0001     .         .
 7 31 ATA55A05     123.2001     .         .
 7 32 GATA145G10   127.6001     .         .
 7 33 GATA43C11    130.0001     .         .
 7 34 GATA63F08    143.0001     .         .
 7 35 GATA32C12    143.0002     .         .
 7 36 GATA104      148.0002     .         .
 7 37 AGAT049      150.8002     .         .
 7 38 GATA189C06   156.0002     .         .
 7 39 TATG002      161.0002     .         .
 7 40 GATA30D09N   167.0002     .         .
 7 41 MFD442-GTTT  171.6002     .         .
M>

Loading and viewing marker maps. A map table is loaded using the load command. The list map command is used to print a table showing marker name, chromosome, mapped order, and position in centiMorgans.

Log and Error Reporting Features

Madeline produces three types of log files (table below). The first is a summary file that has a ".log" extension by default and records each command that was entered and a summary of execution results. The second is a detail file that has a ".dtl" extension by default. It provides details of command results, such as which pedigrees and individuals were included or excluded and why. The third log file is an error log that has a ".err" extension by default. It records warning and error conditions that occur.

Three Types of Log Files

You can change the names of the log files individually or en masse, as shown below:

M>?LogFile
"madeline.log"
M>LogFile="MyLogFile.log"
LogFile has been changed from "madeline.log" to "MyLogFile.log"
M>DetailFile="MyDetailLogFile.dtl"
DetailFile has been changed from "madeline.dtl" to "MyDetailLogFile.dtl"
M>ErrorFile="AreYouKiddingMeIDontMakeMistakes"
ErrorFile has been changed from "madeline.err" to "AreYouKiddingMeIDontMakeMistakes"
M>AllLogFiles="MySuperDuperAnalysis"
All log files now have "MySuperDuperAnalysis" as the base name:
        LogFile    = "MySuperDuperAnalysis.log"
        DetailFile = "MySuperDuperAnalysis.dtl"
        ErrorFile  = "MySuperDuperAnalysis.err"
M>

Display of Warning and Error Levels

As warnings or error conditions are detected while executing commands, Madeline's prompt changes interactively to display the number and type of conditions. For example:

1 SYNTAX ERROR 10 WARNINGS M>

... clearly indicates that one syntax error and ten warnings have occurred. The program tracks warnings and errors in four categories:

1. Syntax errors
2. Warnings
3. Severe Warnings
4. Fatal Errors

A syntax error refers to an error in typing a command on the command line or in a batch file. A warning indicates a manageable data condition, such as having only one instead of both parents listed. A severe warning indicates a more severe condition or logical inconsistency such as having a male listed as the mother of an individual. Madeline will try to manage this type of situation, for example by changing the sex of the "male" mother to "female". Such a change does not guarantee that the situation is remedied, much less correct. Later in the same table, the "male" mother may turn out to be listed as the "father" of another child! This would raise a fatal error condition and termination of the program because there is no way to rectify such inconsistent information. The warning and error conditions may be reviewed in the error log.

Pedigree Reconstruction and the Categorization of Individuals

When a pedigree table is opened, Madeline reconstructs pedigrees based on the core data fields. Individuals with both parents missing are founders. Individuals with one or both parents specified are non-founders. Ideally, non-founder individuals should always have both parents specified. In reality, this doesn't always happen. In cases where one parental ID is present and the other is missing, Madeline creates a random ID for the missing parent. Random IDs are always eight characters in length and begin and end with an exclamation point (e.g., "!EW12M5!", "!G79ER5!", etc.). When a set of siblings all share one parent but are missing an identifier for the other parent, Madeline makes the assumption that all of the sibs are full sibs.

After reconstructing pedigrees, Madeline classifies individuals into the following categories:

Classes of Individuals in Madeline

The distribution of individuals by category is summarized in a table printed by the program:

M> open "test/test.data.mfh"
         .
         .
         .
-----------------------------  --------- --------- ---------
Pedigrees and Individuals       Included  Excluded     Total
-----------------------------  --------- --------- ---------
Pedigrees ...................        590         0       590
Individuals .................      3,317         0     3,317
 + In database ..............      2,178         0     2,178
 |  + Attached ..............      2,164         0     2,164
 |  + Childless spouses .....         14         0        14
 |  + Unattached ............          0         0         0
 + Not in database ..........      1,139         0     1,139
M>

Summary table of pedigree count and distribution of individuals by category in Madeline. After a database is opened and pedigrees reconstructed, Madeline displays a table showing the number of pedigrees and distribution of individuals by category.

Attached individuals are individuals in the database who have either parents, or offspring, or both. Unattached individuals are in the database, but remain unconnected because they dont have parents or offspring. A legitimate class of unattached individuals is a set of unrelated singleton controls. The appearance of other unattached individuals is often due to data coding errors in the identifiers.

Madeline provides _IsUnattached, _ChildlessSpouse, and _IsInDatabase as references which return boolean status information regarding the categorization of an individual. These references can be easily used in queries to find out about the categorization of individuals:

M>view for _IsUnattached
N00444 in L0049 (rec. no.   104) * unattached *
M00005 in L1006 (rec. no.   921) * unattached *

2 individuals in 2 pedigrees matched as follows:

Individuals ..............          2
 + In database ...........          2
 |  + Attached ...........          0
 |  + Childless spouses ..          0
 |  + Unattached .........          2
 + Not in database .......          0
M>

References returning boolean status information about individuals, such as _IsUnattached, can be easily incorporated into queries in Madeline.

Data Classifications of Individuals

Before writing a file in a specific format using the write command, Madeline determines which individuals in a pedigree have data that can be used in an analysis of that pedigree. Madeline does this by examining the phenotype "Po" and genotype "Go" fields toggled on for output. Madeline uses this information when deciding which individuals are required in output. This is described in more detail in Data Evaluation and Management.

After the file has been written, Madeline displays a summary table showing the distribution of included and excluded pedigrees and individuals by category:

M>write to "test/test.ped" in genehunter format
          .
          .	
          .
-----------------------------  --------- --------- ---------
Pedigrees and Individuals       Included  Excluded     Total
-----------------------------  --------- --------- ---------
Pedigrees ...................        574        16       590
Individuals .................      3,247        70     3,317
 + In database ..............      2,140        38     2,178
 |  + Attached ..............      2,140        24     2,164
 |  |  + With data ..........      2,139        15     2,154
 |  |  + Without data .......          1         9        10
 |  |  + Marked for exclusion          0         0         0
 |  + Childless spouses .....          0        14        14
 |  + Unattached ............          0         0         0
 + Not in database ..........      1,107        32     1,139
M>

Summary table after a write command in Madeline. Madeline displays a summary table showing the distribution of included and excluded pedigrees and individuals by category. Attached individuals (in bold) are sub-categorized based on whether they have data or not, or have been marked for exclusion by the user.

Twin Management

When present, Madeline relies on information contained in the MZTwinField, DZTwinField, and DateOfBirthField to evaluate monozygotic and dizygotic twinships. When the optional DateOfBirthField is included, Madeline verifies that birth dates of twins match. Verification is extended to dizygotic twins when the optional DZTwinField is also included.

When the DateOfBirthField is included, Madeline looks for twins who are not marked in the either MZTwinField or DZTwinField (if present). Apparent twins of opposite sex are categorized as dizygotic twins. Apparent same-sex twins are assigned to a special twin of unknown type category. Twins whose type is unknown are shown with a question mark between them in pedigree drawings.

If Madeline encounters single, unpaired individuals marked as twins in the MZTwinField or DZTwinField, the program automatically removes the twin flag and informs the user of the change. The flag is only altered in memory -- the data table itself remains unchanged.

Messages about twinships are recorded in the summary and detail log files.

Consanguinity

Madeline automatically detects consanguinity in pedigrees. Messages about consanguinity are recorded in the summary and detail log files. Consanguineous marriages are shown with double lines on pedigree drawings.

Multiple Mates

There is no limit to the number of spouses that an individual in a pedigree may have. Currently, pedigree drawings can only display up to 10 spouses of a single individual.

Multiple Original Founders

Founders are individuals with both parents missing. Original founders are the most ancestral founders who appear at the top of the v-shaped descent trees on pedigree drawings.

Madeline can model pedigrees having multiple original founders. When the DividedPages flag is on (the default), Madeline's draw command will draw pedigrees consisting of an ancestral founder with one or more founding spouses on a single page. Pedigrees consisting of two or more founding groups will be printed on multiple pages.

Note: Pedigree drawing functionality in version 0.935, while useful, still leaves much to be desired. We hope to improve the drawing facilities greatly in the next release.

Data Evaluation And Management

Prior to writing output in a specific format, Madeline determines which individuals in a pedigree have data that can be used for analysis by examining the genotype "Go" fields and, if appropriate, the phenotype "Po" and covariate "Vo" fields toggled on for output.

In general, an individual is considered to have genotype data if he is typed for at least one marker among the set of "Go" fields.

Missingness among phenotype fields "Po" and covariate fields "Vo" turned "on" for output is not considered when deciding whether to include individuals for output.

After flagging individuals in a pedigree who have usable data, Madeline decides whether the entire pedigree is usable or not. Madeline's decisions depend on the specific format keyword associated with the write command. For example, using the GenehunterNpl keyword (for a non-parametric analysis) will result in a different set of pedigree exclusions than the genehunter keyword (for a parametric analysis), although there will be overlap in the sets.

Only required individuals in included pedigrees are written to output. Required individuals consist of individuals who:

• Have data -- or --
• Are required to maintain pedigree structure for individuals who have data

For example, records for unsampled parents are often required to show relationships among siblings. Terminal individuals without offspring who do not have data are excluded from output. Individuals who have been marked for exclusion by the user using the exclude command will be included, but without their data, only if they are required to maintain pedigree structure. Otherwise, they will be excluded.

It is possible to turn off Madeline's data evaluation machinery for most formats in order to force the inclusion of all pedigrees and individuals in output by issuing the command set autoexclude off. Modern programs like Merlin, Mendel, and Allegro are smart enough to trim uninformative individuals from data sets as required.

Tracking Inclusion and Exclusion of Pedigrees and Individuals

Madeline's detail log file records which pedigrees were excluded from output. Below is an example detail log produced after requesting an output file in GenehunterNpl format:

         .
         .
         .
GenehunterPedigreeHasData(): excluding pedigree 0547: contains only a single affected 
individual.
GenehunterPedigreeHasData(): excluding pedigree 0557: contains only a single affected 
individual.
GenehunterPedigreeHasData(): excluding pedigree 0558: lacks an individual with data.
GenehunterPedigreeHasData(): excluding pedigree 0560: contains only a single affected 
individual.
GenehunterPedigreeHasData(): excluding pedigree 0572: contains only a single affected 
individual.
GenehunterPedigreeHasData(): excluding pedigree 0583: contains only a single affected 
individual.
GenehunterPedigreeHasData(): excluding pedigree 0587: contains only a single affected 
individual.
         .
         .
         .

Excerpt from a Madeline detail log file produced after requesting output in GenehunterNpl format. Madeline's detail log file records which pedigrees were excluded from output and why.

In addition, a draw command executed after a write command will automatically produce annotated pedigree drawings showing which individuals:

• Were marked for exclusion by the user ("EXCLUDED")
• Have usable data ("HAVE DATA")
• Were included ("INCLUDED") in output

An example is shown below. In this example, the user marked individuals with a body mass index (BMI) greater than or equal to 35 for exclusion using the exclude command and then requested an output file in GenehunterNpl format.

Annotated pedigree drawing produced by draw after an exclude for bmi>=35 followed by a write command. Madeline dummied-in the two founding parents, "200" and "300", who are indicated by dashed lines. They were included ("INCLUDED") in output. Two individuals, "500" and "601", were marked for exclusion by the user. The terminal individual, "601" with a bmi of 43.8, was not included in the Genehunter output ("EXCLUDED"), but "500" was retained with data excluded in order to preserve pedigree structure ("DATA EXCL INDV INCL"). The remaining individuals are all annotated as having genotype data and were included in output ("HAS DATA - INCLUDED"). Affected individuals are shaded and labeled with "A", while unaffected individuals are unshaded and labeled with "U".

Queries and Subsetting

Madeline provides powerful mechanisms for querying and subsetting records in pedigree tables. General database management systems match query criteria one record at a time. In contrast, Madeline's query engine recognizes that individuals are connected in a network of relationships that begins with each individual's parents, mates, and offspring. Madeline provides references that begin with the underscore character, "_", for referring to the records of related individuals within a single query statement. For example:

M>// Query for individuals born to very young mothers:
M>view for _mother.age-_self.age<=17
   ...

You can also reference aggregate or summary information related to an entire sibship, such as the mean sibship value of a variable, as easily as you can reference values related to single individuals. These two mechanisms -- referencing related individuals and referencing sibship aggregate data -- make it easy to get answers to many questions in Madeline that would be quite tedious to obtain in a general database management system. Refer to Table 4.5. Individual Attributes and Table 4.8. Aggregate Functions for complete lists and numerous query examples.

Note: We are exploring ways in which we might expand Madeline's set of aggregate data functions. The next version might include the ability to calculate pedigree-wide or affecteds-only calculations.

Referencing Meta Information About An Individual And Relatives

Madeline allows the user to look at meta information about an individual and his or her relatives using references or attributes. References are a subset of keywords which begin with an underscore character,"_", to distinguish them from similarly-named variables or fields in databases. There are two types of references:

• references to meta information about an individual, such as _NumberOfOffspring
• references which point to relatives of an individual, such as _father

References References to Internal Information About An Individual

Madeline provides references to many items of internal information about an individual, such as the number of offspring (_NumberOfOffspring) and number of mates (_NumberOfMates) an individual has, and total number of individuals in the individual's pedigree (_NumberInPedigree):

M>go 384
M>? _id
"N00562"
M>? _NumberOfMates
2
M>? _NumberOfOffspring
2
M>? _NumberInPedigree
13

Table 4.5 lists all references to internal information.

References References To Relatives

Madeline also maintains references which point to relatives of an individual. The references to mates, _mate[], and offspring, _offspring[], are treated as arrays. Alternate references such as _spouse for _mate[1] and _FirstChild for _offspring[1], are also provided for convenience:

M>? _spouse._id
"N00564"
M>? _mate[1]._id Equivalent to _spouse._id
"N00564"
M>? _mate[2]._id
"N00563"

References can be chained using the dot operator, ".", in order to access information related to more distant relatives. For example, a paternal grandmother may be referenced using _father._mother. Convenience references such as _PaternalGrandmother are also provided:

M>? _father._mother._NumberOfOffspring
2
M>? _PaternalGrandmother.caff_broad
"I"
M>? _PaternalGrandmother._id
"N00569"

A complete list of references to relatives is provided in Table 4.5.

Aggregate Functions

In addition to references to individual information and relatives, Madeline provides aggregate functions that allow one to look at aggregate or summary information -- such as means and standard deviations -- of the offspring:

M>go 391
M>? _self._id
"N00569"
M>? _NumberOfOffspring  How many offspring?
2
M>? _FirstChild.sex Gender of first child?
"F"
M>? _SecondChild.sex Gender of second child?
"M"
M>? _OffspringCountTrue( sex="M" ) How many offspring are male?
1
M>? _OffspringCountTrue( caffected="A" ) How many offspring are affected?
2
M>? _OffspringMean( age_dx ) Mean age of diagnosis?
39.5
M>show _Offspring[1].bmi Body mass index of first child
31.1327
M>show _Offspring[2].bmi Body mass index of second child?
32.7896
M>show _OffspringMean(bmi) Mean BMI?
31.9612
M>show _OffspringStdDev(bmi) Standard deviation of BMI?
1.17156
M>

Aggregate Functions In Madeline. Aggregate functions allow one to look at summary information such as means and standard deviations of attribute data of the offspring of individuals.

All aggregate functions take as an argument an expression which evaluates to a numeric result. Table 6.2 lists the aggregate functions available in Madeline.

Query and Subsetting Commands

The view command retrieves a subset of records that match query criteria. The exclude command allows the user to mark a subset of records for exclusion from output. The unexclude command performs the opposite function -- unmarking a subset of records previously marked for exclusion. The draw command can also be invoked with a query expression in order to draw a subset of pedigrees. Example usage is shown below:

M>view for _noffspring>=3 and _omean(bmi)>=50
2113-100 in 2113 (rec. no.    32)
2113-500 in 2113 (rec. no.    35)

2 individuals in 1 pedigree matched as follows:

Individuals ..............          2
 + In database ...........          2
 |  + Attached ...........          2
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0

M>exclude for _noffspring>=3 and _omean(bmi)>=50
2113-100 has been marked for exclusion
2113-500 has been marked for exclusion

2 individuals in 1 pedigree marked for exclusion as follows:

Individuals ..............          2
 + In database ...........          2
 |  + Attached ...........          2
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
M>draw pedigrees for _noffspring>=3 and _omean(bmi)>=50
1 pedigree in result set
calling "gs madeline.ps"

Query and Subsetting Commands. In this example, the view command is used to identify parents having three offspring whose mean body mass index is greater than or equal to 50. The query result set contains one pair who are excluded using exclude. The draw command is then invoked with the same query expression in order to draw the relevant pedigree. The command draw pedigree '2113' could also have been used.

Pedigree Drawings

Madeline's draw command produces drawings of pedigrees using Adobe Postscript language procedures and document structuring conventions:

An example pedigree drawn by Madeline. In this example, two categorical variables indicating disease conditions are graphically displayed on the left and right halves of the icons. The status of the first condition, on the left side, is coded using "U" for unaffected and "A" for affected. On the right side, the status of the second condition is coded using "U" for unaffected, "M" for moderate, and "S" for severe. Missing values are indicated by dots, ".". The icon drawn with a dashed line perimeter indicates an individual whose record was not found in the database. No ID was provided in the FatherIDField of the gender-unknown offspring, and so the program has assigned a random ID of !21A3F8! to the missing father. The displayed data were invented to illustrate the drawing capabilities of the program).

Pedigree drawings can display any number of field variables present in a dataset. The toggle command is used to select fields for inclusion on a pedigree drawing.Toggle output flags toggles which fields appear as labels under the icons on a pedigree drawing. The set field order command is used to order selected fields within their respective categories, "C" ,"P", or "G". On drawings, core "Co" fields always appear first, followed by phenotype "Po" fields, and finally genotype "Go" fields.

Toggle icon flags toggles on or off the set of categorical variables to be displayed graphically by shading or coloring regions of the male and female icons. Madeline divides the icon into pie-slice shading regions based on the number of categorical variables selected. The program does not impose a limit on the number of categorical variables that can be graphed simultaneously.

The manner in which subtrees are divided across pages, the paper orientation, size, margins, and color may all be set using various set commands.

The pedigree drawing routines are currently limited. DividedDrawings is set on by default, which causes subtrees of a pedigree originating with different original founding groups to be printed on separate pages. In the current version, turning DividedDrawings off has no affect.

Note: DividedDrawings will cease to exist in the next version of the program.

Orientation may be set to portrait, landscape, automatic, or MultiPage. When orientation is set to automatic or MultiPage, Madeline decides on the orientation of individual pedigrees depending upon the width and height of each drawing. In the event that a drawing would require excessive reduction to fit on a single page, Madeline will automatically include Postscript commands to print the drawing in poster-style across several physical pages.

Madeline's Postscript drawing routines are efficient, typically permitting the construction of hundreds of drawings per second on a modern workstation. The internal variable PostscriptViewer holds the name of a Postscript viewing application. The configuration scripts which you run to set up Madeline will normally detect the presence of a program such as gv on Linux and similar operating systems. On Windows or Mac OS X, you may need to manually assign the name of an accessible viewer such as GhostView or GSView to this variable. Such an assignment can be made in initial.script.

  14.GAD_DUP    Po__7   33.D20S477    Go_19   52.D20S840    Go_38
  15.D20S103    Go__1   34.D20S874    Go_20   53.D20S120    Go_39
  16.D20S117    Go__2   35.D20S195    Go_21   54.D20S100    Go_40
  17.D20S906    Go__3   36.D20S909    Go_22   55.D20S102    Go_41
  18.D20S193    Go__4   37.D20S107    Go_23   56.D20S171    Go_42
  19.D20S889    Go__5   38.D20S170    Go_24   57.D20S173    Go_43
 M>toggle output flags for 1,3-6,20-57
 M>PostscriptViewer="gv"
 M>draw pedigrees for bmi>=45
 Drawing pedigree 0009, 0009-300's subtree (page 1 of 1) ...
 Drawing pedigree 0086, 0086-300's subtree (page 1 of 1) ...
 Drawing pedigree 0213, 0213+300's subtree (page 1 of 1) ...
 Drawing pedigree 0235, 0235-300's subtree (page 1 of 1) ...
 Drawing pedigree 0305, 0305-300's subtree (page 1 of 1) ...
 Drawing pedigree 0322, 0322-300's subtree (page 1 of 1) ...
 Drawing pedigree 0547, 0547-300's subtree (page 1 of 1) ...
 Drawing pedigree 0572, 0572-300's subtree (page 1 of 1) ...
 Drawing pedigree 0808, 0808+300's subtree (page 1 of 1) ...
 Drawing pedigree 1082, 1082-300's subtree (page 1 of 1) ...
 Drawing pedigree C161, C161+500's subtree (page 1 of 1) ...

 11 pedigrees in result set.

 Calling "gv madeline.pedigree.ps" ...

Drawing pedigrees in Madeline. Toggle output flags specifies which fields will appear on the pedigree drawings. Draw pedigrees for ... specifies a subset of pedigrees that match the query criteria. Madeline calls the Postscript viewing application named in PostscriptViewer (gv in this case).

The Postscript viewer gv displaying a pedigree drawing created by Madeline.

Producing Output Files for Analysis

The write command is used to produce locus, pedigree, and control or parameter files for analysis. Keywords like Mendel and GenehunterNpl are used to specify the analysis file format.

For most formats which require a control or parameter file, a single write command suffices to produce both the pedigree and control file. In these cases, the control file often contains the required locus information.

For some other formats, the command write locus file ... is used to produce the locus file separately, while write pedigree ... is used to create the pedigree file. Section 3. Write Formats, documents what is required for every supported format.

Section 2 Commands

Introduction to Commands

This section describes Madeline's commands. Commands are presented in alphabetical order. A heading shows the name of each command. Below the heading, the syntax for the command is given. Note the following conventions:

Table 3.1. Command syntax conventions used in this document.

A typical command syntax chart is shown below:

A typical command syntax chart

The syntax charts shows you how to construct a command with valid options. For example, piecing together the options highlighted in green above leads one to command constructs such as the following:

M>toggle on output flags for 12-15

A description follows after the syntax. At least one example of command usage is provided.

Commands with multiple usage patterns may be broken down into multiple sub-sections.

Banner

banner

Displays the program banner. Also see: hello, and status.

M>banner
______________________________________________________________________________
 ______________________________________________________________________________
  __    __       _       ______     _______   _          _   __    _   _______
 |  \  /  |     / \     |  ___  \  |  _____| | |        | | |  \  | | |  _____|
 |   \/   |    / ^ \    | |   \  \ | |___    | |        | | |   \ | | | |___
 | |\  /| |   / /_\ \   | |    | | |  ___|   | |        | | | |\ \| | |  ___|
 | | \/ | |  /  ___  \  | |___/  / | |_____  | |______  | | | | \   | | |_____
 |_|    |_| /__/   \__\ |_______/  |_______| |________| |_| |_|  \__| |_______|
 ______________________________________________________________________________
 ______________________________________________________________________________

                                 Version  0.935
                           Written by Edward H. Trager
                              <ehtrager@umich.edu>

COPYRIGHT  © 2004
THE REGENTS OF THE UNIVERSITY OF MICHIGAN
PORTIONS COPYRIGHT  1995 EDWARD H. TRAGER
ALL RIGHTS RESERVED

Madeline comes with ABSOLUTELY NO WARRANTY.  This is free software and
you are welcome to redistribute it under certain conditions.  For details,
type "license"

M>

Check

check inheritance

Checks for simple Mendelian inheritance inconsistencies among autosomal markers within nuclear families. Madeline detects the following types of errors:

• More than 4 alleles in sibships.
• More than 3 alleles in sibships with a homozygote present or 1 allele shared by typed parents.
• More than 2 alleles in sibships with 2 homozygotes present or 2 alleles shared by typed parents.
• Inheritance inconsistencies in sibships with 0, 1, or 2 typed parents.

At the nuclear family level, Madeline's algorithm detects the same inconsistencies as Level 1 and Level 2 of Jeff O'Connell's PedCheck program.

When AutoCheckInheritance is set on (the default), Madeline automatically runs check inheritance whenever a new pedigree table is opened using open. Any inheritance inconsistencies detected are reported as INHERITANCE INCONSISTENCIES in the error log (madeline.err by default).

When AutoCheckInheritance is set off, inheritance checking does not occur until you manually execute the command. In this case, inconsistencies are reported in the general log (madeline.log by default) and are not listed in the error log at all.

A draw pedigrees command executed after check inheritance produces pedigree drawings in which inconsistent markers are flagged in red on color drawings and in bold text on black and white drawings (see figure below). To view only pedigrees with Mendelian inconsistencies, use the command, draw pedigrees for _IsMendelianInconsistent.

The command check inheritance followed by draw pedigrees produces drawings highlighting mendelian inheritance inconsistencies in red (bold text on black and white drawings).

Programs such as PedCheck and Merlin have additional levels of error analysis that Madeline does not. Madeline examines each nuclear family and marker in isolation and cannot detect errors that require a wider view of the data. Also, Madeline does not currently handle the case of X-linked markers. Use Madeline as a rapid and convenient tool for detecting many of the possible errors that may be present in your data. After resolving errors that can be detected by Madeline, use PedCheck, MERLIN, or another program to be sure that all errors have been eliminated. Gonçalo Abecasis, the author of Merlin, provides a good example of how much LOD scores can be influenced by even a few problematic genotypes in your data.

Note: The next version of Madeline will have a way of annotating X-linked markers and will check Mendelian inheritance among X-linked markers correctly.

Clear

clear exclusions

Clears exclusion flags from all individuals previously marked for exclusion using the exclude command. To clear exclusion flags from only a subset of individuals, use the unexclude command. See: exclude, unexclude.

M>exclude for bmi>=35
213 individuals in 162 pedigrees marked for exclusion as follows:
Individuals ..............        213
 + In database ...........        213
 |  + Attached ...........        212
 |  + Childless spouses ..          1
 |  + Unattached .........          0
 + Not in database .......          0
M>clear exclusions
M>

Compose

compose “InputFile” [ to “OutputFile” ]

The compose command converts a table in which each record contains the alleles of a single marker for a single individual to a Madeline pedigree table which contains a single record for each individual, marker names as column headings, and genotypes as field data. This command is designed for converting the output from genotyping machine software (such as ABI Genotyper) or from a normalized database storage format into the pedigree table format required by Madeline.

A typical input file looks like this:

 FAMID
 INDIVIDUAL
 MARKERNAME
 ALLELE1
 ALLELE2
 IGNORED

 0001 0001-100 d20s100  112 114  G323
 0001 0001-100 d20s898  120 122  G364
 0001 0001-100 d20s129   98 100  G311
 0002 0002-100 d20s100  116 116  G112
 0002 0002-100 d20s898  115 118  G918
 0002 0002-100 d20s129   94  96  G454
 .    .        .          .   .  .
 .    .        .          .   .  .
 .    .        .          .   .  .

Before running compose, be sure to specify the names of the three required key fields (FamilyIDField, IndividualIDField, and MapMarkerField) and the two allele fields (Allele1Field and Allele2Field). The input table may contain additional fields, but only FamilyIDField, IndividualIDField, and the marker fields will appear in the output. For example, as shown above, the "IGNORED" field of the input table does not appear in output.

If an output file name is not provided, Madeline creates an output file with a ".trp" extension for the Mbase flat file output and a ".tfh" extension for the binary Mbase header if a .mfh file already exists.

A typical command session appears below:

M>FamilyIDField     = "FAMID"           
M>IndividualIDField = "INDIVIDUAL"      
M>MapMarkerField    = "MARKERNAME"   
M>Allele1Field      = "ALLELE1"         
M>Allele2Field      = "ALLELE2"         
M>compose "marker.mfh" to "genotypes.data"
Composing "marker.mfh" to "genotypes.data"
Composed file created.
M>

Output looks like this:

 FAMID
 INDIVIDUAL
 D20S100
 D20S898
 D20S129

 0001 0001-100  112/114  120/122   98/100
 0002 0002-100  116/116  115/118    94/96
 .    .         .        .        .
 .    .         .        .        .
 .    .         .        .        .

Core family structure information fields (gender, parental IDs, twin status) or other phenotype or genotype data can be added to the composed genotype table using the merge command.

Note: The "compose" command was called "transpose" in previous versions of the program. The name was changed to complement the decompose command name.

Convert

convert

comma space tab “other” delimited file “InputFile” [ to “OutputFile” ] crimap | map marshfield simwalk weber file “InputFile” [ to “OutputFile” ]

Convert certain types of files into the flat-file format that Madeline can use directly. The various versions of this command are described below.

Convert Delimited Files

The first form of the convert command allows you to convert a comma-, space-, tab- or other-character delimited file to a space-delimited, column-aligned Madeline file that can be read by the recognize command. The keywords comma, space or tab can be used to specify comma-, space-, or tab-delimited files, respectively.

Alternatively, you can specify another character delimiter within single or double quotes. If you specify more than one character within quotes, only the first character will be recognized.

Specifying an output file with the keyword to is optional. If an output file is not specified, Madeline will create an output file having the same name as the input file, but with a ".mod" (i.e., modified) extension at the end. See: recognize.

M>convert "*" delimited file "mydata.stars" to "mydata.dat"
Converting "mydata.stars" to "mydata.dat"
3547 lines were written.      
M>

Convert Crimap File

Converts a genetic map file produced by Crimap into a Madeline-formatted map file. Conversion of both sex-averaged and sex-specific maps is supported.

Specifying an output file with the keyword to is optional. If an output file is not specified, Madeline uses the name of the input file with ".map" appended to the end as the name of the output file.

Convert Marshfield File

Converts a genetic map file produced by the Marshfield Center for Medical Genetics' online Build Your Own Map web service. Most web browsers provide a Save As or Save Frame As menu option. Simply save the file returned to your web browser in the native HTML format (be sure to save the specific frame containing your map!). Convert ignores the HTML markup in the file while looking for the embedded genetic map. Madeline converts both the sex-averaged and sex-specific maps produced by this online resource.

Note: When converting a map of Chromosome X markers, be sure to manually change the "Chromosome X" to "Chromosome 23" in the header of the Marshfield file so that Madeline can correctly assign a numeric chromosome number in the converted file.

Specifying an output file with the keyword to is optional. If an output file is not specified, Madeline uses the name of the input file with ".map" appended to the end as the name of the output file.

Convert Simwalk File

Converts a Simwalk2 parametric or non-parametric results file to Madeline-formatted (1)map and (2)results tables which can be used by the graph load and graph open commands, respectively, for plotting the results. See: graph.

Convert Weber File

Converts files in the Weber Lab format from the Marshfield clinic into Madeline-formatted pedigree tables. Weber Lab files are in a composed format. If you need to decompose files so that data from Marshfield can be stored in normalized database tables, see decompose.

Decompose

decompose

madeline weber

file “InputFile” [ to “OutputFile” ]

Decompose composed tables so that the marker data can be efficiently stored in normalized form in a database.

Decompose Madeline Tables

Decompose a Madeline-formatted pedigree table.

Note: This version of the command is not yet supported in version 0.935 of the program.

Decompose Weber Lab Format Tables

The Weber Lab format is used in Dr. Weber's lab at the Marshfield Clinic. Data in these files are in a composed format using tabs as delimiters between columns. Records begin with numeric columns for the family ID, individual ID, father ID, mother ID, and sex. Following these, for each typed marker there are columns for allele 1, allele 2, a confidence value, and finally an indicator value. The indicator value is generally missing unless the genotypes were bad: bad genotypes are usually assigned quality values of zero:

Chromosome 17
                                   MARKER_01                 MARKER_02               ...
Family_ID  Individual_ID  Father_ID  Mother_ID  Sex  Allele_1  Allele_2  Confidence  Indicator  ...
0098    2592    285    286    2    149    145    0.99        279    279    0.99    ...
0098    6061    285    286    2    161    157    0.99        0      0      0.00    ...
0098    6088    285    286    2    157    149    0.99        0      0      0.00    ...
  .              .              .                .               .                 .
  .              .              .                .               .                  .
  .              .              .                .               .                   .

Madeline captures the allele and confidence columns but ignores the indicator column. The following example uses the file "weber_example.dos_file" which is included in the examples subdirectory of the software distribution:

M>decompose weber file 'weber_example.dos_file'
Decomposing input file "weber_example.dos_file"
to "weber_example.dos_file.dcmp"
This file appears to contain genotype data for 5 markers on chromosome 17
File written.
M>

The decomposed output is tab-delimited to facilitate importation into a database system:

FAMID      C
STUDYID    C
MOTHER     C
FATHER     C
SEX        X
MARKERNAME C
ALLELE1    N
ALLELE2    N
CONFIDENCE N
INDICATOR  C

0098	02592	00286	00285	F   	MARKER_01  	 145	 149	0.99
0098	02592	00286	00285	F   	MARKER_02  	 279	 279	0.99
0098	02592	00286	00285	F   	MARKER_03  	 208	 208	0.99
0098	02592	00286	00285	F   	MARKER_04  	 106	 122	0.99
0098	02592	00286	00285	F   	MARKER_05  	 159	 159	0.99
0098	06061	00286	00285	F   	MARKER_01  	 157	 161	0.99
0098	06061	00286	00285	F   	MARKER_02  	   0	   0	0.00
0098	06061	00286	00285	F   	MARKER_03  	 196	 200	0.99
0098	06061	00286	00285	F   	MARKER_04  	 101	 104	0.99
  . . .

If you need to convert decomposed tables into a composed format for use in Madeline, see compose.

Draw

draw pegigree[s]

“FamilyIdi” [ , “FamilyIdj” , “FamilyIdk” - “FamilyIdz” ] for Expressionlogical

Draws pedigrees to the file named in PedigreeDrawingFile. The output file typically contains multiple drawings. The resulting drawings are displayed using the Postscript viewer named in PostscriptViewer. On Linux, this is often Gv.

Draw Using Pedigree Identifiers

Specify one or more pedigree (family) identifiers (IDs) separated by commas, or an alphabetically increasing range of pedigrees IDs with a dash. Be sure to enclose pedigree IDs in quotes:

M>draw pedigrees "F0001", "F0003", "F0005" - "F0017"
Drawing pedigree F0001 ...
Printing drawing scaled to 0.91.

Drawing pedigree F0003 ...
Printing drawing scaled to 0.94.

Drawing pedigree F0005 ...
Printing virtual portrait drawing scaled to 1.02 on
4 physical pages wide by 2 physical pages tall.
(You may not be able to view entire drawing in Postscript viewing application).
Physical page print order index:

[5][6][7][8]
[1][2][3][4]
 
 ...

Calling viewer "gv madeline.pedigree.ps" ...
M>

Draw Using Logical Expressions

A subset of pedigrees in which one or more individuals in each pedigree matches a query expression may be drawn using the syntax, draw pedigrees for ExpressionLogical:

M>draw pedigrees for _IsMendelianInconsistent
Drawing pedigree F0129 ...
Printing drawing scaled to 0.92.

Drawing pedigree F0177 ...
Printing drawing scaled to 0.86.

 ...

Calling viewer "gv madeline.pedigree.ps" ...
M>

Draw Details of Usage

Orientation, paper size, margins, and color versus black-and-white printing may be set using set commands. In version 0.935, the left-to-right sort order of siblings within sibships and multiple spouses connected to a single spouse may be explicitely set using the sort command. A typical command session and a typical drawing are shown below:

M>// Load a marker map:
M>load "mydata.map.mfh"
M>// Open a data table (with CAFF_BROAD as the affection status indicator):
M>AffectionStatusField="CAFF_BROAD"
M>open "mydata.ped.mfh"
M>// Toggle off columns that we don't need or want to show:
M>toggle output flags off for FAMID,SEX,FATHER,MOTHER,AGE_LAST_EXAM
M>// Toggle off markers for chromosomes that we don't want to show:
M>toggle output flags off for chromosome 1 markers
M>toggle output flags off for chromosome 5 markers
M>toggle output flags off for chromosome 12 markers
M>// Add the restricted affection category, CAFF_RESTR, to the icon display:
M>toggle icon flag for CAFF_RESTR
M>// We are going to use a black and white printer (color defaults to "on"):
M>set color off
M>// Set margins to 2 cm on all edges (default is 1 cm):
M>set PaperMargin to 2
M>// Force all drawings to print in Landscape (default is Automatic):
M>set orientation to landscape
M>// Change the name of the output file:
M>PedigreeDrawingFile="MyCompletePedigreeSet.ps"
M>// Draw all pedigrees:
M>draw pedigrees for #true
...
 calling "gv MyCompletePedigreeSet.ps" ...
...
M>

Typical output produced by Madeline's draw command. In this example, a set color off command preceded the draw command in order to produce black and white output suitable for printing.

Madeline v. 0.935 can draw most single- and multiple-founder pedigrees. When a pedigree has more than one founding ancestral group, subtrees of the pedigree originating from different founding ancestral groups are printed on separate pages. A founding ancestral group consists of an ultimate founder and his or her one to many spouses. Currently, there is no option for printing complex pedigrees of this sort on a single page. This limitation will be remedied in the next version of the program.

The options for orientation are landscape, portrait, and automatic. When orientation is set to portrait or landscape, pedigree drawings are scaled to fit the dimensions of the physical page. The scaling factor required to reduce large pedigrees to small pages may result in loss of legibility (or new corrective lenses!) --in these cases automatic is preferred.

When automatic is selected, Madeline chooses the best orientation based on the dimensions of the virtual drawing. If rescaling to fit a single physical page is likely to result in reduced legibility, the program automatically divides the drawing for printing across two or more physical pages (poster mode). Madeline automatically selects the number and orientation of physical pages that requires the least amount of rescaling.

Madeline produces a schematic index for assembling the individual pages after printing in poster mode. The program may use up to 5 pages across and 5 pages down, or a total of not more than 25 pages, for printing a drawing in automatic poster mode. Normally only 2 to 4 pages are required for large drawings. Pages overlap by exactly the number of centimeters specified in PaperMargin.

Due to the way that Madeline's Postscript routines manage the splitting of a large drawing for printing across multiple physical pages in poster mode, Postscript viewing applications like gv, Ghostview, or GSView will generally only display the last section, or the viewer may appear to cycle through the individual pages of a split drawing without pausing. This limitation does not impair the correct printing of such drawings on a Postscript printer.

Up to ten mates of a single individual may be drawn. At the time of this writing, the drawing routines are being extensively revised to provide better support for drawing consanguinous loops and other complicated pedigree structures not handled well by the current version of the program.

Edit

Edit or view a file using the editor specified in the editor variable. This allows you to edit or view files without having to leave Madeline. You can use either a console-based editor like vi (or Vim), or an X-windows editor like Edith.

M>editor="vi"
M>edit "map.data"

CHROMOSOME N  ORDINAL    N  MARKERNAME C
POSITION   N  THETA      N  DISTANCE   N
POSITION_F N  THETA_F    N  DISTANCE_F N
POSITION_M N  THETA_M    N  DISTANCE_M N

23   1 DXS1060         15.12 0.02169     2.17       7.66 0.04359     4.37      22.77 0.00000     0.00
23   2 DXS8051         17.29 0.04874     4.89      12.03 0.09878    10.01      22.77 0.00000     0.00
23   3 DXS987          22.18 0.05389     5.41      22.04 0.10769    10.94      22.77 0.00000     0.00
23   4 DXS1226         27.59 0.05922     5.95      32.98 0.11775    12.00      22.77 0.00000     0.00
23   5 DXS1214         33.54 0.03783     3.79      44.98 0.07591     7.65      22.77 0.00000     0.00
23   6 DXS8102         37.33 0.00000     0.00      52.63 0.00000     0.00      22.77 0.00000     0.00
23   7 DXS1068         37.33 0.00540     0.54      52.63 0.01080     1.08      22.77 0.00000     0.00
23   8 DXS8015         37.87 0.04329     4.34      53.71 0.08701     8.79      22.77 0.00000     0.00
23   9 DXS993          42.21 0.02638     2.64      62.50 0.05340     5.36      22.77 0.00000     0.00
:wq                                                                                          1,1           Top
M>

Exclude

exclude [families] for Expression_logical

Mark individuals for exclusion. If exclude families is used, all individuals who match the criteria and their spouses and descendants will be excluded. See: clear, unexclude

M>exclude for _familyID="0049"
0049-100 has been marked for exclusion
0049-401 has been marked for exclusion
0049-701 has been marked for exclusion
0049-801 has been marked for exclusion
0049-802 has been marked for exclusion
M>

Go

go n_record

Go to a specified record, n_record, in a database. Records are numbered from 0 to n-1 where n is the total number of records in the table (virtual parents do not contribute to this count, and you cannot go to the (non-existant) record of a virtual parent).

M>go 197
M>show studyid
"0052-100"
M>view record
...

Note: This command is slated for significant revision (Record numbering should start at 1; should support "go to record 787" and "go to individual "I0245-12"", etc...).

Goodbye

goodbye quit

Terminate the current Madeline session. Equivalent to the quit command. See: quit.

M>goodbye
Releasing resources ...
Goodbye!

Graph

graph

load “MapTable” open “DataTable” add arrow “TextLabel” at Xposition centiMorgans centimeters | cm [,] Yposition centiMorgans centimeters | cm [,] αdegrees label “TextLabel” at Xposition centiMorgans centimeters | cm [,] Yposition centiMorgans centimeters | cm horizontal line at Yposition LodUnits | VerticalUnits | vu centimeters | cm vertical line at Xposition centiMorgans centimeters | cm black | blue brown | cyan gray | green orange | peach purple | red white | yellow | ... bar “TextLabel” from Xstart to Xend centiMorgans centimeters | cm [,] Yposition centiMorgans centimeters | cm plot

All of the commands used to create and annotate a graphical plot begin with the word graph . All variables associated with graphs also begin with the word graph. For a complete list, use the lookup command:

M>lookup "graph"
graph is a command.
GraphAnnotations is an associative array. It accepts character string keys and maps them to character string values.
GraphDrawingFile is an internal variable. Its current value is "madeline.graph.ps".
GraphPositionField is an internal variable. Its current value is "POSITION".
GraphScoreField is an internal variable. Its current value is "SCORE".
GraphTitle is an internal variable. Its current value is "Multipoint Analysis".
GraphXAxisLabel is an internal variable. Its current value is "Map Position (cM)".
GraphXAxisMajorTick is an internal variable. Its current value is 0.000.
GraphXAxisMaximum is an internal variable. Its current value is 0.000.
GraphXAxisMinimum is an internal variable. Its current value is 0.000.
GraphXAxisMinorTick is an internal variable. Its current value is 0.000.
GraphYAxisLabel is an internal variable. Its current value is "LOD Score".
GraphYAxisMajorTick is an internal variable. Its current value is 0.000.
GraphYAxisMaximum is an internal variable. Its current value is 0.000.
GraphYAxisMinimum is an internal variable. Its current value is 0.000.
GraphYAxisMinorTick is an internal variable. Its current value is 0.000.
M>

The various graph commands are described below.

Graph Load

Loads a marker map for annotating a graph.

A Logarithm of Odds (LOD) plot provides more information to the viewer when labels showing the location of genetic markers are included on the plot. Madeline makes it trivially easy to include such labels on a plot. All you need to do is to load a marker map. Normally, you will have already prepared a marker map in Madeline format for use in the analysis itself. The graph load command is identical to the load command. Once a marker map has been loaded, Madeline will automatically include marker labels on graphs:

M>graph load "chr17.map.mfh"
Marker maps based on chr17.map.mfh are now installed.

Graph Open

Opens a Madeline-formatted results file for plotting. Opening a results table automatically sets reasonable defaults for the x- and y-axis minima, maxima, and tick intervals:

M>graph open "chr17.results.mfh"
Low=-50.00 High=218.78 Range=268.78 Magnitude=1
Stt=-50.00 End =220.00 NewRange=270.00
TickBasis=10.00
...
M>

Analysis results must be placed into a table containing at least a POSITION and a SCORE column. Other columns may also be present. The name of the POSITION column is controlled by the value of GraphPositionField. The name of the SCORE column is controlled by GraphScoreField. Of course, the easiest thing to do is to comply with Madeline's defaults and use "POSITION" and "SCORE" as the names of the respective columns in your results table. The results table is prepared using the recognize command. Once Madeline has recognized an ASCII results table, you are ready to plot the data:

M>graph plot 'chr17.multipoint.mfh'
Graph printed to "madeline.graph.ps"
Calling external viewer using the command "gv madeline.graph.ps" ...

Here is the resulting plot:

Default LOD plot generated by graph load and graph plot with no additional options.

M>convert simwalk file 'sw_chr10.out' to 'chr10.results'
Converting input file "sw_chr10.out" to Madeline-formatted output files ...
...
M>graph load 'chr10.results.map.mfh'
Marker maps based on chr10.results.map.mfh are now installed.
M>graph open 'chr10.results.mfh'
M>graph plot
Graph printed to "madeline.graph.ps"
Calling external viewer using the command "gv madeline.graph.ps" ...
M>

Graph Finishing the Plot

As you can see above, just two commands -- graph load and graph plot -- are sufficient for quick visualization of results. However, the plot is not perfect. The marker labels are overlapping portions of the highest peak, and the default title is not informative. Below, we will add annotations and perfect the plot. Here are the remaining commands used to obtain a publication-ready plot:

M>GraphTitle="Chromosome 17 Multipoint Analysis"
M>GraphXAxisMaximum=225
M>GraphYAxisMaximum+=9
M>graph add red bar "CANDIDATE-1" from 12.5 to 26.7 centiMorgans, 5.0 lodunits
M>graph add green bar "CANDIDATE-2" from 50.3 to 74.1 centiMorgans, 5.0 lodunits
M>graph add blue bar "CANDIDATE-3" from 147.2 to 157.41 centiMorgans, 5.0 lodunits
M>graph add arrow "This is Great!" at 61.5 centiMorgans, 6.3 lodunits
M>graph plot
Graph printed to "madeline.graph.ps"
Calling external viewer using the command "gv madeline.graph.ps" ...

GraphTitle is the variable that holds the title. Additional variables maintain the labels for the X- and Y-axes themselves.

The X- and Y-axis ranges and tick intervals were determined automatically by the program based on the data when the graph open command was executed. The X-axis on the default graph stretches out to 250 centiMorgans, making the plot off-center. Changing GraphXAxisMaximum to 225 (centiMorgans) fixes this. We then add 9 (lodunits) to GraphYAxisMaximum so that there will be enough room for the "raining" label markers, plus some to spare for additional bar annotations. Additional variables maintain the X- and Y-axis minimums and major and minor tick intervals.

We next add three bar annotations to indicate regions occupied by known candidate genes. Note that the program allows us to specify positions directly in centiMorgans (shown) or centimeters (not shown). In the example shown above, a different color is used for each bar. If you do not specify a color, gray is used by default.

Finally, just to demonstrate the capabilities of the program, we add a label with an arrow pointing at the largest peak. Labels without arrows are also possible, as are labels with arrows pointing in any direction. The arrow defaults to the 45-degree angle shown below.

The final plot is shown below:

Final annotated plot.

On systems such as Linux, you can use a utility such as ps2pdf to convert a Madeline-generated Postscript file to PDF. You should also be able to import Madeline-generated Postscript files directly into programs like Adobe Illustrator.

Hello

hello status

Displays the current setting of Madeline's boolean state flags and other status information. Identical to the status command.

M>hello
+-----------------------+-----------+-----------------------------------------+
| Variable or State Flag| Setting   | Description                             |
+-----------------------+-----------+-----------------------------------------+
| EXTERNAL PROGRAMS     |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| Editor                | edith     | Program used to edit files              |
| PostscriptViewer      | gv        | Program used to view Postscript drawings|
| PrintCommand          | lpr       | System program used to print files      |
| WebBrowser            | netscape  | Program used to view HTML documentation |
+-----------------------+-----------+-----------------------------------------+
| EVALUATION SETTINGS   |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| EvaluationInterval    |   0.50 cM | Value to write to control file.         |
| OffEndDistance        |  10.00 cM | Value to write to control file          |
+-----------------------+-----------+-----------------------------------------+
| DRAWING SETTINGS      |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| Color                 | ON        | Draw pedigrees in color                 |
| ReverseShading        | OFF       | Black is first icon shade               |
| DividedDrawings       | ON        | Paginate drawings by founding group     |
| HighlightRows         | ON        | Alternately highlight data on drawings  |
| LabelCreatedIndividual| ON        | Label virtuals created by Madeline      |
| Orientation           | AUTOMATIC | Automatic based on drawing dimensions   |
| PaperMargin           | 1.00 cm   | Margin (in cm) on all four sides        |
| PaperSize             | USLETTER  | 8.5 x 11.0 inches                       |
+-----------------------+-----------+-----------------------------------------+
| OTHER SETTINGS        |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| AutoExclude           | ON        | Exclude pedigrees automatically         |
| AutoCheckInheritance  | ON        | Check inheritance on OPEN               |
| ConsoleHighlights     | ON        | Use bold/color highlights on console    |
| Delimiter             | TAB       | Delimiter for tables and other output.  |
| FusionSupport         | OFF       | FUSION customizations disabled          |
| HaplotypeDisplay      | OFF       | Display genotypes delimited with "/"    |
| Language              | American E| Language convention used for date, time |
| MapDetails            | OFF       | LIST MAP summary display                |
| SaveAlleleFrequencies | OFF       | Calculate new frequencies on next OPEN  |
| Time                  |           | Tuesday, May 6, 2003                    |
| Verbosity             | VERBOSE   | All messages are printed to the console |
+-----------------------+-----------+-----------------------------------------+
M>

Help

Invokes HTML-based help. Madeline will invoke the world wide web browser named in WebBrowser with the URL named in WebAddress. The default WebBrowser is usually "mozilla". The default WebAddress refers to the installed local copy of the Madeline documentation or, if unavailable, to the current URL of the online documentation.

The quoted string argument to help is added to the end of the URL as a bookmark reference. Valid bookmarks include all tokens recognized by the program (i.e., commands, variables, arrays, symbolic constants ...) as well as topical and section bookmarks such as "contents" and "tutorial".

M>help "contents"
Calling mozilla with "file:///usr/local/share/madeline/docs/madeline.html#contents" ...
(If you don't find what you want in the HTML documentation, try the LOOKUP command).
M>

See Lookup if you need to determine the name or correct spelling of a command, variable, or other token.

List

list

fields map [ for chromosome nchr. ] stats | statistics Arrayinternal Arrayuser Arrayassociative allele frequencies for Fieldi [ , Fieldj, Fieldk, Fieldm - Fieldz ]

Displays current values in a list of items. The list may consist of:

• fields in the currently open pedigree table.
• markers and marker information in a map table.
• statistics regarding the number of pedigrees and individuals.
• values in an array or associative array.
• allele frequencies for one or more markers in a pedigree table.

Usage of each form of the command is provided below.

List Fields

List the fields (columns) in a pedigree table:

M>open "chr8.dbf"
. . .
M>toggle off output flags for D8S270-GATA101F01
M>list fields
1.FAMID      Co__1   10.D8S504     Go__1   19.D8S1757     Go_10
2.STUDYID    Co__2   11.D8S550     Go__2   20.D8S270      G
3.SEX        Co__3   12.D8S258     Go__3   21.D8S1778     G
4.FATHER     Co__4   13.D8S1771    Go__4   22.D8S276      G
5.MOTHER     Co__5   14.D8S1820    Go__5   23.GATA101F01  G
6.TWIN       Co__6   15.D8S283     Go__6   24.D8S514      Go_11
7.BMI        Po__1   16.D8S285     Go__7   25.D8S284      Go_12
8.NAFFECTE   Co__7+  17.D8S260     Go__8   26.D8S534      Go_13
9.STUDYAGE   Po__2   18.D8S530     Go__9   27.D8S1836     Go_14
M>

For each field, the following information is displayed:

1. An ordinal number indicates the physical order of the column in the pedigree table.
2. The name of the field.
3. The category of the field (C for core, P for phenotype,G for genotype, etc.).
4. On/off status. A lower-case "o" indicates the field is toggled on for output. Absence of an "o" indicates the field is toggled off for output.
5. Another ordinal number indicates the print order within each category (C,P,G) of fields which are toggled on for output. The output order is affected by the load and set field order commands.
6. A Plus + sign indicates categorical fields which have been selected for shading the icons in pedigree drawings. If more than one field is selected, the icons are divided into pie-shaped shading regions. These are selected using the command, "toggle icon flags ...".

Occasionally you might see an asterisk "*" in field category for a field containing no data. "V" for covariate and "A" for allele are also possible.

List Map

Lists genetic maps. By itself, list map lists maps for all chromosomes which may be present in the map table. Alternatively, specify a chromosome as shown here:

M>load 'm.map.mfh'
Marker maps based on m.map.mfh are now installed.
M>list map for chromosome 22

    Map Position (Kosambi cM)
  -----------------------------
Ch Or Marker Name Sex-avg.   Female     Male
-- -- ----------- --------- --------- ---------
22  1 GATA198B05N    0.0000     .         .
22  2 AGAT120        9.9000     .         .
22  3 GGAA10F06     11.6000     .         .
22  4 TTA015        13.3000     .         .
22  5 ATTT019       13.8000     .         .
22  6 AGAT055Z      23.0000     .         .
22  7 GATA21F03     27.0000     .         .
22  8 GATA6F05      30.4000     .         .
22  9 GATA11B12     34.0000     .         .
22 10 TCAT006Z      36.0000     .         .
22 11 ATA37D06      41.0000     .         .
22 12 GTAT005Z      44.2000     .         .
22 13 TTAT020       46.1000     .         .
22 14 UT7136        51.0000     .         .
22 15 SCA10         51.2000     .         .
22 16 GATA030       56.2000     .         .
22 17 TCTA015       59.4000     .         .
M>

Information displayed by the list map command is affected by the setting of MapDetails. When MapDetails is set on, inter-marker distances and recombination fractions are also displayed:

M>set MapDetails on
...
M>list map for chromosome 22

   Sex-averaged Map   Female-specific Map  Male-specific Map
  ------------------- ------------------- -------------------
Ch Or Marker Name Kosambi   Dist (RF) Kosambi   Dist (RF) Kosambi   Dist (RF)
-- -- ----------- --------- --------- --------- --------- --------- ---------

--------------
Chromosome 22
--------------
22  1 GATA198B05N    0.0000              .                  .
	       9.9000
	      (0.0977)
22  2 AGAT120        9.9000              .                  .
	       1.7000
	      (0.0170)
22  3 GGAA10F06     11.6000              .                  .
	       1.7000
	      (0.0170)
...
M>

MapDetails is off by default. See the load command for more information about genetic maps. See the convert command for ways to import genetic maps into Madeline.

List Statistics

Displays a summary table showing the included, excluded, and total number of pedigrees and individuals processed by a preceding command:

M>open "MyData.mfh"
...
M>write to "MyMerlinFile" in merlin format
...
M>list stats
-----------------------------  --------- --------- ---------
Pedigrees and Individuals       Included  Excluded     Total
-----------------------------  --------- --------- ---------
Pedigrees ...................        107         5       112
Individuals .................        895        21       916
+ In database ..............        857        21       878
|  + Attached ..............        857        20       877
|  |  + With data ..........        439         0       439
|  |  + Without data .......        418        20       438
|  |  + Marked for exclusion          0         0         0
|  + Childless spouses .....          0         0         0
|  + Unattached ............          0         1         1
+ Not in database ..........         38         0        38

List Arrays

Lists the values in an internal or user array or associative array:

M>//
M>// CharacterMissingValue[ ] stores the list of
M>// missing value indicators for character fields:
M>//
M>list CharacterMissingValue
CharacterMissingValue has 5 elements:
CharacterMissingValue[ 1]="."
CharacterMissingValue[ 2]="/"
CharacterMissingValue[ 3]="0/0"
CharacterMissingValue[ 4]="0/ 0"
CharacterMissingValue[ 5]="0/  0"
M>//
M>// GenderStatus[ ] is an associative array
M>// which maps table values for gender to
M>// Madeline's internal gender values:
M>//
M>list GenderStatus
GenderStatus has 4 elements:
GenderStatus[1]=0 <-- i.e., #male 
GenderStatus[2]=1 <-- i.e., #female 
GenderStatus["F"]=1
GenderStatus["M"]=0
M>

See the Table 4.4. System Arrays table for a list of arrays and associative arrays.

List Allele Frequencies

List allele frequencies for one or more genetic markers in a pedigree table. When a pedigree table is opened, Madeline automatically calculates allele frequencies using gene counting. Gene counting does not take familial relationships into account. Gene counting is sufficient if your data contains large numbers of pedigrees and/or controls. For smaller data sets containing fewer pedigrees, you may want to run a program such as Mendel to calculate allele frequencies taking familial relationships into account. You can then use the read command to read the results from Mendel or another program into Madeline. An alternative approach is to calculate allele frequencies in Madeline using gene counting on a large data set containing many pedigrees or controls, save the results using the save command, open a smaller data set for analysis, and use the read command to read in the previously-saved allele frequencies.

You can specify markers either by name or by field ordinal. The example below uses the "chr12.corrected.data" data set included in the examples subdirectory of the software distribution:

M>open 'chr12.corrected.data.mfh'

Calculating allele frequencies for  11. MARKER01...
Calculating allele frequencies for  12. MARKER02...
Calculating allele frequencies for  13. MARKER03...
Calculating allele frequencies for  14. MARKER04...
Calculating allele frequencies for  15. MARKER05...

...

1.FAMID      Co__1    6.MZTWIN     Co__6   11.MARKER01   Go__1
2.STUDYID    Co__2    7.DZTWIN     Co__7   12.MARKER02   Go__2
3.SEX        Co__3    8.AFFECTED_B Po__1   13.MARKER03   Go__3
4.FATHER     Co__4    9.AFFECTED_R Po__2   14.MARKER04   Go__4
5.MOTHER     Co__5   10.AGE_DX     Po__3   15.MARKER05   Go__5

...

M>list allele frequencies for 11, MARKER02, 13-15

11. MARKER01:

302         5/   94     0.0532
304         2/   94     0.0213
307         1/   94     0.0106
308         9/   94     0.0957
312         8/   94     0.0851
316         9/   94     0.0957
320        58/   94     0.6170
324         2/   94     0.0213

12. MARKER02:

263         1/   82     0.0122
271        16/   82     0.1951
275        16/   82     0.1951
279        41/   82     0.5000
283         8/   82     0.0976

13. MARKER03:

236        39/   98     0.3980
240         3/   98     0.0306
244         5/   98     0.0510
248        25/   98     0.2551
252         4/   98     0.0408
256        22/   98     0.2245

14. MARKER04:

137        11/   96     0.1146
141         5/   96     0.0521
145        21/   96     0.2188
149        13/   96     0.1354
153        22/   96     0.2292
157        21/   96     0.2188
161         3/   96     0.0312

15. MARKER05:

101         3/   82     0.0366
104        24/   82     0.2927
105         6/   82     0.0732
106         7/   82     0.0854
107         1/   82     0.0122
110         1/   82     0.0122
116        11/   82     0.1341
119        18/   82     0.2195
122         9/   82     0.1098
125         2/   82     0.0244

Load

Load a genetic map table. A map table may contain genetic maps for one or more chromosomes. The table must contain fields for chromosome number, marker name, ordinal position of the marker in the map for the chromosome, and sex-averaged distance in centiMorgans (see table below). The table may also optionally contain fields for sex-specific maps.

The map database can contain maps for any number of chromosomes, but may contain only one map for each chromosome. As soon as Madeline detects that a map database has been installed, genotype fields in an open pedigree table will automatically be placed in map order. When possible, execute load prior to any open command. When a pedigree table is subsequently opened, genotype fields will then automatically appear in map order from the outset.

M>load "amd.map.mfh"
Marker maps based on amd.map.mfh are now installed.
M>list map for chromosome 23

    Map Position (Kosambi cM)
  -----------------------------
Ch Or Marker Name Sex-avg.   Female     Male
-- -- ----------- --------- --------- ---------
22  1 GATA198B05N    0.0000     .         .
22  2 AGAT120        9.9000     .         .
22  3 GGAA10F06     11.6000     .         .
22  4 TTA015        13.3000     .         .
22  5 ATTT019       13.8000     .         .
22  6 AGAT055Z      23.0000     .         .
22  7 GATA21F03     27.0000     .         .
22  8 GATA6F05      30.4000     .         .
22  9 GATA11B12     34.0000     .         .
22 10 TCAT006Z      36.0000     .         .
22 11 ATA37D06      41.0000     .         .
22 12 GTAT005Z      44.2000     .         .
22 13 TTAT020       46.1000     .         .
22 14 UT7136        51.0000     .         .
22 15 SCA10         51.2000     .         .
22 16 GATA030       56.2000     .         .
22 17 TCTA015       59.4000     .         .
M>

Note: Most genetic maps created by Crimap and online resources can be quickly converted to the Madeline table format using the convert command.

Lookup

Lookup a command, variable, array name, symbolic constant, or keyword by supplying a quoted string containing at least the first few letters. Lookup searches the token tree for matches:

M>lookup "_p"
_PaternalGrandfather is a pointer belonging to an individual that points to another individual.
_PaternalGrandmother is a pointer belonging to an individual that points to another individual.
_PercentGenotyped is a variable belonging to an individual in a pedigree.
_PercentMendelianInconsistent is a variable belonging to an individual in a pedigree.

M>lookup "#"
#affected is a numeric constant. It's value is 1.
#alive is a numeric constant. It's value is 0.
#dead is a numeric constant. It's value is 1.
#e is a numeric constant. It's value is 2.71828.
#false is a numeric constant. It's value is 0.
#female is a numeric constant. It's value is 1.
#male is a numeric constant. It's value is 0.
#missing is a numeric constant. It's value is 2.22507e-308.
#pi is a numeric constant. It's value is 3.14159.
#true is a numeric constant. It's value is 1.
#unaffected is a numeric constant. It's value is 0.

M>lookup "gene"
genehunter is a keyword.
GenehunterNPL is a keyword.
GenehunterQTL is a keyword.
generic is a keyword.
M>

Also see: help.

Map

map AssociativeArrayName Key

as to

Value

Creates a one-to-one association, between a Key and a Value. The key and value are stored in an associative array, AssociativeArrayName. The map command is primarily a syntactical convenience, since Madeline also permits direct assignments to associative arrays, making the following statements equivalent:

M>map AffectionStatus "AFF" as #affected
M>map AffectionStatus "AFF" to #affected
M>AffectionStatus["AFF"]=#affected

Depending upon how they are defined and used, associative arrays in Madeline may accept keys and values of a single type or multiple types. For example, the AffectionStatus array used to map affection status codes accepts both numeric and character keys since a data set may use either numeric or character codes to represent affection status. The values in AffectionStatus must however be numeric because the program uses numeric codes internally:

M>// Map a character code for the key - OK:   
M>map AffectionStatus "DISEASE" as #affected
M>// Map a numeric code for the key - OK:   
M>map AffectionStatus 20 as #affected
M>// Map a numeric value (via a symbolic constant here) - OK:   
M>map AffectionStatus "DISEASE" as #affected
M>// Map a character value - Should generate an error:  
M>map AffectionStatus "DISEASE" as "AFFECTED"
MapAssignmentCommand(): The value you specified is a character string value,
but this associative array only accepts numeric values.
map AffectionStatus "DISEASE" as "AFFECTED"
1 SYNTAX ERROR M>

You can determine the types of keys and values accepted by an associative array using the lookup command:

M>lookup "AffectionStatus"
AffectionStatus is an associative array. It accepts any keys and maps them to numeric values.   

Merge

merge “InputFile1” [ , “InputFile2” , ... “InputFilen” ] [ to “OutputFile” ] [ in

alpha physical “UserDefinedFile”

order ]

Merges any number of input tables to an output table. All input tables must contain identically-named FamilyIDField and IndividualIDField names which are used as the keys for constructing records in the output table.

Output is in Madeline's Mbase format which consists of a rectangulra ASCII or UTF-8 data table and an associated binary header file. The binary header file usually has the same name as the data table, but with a .mfh extension.

The to "OutputFile" clause is optional. When present, data are written to the specified output file and an associated header is created with a .mfh extension. When absent, Madeline creates a file name based on the name of the first table by adding a .mrg extension to the end. The associated binary header will have a .mfh extension. In the event that a .mfh file already exists, Madeline uses an extension of .cfh instead.

The in alpha | physical | "UserDefinedFile" order clause is also optional. When absent, the default alpha order is used. When alpha order is used, fields from all input tables are arranged alphabetically in the output table. When physical order is specified, fields in the output table are arranged in the same order that they appear in the source tables starting with the first table. Even though the key index fields FamilyIDField and IndividualIDField are present in every input table, they only appear once in the output table, as you would expect.

As an alternative to alpha and physical order, you can specify the order of fields precisely by creating a text file containing the field names in the order you want separated by white space (i.e., spaces and/or carriage returns). For example, you can create a text file containing the marker fields listed in genetic map order (along with any other fields from the source tables). Assuming this file was called "map.order", the clause in "map.order" order would instruct Madeline to read field order from this file.

When physical or "UserDefinedFile" order are used, make sure that the only fields duplicated in all source tables are the key index fields, FamilyIDField and IndividualIDField. Other fields cannot appear multiple times. Be especially careful with core fields like GenderField, FatherIDField, and MotherIDField which may quite possibly appear in more than one table. If it is not possible to remove non-index fields that appear multiple times, simply rename them so that name conflicts do not occur.

When alpha order is used, fields that appear more than once are not a problem and will appear only once in the output table. The field type, width, and numeric precision of duplicate fields are based on the first table in which the fields appear. The data for such fields are also pulled from the first table in which the fields appear.

As you would expect, tables are merged horizontally or side-by-side. Note that Madeline also permits you to merge tables vertically, but only in the case where alpha order is used. For example, if you had two tables containing identical fields but with one containing one set of individuals in your study, and the other containing another set of individuals, merge ... in alpha order will permit you to join the two tables vertically. The restriction that fields be sorted in alphabetic order is necessary so that Madeline can map individual field data correctly even though it appears that field names are "duplicated". After a "vertical" merge, one can always do a subsequent merge in which a preferred field order is specified -- Madeline allows you to "merge" a single table in order to redefine field order!

Individuals present in some but not all tables will naturally have missing values in the result table for columns that only existed in input tables where those individuals did not appear.

M>//
M>// merge uses FamilyIDField and IndividualIDField
M>// as the keys for merging:
M>//
M>FamilyIDField    ="FAMID"
M>IndividualIDField="INDIVIDUAL"
M>merge 't1.dbf','t2.dbf','t3.dbf','t4.dbf','t5.dbf' to 'out.dat' in 'map.order' order
Building field and record trees ...
Writing 2711 records to "out.dat"
5 databases merged to "out.mfh" in 8.5 seconds
M>open 'out.mfh'
...

Merge is part of Madeline's arsenal of commands designed to ease the task of manipulating flat files. Also see: convert, rectify, compose, and decompose.

Open

Open a pedigree table. Madeline currently supports the following table formats:

1. Madeline column-aligned, space-delimited ASCII and UTF-8 flat files. (recommended format).
2. FoxPro and other generic xbase databases (such as dBaseIII, IV).
3. Visual FoxPro which is a variant on the xbase structure.
4. SAS transport file format (theoretically regardless of platform of origin).

Note: Of these four formats, we now recommend using only the Madeline native format which is open, non-proprietary, and human-readable and editable in any text editor (in the case of UTF-8 files, any UTF-8 capable text editor: see A Quick Primer On Unicode and Software Internationalization Under Linux and UNIX). The remaining three formats are deprecated and we may not support them at all in future versions of the program.

Madeline's database engine detects file byte-ordering at run time, permitting database files from PCs to be opened on Unix RISC workstations, and vice-versa. The user does not need to tell Madeline the file type. Madeline does not make use of index files associated with data tables, such as the .cdx files used by FoxPro.

To open an ASCII or UTF-8 flat-file table, use recognize to first create a Madeline binary guide/index file associated with the flat-file table. The binary guide files normally have a ".mfh" extension (Madeline file header). ".mfh" files are platform-specific, but Madeline is theoretically smart enough to recognize them across platforms.

When Madeline opens a pedigree table, the following events occur:

1. The file is opened and buffered in memory.
2. Fields are automatically categorized as core "C", genotype "G", phenotype "P", or "*" null.
3. If genotype fields are present, allele frequencies are estimated from all of the data using gene counting ignoring family relationships.
4. If a map database is already loaded and contains a map for markers in the database, the genotype fields are automatically ordered according to the map.
5. Pedigree structures are reconstructed from core information.
6. Individuals are categorized by Madeline based on whether they are in the database or virtual (i.e., unsampled parents), attached or unconnected.
7. Madeline performs additional data operations when optional core fields such as AffectionStatusField, DateOfBirthField, or DateOfDeathField are included.
8. If AutoCheckInheritance is set on (the default), the data are checked for simple Mendelian inheritance errors.
9. Madeline's command prompt changes to indicate any warnings, severe warnings, or inheritance inconsistencies detected while processing the pedigree table.
10. Madeline displays a summary table showing the count of pedigrees and distribution of individuals by category.

M>AffectionStatusField="CAFF_BROAD"
M>open "cicada.2002.04.26.data.mfh"
12. CAFF_BROAD has 3 levels.
WARNING #0001: SetFieldFlags(): 8. CAFFECTED contains no data!
Calculating allele frequencies for  16. D1S245...
Calculating allele frequencies for  17. D1S249...
Calculating allele frequencies for  18. D1S425...
Calculating allele frequencies for  19. D1S466...
.                                   .
.                                   .
.                                   .
Pedigree table "cicada.2002.04.26.data.mfh" opened with       878 records
NOTE: Dates of birth missing for twins M05224 and M05688 in pedigree L0261.
Consanguinity detected between N00562 and N00563 in pedigree L0299.
NOTE: Dates of birth missing for twins N00101 and N00103 in pedigree L0329.
NOTE: Dates of birth missing for twins M06008 and M06069 in pedigree L0703.
NOTE: Dates of birth missing for twins M06297 and M06353 in pedigree L0919.
NOTE: Pedigree L1006 has 1 unconnected individual.
Pedigrees reconstructed in 0.0000 seconds
Checking simple Mendelian inheritance in nuclear families... :
==============================================================
Inheritance inconsistency:    PEDIGREE    MOTHER  FATHER  MARKER
--------------------------    --------    ------  ------  ------
INHERITANCE #0001:            L0004       M05758  N00167  D1S425
INHERITANCE #0002:            L0035       N00403  N00402  D10S1237
INHERITANCE #0003:            L0038       M02583  N00201  D1S245
INHERITANCE #0004:            L0038       M02583  N00201  D1S425
INHERITANCE #0005:            L0038       M02583  N00201  D9S1118
.                                   .
.                                   .
.                                   .
==============================================================

================================================
Summary of Mendelian Inheritance Inconsistencies
   by Marker
================================================
#      MARKERNAME             NUCLEAR FAMILIES
----    ------------------     ----------------
16.    D1S245                  6
17.    D1S249                  1
18.    D1S425                  4
19.    D1S466                  1
.                                  .
.                                  .
.                                  .
45.    D17S949                 4
46.    D17S1807                4
------------------------------------------------
Inconsistencies present among 30 of 32 markers.
================================================

 1.FAMID      Co__1   17.D1S249     Go__2   33.D10S217    Go_18
 2.STUDYID    Co__2   18.D1S425     Go__3   34.D10S575    Go_19
 3.SEX        Co__3   19.D1S466     Go__4   35.D10S587    Go_20
 4.FATHER     Co__4   20.D1S1647    Go__5   36.D10S1230   Go_21
 5.MOTHER     Co__5   21.D1S1660    Go__6   37.D10S1237   Go_22
 6.MZTWIN     Co__6   22.D1S2640    Go__7   38.D10S1248   Go_23
 7.DZTWIN     Co__7   23.D1S2757    Go__8   39.D10S1693   Go_24
 8.AFFECTED   Po__1   24.D1S2877    Go__9   40.D10S1741   Go_25
 9.CAFFECTED  *       25.D1S3725    Go_10   41.D17S784    Go_26
10.AGE        Po__2   26.D9S169     Go_11   42.D17S914    Go_27
11.AFF_BROAD  Po__3   27.D9S171     Go_12   43.D17S928    Go_28
12.CAFF_BROAD Co__8+  28.D9S269     Go_13   44.D17S939    Go_29
13.AFF_RESTR  Po__4   29.D9S285     Go_14   45.D17S949    Go_30
14.CAFF_RESTR Po__5   30.D9S1118    Go_15   46.D17S1807   Go_31
15.AGE_DX     Po__6   31.D9S1121    Go_16   47.D17S1847   Go_32
16.D1S245     Go__1   32.D9S1874    Go_17
-----------------------------  --------- --------- ---------
Pedigrees and Individuals       Included  Excluded     Total
-----------------------------  --------- --------- ---------
Pedigrees ...................        112         0       112
Individuals .................        916         0       916
 + In database ..............        878         0       878
 |  + Attached ..............        877         0       877
 |  + Childless spouses .....          0         0         0
 |  + Unattached ............          1         0         1
 + Not in database ..........         38         0        38
1 WARNING, 121 INHERITANCE INCONSISTENCIES M>

Quiet

Specifies that "detail" messages are not shown on the screen. Summary log messages still appear on the screen, and both detail and summary messages are still written to the .dtl and .log files, respectively. See: silent, verbose.

M>quiet
Madeline is now in quiet mode.
M>

Quit

goodbye quit

Terminates the program session. Equivalent to goodbye. See: goodbye.

M>quit
Releasing resources ...
Goodbye!

Read

Read allele frequencies calculated by an external program or saved during a previous session into Madeline. When the "from ..." clause is omitted, Madeline attempts to read allele frequencies from a default file called "madeline.alf.mfh".

When a pedigree table is opened, the program automatically calculates allele frequencies using gene counting which does not take familial relationships into account. These allele frequencies can be saved to a table for later use using the save command.

Gene counting is sufficient for estimating allele frequencies from large data sets containing many pedigrees or unrelated controls. For smaller data sets containing fewer pedigrees, better estimates can be obtained using a program like Mendel which can account for familial relationships in its calculations.

The following fields are required to be present in an allele frequency table:

The output from Mendel v. 4.1 is already in a tabular format. You need only change the header to correspond with Madeline requirements:

 LOCUS      ALLELE       ESTIMATED    STANDARD
 NAME       NAME         FREQUENCY     ERROR

 MARKER01    302           0.0445      0.0308
 MARKER01    304           0.0218      0.0216
 MARKER01    307           0.0215      0.0213
 MARKER01    308           0.1384      0.0549
  ...

summary.out result file from Mendel v. 4.1 ...

MARKERNAME C
ALLELE     N
FREQUENCY  N
STDERR     N

 MARKER01    302           0.0445      0.0308
 MARKER01    304           0.0218      0.0216
 MARKER01    307           0.0215      0.0213
 MARKER01    308           0.1384      0.0549
  ...

... and the same file after adding the header that Madeline requires.

Once the header is in the right format, use the recognize command to recognize the table. You can now read the table. Only the allele frequencies of markers which are present in the allele frequency table are adjusted: the allele frequencies of other markers which are not in the allele frequencies table remain unadjusted. Warnings are issued when markers present in the allele frequencies table are not present in the pedigree table.

Note: Since actual allele counts are not available for allele frequencies read in from external sources, Madeline arbitrarily multiplies the frequencies by 10,000 in order to display allele "counts". Due to rounding error, the counts will sometimes only sum up to 9,999 instead of 10,000. This does not affect locus files or allele frequency tables produced by the program.

Example:

M>open 'chr12.corrected.data.mfh'
Calculating allele frequencies for  11. MARKER01...
 ...
M>read allele frequencies from "chr12frequencies.data.mfh"
WARNING #0001: Marker "MARKER06" was not found in the pedigree table.
 ...
Allele frequencies have been read from chr12frequencies.data.mfh
4 WARNINGS M>list allele frequencies for marker01, marker02

11. MARKER01:

302       445/ 9999     0.0445
304       218/ 9999     0.0218
307       215/ 9999     0.0215
308      1384/ 9999     0.1384
312      1225/ 9999     0.1225
316      1007/ 9999     0.1007
320      5290/ 9999     0.5291
324       215/ 9999     0.0215

12. MARKER02:

263       221/10000     0.0221
271      2190/10000     0.2190
275      2409/10000     0.2409
279      4734/10000     0.4734
283       446/10000     0.0446

4 WARNINGS M>

Recognize

Recognize a column-aligned, space-delimited rectangular ASCII or UTF-8 data file (i.e., a "flat file") as a database table by creating a binary header file that contains key information about the number of records in the table, number of columns, column names, column data types, and other relevant information. A table in the correct format for processing by recognize will typically have a header declaring the column names and data types at the top, followed by a rectangular data grid, as shown in the example below:

FAMID C  STUDYID C  SEX X  FATHER C  MOTHER C  
MZTWIN C  DZTWIN C  CAFFECTED C  AGEDX N
DXS1010 G DXS1074 G DXS1550

Z0400  Y02221  M  Y02225  Y02224  . . A 57    200/200  163/163  146/146
Z0400  Y02222  M  Y02225  Y02224  . . A 61    200/200  163/163  146/146
Z0400  Y02223  F  .       .       . . U  0    198/198  151/159  146/148
Z0400  Y02224  F  X00018  Y02223  . . U  0    198/200  151/163  146/146
Z0400  Y02225  M  .       .       . . U  0    200/200  165/165  150/150
Z0400  Y02226  F  X00018  Y02223  . . U  0    198/200  159/163  146/148
Z0400  Y02227  M  Y02225  Y02224  . . U  0    198/198  151/151  146/146
Z0400  Y02228  M  X00036  Y02230  . . A 54    200/200  163/163  146/146
Z0400  Y02229  F  X00036  Y02230  . . U  0    196/200  163/163  146/146
Z0400  Y02230  F  Y02231  X00022  . . U  0    192/200  157/163  146/152

A flat-file table in the correct format typically has a header (blue area with dotted border) declaring column names and data types, followed by a rectangular grid of data.

By default, Madeline adds ".mfh" to the name of the input file to create the name of the output file. Optionally, you can specify a name for the binary header file using the "to" clause.

If necessary, a flat file in the appropriate space-delimited column format can usually be created using Madeline's rectify or convert commands.

When the data file is in the correct form, the program quickly parses the file and creates an ".mfh" header file:

M>recognize 'z0400.data'
Starting to recognize file "z0400.data" to "z0400.data.mfh" ...
Skipping a total of 13 lines at top.
There are 4 non-empty header lines and 80 data lines.
Data records are 299 bytes long.

The gender field has been identified.
The individual, father, and mother ID fields have been identified.

 # . Field Name  Start End   Length Prec. Space Type
---- ----------- ----- ----- ------ ----- ----- -----
  1. FAMID           1     5     5     0     2 C
  2. STUDYID         8    13     6     0     9 C
  3. SEX            23    23     1     0     1 X
  4. FATHER         25    30     6     0     9 C
  5. MOTHER         40    45     6     0     9 C
  6. MZTWIN         55    55     1     0     1 C
  7. DZTWIN         57    57     1     0     1 C
  8. CAFFECTED      59    59     1     0     1 C
  9. AGE            61    61     1     0     4 N
 10. DXS1001        66    72     7     0     2 G
 11. DXS1047        75    81     7     0     2 G
 12. DXS1055        84    90     7     0     2 G
 13. DXS1060        93    99     7     0     2 G
 14. DXS1068       102   108     7     0     2 G
 15. DXS1073       111   117     7     0     2 G
 16. DXS1106       120   126     7     0     2 G
 17. DXS1205       129   135     7     0     2 G
 18. DXS1214       138   144     7     0     2 G
 19. DXS1226       147   153     7     0     2 G
 20. DXS1227       156   160     5     0     4 G
 21. DXS8015       165   171     7     0     2 G
 22. DXS8043       174   180     7     0     2 G
 23. DXS8045       183   189     7     0     2 G
 24. DXS8051       192   198     7     0     2 G
 25. DXS8055       201   207     7     0     2 G
 26. DXS8080       210   214     5     0     4 G
 27. DXS8083       219   225     7     0     2 G
 28. DXS8091       228   232     5     0     4 G
 29. DXS8102       237   243     7     0     2 G
 30. DXS8106       246   252     7     0     2 G
 31. DXS986        255   261     7     0     2 G
 32. DXS987        264   270     7     0     2 G
 33. DXS990        273   279     7     0     2 G
 34. DXS991        282   288     7     0     2 G
 35. DXS993        291   297     7     0     2 G
Binary recognition header file ("z0400.data.mfh") written.
This appears to be a PEDIGREE TABLE which can be opened using:

        open "z0400.data.mfh"

M>

As illustrated above, the recognize command is often able to determine what type of data table you have and will remind you, based on table type, what command to use to open the file.

If recognize finds that the data rows in a table are not of a consistent length or contain embedded tabs or extra spaces or tabs, the command will abort as shown below:

FAMID C  STUDYID C  SEX X  FATHER C  MOTHER C  
MZTWIN C  DZTWIN C  CAFFECTED C  AGEDX N
DXS1010 G DXS1074 G DXS1550

Z0400  Y02221  M  Y02225  Y02224  . . A 57    200/200  163/163  146/146
Z0400  Y02222  M  Y02225  Y02224  . . A 61    200/200  163/163  146/146
Z0400  Y02223  F  .       .       . . U  0    198/198  151/159  146/148
Z0400  Y02224  F  X00018  Y02223  . . U  0    198/200  151/163  146/146         
Z0400  Y02225  M  .       .       . . U  0    200/200  165/165  150/150    
Z0400  Y02226  F  X00018  Y02223  . . U  0    198/200  159/163  146/148   
Z0400  Y02227  M  Y02225  Y02224  . . U  0    198/198  151/151  146/146
Z0400  Y02228  M  X00036  Y02230  . . A 54    200/200  163/163  146/146
Z0400  Y02229  F  X00036  Y02230  . . U  0    196/200   163/163  146/146
Z0400  Y02230  F  Y02231  X00022  . . U  0    192/200  157/163  146/152

Same table as above, but with extra embedded tabs or extra spaces or tabs at the ends of lines(blue areas with dotted border) that create a non-rectangular data array will ...

M>recognize 'z0400.data'
Starting to recognize file "z0400.data" to "z0400.data.mfh" ...
HEADER block spans lines 1 to 3.
DATA block spans lines 5 to 40.
It appears that the DATA block contains TAB characters.
Please examine the file carefully to verify if this is
the true problem.  If this is the problem, try running
the RECTIFY command which will expand tabs to the
appropriate number of spaces in most cases. Then rerun
RECOGNIZE after correcting all problems.

WARNING #0001: AssignRecordTypes(): The file is not in the required format.
No ".mfh" or ".run" files were created
1 WARNING M>

... require using rectify, convert, or manual editing, as the program suggests here.

A non-rectangular data grid can be caused by many things. Just a few embedded tabs or extra spaces among the data rows will be enough to give you problems. To avoid such problems, we recommend that you store both phenotype and genotype data in a relational database system and use a scripting language like Perl, PHP, or Python to extract the data into the correct format.

A detailed description of the recognize command and the table format expected by Madeline is provided below.

Recognize Detailed Description and Table Requirements

In its simplest form, a database table has two parts:

1. A rectangular array of data consisting of rows and columns.
2. A header that defines the column names, types, number of records, file size, file type, and other key information.

An ASCII or UTF-8 flat file that contains a rectangular array of data with spaces separating aligned columns can be considered a simple form of a database table:

0001 0001-100 F 0001-200 0001-300  23.45  14.2  141/142
0001 0001-200 M .        .             .  10.2  138/141
0001 0001-300 F .        .         78.21  15.2  140/142
.    .        . .        .             .     .  .
.    .        . .        .             .     .  .
.    .        . .        .             .     .  .
.    .        . .        .             .     .  .

A simple flat file data table.

The biggest problem with this table "format" is that it has no header containing "meta data". Meta data are simply "data about the data". The omission of meta data to tell the user what each column represents is a serious obstacle and, without this information, the file is in fact completely useless to an uninformed user.

A secondary problem, perhaps of more concern to a computer program than to a person, is that the file lacks meta data declaring 1) the data type of each column (character, numeric, date, etc.), 2) the total number of columns, or 3) the total number of rows (records) in the table.

Madeline tackles the "meta data" problem by constructing a separate binary header file which is used to open the table indirectly. The binary header file is built by the recognize command and usually has a ".mfh" (i.e., Madeline Flat file Header) extension. The combination of a ".mfh" binary header and an ASCII or UTF-8 flat file table is referred to as the Madeline Database, or Mbase file format.

Madeline can determine much of the key meta data just by examining the flat file table itself. From a table with unlabeled columns (such as illustrated above), the recognize command can:

Always determine:

• Number of records
• Number of columns
• Where each column begins and ends
• How many trailing spaces follow after each column

Almost always determine:

• Column data type (numeric vs. character vs. date)

...and often determine:

• Which column represents gender
• Which column represents individual ID
• Which column represents father ID
• Which column represents mother ID

The ability to determine the gender, individual, father, and mother ID fields provides a fruitful start to deciphering a file with unmarked columns. This is most useful when you receive unlabeled data files from your absent-minded colleagues and collaborators!

Still, there is no way for Madeline to know what all columns in an unmarked file represent. In the absence of additional information, Madeline provides default names based on whether the columns contain character, numeric, or date data. This is usually not what you want, unless you are in a great hurry!

The solution is to provide column names and column data types at the top of the flat file before the first record. When present, the recognize command reads this "header" before parsing the rectangular data array. Madeline requires this header in many cases.

The only information that you need to provide in the header at the top of a flat file data table is:

1. Column name -- Up to 10 letters or digits without spaces can be used to represent field names.
2. Column type -- Data type of the column.

The following set of single-letter options is permitted for designating column type:

• "C" for character.
• "N" for numeric.
• "D" for date.
• "X" for a character-based gender field. This is a field which uses labels like "F" and "M" to designate gender. (Numeric gender fields are also permitted but must be designated "N").
• "G" for a genotype field. Genotypes must be represented using two numeric labels separated by a forward slash character. A "G" designation can be viewed as a derivative of the more generic "C" character field.
• "A" for allele fields. Allele fields contain a single numeric label representing one allele. Allele fields must always come in pairs in order to reconstruct genotypes.

The column type designation is technically optional. If not provided, Madeline will make a determination. The program determines data type by looking at what characters are present in a column and how they are formatted. For example, if a "/" slash occurs in a column, the column cannot be numeric. additional processing is used to decide if the column contains dates or genotypes, or something else. If you are uncertain whether Madeline will make the correct determination, then provide column types. Providing column type designators also assists your human colleagues and collaborators.

A column type designator must follow immediately after a column name by at least one space. Column names must themselves be separated from one another by one or more spaces. Other than this, column names and types can appear on any number of lines. The only other requirement is that the lines of the header must be shorter in length than those of the records. This rule is maintained so that the program knows which lines are header lines and which are data records.

The four core fields FamilyIDField, IndividualIDField, FatherIDField, and MotherIDField must always be treated as "C" character fields, even when the identifiers themselves consist of only numbers. This is necessary requirement of the algorithms the program uses to sort and store individuals. So, at a minimum, it may be necessary to supply the field types of these core fields. Here is an example:

FAMID C
INDIVIDUAL
GENDER C
FATHER MOTHER   STUDYAGE  GLUCOSE  D20S119

0001 0001-100 F 0001-200 0001-300  23.45  14.2  141/142
0001 0001-200 M .        .             .  10.2  138/141
0001 0001-300 F .        .         78.21  15.2  140/142
.    .        . .        .             .     .  .
.    .        . .        .             .     .  .
.    .        . .        .             .     .  .
.    .        . .        .             .     .  .

A data table with a header declaring column names. Only a few columns (FAMID,GENDER) are labeled with type designators.

In the example above, the INDIVIDUAL, FATHER, and MOTHER columns (corresponding to the IndividualIDField, FatherIDField, and MotherIDField, respectively) contain dash characters, so the program will automatically interpret them as "C" character fields without being marked so (the program can see that they are not date fields). However, FAMID consists entirely of digits and would be interpreted as "N" numeric were it not designated "C". The above example is now ready to be processed by the recognize command.

Recognize Special Situations

There are a couple of special situations to pay attention to when constructing the flat file header.

First, only a gender field containing character string labels such as "M" and "F" or "male" and "female" should be designated as being of type "X". You can also designate such a gender field with the more generic "C" (as was done above), or not designate any type at all, and Madeline will figure it out for you.

Secondly, Madeline provides the opportunity to specify a special column type of "A" for allele fields. Allele fields are present in file formats such as the Genehunter/Linkage format where two contiguous space-delimited columns contain the allele labels that taken together represent the genotype for one marker. Since two columns are present, in the flat file header you must show the same column name twice -- once for the first allele column, and once for the second allele. The column names should be the marker names. For example:

FAMID C
STUDYID C
FATHER C
MOTHER C
SEX X
NAFFECTE N
D20S100 A
D20S100 A
D20S200 A
D20S200 A

0001 0001-200                   M .  0 0  0 0
0001 0001-300                   F .  0 0  0 0
0001 0001-100 0001-200 0001-300 M 1  1 1  4 5
0001 0001-401 0001-200 0001-300 F 0  1 2  5 5
0001 0001-402 0001-200 0001-300 F 0  2 2  4 4
0001 0001-403 0001-200 0001-300 F 1  1 2  4 4
0001 0001-404 0001-200 0001-300 M 0  2 2  4 4
0001 0001-408 0001-200 0001-300 M 1  2 2  4 5
0001 0001-409 0001-200 0001-300 M 1  1 1  4 4
  .      .        .        .    . .  . .  . .
  .      .        .        .    . .  . .  . .
  .      .        .        .    . .  . .  . .

A data table in Genehunter/Linkage format has paired allele columns. Notice the repeated marker name labels in the header that has been added for Madeline.

Errors will result with unpaired "A" fields, so be careful! Madeline will combine the paired allele fields into genotype fields, as shown below. The column "Start" and "End" values confirm that Madeline has merged pairs of columns:

M>recognize "flat.test"
Recognizing file "flat.test" to "flat.test.mfh" ...
Skipping a total of 11 lines at top.
There are 10 non-empty header lines and 27 data lines.
Data records are 45 bytes long.

The gender field has been identified.

 # . Field Name  Start End   Length Prec. Space Type
---- ----------- ----- ----- ------ ----- ----- -----
  1. FAMID           1     4     4     0     1 C
  2. STUDYID         6    13     8     0     1 C
  3. FATHER         15    22     8     0     1 C
  4. MOTHER         24    31     8     0     1 C
  5. SEX            33    33     1     0     1 X
  6. NAFFECTE       35    35     1     0     2 N
  7. D20S100        38    40     3     0     2 G
  8. D20S200        43    45     3     0     0 G

Madeline recognition header written.
Type 'open "flat.test.mfh" ' to open the database.

M>

Recognizing a table with paired allele columns (see above).

After recognizing a file, the ".mfh" file is used as the parameter to the open, load, compose, merge, or read command.

Rectify

In order for Madeline to use a flat file table, the data block must contain aligned columns that are delimited by space characters. Extra space characters are used to pad column widths so that the columns always line up. In addition, the data block must be truly rectangular, which means that all data lines must be of equal length.

Embedded tab characters are usually replaced by space characters when a file is viewed in an editor or word processor on screen, leading to the false impression of a rectangular array with even line lengths, when in fact lines are actually of varying byte-lengths (A single tab contributes only one byte to the row length even though up to eight spaces may be used for displaying the tab's "space" on screen). Extra (but invisible!) space or tab characters after the last column in a table can also result in varying line lengths.

The rectify command (1) replaces all tab characters embedded in the data block with the appropriate number of space characters, and (2) trims or pads lines so that all records become equal in length. Although most file editors default to a tab interval of eight character-columns, this is often a user-settable variable and some users will choose to use narrower tab intervals. Rectify contains an algorithm for determining what tab interval --from one to eight spaces-- must have been used in order to create the impression of aligned columns when the file was originally hand-edited in a file editor on screen.

Sometimes a set of different tab intervals would all result in aligned columns in an editor. Madeline chooses the smallest tab expansion interval that will produce aligned columns in the result file. Pathological cases (i.e., corrupted files) may exist that the algorithm cannot handle: manual review of the results is recommended.

The tabset_3_7 demonstration file in the examples/DataSetsContainingTabsAndUnevenLines subdirectory of the software distribution contains a number of tabs between the second and third data columns (shown as small dots). The data columns appear unaligned because the file was originally edited with a different (unknown) tab interval.

M>rectify 'tabset_3_7'
Rectifying file "tabset_3_7" to "tabset_3_7.mod" ...
HEADER block spans lines 1 to 5.
DATA block spans lines 7 to 40.
There are 2 equally valid tab expansion solutions:

Tab size = 7
Tab size = 3

Madeline will convert the file using a tab setting of 3 spaces.
Writing header lines to tabset_3_7.mod...
Writing tab-expanded data rows to tabset_3_7.mod...
Rectified file "tabset_3_7.mod" has been written.
M>

The rectify algorithm finds two possible tab expansion solutions for the "tabset_3_7" file and chooses the smallest expansion.

FAMILYID
INDIVIDUAL
MARKERNAME
ALLELE1
ALLELE2

F0921     I00081     D10S1651  211  231
F0921     I00081     D10S1652  293  295
F0921     I00081     D10S1653  126  128
F0921     I00081     D10S1686  257  273
F0921     I00081     D10S1693  219  221
F0921     I00081     D10S185   205  213
F0921     I00081     D10S189   187  189
F0921     I00081     D10S192   258  264
F0921     I00081     D10S196   110  114
F0921     I00081     D10S197   173  179
F0921     I00081     D10S208   187  189
F0921     I00081     D10S212   196  202
F0921     I00081     D10S217   104  104
F0921     I00081     D10S249   124  136
F0921     I00081     D10S537   155  161
F0921     I00081     D10S547   242  260
F0921     I00081     D10S548   190  194
F1231     I00207     D10S1651  215  217
F1231     I00207     D10S1652  291  295
F1231     I00207     D10S1653  124  128
F1231     I00207     D10S1686  259  273
F1231     I00207     D10S1693  221  221
F1231     I00207     D10S185   213  227
F1231     I00207     D10S189   189  195
  .        .          .         .    .

The tabset_3_7 file after rectification.

Run

Load and run a batch file. Batch files can themselves contain nested run commands. When commands from a batch file are being processed, Madeline displays the "M-Batch>" prompt in place of the "M>" prompt, and returns to the "M>" prompt after successful completion of batch commands. Madeline goes into quiet mode whenever a batch file is invoked with run: issue verbose after run if you want to return to verbose mode.

Contents of load.bat:

run task.bat

Contents of task.bat:

quiet
open "thursday.dbf"
write to "mendel.ped" in mendel format
load "geneticmap.dbf"
write to "siblink.ped" in siblink format

Here is the interactive session:

M>run "load.bat"
M-Batch> Running batch file "load.bat"... ***
M-Batch> run task.bat
M-Batch> Running batch file "task.bat"... ***
M-Batch> quiet
Madeline is now in quiet mode
M-Batch> open "thursday.dbf"
         ...        ...
M-Batch> write to "mendel.ped" in mendel format
...        ...
M-Batch> load "geneticmap.dbf"
Marker maps based geneticmap.dbf are now installed
M-Batch> write to "siblink.ped" in siblink format
...        ...
M-Batch>
M-Batch> Finished batch file "task.bat"... ***
M-Batch>
M-Batch> Finished batch file "load.bat"... ***
M>

Batch processing can also be invoked from the command line. In addition, a script named "initial.script" can be automatically invoked at program startup.

Save

Save allele frequencies calculated by Madeline using gene counting to a table on disk. If the "from ..." clause is omitted, a default name of "madeline.alf" is used. The saved table is in Madeline format and can be read back into the program using the read command. A typical operation is to use Madeline to obtain allele frequencies from a large data file containing many pedigrees, save these frequencies, open up a smaller subset of pedigrees for analysis, and use the the read command to restore allele frequencies based on the larger data set.

M>open "full.data.mfh"
 ...
M>save allele frequencies
Table of allele frequencies for 5 markers written to "madeline.alf"
 ...
M>open "analysis.subset.data.mfh"
 ...
M>read allele frequencies from "madeline.alf.mfh"
Allele frequencies have been read from madeline.alf.mfh
M>list allele frequencies for marker03
13. MARKER03:

236      3828/10000     0.3828
240       431/10000     0.0431
244       535/10000     0.0535
248      2400/10000     0.2400
252       647/10000     0.0647
256      2159/10000     0.2159

Set | Turn

set turn

AutoCheckInheritance AutoExclude Color ConsoleHighlights on off FusionSupport HaplotypeDisplay MapDetails ReverseShading on off field order to fieldi, fieldj, fieldk - fieldz language to AmericanEnglish | BritishEnglish Arabic | Chinese | French German | Finnish | Greek Italian | Japanese | Portugese Russian | Spanish | Thai orientation to landscape portrait automatic PaperSize to A4 A4Long A4Super USLegal USLetter PaperMargin to Valuecentimeters

The set and turn commands are identical. See turn for a complete description.

Show

Show the value of a single expression. You can abbreviate show to "?". The commmand is equivalent to "what is" but requires less typing.

To display values in any kind of list, including field lists, arrays, and marker maps, use the list command instead. See list, what is.

M>show sin(pi/4)
0.707107
M>? DateToJulian({2004.04.22})
   2,453,118
M>? PedigreeDrawingFile
"madeline.pedigree.ps"
M>

Silence

Suppress detail and summary log messages from the screen (messages are still written to the log files). Identical to silent. See silent.

Silent

Suppress detail and summary log messages from the screen (messages are still written to the log files). Identical to silence. See silence.

Sort

Sets the sort order for displaying siblings in a sibship and multiple spouses on pedigree drawings. Expression can be any expression that can be evaluated by Madeline. The default sort order is ascending.

M>//
M>// show siblings in descending order by date of birth:
M>//
M>sort on dob descending
M>draw pedigree '0535'
Drawing page 1 of 1 page for pedigree 0535...
M>//
M>// show siblings in ascending order by the number of offspring they have:
M>//
M>sort on _NumberOfOffspring ascending
M>draw pedigree '0535'
Drawing page 1 of 1 page for pedigree 0535...
M>

Pedigree drawings created after using the sort command. The drawing on the left has sibships sorted by date of birth descending. The drawing on the right has sibships sorted by the number of offspring that each sib has. Both drawings represent the same pedigree.

For more information on drawing pedigrees, see the draw and set commands.

Status

Displays the current setting of Madeline's boolean state flags and other status information. Identical to the hello command.

M>status
+-----------------------+-----------+-----------------------------------------+
| Variable or State Flag| Setting   |Description                              |
+-----------------------+-----------+-----------------------------------------+
| EXTERNAL PROGRAMS     |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| Editor                | edith     |Program used to edit files               |
| PostscriptViewer      | gv        |Program used to view Postscript drawings |
| PrintCommand          | lpr       |System program used to print files       |
| WebBrowser            | netscape  |Program used to view HTML documentation  |
+-----------------------+-----------+-----------------------------------------+
| EVALUATION SETTINGS   |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| EvaluationInterval    |   0.50 cM |Value to write to control file.          |
| OffEndDistance        |  10.00 cM |Value to write to control file           |
+-----------------------+-----------+-----------------------------------------+
| DRAWING SETTINGS      |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| Color                 | ON        |Draw pedigrees in color                  |
| ReverseShading        | OFF       |Black is first icon shade                |
| DividedDrawings       | ON        |Paginate drawings by founding group      |
| HighlightRows         | ON        |Alternately highlight data on drawings   |
| LabelCreatedIndividual| ON        |Label virtuals created by Madeline       |
| Orientation           | AUTOMATIC |Automatic based on drawing dimensions    |
| PaperMargin           | 1.00 cm   |Margin (in cm) on all four sides         |
| PaperSize             | USLETTER  |8.5 x 11.0 inches                        |
+-----------------------+-----------+-----------------------------------------+
| OTHER SETTINGS        |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| AutoExclude           | ON        |Exclude pedigrees automatically          |
| AutoCheckInheritance  | ON        |Check inheritance on OPEN                |
| ConsoleHighlights     | ON        |Use bold/color highlights on console     |
| Delimiter             | TAB       |Delimiter for tables and other output.   |
| FusionSupport         | OFF       |FUSION customizations disabled           |
| HaplotypeDisplay      | OFF       |Display genotypes delimited with "/"     |
| Language              | American E|Language convention used for date, time  |
| MapDetails            | OFF       |LIST MAP summary display                 |
| SaveAlleleFrequencies | OFF       |Calculate new frequencies on next OPEN   |
| Date                  |           |Friday, April 23, 2004                   |
| Verbosity             | VERBOSE   |All messages are printed to the console  |
+-----------------------+-----------+-----------------------------------------+
M>

System

Transfers a quoted command to the shell for execution by the operating system. This allows you to obtain directory and file information, copy or move files, or run analysis software without having to exit Madeline.

M>system "ls -l test/*.dbf"
-rw-rw-rw-a   8061 Tue Dec 02 14:34:24 1997  chr20dic.dbf
-rw-rw-rw-a 550246 Tue Jan 13 15:08:10 1998  c14.dbf
-rw-rw-rw-a 777954 Tue Dec 02 14:40:18 1997  chr20.dbf
-rw-rw-rw-a1001786 Mon Feb 16 14:53:10 1998  sib20.dbf
-rw-rw-rw-a 369746 Thu Feb 26 11:10:16 1998  draw.dbf
M>

Toggle

toggle

covariate icon genotype phenotype flags for fieldi [ , fieldj , fieldk - fieldz ] on off output flags for fieldi [ , fieldj , fieldk - fieldz ] for chromosome n markers for _IsMendelianInconsistent

Toggle database field category and status flags.

Toggle Genotype, phenotype, and covariate flags

Madeline automatically categorizes fields in a database table as being core "C", genotype "G", or phenotype "P" fields. Core "C" fields contain core information used to reconstruct pedigrees and classify individuals, such as the StudyIDField, GenderField, and AffectionStatusField. Genotype "G" fields contain marker information. The names of genotype fields should correspond with the marker names exactly. Fields that are not "C" or "G" fields are classified as phenotype "P" fields.

Core fields are determined by matching up field names in the database table with names stored in internal variables. Genotype fields are determined by sampling the data to find character fields that contain numeric labels separated by slash characters. By elimination, remaining fields are classified as phenotype fields.

Certain output formats may require knowing which of the phenotype fields are to be used as covariates. Hence, there is also a covariate "V" category. By default, "C", "G" and all "P" fields except date fields are marked for output with the "o" flag. Excepting core fields which Madeline handles automatically in most cases, only the fields marked for output with the "o" flag will be processed and appear in output from write, draw, and and similar commands.

The most common use of the toggle command is to toggle the output flags on or off. Occasionally you might need to change the status of a phenotype "P" field to that of a covariate "V" field. Covariate "V" fields are still recognized as phenotype "P" fields when writing formats that do not require covariates.

M>open "/m55/newtest.dbf"
      ...    ...
  1.STUDYID    Co__1   19.D20S889    Go__4   37.D20S481    Go_22  
  2.SEX        Co__2   20.D20S482    Go__5   38.D20S836    Go_23  
  3.FATHER     Co__3   21.D20S905    Go__6   39.D20S888    Go_24  
  4.MOTHER     Co__4   22.D20S115    Go__7   40.D20S886    Go_25  
  5.TWIN       Co__5   23.D20S851    Go__8   41.D20S197    Go_26  
  6.FUSION2    Po__1   24.D20S917    Go__9   42.D20S178N   Go_27  
  7.CONTROL    Po__2   25.D20S189    Go_10   43.D20S866    Go_28  
  8.CPEP       Po__3   26.D20S898    Go_11   44.D20S196    Go_29  
  9.GLU_FAST   Po__4   27.D20S114    Go_12   45.D20S857    Go_30  
 10.GLU_2H     Po__5   28.D20S912    Go_13   46.D20S480    Go_31  
 11.STUDYAGE   Po__6   29.D20S477    Go_14   47.D20S211    Go_32  
 12.LOGSI      Po__7   30.D20S874    Go_15   48.D20S840    Go_33  
 13.BMI        Po__8   31.D20S195    Go_16   49.D20S120    Go_34  
 14.TP         Po__9   32.D20S909    Go_17   50.D20S100    Go_35  
 15.NAFFECTE   C    +  33.D20S107    Go_18   51.D20S102    Go_36  
 16.D20S103    Go__1   34.D20S170    Go_19   52.D20S171    Go_37  
 17.D20S117    Go__2   35.D20S96     Go_20   53.D20S173    Go_38  
 18.D20S906    Go__3   36.D20S119    Go_21  
M>toggle output flags for 6-7,glu_fast,glu_2h,12-14
M>toggle covariate flag for studyage
M>list fields
  1.STUDYID    Co__1   19.D20S889    Go__4   37.D20S481    Go_22  
  2.SEX        Co__2   20.D20S482    Go__5   38.D20S836    Go_23  
  3.FATHER     Co__3   21.D20S905    Go__6   39.D20S888    Go_24  
  4.MOTHER     Co__4   22.D20S115    Go__7   40.D20S886    Go_25  
  5.TWIN       Co__5   23.D20S851    Go__8   41.D20S197    Go_26  
  6.FUSION2    P       24.D20S917    Go__9   42.D20S178N   Go_27  
  7.CONTROL    P       25.D20S189    Go_10   43.D20S866    Go_28  
  8.CPEP       Po__1   26.D20S898    Go_11   44.D20S196    Go_29  
  9.GLU_FAST   P       27.D20S114    Go_12   45.D20S857    Go_30  
 10.GLU_2H     P       28.D20S912    Go_13   46.D20S480    Go_31  
 11.STUDYAGE   Vo__2   29.D20S477    Go_14   47.D20S211    Go_32  
 12.LOGSI      P       30.D20S874    Go_15   48.D20S840    Go_33  
 13.BMI        P       31.D20S195    Go_16   49.D20S120    Go_34  
 14.TP         P       32.D20S909    Go_17   50.D20S100    Go_35  
 15.NAFFECTE   C    +  33.D20S107    Go_18   51.D20S102    Go_36  
 16.D20S103    Go__1   34.D20S170    Go_19   52.D20S171    Go_37  
 17.D20S117    Go__2   35.D20S96     Go_20   53.D20S173    Go_38  
 18.D20S906    Go__3   36.D20S119    Go_21
M>

Toggle On or off output flags for specified fields

The most frequent use of the toggle command is to toggle fields on or off for output. When the keyword on is included, fields in the specified range are forced on. When off is used, they are forced off. When on or off are ommitted, fields that were on are turned off, and those that were off are turned on:

M> toggle on output flags for 15-17, CAFF_BROAD, D1S211 - D3S455

Toggle On or off output flags for markers of a specific chromosome

You can turn all of the markers for a specific chromosome on or off by specifying for chromosome n as part of the toggle command. This version of the command only works when a marker map is already loaded, since the marker map provides the association between marker names and chromosomes. See the load command.

M> load "allmarkers.map.mfh"
  ...
M> toggle on output flags for chromosome 22 markers

Omitting the keyword on or off has the result of turning the specified columns off. It is also possible to omit the keyword markers. For example, the following is legal and results in turning off markers for chromosome 17:

M> toggle output flags for chromosome 17

Toggle Icon flags

Toggle icon flag enables you to designate one or more categorical variables to display graphically on the male and female icons of a pedigree drawing. By default, the AffectionStatusField is automatically toggled with the icon flag on when a pedigree table is opened. You can designate any number of additional fields for graphical display. The number of fields you select determines the number of pie-slice regions into which the icons on the drawing will be divided. Each pie-slice region will be shaded to display the categorical level of the respective variable. Fields toggled with the icon flag on are displayed in the field list with a plus sign, "+" at the end. For example:

...
15. AFFECTED   C   +
16. HEARTCOND  N   +
...

When the icon flag of a field is toggled on, Madeline automatically determines how many non-missing categorical levels are present in the field:

15. AFFECTED has 3 levels.
16. HEARTCOND has 3 levels.

Madeline also automatically constructs three associative arrays for each such categorical variable. The names of the arrays are constructed by taking the variable name ("affected" in this case) and appending "_color", "_gray", and "_label", respectively:

M>lookup 'affected'
Affected_Color is an associative array. It accepts character string keys and maps them to character string values.
Affected_Gray is an associative array. It accepts character string keys and maps them to numeric values.
Affected_Label is an associative array. It accepts character string keys and maps them to character string values.
M>

These arrays are used when drawing pedigrees. In this example, Affected_Label stores a set of labels for labeling each level on the pedigree drawing:

M>list Affected_Label
Affected_Label has 3 elements:
Affected_Label["A"]="A"
Affected_Label["I"]="I"
Affected_Label["U"]="U"
M>

The Affected_Gray array stores a set of evenly-spaced numeric gray values ranging from 0 (black) to 1 (white) for use when drawing pedigrees in black and white (i.e., when set color off):

M>list Affected_Gray
Affected_Gray has 3 elements:
Affected_Gray["A"]=0
Affected_Gray["I"]=0.5
Affected_Gray["U"]=1
M>

(You can set ReverseShading on to make 0 represent white and 1 represent black if required).

Here's what a pedigree in black and white will look like with these default settings:

An example pedigree drawn with color set off using the default values in Affected_Label and Affected_Gray shown above.

Finally, the "_Color" array stores a set of red-green-blue (RGB) color triplets as strings which are used when drawing pedigrees in color (color is on by default). Each color component varies from 0 (no intensity) to 1 (full intensity):

M>list Affected_Color
Affected_Color has 3 elements:
Affected_Color["A"]="0.13 0.43 0.92"
Affected_Color["I"]="0.97 0.89 0.01"
Affected_Color["U"]="0.26 0.99 0.24"
M>

Here's what a pedigree in color will look like with these default settings:

An example pedigree drawn with color set on using the default values in Affected_Label and Affected_Color shown above.

Because these parameters are stored in arrays, you can easily change the values to suit your needs:

M>//
M>// Change labels: AFF=Affected, IND=Indeterminate.
M>// "U"s are unaffected (no labels):
M>//
M>Affected_Label["A"]="AFF"
M>Affected_Label["I"]="IND"
M>Affected_Label["U"]=""
M>//
M>// Change colors:
M>//
M>Affected_Color["I"]=lightgray
M>//
M>// Draw pedigree:
M>//
M>draw pedigree "F004"
Drawing pedigree F004, U0166's subtree (subtree 1 of 1) ...
M>

Example pedigree drawn after modifying values in the Affected_Label and Affected_Color arrays.

Keep in mind that normally not more than three characters will fit on the labels within the male or female symbols when displaying one categorical variable. When displaying more than one categorical variable, not more than one character can be displayed within the pie-slice divisions. As shown above, you can assign a null string, "", to an element in the "_Label" array when you don't want a label shown on the drawing.

Watch out for two conditions! First, selecting too many categorical variables will cause the icons on the drawing to be divided into illegibly narrow pie-sliced regions. Although Madeline imposes no limit, four categorical variables is about the limit for human legibility.

Secondly, guard against selecting a variable with too many levels. At best, the human eye can only distinguish about eight shades of gray. Even if you choose to draw pedigrees in color, if you have more than about eight or nine categorical levels, the drawing is likely going to be difficult to decipher, so its up to you to determine how to present your data legibly. Madeline however imposes no limit on the number of levels that can be drawn. The program uses a preset table of easily-distinguishable colors for the first nine levels of a categorical variable (figure below): after that, colors are generated randomly.

(a) Set of nine preset colors used to represent levels of a categorical variable on pedigree drawings. (b) The same set of colors as they might appear to an individual with a red-green color vision deficiency.

Putting all of this together, we have:

M>open 'utf8.data.mfh'
   ...
M>toggle icon flag for heartcond
  8. AFFECTED has 3 levels.
  9. HEARTCOND has 3 levels.
M>heartcond_label["1"]="H"
M>heartcond_label["2"]="B"
M>heartcond_label["3"]="M"
M>heartcond_color["1"]=yellow
M>heartcond_color["2"]=orange
M>heartcond_color["3"]=red
M>affected_color["A"]=green
M>affected_color["I"]=lightgray
M>affected_color["U"]=white
M>draw pedigree 'F004'
Drawing pedigree F004, U0166's subtree (subtree 1 of 1) ...
M>>

Pedigree resulting from commands shown above.

Set | Turn

set turn

AutoCheckInheritance AutoExclude Color ConsoleHighlights on off FusionSupport HaplotypeDisplay MapDetails ReverseShading on off delimiter to comma | space | tab | "OtherDelimiter" field order to fieldi, fieldj, fieldk - fieldz language to AmericanEnglish | BritishEnglish Arabic | Chinese | French German | Finnish | Greek Italian | Japanese | Portugese Russian | Spanish | Thai orientation to landscape portrait automatic PaperSize to A4 A4Long A4Super USLegal USLetter PaperMargin to Valuecentimeters

In Madeline, the set and turn commands are identical. Just select the command verb that makes the most sense to you in English. Descriptions of all forms of the command follow.

The first set of descriptions covers boolean flags that can be turned on or off. See Table 5.5 for a tabular summary of all boolean state flags.

SET | TURN AutoCheckInheritance on | off

When AutoCheckInheritance is on (the default), Mendelian inheritance checking is performed whenever a new pedigree table is opened using the open command. See check inheritance for a detailed description. See: check, open.

SET | TURN AutoExclude on | off

AutoExclude instructs Madeline, on a subsequent write command, to automatically exclude individuals and, if necessary, pedigrees with insufficient data. Individuals with no usable genotypes are excluded unless their presence is required to maintain pedigree structure. If AutoExclude is off, no pedigrees will be excluded. Autoexclude is on by default. See also: exclude, write.

M>turn AutoExclude off
Autoexclude is now off
M>

SET | TURN Color on | off

When color is on (the default), pedigrees are drawn in color. When color is off, pedigrees are drawn in black and white. The setting of ReverseShading, described below, affects whether black or white is used to represent the first shade of gray on black and white pedigree drawings: see below.

In reality, this toggle affects a single boolean flag located near the top of the Postscript file. (named madeline.pedigree.ps by default) that Madeline generates after a draw command has been issued. Thus, any saved pedigree drawing can be printed in color or in black-and-white at any time by simply changing the boolean INCOLOR flag in the Postscript file from true to false or vice-versa:

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
%
% Boolean toggle for color shading/printing:
%
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
/INCOLOR true def

Changing the boolean state of the INCOLOR flag in the Postscript pedigree drawing file generated by Madeline allows you to print a saved drawing in either black-and-white or color at any time.

SET | TURN ConsoleHighlights on | off

When ConsoleHighlights is on (the default), Madeline will apply bold or color attributes to certain text displayed in your terminal. Set ConsoleHighlights off disables terminal text attributes.

M>lookup 'h'
h is an internal variable. Its current value is 0.000.
HaldaneToTheta is a function taking and returning a number.
HaplotypeDisplay is a keyword.
hello (status) is a command.
help is a command.
HighlightRows is a keyword.
horizontal is a keyword.
html is a keyword.
M>turn consoleHighlights off
M>lookup 'h'
h is an internal variable. Its current value is 0.000.
HaldaneToTheta is a function taking and returning a number.
HaplotypeDisplay is a keyword.
hello (status) is a command.
help is a command.
HighlightRows is a keyword.
horizontal is a keyword.
html is a keyword.
M>

SET | TURN Delimiter

By default, Madeline uses a TAB character as the delimiter when displaying certain tabular data. You can change this to a comma, space, or any other single-character delimiter. This facilitates cutting tabular data out of Madeline for pasting into other programs:

M>view data CAFFECTED,AGE_DX for AGE_DX>=90

L0197   M05266  .       91
L0878   M06267  .       91
 ...
M>set delimiter to comma 
M>view data CAFFECTED,AGE_DX for AGE_DX>=90

L0197,M05266,.,91,
L0878,M06267,.,91,
 ...
M>set delimiter to space
M>view data CAFFECTED,AGE_DX for AGE_DX>=90

L0197 M05266 . 91
L0878 M06267 . 91
 ...
M>set delimiter to "*"
M>view data CAFFECTED,AGE_DX for AGE_DX>=90

L0197*M05266*.*91*
L0878*M06267*.*91*
 ...

SET | TURN FusionSupport on | off

Madeline was originally written for use in the Finland-United States Investigation of NIDDM Genetics (FUSION). In that study, individual identifiers were originally coded in a way which revealed the relationship of an individual to the proband. When FusionSupport is turned on, the program makes use of the relationship information revealed by the FUSION identifiers to reconstruct pedigrees even when certain individuals are not present in the pedigree table. While the program continues to maintain this option, it is of no use in other investigations and is therefore off by default.

SET | TURN HaplotypeDisplay on | off

When HaplotypeDisplay is on, genotypes are shown with alleles delimited by "|" on pedigree drawings. When off, alleles are shown delimited by "/". Off is the default setting.

Note: Madeline is not capable of inferring haplotypes and has no way of knowing whether alleles in a pedigree file are arranged to show haplotypes or not. If alleles in a pedigree table have been arranged to show haplotypes known or inferred from an external program, then Madeline provides a convenient way to draw pedigrees of such data using set HaplotypeDisplay on followed by draw pedigree commands.

SET | TURN MapDetails on | off

After a genetic map has been loaded using the load command, you can use list map or list map for chromosome n to display the genetic map in a tabular format:

M>load 'map.data.mfh'
Marker maps based on map.data.mfh are now installed.
M>list map for chromosome 23

                    Map Position (Kosambi cM)
                  -----------------------------
Ch Or Marker Name Sex-avg.   Female     Male
-- -- ----------- --------- --------- ---------
23  1 DXS1060       15.1200    7.6600   22.7700
23  2 DXS8051       17.2900   12.0300   22.7700
23  3 DXS987        22.1800   22.0400   22.7700
 .  .   .             .         .         .
 .  .   .             .         .         .
 .  .   .             .         .         .

When MapDetails is turned on, Kosambi inter-marker distances and recombination fractions are also shown:

M>set MapDetails on
M>list map for chromosome 23

                   Sex-averaged Map   Female-specific Map  Male-specific Map
                  ------------------- ------------------- -------------------
Ch Or Marker Name Kosambi   Dist (RF) Kosambi   Dist (RF) Kosambi   Dist (RF)
-- -- ----------- --------- --------- --------- --------- --------- ---------

--------------
Chromosome 23
--------------
                              15.1200             7.6600            22.7700
                              (0.1468)           (0.0760)           (0.1468)
23  1 DXS1060       15.1200             7.6600            22.7700
                               2.1700             4.3700              .
                              (0.0217)           (0.0436)             .
23  2 DXS8051       17.2900            12.0300            22.7700
                               4.8900            10.0100              .
                              (0.0487)           (0.0988)             .
23  3 DXS987        22.1800            22.0400            22.7700
                               5.4100            10.9400              .
                              (0.0539)           (0.1077)             .
.                               .                  .                  .
.                               .                  .                  .
.                               .                  .                  .

MapDetails is off by default.

SET | TURN ReverseShading on | off

When drawing pedigrees in black and white, Madeline normally uses black for the first level of a displayed categorical variable (such as the AffectionStatusField which is toggled for display by default), white for the last level, and evenly-spaced intermediate shades of gray for every level in between. If your AffectionStatusField is coded using "A" for affected, "I" for indeterminate, and "U" for unaffected, then affected individuals will be shown on your pedigree drawings in black, unaffected in white, and indeterminate in 50% gray.

When ReverseShading is turned on, the opposite would apply: the first level would appear in white, the second level in gray, and so on out to the last level which would be in black. This is useful, for example, if you happend to have the AffectionStatusField coded using 1 for unaffected and 2 for affected, as is the custom in Linkage/Genehunter files. In this case with just two non-missing levels present, individuals marked with 1 will appear white, while the affecteds marked with 2 would appear black, just as you would expect.

Note that Madeline provides other ways for you to adjust the color of the male or female icons on a pedigree drawing: see the toggle icon flags for all the details.

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
%
% Boolean toggle for color shading/printing:
%
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
/INCOLOR true def
/REVERSE_SHADING false def
 

Set | Turn Field order

Reorder fields by specifying field names or field indices separated by commas, or a range of contiguous field names or indices separated by a dash. Fields are ordered within their category (i.e., "C","P", or "G"). Covariate "V" fields are simply a subset of phenotype "P" fields and, thus, are numbered along with phenotype fields.

If you specify the order of some but not all of the fields within a given category, the remaining fields will be ordered after your fields based on their physical order in the database.

When specifying field order, you can mix and match any sequence of "C", "P", and "G" fields within a single set command. Specified fields not already toggled for output are ignored. Issuing a load command after a set field order command resets the order of all "Co" and "Po" fields, while "Go" field ordering is set to the map order. To avoid this behaviour, just issue load prior to any set field order command.

Madeline controls the order of C core fields when writing most output formats. Reordering of core fields is honoured by the view record and draw pedigree commands, and by the CommaDelimited and SpaceDelimited write formats.

Issuing set field order without the to clause resets the order of "Co" and "Po" fields to their natural order, while the order of "Go" fields will depend on whether a map table is loaded or not.

M>open 'chr20.data.mfh'
  ...    ...
  1.STUDYID    Co__1   19.D20S889    Go__5   36.D20S836    Go_22  
  2.SEX        Co__2   20.D20S103    Go__6   37.D20S888    Go_23  
  3.FATHER     Co__3   21.D20S115    Go__7   38.D20S886    Go_24  
  4.MOTHER     Co__4   22.D20S851    Go__8   39.D20S197    Go_25  
  5.TWIN       Co__5   23.D20S912    Go__9   40.D20S178N   Go_26  
  6.CPEP       Po__1   24.D20S917    Go_10   41.D20S866    Go_27  
  7.GLU_FAST   Po__2   25.D20S898    Go_11   42.D20S196    Go_28  
  8.GLU_2H     Po__3   26.D20S114    Go_12   43.D20S857    Go_29  
  9.STUDYAGE   Po__4   27.D20S477    Go_13   44.D20S480    Go_30  
 10.LOGSI      Po__5   28.D20S874    Go_14   45.D20S211    Go_31  
 11.BMI        Po__6   29.D20S195    Go_15   46.D20S120    Go_32  
 12.TP         Po__7   30.D20S909    Go_16   47.D20S102    Go_33  
 13.AFFECTED   C       31.D20S107    Go_17   48.D20S173    Go_34  
 14.ISTYPED    Po__8   32.D20S170    Go_18   49.D20S171    Go_35  
 15.D20S117    Go__1   33.D20S96     Go_19   50.D20S840    Go_36  
 16.D20S906    Go__2   34.D20S119    Go_20   51.D20S189    Go_37  
 17.D20S482    Go__3   35.D20S481    Go_21   52.D20S100    Go_38  
 18.D20S905    Go__4  
M>load 'chr20.map.mfh'
Marker maps based on chr20.map.mfh are now installed.
Note: genotype fields ordered according to current map
Field ordering now set based on chr20.map.mfh
M>list fields
  1.STUDYID    Co__1   19.D20S889    Go__4   36.D20S836    Go_23  
  2.SEX        Co__2   20.D20S103    Go__1   37.D20S888    Go_24  
  3.FATHER     Co__3   21.D20S115    Go__7   38.D20S886    Go_25  
  4.MOTHER     Co__4   22.D20S851    Go__8   39.D20S197    Go_26  
  5.TWIN       Co__5   23.D20S912    Go_13   40.D20S178N   Go_27  
  6.CPEP       Po__1   24.D20S917    Go__9   41.D20S866    Go_28  
  7.GLU_FAST   Po__2   25.D20S898    Go_11   42.D20S196    Go_29  
  8.GLU_2H     Po__3   26.D20S114    Go_12   43.D20S857    Go_30  
  9.STUDYAGE   Po__4   27.D20S477    Go_14   44.D20S480    Go_31  
 10.LOGSI      Po__5   28.D20S874    Go_15   45.D20S211    Go_32  
 11.BMI        Po__6   29.D20S195    Go_16   46.D20S120    Go_34  
 12.TP         Po__7   30.D20S909    Go_17   47.D20S102    Go_36  
 13.AFFECTED   C       31.D20S107    Go_18   48.D20S173    Go_38  
 14.ISTYPED    Po__8   32.D20S170    Go_19   49.D20S171    Go_37  
 15.D20S117    Go__2   33.D20S96     Go_20   50.D20S840    Go_33  
 16.D20S906    Go__3   34.D20S119    Go_21   51.D20S189    Go_10  
 17.D20S482    Go__5   35.D20S481    Go_22   52.D20S100    Go_35  
 18.D20S905    Go__6  
M>set field order to father,mother,logsi,studyage,sex,twin,tp,bmi
M>list fields
  1.STUDYID    Co__5   19.D20S889    Go__4   36.D20S836    Go_23  
  2.SEX        Co__3   20.D20S103    Go__1   37.D20S888    Go_24  
  3.FATHER     Co__1   21.D20S115    Go__7   38.D20S886    Go_25  
  4.MOTHER     Co__2   22.D20S851    Go__8   39.D20S197    Go_26  
  5.TWIN       Co__4   23.D20S912    Go_13   40.D20S178N   Go_27  
  6.CPEP       Po__5   24.D20S917    Go__9   41.D20S866    Go_28  
  7.GLU_FAST   Po__6   25.D20S898    Go_11   42.D20S196    Go_29  
  8.GLU_2H     Po__7   26.D20S114    Go_12   43.D20S857    Go_30  
  9.STUDYAGE   Po__2   27.D20S477    Go_14   44.D20S480    Go_31  
 10.LOGSI      Po__1   28.D20S874    Go_15   45.D20S211    Go_32  
 11.BMI        Po__4   29.D20S195    Go_16   46.D20S120    Go_34  
 12.TP         Po__3   30.D20S909    Go_17   47.D20S102    Go_36  
 13.AFFECTED   C       31.D20S107    Go_18   48.D20S173    Go_38  
 14.ISTYPED    Po__8   32.D20S170    Go_19   49.D20S171    Go_37  
 15.D20S117    Go__2   33.D20S96     Go_20   50.D20S840    Go_33  
 16.D20S906    Go__3   34.D20S119    Go_21   51.D20S189    Go_10  
 17.D20S482    Go__5   35.D20S481    Go_22   52.D20S100    Go_35  
 18.D20S905    Go__6  
M>

Set | Turn Language

Sets the language and locale conventions used for displaying dates and times in Madeline.

M>quiet
M>set language to AmericanEnglish
M>?{1776.07.04}
{Thursday, July 4, 1776}
M>set language to BritishEnglish
M>?{1776.07.04}
{Thursday, July 4, 1776}
M>set language to Japanese
M>?{1776.07.04}
{1776年7月4日 (木曜日)}
M>set language to Italian
M>?{1776.07.04}
{giovedé, 4 luglio 1776}
M>set language to Chinese
M>?{1776.07.04}
{1776年7月4日 (星期四)}
M>set language to Thai
M>?{1776.07.04}
{วันพฤหัสบดีที่่ 4 กรกฏาคม พ.ศ. 2319 }
M>

Set | Turn Orientation of pedigree drawings

In landscape and portrait modes, Madeline resizes a pedigree drawing to fit on a single physical page in the desired orientation. For large pedigrees, the reduction necessary to fit a drawing on a single page may result in labels that are too small to read. In general, the default automatic mode is a better choice.

When orientation is set to automatic, Madeline chooses the best orientation for a drawing based on it's height and width. If Madeline determines that the reduction necessary to fit the drawing on a single page may make the labels difficult to read or illegible, the program inserts additional Postscript code to print the drawing as a "poster" across multiple physical pages. The program selects the number and orientation of physical pages that require the least amount of rescaling of a drawing. A schematic index is produced as a guide for assembling the drawing after printing. See draw for more information.

M>set orientation to landscape
...
M>

Set | Turn PaperSize of pedigree drawings

Sets the paper size to the specified standard printer paper size. Madeline does not send special commands to multi-tray printers, so be sure that the correct paper size is in the selected printer tray.

M>iset papersize to usletter
...
M>

Set | Turn PaperMargin of pedigree drawings

Sets the paper margins on all four sides to the specified value in centimeters. The default margin size is one centimeter. If a multiple-page drawing is produced, the pages will also overlap by the specified margin along the joining edges of the poster.

Do not set the margins to much less than one centimeter because most printers cannot print out to the physical edge of the paper.

M>set papermargin to 1.5
+-----------------------+-----------+-----------------------------------------+
| Variable or State Flag| Setting   |Description                              |
+-----------------------+-----------+-----------------------------------------+
| EXTERNAL PROGRAMS     |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| Editor                | edith     |Program used to edit files               |
| PostscriptViewer      | gv        |Program used to view Postscript drawings |
| PrintCommand          | lpr       |System program used to print files       |
| WebBrowser            | netscape  |Program used to view HTML documentation  |
+-----------------------+-----------+-----------------------------------------+
| EVALUATION SETTINGS   |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| EvaluationInterval    |   0.50 cM |Value to write to control file.          |
| OffEndDistance        |  10.00 cM |Value to write to control file           |
+-----------------------+-----------+-----------------------------------------+
| DRAWING SETTINGS      |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| Color                 | ON        |Draw pedigrees in color                  |
| ReverseShading        | OFF       |Black is first icon shade                |
| DividedDrawings       | ON        |Paginate drawings by founding group      |
| HighlightRows         | ON        |Alternately highlight data on drawings   |
| LabelCreatedIndividual| ON        |Label virtuals created by Madeline       |
| Orientation           | AUTOMATIC |Automatic based on drawing dimensions    |
| PaperMargin           | 1.50 cm   |Margin (in cm) on all four sides         |
| PaperSize             | USLETTER  |8.5 x 11.0 inches                        |
+-----------------------+-----------+-----------------------------------------+
| OTHER SETTINGS        |           |                                         |
+-----------------------+-----------+-----------------------------------------+
| AutoExclude           | ON        |Exclude pedigrees automatically          |
| AutoCheckInheritance  | ON        |Check inheritance on OPEN                |
| ConsoleHighlights     | ON        |Use bold/color highlights on console     |
| Delimiter             | TAB       |Delimiter for tables and other output.   |
| FusionSupport         | OFF       |FUSION customizations disabled           |
| HaplotypeDisplay      | OFF       |Display genotypes delimited with "/"     |
| Language              | American E|Language convention used for date, time  |
| MapDetails            | OFF       |LIST MAP summary display                 |
| SaveAlleleFrequencies | OFF       |Calculate new frequencies on next OPEN   |
| Date                  |           |Saturday, May 1, 2004                    |
| Verbosity             | VERBOSE   |All messages are printed to the console  |
+-----------------------+-----------+-----------------------------------------+
M>

Unexclude

unexclude [ families ] for Expression_logical

Includes previously excluded individuals and pedigrees in output. If unexclude families is used, all individuals who match the criteria and their spouse(s) and descendants who were excluded by a previous exclude families or other exclude command will be included again. See exclude

M>exclude for _famid=='0172'
0172-100 has been marked for exclusion
0172-401 has been marked for exclusion
0172-402 has been marked for exclusion
0172-500 has been marked for exclusion
0172-601 has been marked for exclusion
0172-602 has been marked for exclusion
0172-603 has been marked for exclusion
0172-604 has been marked for exclusion
0172-605 has been marked for exclusion
M>unexclude for _famid=='0172'
0172-100 has been marked for inclusion
0172-401 has been marked for inclusion
0172-402 has been marked for inclusion
0172-500 has been marked for inclusion
0172-601 has been marked for inclusion
0172-602 has been marked for inclusion
0172-603 has been marked for inclusion
0172-604 has been marked for inclusion
0172-605 has been marked for inclusion
M>

Verbose

verbose

Prints all summary and detail messages to the screen. See quiet, silent.

M>verbose
Madeline is now in verbose mode.
M>

View

view

[ record ] [ for Expressionlogical ] data [ Expression1, Expression2, ... Expressionn ] for Expressionlogical distinct values of Field1, Field2, ... Fieldn

The view command has three forms, described below:

View Records for a Logical Expression

When view is used without the record keyword, only the IndividualID, FamilyID, and record number of individuals matching the query criteria are shown. If the record keyword is included, then those fields in the database currently toggled on for output are also shown.

If view record is typed without a for query expression, then only the current record is shown. After displaying matching results, view prints a summary tally of the number of individuals and pedigrees which matched.

M>open 'mini.data.mfh'
  1.FAMID      Co__1    9.CAFFECTED  *       17.ATA84D02   Go__2
  2.STUDYID    Co__2   10.AGE        Po__1   18.ATAG053    Go__3
  3.SEX        Co__3   11.AFF_BROAD  Po__2   19.GATA167C12 Go__4
  4.FATHER     Co__4   12.CAFF_BROAD Po__3   20.GATA22H02  Go__5
  5.MOTHER     Co__5   13.AFF_RESTR  Po__4   21.GATA26D02N Go__6
  6.MZTWIN     Co__6   14.CAFF_RESTR Po__5   22.AAAT007    Go__7
  7.DZTWIN     Co__7   15.AGE_DX     Po__6   23.AAT034     Go__8
  8.AFFECTED   Co__8+  16.ATA80B10Z  Go__1   24.AAT247     Go__9
-----------------------------  --------- --------- ---------
Pedigrees and Individuals       Included  Excluded     Total
-----------------------------  --------- --------- ---------
Pedigrees ...................        125         0       125
Individuals .................      1,013         0     1,013
 + In database ..............        939         0       939
 |  + Attached ..............        937         0       937
 |  + Childless spouses .....          0         0         0
 |  + Unattached ............          2         0         2
 + Not in database ..........         74         0        74

M>view for _PercentGenotyped>0 and _PercentGenotyped<80
M02454 in L0005 (rec. no.    17)
M02456 in L0006 (rec. no.    23)
M05146 in L0022 (rec. no.    45)
    .   .    .              .
    .   .    .              .
    .   .    .              .
M06357 in L0960 (rec. no.   909)
M06392 in L0990 (rec. no.   918)
M06488 in L1050 (rec. no.   925)
M06487 in L1051 (rec. no.   935)

52 individuals in 45 pedigrees matched as follows:

Individuals ..............         52
 + In database ...........         52
 |  + Attached ...........         52
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0

M>go 935
M>view record
CORE FIELDS:
L1051 M06487 F N00639 N00640 . . 0
PHENOTYPE FIELDS:
 0 2 A 0 I  0
GENOTYPE FIELDS:
165/189 ....... ....... ....... 254/270 153/161 309/309 ....... 284/287
M>

Note: The view [ record ] command shown above has now been largely supplanted by the more powerful view data command described below. We recommend using view data for most cases.

View Data

View data related to individuals matching query criteria. The data items can consist of any expressions that Madeline's interpreter can evaluate. By default the pedigree and individual identifiers are always reported, even if you omit a data expression. By default, tabs are used to separate columns in the result table; you can change this using the set delimiter command.

M>view data for _FamilyID="L0990"

L0990   M06392
L0990   M06398
L0990   M06400
L0990   N00600
L0990   N00601

5 individuals in 1 pedigree matched as follows:

Individuals ..............          5
 + In database ...........          3
 |  + Attached ...........          3
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          2

M>view data _PercentGenotyped, _IsMendelianInconsistent, CAFF_BROAD,CAFF_RESTR for _FamilyID="L0246"

L0246   M05209  88.8889 1       A       A
L0246   M05494  100     1       A       A
L0246   M05629  88.8889 1       A       I
L0246   N00352  0       1       I       I
L0246   N00353  0       1       I       I

5 individuals in 1 pedigree matched as follows:

Individuals ..............          5
 + In database ...........          5
 |  + Attached ...........          5
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
 
M>

View Distinct Values of Fields

View a histogram of the distinct values in a field or set of fields. A list of field names or field indices may be specified separated by commas. A range may be specified by separating the first and last field in a range with a dash. Madeline reports the number of non-missing levels of a variable. The number of missing cases is printed at the end of the list.

M>list fields
  1.FAMID      Co__1    9.CAFFECTED  *       17.ATA84D02   Go__2
  2.STUDYID    Co__2   10.AGE        Po__1   18.ATAG053    Go__3
  3.SEX        Co__3   11.AFF_BROAD  Po__2   19.GATA167C12 Go__4
  4.FATHER     Co__4   12.CAFF_BROAD Po__3   20.GATA22H02  Go__5
  5.MOTHER     Co__5   13.AFF_RESTR  Po__4   21.GATA26D02N Go__6
  6.MZTWIN     Co__6   14.CAFF_RESTR Po__5   22.AAAT007    Go__7
  7.DZTWIN     Co__7   15.AGE_DX     Po__6   23.AAT034     Go__8
  8.AFFECTED   Co__8+  16.ATA80B10Z  Go__1   24.AAT247     Go__9
M>view distinct values of 10, CAFF_BROAD

10. AGE has 21 levels:

Level  Va Cases Percent
------ -- ----- -------
    1.  0   151   16.1  -+-
    2. 38     1    0.1
    3. 47     1    0.1
     .  .     .     .
     .  .     .     .
     .  .     .     .
   19. 73     2    0.2
   20. 75     2    0.2
   21. 84     2    0.2
------ -- ----- -------
    .. ..   183   19.5   non-missing values in database
    .. ..   756   80.5       missing values in database

12. CAFF_BROAD has 3 levels:

Level  V Cases Percent
------ - ----- -------
    1. A   355   37.8  -+-+-+-
    2. I   460   49.0  -+-+-+-+-
    3. U    82    8.7  -
------ - ----- -------
    .. .   897   95.5   non-missing values in database
    .. .    42    4.5       missing values in database

M>

What Is

Shows the value of an expression. Equivalent to show command. See show.

M>what is studyid
"0052-100"
M>what is d20s889
"201/216"
M>

Write

write

locus file [pedigree file]

to “FileName” in

Generic: CommaDelimited1 | SpaceDelimited | TabDelimited | Generic2 Aspex: Kinship3 SibIBD | SibMap | SibPhase | SibTDT | Crimap: Crimap Genehunter: GeneHunter4 | GeneHunterNPL | GeneHunterQTL Linkage Disequilibrium: LDEQMarker | LDEQAffectedSpouse | LDEQTDT Mendel & Fisher: Fisher0 | Fisher1 | Mendel | UserM13 Merlin: Merlin Pedcheck: Pedcheck Relpair: Relpair Sage: FSP0 | FSP | Sage | Sibpal1 | Sibpal2 | Sibpal3 | Sibpal4 Siblink: SiblinkAffectedPairs | SiblinkUnaffectedPairs | SiblinkAllPairs | SiblinkDiscordantPairs Simwalk: Simwalk UserFQTL: UserFQTL | UserFQTLAll | UserFQTLFounders | UserFQTLOffspring

format

There are two forms of the write command:

• write pedigree file
• write locus file

Each form of the command is described below.

Write Pedigree files

Write pedigree file ... writes the current set of core "C" fields and flagged output fields (e.g., "Go", "Po" and "Vo" fields) to a pedigree file in the format specified by the format keyword (genehunter, merlin, simwalk, etc.). The command "write pedigree file" can be shortened to just "write"; the program assumes you want to create a pedigree file when a keyword is not otherwise specified.

After a write command, the value of OutputFile will be set to the FileName that you specified in the write command.

For certain formats, such as the GenehunterNPL and Siblink formats, Madeline will automatically create a parameter or control file at the same time the pedigree file is created. A parameter or control file contains a template for running an analysis, along with other core information required by the specific package, such as number of families or sib pairs in the corresponding pedigree file. Madeline fills in as much information as possible. However, the program generally will not know what sort of analysis is to be conducted, what genetic model to specify, and so on. Thus, the user will generally need to edit the parameter file and customize it to meet his or her specific analysis needs.

For these formats, the value of OutputParameterFile will become the FileName with an extension of ".par", ".ctl", or something similar added to the end, depending upon the naming conventions common to that format. Madeline will print a message informing the user of creation of a complementary .par or .ctl file.

Some formats, such as the Genehunter and Simwalk formats, incorporate map distance information into either a control file or locus file, and therefore require that a map database be loaded prior to the write command. Madeline will issue an error if you try to write such a file without first loading a map.

For specific formats and usage, see Section 3. Write Formats.

M>write to 'simwalk.ped' in simwalk format
NOTE: Simwalk batch file, "BATCH2.DAT.simwalk.ped", has been created.
      Edit this file to change the parameters of your analysis.

NOTE: Simwalk map file "simwalk.ped.map" has been created.
Writing pedigree data to "simwalk.ped"
-----------------------------  --------- --------- ---------
Pedigrees and Individuals       Included  Excluded     Total
-----------------------------  --------- --------- ---------
Pedigrees ...................        107        18       125
Individuals .................        901       109     1,010
 + In database ..............        858        81       939
 |  + Attached ..............        858        79       937
 |  |  + With data ..........        439         0       439
 |  |  + Without data .......        419        79       498
 |  |  + Marked for exclusion          0         0         0
 |  + Childless spouses .....          0         0         0
 |  + Unattached ............          0         2         2
 + Not in database ..........         43        28        71
M>

Write Locus files

Write locus file ... creates a locus file containing allele frequency information for the set of "Go" genotype fields flagged for output in the current pedigree table.

Formats such as the Siblink format incorporate locus file information directly into the control file. In these cases, you do not need to create a separate locus file. Other packages, such as Crimap, do not require a locus file at all.

Some formats, such as the Siblink and Genehunter formats, incorporate map distance information into either a control file or locus file, and therefore require that a map database be loaded prior to the write command. Madeline will issue an error if you try to write such a file without first loading a map.

For specific formats and usage, see Section 3. Write Formats.

M>write locus file to 'mendel.loc' in mendel format
Locus file "mendel.loc" has been written.
M>

Section 3 Write Formats

Introduction to Write Formats

This section describes all formats currently supported by the write pedigree file ... and write locus file ... commands.

Format keywords are listed alphabetically within each group. Some keywords can be used for creating both a pedigree file and a locus file, while others cannot. To make these distinctions clear, one of the following codes may appear in parentheses following a heading:

For example, the sibpal3 keyword can only be used to create a pedigree file, while the sage keyword can only be used to create the corresponding locus file, so you will see Sibpal3 (PED) and Sage (LOC) as headings.

Depending upon analysis package, the parameter file may be called a control file or may have some other name. In Madeline, any file containing analysis control or parameter information is referred to as a parameter file. For many formats, the parameter file also contains locus (and sometimes map) information which eliminates the need for writing a locus file in a separate step.

Any one program may contain numerous settable parameters in the parameter file. For those formats that require it, Madeline provides a template parameter file that may be edited to set parameters to pass to an analysis program. Madeline provides default parameters to the extent possible, but these defaults are not necessarily the best choices for any given analysis and, in some cases, they may only be place-holder values which need to be edited by the user.

Generic Formats

Generic CommaDelimited (PED)

Used to output a pedigree file as a comma-delimited flat file. Since this is a generic format, there is no fixed set of required core fields. It is necessary to toggle output flags on or off and set field order, as required, for core fields as well as for general phenotype and genotype fields. For readability, fields in the output are padded with white space so that columns align, just as in the SpaceDelimited format. Missing numeric values are printed using the value specified in the first cell of the numeric missing value array, NumericMissingValue[1]. Missing character values are printed using the value specified in the first cell of the character missing value array, CharacterMissingValue[1].

M>nmv[1]=-9
M>list nmv
NMV has 1 elements:
NMV[ 1]=            -9
M>list cmv
CMV has 5 elements:
CMV[ 1]="."
CMV[ 2]="/"
CMV[ 3]="0/0"
CMV[ 4]="0/ 0"
CMV[ 5]="0/  0"
M>write pedigree file to 'commadelimited.data' in CommaDelimited format
  . . .
M>

Generic SpaceDelimited (PED)

Used to output a pedigree file as a column-aligned, space-delimited flat file. Since this is a generic format, there is no fixed set of required core fields. It is necessary to toggle output flags on or off and set field order, as required, for core fields as well as for general phenotype and genotype fields. Missing numeric values are printed using the value specified in the first cell of the numeric missing value array, NumericMissingValue[1]. Missing character values are printed using the value specified in the first cell of the character missing value array, CharacterMissingValue[1].

M>nmv[1]=-9
M>list nmv
NMV has 1 elements:
NMV[ 1]=            -9
M>list cmv
CMV has 5 elements:
CMV[ 1]="."
CMV[ 2]="/"
CMV[ 3]="0/0"
CMV[ 4]="0/ 0"
CMV[ 5]="0/  0"
M>write pedigree file to 'spacedelimited.data' in SpaceDelimited format
  . . .
M>

Generic TabDelimited (PED)

Used to output a pedigree file as a tab-delimited flat file. Since this is a generic format, there is no fixed set of required core fields. It is necessary to toggle output flags on or off and set field order, as required, for core fields as well as for general phenotype and genotype fields. Missing numeric values are printed using the value specified in the first cell of the numeric missing value array, NumericMissingValue[1]. Missing character values are printed using the value specified in the first cell of the character missing value array, CharacterMissingValue[1].

M>nmv[1]=-9
M>list nmv
NMV has 1 elements:
NMV[ 1]=            -9
M>list cmv
CMV has 5 elements:
CMV[ 1]="."
CMV[ 2]="/"
CMV[ 3]="0/0"
CMV[ 4]="0/ 0"
CMV[ 5]="0/  0"
M>write pedigree file to 'tabdelimited.data' in TabDelimited format
  . . .
M>

Generic Generic (LOC)

Used to output a locus file in a generic flat-file format that provides allele frequencies as well as the raw allele counts and allele ranks (see example below). The output file is useful for checking alleles, and for matching up allele ranks (used in formats such as Siblink and Genehunter) against the original allele labels.

D20S103 has 7 alleles:
1.  90  454/ 4296 = 0.1057
2.  92   27/ 4296 = 0.0063
3.  94  909/ 4296 = 0.2116
4.  96  663/ 4296 = 0.3871
5.  98  094/ 4296 = 0.2547
6. 100   44/ 4296 = 0.0102
7. 104  105/ 4296 = 0.0244

D20S117 has 14 alleles:
1. 166    4/ 4198 = 0.0010
2. 168  153/ 4198 = 0.0364
3. 176  658/ 4198 = 0.1567
4. 178   22/ 4198 = 0.0052
5. 183    9/ 4198 = 0.0021
6. 185  132/ 4198 = 0.0314
   . . .

Excerpt from a locus file in generic format produced by Madeline.

Aspex Formats

The programs in Aspex use a single pedigree file format. However, each program requires a different set of control parameters in the associated .tcl control file. Madeline therefore provides a format keyword for each program in the package and produces well-commented .tcl template files containing the default values for all relevant parameters. Two of the programs, sib_ibd and sib_phase (Madeline's sibibd and sibphase keywords), require marker information and so a marker map must be loaded prior to issuing the write command for these formats.

Aspex KINSHIP (PED, PAR/CTL)

Used to specify the pedigree file format along with the .tcl parameter file used by the Aspex kinship program. Madeline creates a well-commented .tcl parameter file at the same time that the pedigree file is created.

Aspex SIBIBD (PED, PAR/CTL)

Used to specify the pedigree file format along with the .tcl parameter file used by the Aspex sib_ibd program. Madeline creates a well-commented .tcl parameter file at the same time that the pedigree file is created. A map must be loaded prior to issuing the write command for this format.

Aspex SIBMAP (PED, PAR/CTL)

Used to specify the pedigree file format along with the .tcl parameter file used by the Aspex sib_map program. Madeline creates a well-commented .tcl parameter file at the same time that the pedigree file is created.

Aspex SIBPHASE (PED, PAR/CTL)

Used to specify the pedigree file format along with the .tcl parameter file used by the Aspex sib_phase program. Madeline creates a well-commented .tcl parameter file at the same time that the pedigree file is created. A map must be loaded prior to issuing the write command for this format.

Aspex SIBTDT (PED, PAR/CTL)

Used to specify the pedigree file format along with the .tcl parameter file used by the Aspex sib_tdt program. Madeline creates a well-commented .tcl parameter file at the same time that the pedigree file is created.

Crimap Format

Crimap CRIMAP (PED)

Used to specify Crimap ".gen" file format. Non-numeric characters in the study IDs are converted to their ASCII decimal equivalents. For example, "-" is converted to "45". Although this process lengthens the IDs, it does maintain the uniqueness of each ID and provides the completely numeric IDs required by Crimap. Note that the integer value of a converted ID must not exceed the maximum integer that can be represented within Crimap on your platform (Crimap uses a signed long int for IDs, the maximum value of which is 2,147,483,647 on many systems.

Madeline's Crimap routine currently only handles pedigrees with a single pair of founders (the founders may be dummied-in, as is done for FUSION sibship pedigrees). Criteria for including a pedigree are:

• There must be at least one nuclear family with both parents typed (either the founding pair or a proband-spouse or sibling-spouse pair) with at least one typed offspring.
• If only one parent is typed, then one grandparent must also be typed in addition to at least one typed offspring.

These criteria were defined by Dr. Beth Hauser and Dr. Mike Boehnke to prevent biased map lengths that occur when data are available on only a single generation of individuals.

Genehunter Formats

For the Genehunter formats (genehunter, genehunternpl and genehunterqtl), any pedigrees consisting of just a trio of two parents and a single offspring are excluded.

When the genehunternpl keyword is used to specify a file for non-parametric analysis, the following types of pedigrees are also excluded:

• Pedigrees which contain only a single affected individual.
• Pedigrees which contain a single pair of affected individuals and the pair form a parent-offspring relation.
• Pedigrees which contain a single trio of affected individuals and the trio form a parent-parent-offspring relation.

Genehunter GENEHUNTER (PED,PAR/CTL, LOC)

Used to specify a Genehunter pedigree file for parametric linkage analysis. Also used to create a Genehunter locus file. Madeline automatically converts the allele labels in the pedigree database to ordinals and prints these ordinal labels in both the locus and pedigree file. For cross-reference purposes, you may find it useful to also produce a generic locus file -- see GENERIC (LOC). A Genehunter locus file also contains inter-marker distance information. Be sure to load a map database prior to generating the locus file.

When used to create a pedigree file, the genehunter keyword instructs Madeline to exclude pedigrees that do not contribute to a parametric analysis. For a non-parametric analysis, use the genehunternpl keyword (below).

Genehunter GENEHUNTERNPL (PED,PAR/CTL)

Used to specify a Genehunter pedigree file for non-parametric linkage analysis. Pedigrees that cannot be used or do not contribute to a non-parametric analysis will be excluded. For a parametric linkage analysis, use the genehunter keyword (see above). To create the corresponding locus file, use the plain genehunter keyword. Read above to learn about Madeline's exclusion rules for this format.

Genehunter GENEHUNTERQTL (PED,PAR/CTL)

Used to specify a Genehunter pedigree file for quantitative trait linkage analysis. Pedigrees are excluded using the same rule as for the parametric case using the plain "genehunter" keyword. Using genehunterqtl differs from using the genehunter keyword in that the complementary control file is customized for a quantitative trait linkage analysis. To create the corresponding locus file, use the plain genehunter keyword.

Linkage Disequilibrium (LDEQ) Formats

For linkage disequilibrium analyses, Madeline selects a single parent-offspring trio providing the most genetic information possible from each pedigree. The output file format is a flat file similar to that produced by the generic SpaceDelimited format. In addition to toggling the genotype fields required for output, the user must also designate which core fields are required, and the order in which the core fields are required, prior to executing the write command. Note that the AffectionStatusField is required in output. The three options for linkage disequilibrium analyses are presented below.

Linkage Disequilibrium LDEQMARKER (PED)

For the ldeqmarker format, Madeline selects a trio providing the most information for a linkage disequilibrium analysis without regard to the affection status of the three individuals in the trio.

Linkage Disequilibrium LDEQAFFECTEDSPOUSE (PED)

For the ldeqaffectedspouse format, Madeline selects a trio providing the most information for a linkage disequilibrium analysis with the additional condition that at least one of the parents must be affected. The status of the other parent and offpsring can be affected, unaffected, or unknown (missing).

Linkage Disequilibrium LDEQTDT (PED)

For the ldeqtdt format, Madeline selects a trio providing the most information for a linkage disequilibrium analysis with the additional condition that the offspring must be affected. The status of the two parents can be affected, unaffected, or unknown (missing).

Mendel and Fisher Formats

The Mendel and Fisher programs cannot use individuals whose gender is listed as missing and therefore Madeline excludes such individuals. In general, however, it is unlikely you will have genotypes for individuals whose gender is unknown anyway. In addition, in Madeline only terminal individuals without offspring may retain gender status as missing because the program will, when required to do so, infer the gender of all non-terminal individuals from the mother and father fields of the offspring.

Mendel FISHER0 (PED)

Used to specify Fisher file format with no ascertainment correction. Zeros are written in the header for each pedigree to indicate no proband ascertainment. Use the mendel keyword to write the corresponding locus file.

Mendel FISHER1 (PED)

Used to specify Fisher file format with ascertainment correction. Ones are written in the header for each pedigree that has a proband to indicate proband ascertainment. Under fisher1, at least one non-proband individual in the pedigree must have sufficient data for the pedigree to be included in output. Use the mendel keyword to write the corresponding locus file.

Mendel MENDEL (PED, LOC)

Used to specify generic Mendel pedigree and locus file formats. This works for both older and newer versions of Mendel

Mendel USERM13 (PED)

Used to specify the Mendel UserM13 file format. UserM13 is the non-intuitive name of the Mendel module used to calculate allele frequencies taking family relationships into account in old versions of the Mendel suite. Use the mendel keyword to write corresponding locus file. When userm13 is specified, all non-excluded genotyped individuals, including childless spouses and unattached individuals, are included in output.

Merlin

Merlin MERLIN (PED)

Used to specify the Merlin file format. Madeline creates both the pedigree file as well as the accompanying ".data" file which serves as an index to the fields in the pedigree table.

PedCheck

PedCheck PEDCHECK (PED)

The pedcheck keyword produces an output file for use with the Pedcheck program by Jeff O'Connell of the University of Pittsburgh. The format is essentially the Linkage program format. Records for all individuals with genotype data are written to output.

Relpair

Relpair RELPAIR (PED, LOC)

Used to specify the Relpair file format. Relpair's locus file format is very similar to the UserFQTL format, while the pedigree file format is identical to generic Mendel format.

The locus file contains map information, and therefore a map database must be loaded prior to the write locus file command.

Sage Formats

To run a module in Sage such as Sibpal, you will need to have an FSP family data input file in addition to a Sibpal pedigree file. Be careful to use the same set of exclusions when creating both files. The Sage modules also require parameter files to run. Madeline provides template parameter files that require editing. The parameter files are generated at the same time as the pedigree files.

Note that since the FSP and Sibpal .ped or .par files could easily end up having the same names, be sure to differentiate the file names somewhere other than just in the file extension (Madeline will automatically provide .par as the extension for any of the Sage package parameter files).

Sage FSP0 (PED, PAR)

Used to specify the Sage FSP data file format. Madeline creates a corresponding .par file at the same time that the pedigree file is created. When fsp0 is used, Madeline only outputs the core fields that FSP requires for construction of the family structure pointer ".lnk" file which is used as one input to SIBPAL. No genotype fields are output (hence the "0" in the format name). In order to place genotype fields in an FSP segregation analysis data file used as input to ASSOC and LODLINK, use the FSP format (below) instead of FSP0. If your only objective is to obtain a family structure pointer file to run SIBPAL, then you do not need to include any phenotype or genotype fields as input to FSP, and FSP0 is the preferred choice.

Sage FSP (PED, PAR)

Used to specify the Sage FSP data file format. Madeline creates a corresponding .par file at the same time that the pedigree file is created. If you plan to run SIBPAL, it is more convenient to use the FSP0 format above. However, if you plan to run ASSOC or LODLINK, you should use the FSP format here in order to place genotype fields in the FSP segregation analysis data file.

Sage SAGE (LOC)

Used to specify the Sage locus file format.

Sage SIBPAL1 (PED, PAR)

Used to specify Sage Sibpal quantitative trait linkage format. Be sure to toggle the covariate and output flags of any covariates. Madeline creates a corresponding .par file at the same time that the pedigree file is created.

Sage SIBPAL2 (PED, PAR)

Used to specify Sage Sibpal binary trait linkage format. Be sure to toggle the covariate and output flags of any covariates. Madeline creates a corresponding .par file at the same time that the pedigree file is created.

Sage SIBPAL3 (PED, PAR)

Used to specify Sage Sibpal binary trait linkage with variable age of onset format. Be sure to toggle the covariate and output flags of any covariates. Madeline creates a corresponding .par file at the same time that the pedigree file is created.

Sage SIBPAL4 (PED, PAR)

Used to specify Sage Sibpal marker ordering (i.e., mapping) format. There has been no demand for this format in our labs, and so it has not been thoroughly tested. Madeline creates a corresponding .par file at the same time that the pedigree file is created.

Siblink

In addition to the usual set of core fields, the AffectionStatusField must be present so that Madeline can choose sib pairs based on affection status. In addition, a map database must be loaded. Madeline creates a Siblink control file with a .ctl extension at the same time that the pedigree file is created. The control file contains locus information, including map distance information.

Madeline automatically converts the allele labels in the source database to ordinals and prints these ordinal labels in both the locus and pedigree file. For cross-reference purposes, you may find it useful to also produce a generic locus file -- see generic.

Siblink SIBLINKAFFECTEDPAIRS (PED, PAR)

Used to specify a file in Siblink format containing only affected sib pairs.

Siblink SIBLINKUNAFFECTEDPAIRS (PED, PAR)

Used to specify a file in Siblink format containing only unaffected sib pairs.

Siblink SIBLINKALLPAIRS (PED, PAR)

Used to specify a file in Siblink format containing all affected and unaffected sib pairs. Siblings whose affection status is missing are excluded.

Siblink SIBLINKDISCORDANTPAIRS (PED, PAR)

Used to specify a file in Siblink format containing discordant affected-unaffected sib pairs. Siblings whose affection status is missing are excluded.

Simwalk

Madeline creates files for Simwalk version 2. Version 2.83 is the most recent tested version.

Siblink SIMWALK (PED, LOC)

This keyword is used to create Simwalk2 pedigree and locus files.

When creating a pedigree file, Madeline also creates a complementary (1) map file with a ".map" extension, and (2) a parameter file.

If the pedigree file were called "ped.dat", then the complementary files would be called:

• ped.dat.map
• BATCH2.DAT.ped.dat

Finally, Madeline creates "BATCH2.DAT" as a symbolic link pointing to the uniquely-named parameter file (e.g., BATCH2.DAT.ped.dat). This is done so that you can set up multiple Simwalk analysis files (for example, for different chromsomes) in a single directory without clobbering the BATCH2.DAT file that is required by Simwalk.

The "BATCH2.DAT..." parameter files are set up to perform non-parametric linkage analyses by default. Manual editing of these files is required to change the analysis type or specify a number of other important parameters. At the bare minimum, you will need to specify the name of the locus file you are using as well as an informative analysis title.

When creating locus files, Madeline currently assumes that the markers are autosomal. X-linked data would require you to manually edit the locus file.

UserFQTL Formats

UserFQTL requires nuclear family blocks for input. Madeline enumerates each nuclear family block by affixing a dot "." followed by a sequential ordinal identifier after the original pedigree identifier. For example, if the pedigree ID is 0123, successive nuclear family blocks up to n will be identified as 0123.1, 0123.2, 0123.3 ... 0123.n in the family record headers of the resulting data file. A nuclear family must have at least one person with phenotype data for the pedigree to be included.

UserFQTL USERFQTL (LOC)

Used to specify UserFQTL locus file format.

UserFQTL USERFQTLALL (PED)

Used to specify UserFQTL all nuclear families format. All nuclear families constructed by decomposing a full pedigree will be output.

UserFQTL USERFQTLFOUNDERS (PED)

Used to specify UserFQTL founding nuclear families format. Only nuclear families in the founding generation will be output.

UserFQTL USERFQTLOFFSPRING (PED)

Used to specify UserFQTL offspring nuclear families format. Only nuclear families in the offspring generation will be output.

Section 4. Reference Tables

Introduction

Madeline has a rich set of operators, including assignment and increment operators like += and ++. These are shown in Table 4.1.

The program maintains symbolic names for a number of numeric constants such as #pi, the base of natural logarithms #e, and boolean constants such as #true, #false, #affected and #unaffected. All numeric constants begin with the pound sign, "#". Numeric constants are shown in Table 4.2.

The program also maintains a number of system variables whose default values can be modified by the user. These are shown in Table 4.3.

Arrays are containers that can hold lists of values. Madeline has both simple arrays and associative arrays. Values in simple arrays are referenced by positive integer indices, while values in associative arrays are referenced by keys which may be of numeric, character string, or date type. System arrays are shown in Table 4.4.

Individuals have a number of attributes that can be accessed in Madeline. The program maintains two kinds of attributes about individuals. The first kind consists of calculated pieces of information about an individual, such as _NumberOfOffspring. Since the number of offspring cannot be found by simply looking up the value from the pedigree data table, the program has to find out whether the individual has mates and then count the children over possibly multiple matings. Other than the fact that Madeline has performed extra calculations for you, these attributes can be used in much the same way that you use the read-only fields of data in a pedigree table.

The second kind of attribute is a pointer to a relative, such as _mother, _father, or _PaternalGrandfather. Relative-pointing attributes must be followed by the dot operator and a valid field variable or individual attribute, for example: _mother.dob or _PaternalGrandfather._NumberOfMates. Note that relative-pointing attributes can be chained together. For example, _mother._mother.dob is equivalent to _MaternalGrandmother.dob and would return the date of birth of the referenced individual's maternal grandmother, or missing if unknown.

All individual attributes begin with an underscore character, "_". Individual attributes and references to relatives are extremely useful for constructing queries. Attributes are shown in Table 4.5.

Finally, Table 4.6 lists program state flags. Flags can be set using the turn or set command.

Table 4.1. Operators

M>// In the relationships data set,
M>// look for consanguinously mated females:
M>view for _IsConsanguinous AND _IsFemale
I-13 in F-01 (rec. no.    12)

1 individual in 1 pedigree matched as follows:

Individuals ..............          1
 + In database ...........          1
 |  + Attached ...........          1
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
M>
      

M>// In the relationships data set, find all MZ and DZ twins:
M>view data _IsMonozygoticTwin, _IsDizygoticTwin 
     for _IsMonozygoticTwin OR _IsDizygoticTwin

F-01    I-14    0       1
F-01    I-15    0       1
F-01    I-16    0       1
F-01    I-22    1       0
F-01    I-23    1       0

5 individuals in 1 pedigree matched as follows:

Individuals ..............          5
 + In database ...........          5
 |  + Attached ...........          5
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
M>      
      

M>// Find mothers with exactly one affected and one unaffected offspring:
M>view data _Offspring[1]._IsAffected, _Offspring[2]._IsAffected 
     for _IsFemale and _NumberOfOffspring=2
     and (_Offspring[1]._IsAffected XOR _Offspring[2]._IsAffected)

L0033   N00385  1       0
L0151   N00226  1       0
L0295   N00273  1       0
L0337   N00395  1       0
L0347   N00276  0       1
L0407   M05460  0       1
L0703   N00507  1       0

7 individuals in 7 pedigrees matched as follows:

Individuals ..............          7
 + In database ...........          7
 |  + Attached ...........          7
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
M>      
      

M>view for age_dx<45
M05742 in L0006 (rec. no.    25)
M05100 in L0151 (rec. no.   198)
M05336 in L0281 (rec. no.   335)
M05337 in L0281 (rec. no.   336)
M05338 in L0281 (rec. no.   337)
M05743 in L0281 (rec. no.   348)
M05580 in L0479 (rec. no.   572)
M05819 in L0525 (rec. no.   657)

8 individuals in 5 pedigrees matched as follows:

Individuals ..............          8
 + In database ...........          8
 |  + Attached ...........          8
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
M>      
      

M>view data dob for dob>{1955.01.01}

F-01    I-17    1959-09-19
F-01    I-18    1960-08-12
F-01    I-19    1961-05-09
F-01    I-20    1955-11-15
F-01    I-21    1956-03-12
F-01    I-22    1957-12-25
F-01    I-23    1957-12-25

7 individuals in 1 pedigree matched as follows:

Individuals ..............          7
 + In database ...........          7
 |  + Attached ...........          7
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
M>
      

M>exclude for D17S1807="287/287"
Individual M05394 in pedigree L0139 has been marked for exclusion

1 individual in 1 pedigree marked for exclusion as follows:

...
      

 M>exclude for D17S1807=="287/287"
Individual M05394 in pedigree L0139 has been marked for exclusion

1 individual in 1 pedigree marked for exclusion as follows:

...
      

M>view data sex for sex!="F"

F-01    I-01    M
F-01    I-03    M
F-01    I-06    M
F-01    I-08    M
F-01    I-09    M
F-01    I-10    M
F-01    I-12    M
F-01    I-15    M
F-01    I-17    M
F-01    I-18    .
F-01    I-19    .
F-01    I-22    M
F-01    I-23    M
F-01    I-25    M

14 individuals in 1 pedigree matched as follows:

...
      

M>view for age_dx<=40
M05336 in L0289 (rec. no.   335)
M05337 in L0289 (rec. no.   336)
M05338 in L0289 (rec. no.   337)
M05819 in L0527 (rec. no.   657)

4 individuals in 2 pedigrees matched as follows:

...
      

M>view for age_dx>=85
M04758 in L0005 (rec. no.    10)
M04613 in L0057 (rec. no.   105)
M06726 in L0057 (rec. no.   107)
M06137 in L0118 (rec. no.   147)
M06394 in L0130 (rec. no.   178)
M06266 in L0196 (rec. no.   237)
M06335 in L0285 (rec. no.   369)
M04377 in L0286 (rec. no.   377)
M03705 in L0289 (rec. no.   381)
M03169 in L0824 (rec. no.   824)
M05266 in L0870 (rec. no.   837)
M05267 in L0870 (rec. no.   838)

12 individuals in 10 pedigrees matched as follows:

...
      

M>? "FAMILYID = " + FAMID + " ; STUDYID = " + STUDYID
"FAMILYID = F-01 ; STUDYID = I-25"
M>? 25 + 200
225
M>? {2002.06.03}+100
{Wednesday, September 11, 2002}
M>
      

M>?dod-dob
8644
M>? #pi-#e
0.423311
M>      
      

M>?cos(2*#pi)
1
      

M>sin(#pi/4)
0.707107
      

M>?2^0.5
1.41421
      

M>view for !_IsAffected
I-10 in F-01 (rec. no.     9)
I-12 in F-01 (rec. no.    11)
I-13 in F-01 (rec. no.    12)
I-14 in F-01 (rec. no.    13)
I-15 in F-01 (rec. no.    14)
I-17 in F-01 (rec. no.    16)
I-20 in F-01 (rec. no.    19)
I-22 in F-01 (rec. no.    21)
I-23 in F-01 (rec. no.    22)

9 individuals in 1 pedigree matched as follows:

...
      

M>view for not _IsAffected
I-10 in F-01 (rec. no.     9)
I-12 in F-01 (rec. no.    11)
I-13 in F-01 (rec. no.    12)
I-14 in F-01 (rec. no.    13)
I-15 in F-01 (rec. no.    14)
I-17 in F-01 (rec. no.    16)
I-20 in F-01 (rec. no.    19)
I-22 in F-01 (rec. no.    21)
I-23 in F-01 (rec. no.    22)

9 individuals in 1 pedigree matched as follows:

...
      

M>?-tan(#pi/4)
-1
      

M>?(2+1)*5
15      

M>?NumericMissingValue[1]
-9999
M>?GenderStatus["F"]
1      
      

M>?a
0
M>a=50
M>?a
50
M>      

M>a+=50
M>?a
100
      

M>a-=25
M>?a
75      

M>?a
75
M>a*=4
M>?a
300      

M>?OffEndDistance
10
M>OffEndDistance/=0.8
M>?OffEndDistance
12.5      

M>?LegendFontSize
9
M>LegendFontSize++
M>?LegendFontSize
10      

 M>?LabelFontSize
7
M>LabelFontSize--
M>?LabelFontSize
6
      

Table 4.2. Numeric Constants

Table 4.3. System Variables

Table 4.4. System Arrays

M>list AffectionStatus
AFFECTIONSTATUS has 6 elements:
AFFECTIONSTATUS[0]=#MISSING
AFFECTIONSTATUS[1]=0
AFFECTIONSTATUS[2]=1
AFFECTIONSTATUS["A"]=1
AFFECTIONSTATUS["I"]=#MISSING
AFFECTIONSTATUS["U"]=0
M>   
      

M>list CharacterMissingValue
CHARACTERMISSINGVALUE has 5 elements:
CHARACTERMISSINGVALUE[ 1]="."
CHARACTERMISSINGVALUE[ 2]="/"
CHARACTERMISSINGVALUE[ 3]="0/0"
CHARACTERMISSINGVALUE[ 4]="0/ 0"
CHARACTERMISSINGVALUE[ 5]="0/  0"
M>   
      

M>list DeathStatus
DEATHSTATUS has 4 elements:
DEATHSTATUS[0]=0
DEATHSTATUS[1]=1
DEATHSTATUS["N"]=0
DEATHSTATUS["Y"]=1
M>   
      

M>list GenderStatus
GENDERSTATUS has 6 elements:
GENDERSTATUS[1]=0
GENDERSTATUS[2]=1
GENDERSTATUS["F"]=1
GENDERSTATUS["M"]=0
GENDERSTATUS["♀"]=1
GENDERSTATUS["♂"]=0
M>   
      

M>list LiabilityClass
LIABILITYCLASS has 0 elements:
      

M>list NumericMissingValue
NUMERICMISSINGVALUE has 1 element:
NUMERICMISSINGVALUE[ 1]=         -9999
M>   
      

M>list ProbandStatus
PROBANDSTATUS has 4 elements:
PROBANDSTATUS[0]=0
PROBANDSTATUS[1]=1
PROBANDSTATUS["N"]=0
PROBANDSTATUS["Y"]=1
M>
      

Table 4.5. Individual Attributes and References

M>?studyid
"N00561"
M>?_NumberOfOffspring
2
M>// A person with offspring can't 
M>// be a childless spouse, so
M>// this returns #false (0):
M>?_ChildlessSpouse
0
M>
       

M>//
M>// With the database pointer on one
M>// of the offspring in a pedigree
M>// consisting of a single nuclear
M>// family with three offspring:
M>//
M>?_NumberInPedigree
           5
M>?_mother._NumberOfOffspring
           3
M>?_complexity
           4
      

M>exclude for _FamilyID="0300"
      

M>view for _father.bmi>=25
      

M>view for _NumberOfOffspring=2 and 
   _FirstChild._PercentGenotyped>80 and 
   _SecondChild._PercentGenotyped>80
   ...
M>
      

M>// In a set of data with 12 markers 
M>// toggled "on" for output, 
M>// identify individuals typed for less
M>// than 50% of the markers:
M>view for _GenotypeCount>0 and _GenotypeCount<6
      

M>write to 'pedcheck.ped' in pedcheck format
-----------------------------  --------- --------- ---------
Pedigrees and Individuals       Included  Excluded     Total
-----------------------------  --------- --------- ---------
Pedigrees ...................         38        74       112
Individuals .................        354       562       916
 + In database ..............        324       554       878
 |  + Attached ..............        324       553       877
 |  |  + With data ..........        172         0       172
 |  |  + Without data .......        152       553       705
 |  |  + Marked for exclusion          0         0         0
 |  + Childless spouses .....          0         0         0
 |  + Unattached ............          0         1         1
 + Not in database ..........         30         8        38
M>view for _HadData
172 individuals in 38 pedigrees matched as follows:
   ...
M>view for _WasIncluded
354 individuals in 38 pedigrees matched as follows:
   ...
      

M>view record for _id="0125-100"
      

M>view record for _IndividualID="0125-100"
      

M>// These three queries return the same set:
M>view for _IsAffected              
M>view for _IsAffected=#affected
M>view for _IsAffected=#true
M>// Likewise, these two queries return the same answer:      
M>view for _IsAffected=#unaffected
M>view for _IsAffected=#false
M>// Sometimes it's also useful to query on missing entries:
M>view for _IsAffected=#missing
      

M>view for _IsConsanguinous

I-08 in F-01 (rec. no.     7)
I-13 in F-01 (rec. no.    12)

2 individuals in 1 pedigree matched as follows: 
...
      

M>The following two queries return the same result set:
M>view for _IsDeceased
M>view for _IsDeceased=#dead
M>Likewise, the following two queries return the same result set:
M>view for not _IsDeceased
M>view for _IsDeceased=#alive       
      

M>view for _IsDizygoticTwin

I-14 in F-01 (rec. no.    13)
I-15 in F-01 (rec. no.    14)
I-16 in F-01 (rec. no.    15)

3 individuals in 1 pedigree matched as follows: ...
      

M>// The following queries return the same result set:
M>view for _IsFemale
M>view for _IsFemale=#female
M>// Likewise, the following queries return the same result set:
M>view for not _IsFemale
M>view for _IsFemale=#false
M>// You can also query for #missing entries:
M>view for _IsFemale=#missing
      

M>// Query for founders:
M>view for _FamilyID="L0519" and _IsFounder
...
M>// Query for non founders:
M>view for _FamilyID="L0519" and not _IsFounder
...
      

M>view for not _IsInDatabase
     ...
N00590 in L0519 (virtual individual not in pedigree table)
N00135 in L1009 (virtual individual not in pedigree table)
N00136 in L1009 (virtual individual not in pedigree table)

38 individuals in 7 pedigrees matched as follows:
     ...
      

M>draw pedigrees for _IsMendelianInconsistent
...
      

M>view for _IsMonozygoticTwin

I-22 in F-01 (rec. no.    21)
I-23 in F-01 (rec. no.    22)

2 individuals in 1 pedigree matched as follows: 
...
      

M>// Query for primary founders:
M>view for _FamilyID="L0519" and _IsPrimaryFounder
...
      

M>view for _IsProband

I-11 in F-01 (rec. no.    10)

1 individual in 1 pedigree matched as follows:
...
      

M>view for _IsUnattached
      

M>// Exclude Consanguinous pairs and
M>// all of their offspring and descendants:
M>exclude family for _IsConsanguinous
  ...
M>// Now query on the set of individuals 
M>// marked for exclusion:
M>view for _MarkedForExclusion

I-08 in F-01 (rec. no.     7)
I-13 in F-01 (rec. no.    12)
I-24 in F-01 (rec. no.    23)
I-25 in F-01 (rec. no.    24)

4 individuals in 1 pedigree matched as follows:
...
      

M>// Go to record 10 in the relationships data set:
M>go 10
M>// Print some basic information about the person:
M>?_FamilyID + " : " + _IndividualID + " : " + SEX
"F-01 : I-11 : F"
M>?_NumberOfMates
2
M>?_NumberOfChildren
10
M>//How many children from each mate?
M>?_mate[1]._NumberOfChildren
6
M>?_mate[2]._NumberOfChildren
4
      

M>// In the relationships data set, how many 
M>// grandchildren and great-grandchildren 
M>// does I-11's maternal grandfather have?  
M>// NOTE: Because of a consanguinous loop 
M>// in the data set, two of the "grandchildren" 
M>// are also "great grandchildren".
M>go 10
M>?studyid
"I-11"
M>?_MaternalGrandfather._OffspringSum(_NumberOfOffspring)
5
M>?_MaternalGrandfather._OffspringSum(_OffspringSum(_NumberOfOffspring))
12    
      

M>// In the relationships data set, is 
M>// I-11's maternal grandmother affected?
M>go 10
M>?studyid
"I-11"
M>?_MaternalGrandmother._IsAffected
#MISSING    
      

M>// In a data set with nine (9) markers
M>// toggled on for output:
M>go 205
M>?_IndividualId
"M05106"
M>?_MendelianInconsistencyCount
           1
M>?_PercentMendelianInconsistent
 11.11111111

      

M>// Query for individuals born to very young mothers:
M>view for _mother.age-_self.age<=17
      

M>view for _nff>1 
      

M>view for _nfm>1 
      

M>?_NumberAffected
    3
      

M>?_IndividualID
"G00158"
M>?_NumberInPedigree
35
M>       
      

M>go 9
M>?_IndividualId
"M02453"
M>?_NumberInPedigree
           8
M>?_NumberAffected
           2
M>?_NumberOfAffectedPairs
           1
      

M>go 9
M>?_IndividualId
"M02453"
M>?_NumberInPedigree
           8
M>?_NumberOfFounders
           3
M>?_NumberOfNonFounders
           5
M>?_Complexity
           7
M>
      

      M>view for _NumberOfMates>=2
I-11 in F-01 (rec. no.    10)

1 individual in 1 pedigree matched as follows:
 ...
      

M>go 9
M>?_IndividualId
"M02453"
M>?_NumberInPedigree
           8
M>?_NumberOfFounders
           3
M>?_NumberOfNonFounders
           5
M>?_Complexity
           7
M>
      

M>// In the relationships data set, find
M>// mothers with 4 or more offspring.
M>// For matching individuals, report total number 
M>// of offspring, number of affected offspring,
M>// number of unaffected offspring, and number
M>// of affection status indeterminate offspring:
M>view data _NumberOfOffspring, 
  _OffspringCountTrue(_IsAffected),
  _OffspringCountFalse(_IsAffected),
  _OffspringCountMissing(_IsAffected) 
  for _IsFemale and _NumberOfOffspring>=2

F-01    I-02    2       1       0       1
F-01    I-04    2       0       0       2
F-01    I-07    3       1       1       1
F-01    I-11    10      2       6       2
F-01    I-13    2       2       0       0

5 individuals in 1 pedigree matched as follows:

Individuals ..............          5
 + In database ...........          5
 |  + Attached ...........          5
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0

M>// In the relationships data set, how
M>// many mothers have between 1-4 children?
M>// For each matching mother, report the 
M>//total number of her children 
M>// and the STUDYIDs of each child:
M>view data _NumberOfOffspring, 
  _Offspring[1].studyid, 
  _Offspring[2].studyid, 
  _Offspring[3].studyid, 
  _Offspring[4].studyid 
  for _IsFemale and 
  _NumberOfOffspring>0 and 
  _NumberOfOffspring<=4

F-01    I-02    2       I-05    I-06    .       .
F-01    I-04    2       I-07    I-08    .       .
F-01    I-07    3       I-09    I-11    I-13    .
F-01    I-13    2       I-24    I-25    .       .

4 individuals in 1 pedigree matched as follows:

Individuals ..............          4
 + In database ...........          4
 |  + Attached ...........          4
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
      

M>// In the relationships data set, 
M>// go to the proband (record 10):
M>go 10
M>?_IsProband
1
M>// Are both paternal grandparents deceased?
M>?_PaternalGrandfather._IsDeceased and 
  _PaternalGrandmother._IsDeceased
1
M>
      

M>// In a data set with 332 individuals in 27
M>// pedigrees and over 400 markers,
M>// how many individuals in how many pedigrees
M>// are typed for at least
M>// 80% of all markers? Report percentages
M>// for matching individuals:
M>view data _PercentGenotyped for _PercentGenotyped>=80

F0001 G00158 83.1325
F0001 G00164 80.9237
F0001 G00165 82.1285
F0001 G00166 81.1245
F0001 G00169 81.5261
F0001 G00170 81.9277
     .
     .
     .

41 individuals in 7 pedigrees matched as follows:

Individuals ..............         41
 + In database ...........         41
 |  + Attached ...........         36
 |  + Childless spouses ..          0
 |  + Unattached .........          5
 + Not in database .......          0
      

28 INHERITANCE INCONSISTENCIES M>
M>// In a data set with 
M>// inconsistencies, let's first
M>// find the most problematic
M>// cases:
M>view data 
  _PercentMendelianInconsistent 
  for _PercentMendelianInconsistent>=10

L0519   M05790  19.0476
L0519   M05791  19.0476
L0519   M05806  19.0476
L0519   M05852  19.0476
L0519   N00138  19.0476

5 individuals in 1 pedigree matched as follows:

Individuals ..............          5
 + In database ...........          5
 |  + Attached ...........          5
 |  + Childless spouses ..          0
 |  + Unattached .........          0
 + Not in database .......          0
28 INHERITANCE INCONSISTENCIES M>
      

M>view for _record=#missing
H0240K in F0240 (virtual individual not in pedigree table)
 
1 individual in 1 pedigree matched as follows:
 ...
      

M>// Here's a query in the relationships data
M>// set to detect young mothers (age<=17)
M>// calculated from birth dates.
M>// The _self pointer is not needed
M>// by Madeline but is used for clarity:
M>view for ( _self.dob - _mother.dob )/365 <= 17
I-24 in F-01 (rec. no.    23)
I-25 in F-01 (rec. no.    24)
 
2 individuals in 1 pedigree matched as follows: ...
M>// Here's the same query 
M>// without the _self pointer:
M>view for ( dob - _mother.dob )/365 <= 17
  ...
      

M>?_IndividualID
"I-10"
M>?_spouse._IndividualID
"I-11"
M>?_mate[1]._IndividualID
"I-11"
M>      
      

Table 4.6. State Flags

Table 4.7 Numeric Functions

Function Name	Description	Example
abs()	Take the absolute value of a real number.	M>?abs(-15.434) 15.434
acos()	Take the arc cosine of a real number.	M>?acos(0.5) 1.0472 M>
asin()	Take the arc sine of a real number.	M>?asin(1) 1.5708 M>
atan()	Take the arc tangent of a real number.	M>?atan(0.5) 0.463648 M>
ceiling()	Takes the ceiling of a real number (rounds up to the nearest whole number).	M>?ceiling (4.2) 5 M>
cos()	Take the cosine of a real number.	M>?cos(#pi) -1 M>
cosh()	Takes the hyberbolic cosine of a real number.	M>?cosh(1) 1.54308 M>
exp()	Calculates base e raised to the supplied power n	M>exp(1) 2.71828
floor()	Take the floor of a real number (round down to the nearest whole number.	M>?floor(3.9845) 3 M>
HaldaneToTheta()	Converts a genetic map distance expressed in Haldane centiMorgans to a recombination fraction, theta. Recombination fractions are related to Haldane genetic distances by: This leads to the following two formulae for converting between the two:    (eq.1)    (eq.2) Madeline implements eq. 1 in ThetaToHaldane() and eq. 2 in HaldaneToTheta().	M>?HaldaneToTheta(3.375) 0.0?????? M>
inv();	Calculates the inverse of a non-zero real number.	M>?inv(8) 0.125 M>
KosambiToTheta()	Converts a genetic map distance expressed in Kosambi centiMorgans to a recombination fraction, theta. Recombination fractions are related to Kosambi genetic distances by: This leads to the following two formulae for converting between the two:    (eq.1)    (eq.2) Madeline implements eq. 1 in ThetaToKosambi() and eq. 2 in KosambiToTheta().	M>?KosambiToTheta(3.375) 0.0336988 M>
lod()	Calculates the negative logarithm base 10, i.e., the LOD, of a p-value.	M>?lod(0.5) 0.30103 M>
log() ln()	Take the natural logarithm of a real number.	M>?log(#e) 1 M>
log10()	Take the logarithm to the base 10 of a real number.	M>?log10(1000) 3 M>
round()	Rounds a number up or down to the next whole number.	M>?round(49.35) 49 M>?round(49.85) 50 M>
sin()	Take the sine of a real number.	M>?sin(3*#pi/2) -1 M>
sinh()	Take the hyberbolic sine of a real number.	M>?sinh(1) 1.1752 M>
sqrt()	Take the square root of a real number.	M>?sqrt(144) 12 M>
tan()	Take the tangent of a real number.	M>?tan(#pi/4) 1 M>
tanh()	Take the hyberbolic tangent of a real number.	M>?tanh(1) 0.761594 M>
ThetaToHaldane()	Converts a recombination fraction, theta, into a genetic map distance expressed in Haldane centiMorgans. See description above for HaldaneToTheta()	M>?HaldaneToKosambi(0.0???) 3.37??? M>
ThetaToKosambi()	Converts a recombination fraction, theta, into a genetic map distance expressed in Kosambi centiMorgans. See description above for KosambiToTheta()	M>?ThetaToKosambi(0.0337) 3.37512 M>