DATAFILE(5)

NAME
DATAFILE - LINKAGE's DATAFILE

DESCRIPTION
Descriptions of loci and other information are contained in DATAFILE(5). The information in this file is divided into four parts

1.  general information on loci and locus order;

2.  description of loci;

3.  information on recombination;

4.  program-specific information.

In explaining the structure of DATAFILE(5) we will use two concepts of locus order. The first is the input order, or the order in which the phenotypes corresponding to the loci appear in PEDFILE(5). The second is chromosome order, or the physical order assumed for the loci. The input order is fixed once PEDFILE(5) is created, but the chromosome order can be changed to test various hypotheses. Various parameters such as recombination rates, gene frequencies, penetrances, etc., are specified in the DATAFILE(5). These refer to the initial values of these parameters. The analysis programs can modify some of these values for specific purposes, e.g. maximum likelihood estimation.

EXAMPLE
Before we attempt to explain the format of various parts of the DATAFILE, it is useful to consider a complete file as an example. The following is the DATAFILE for three sex-linked loci, one of which is Duchenne muscular dystrophy; creatine kinase measurements are available for heterozygote testing in women:
 3 0 1 5 << no loci, risk locus, sexlinked (if 1), program code
 3 0.001 0.001 0 << mut locus, mut mal, mut fem, hap freq (if 1)
 1 3 2 << order of loci
 2 2 <<< binary factors, # alleles
 5.00000E-01 5.00000E-01 << gene freqs
 2 << number of binary factors
 1 0
 0 1 << allelic codes
 2 2 <<< binary factors, # alleles
 5.00000E-01 5.00000E-01 << gene freqs
 2 << number of binary factors
 1 0
 0 1 << allelic codes
 0 2 <<< quan, # alleles
 9.99800E-01 2.00000E-04 << gene freqs
 1 << number of traits
 1.57000E+00 2.10000E+00 2.10000E+00 << genotype means
 5.90000E-02 << variance
 2.90000E+00 << multiplier for variance in heterozygotes
 0 0 << sex difference (if 1) and interference (if 1)
 0.1 0.1 << recombination values
 1 0.5 0.5 The last line contains information for the mlink(1) program; this is indicated by the program code 5 on the first line. Other parameters are specified as indicated in the comments following certain lines (indicated by << ). Comments are allowed on some lines for easy interpretation of the file.

  Loci and Locus Order
The first two lines of DATAFILE contain information on a variety of parameters, including the number of loci (nlocus), a risk locus (risklocus), sex-linked or autosomal data (sexlink), a mutation locus (mutsys) and mutation rates (mutmale and mutfem ), linkage disequilibrium (disequil ), and a program code (nprogram). The first two lines are followed by a third line giving the chromosome order for the loci. The format is:
     nlocus risklocus sexlink nprogram
     mutsys mutmale mutfem disequil
     (chromosome order) Mutsys and the chromosome order of the loci must begin on new lines; comments can follow at the end of each line. Nprogram is not used by the LINKAGE programs, but is required for interfacing with the shell program LCP. It is used to describe the program for which the file is constructed. LCP can use files constructed for one program as input for a different program. Therefore the datafile is not changed for different programs when using LCP.
Variable Name | Valid Values
nlocus | 1 to maxlocus (as specified by a constant in the programs)
risklocus | 0 if risk is not to be calculated
 | disease locus number (input order) if risk is to be calculated
sexlink | 0 for autosomal data
 | 1 for sex-linked data
nprogram | 1 CILINK
 | 2 CMAP
 | 3 ILINK
 | 4 LINKMAP
 | 5 MLINK
 | 6 LODSCORE
 | 7 CLODSCORE
mutsys | 0 if mutation rates are zero
 | mutation locus number (input order) for non-zero mutation rates
mutmale | male mutation rate
mutfem | female mutation rate
disequil | 0 if loci are assumed to be in linkage equilibrium
 | 1 if loci are in linkage disequilibrium
When loci are in linkage equilibrium, allele frequencies must be given under each locus description; otherwise, haplotype frequencies are provided. When risk is calculated, a disease allele is provided in the locus description for the "risklocus." As an example, consider the analysis of 3 autosomal loci in the chromosome order 1 3 2. The first three lines of the DATAFILE could be:
 3 0 0 3 << no loci, risk locus, sexlinked (if 1), program code
 3 0.1 0.1 0 << mut locus, mut mal, mut fem, haplotype freq (if 1)
 1 3 2 << order of loci The data are autosomal with mutation at the third locus.

  Description of Loci
The loci are described in the order in which they appear in the PEDFILE(5). Assuming linkage equilibrium, the gene frequencies are specified as part of the locus description (linkage disequilibrium will be documented in a later version). The descriptions differ according to the type of locus. A numeric code distinguishes each of the types:
0 | Quantitative variable
1 | Affection status
2 | Binary factors
3 | Numbered alleles
The format for each locus type, assuming linkage equilibrium, is as follows:

  Numbered alleles
The locus description consists of two lines. The first gives the code for numbered alleles and the total number of alleles. The second gives the gene frequencies. For example:
     3 2 << numbered alleles code, total number of alleles
     0.5 0.5 << gene frequencies specifies two alleles with equal gene frequencies.

  Binary factors
The first two lines are similar to those in the previous example. After this the number of factors is specified on a separate line, followed by one line for each allele specification. As an example, consider the case of a recessive trait:
     2 2 << binary factor code, number of alleles
     0.999 0.001 << gene frequencies
     2 << number of factors
     1 1
     0 1 << alleles

  Affection status
The number of liability classes replaces the number of factors, and penetrances are given for each genotype in each class:
     1 2 << affection status code, number of alleles
     0.999 0.001 << gene frequencies
     1 << number of liability classes
     0.0 1.0 1.0 << penetrances describes a fully penetrant, dominant disease locus. The genotypes are in the order 11, 12, 22 where 1 is the first allele and 2 is the second allele specified in the gene frequency list. For three alleles, the genotype order is 11, 12, 13, 22, 23, 33. The same pattern is followed for more alleles. To describe a similar locus, but with reduced penetrance and two liability classes, use the following:
     1 2 << affection status code, number of alleles
     0.999 0.001 << gene frequencies
     2 << number of liability classes
     0.0 0.5 0.5
     0.0 0.9 0.9 << penetrances With sex-linked data, male penetrances must also be defined for each allele. The following describes a sex-linked disease with 50% penetrance in males:
     1 2 << affection status code, number of alleles
     0.999 0.001 << gene frequencies
     1 << number of liability classes
     0.0 0.0 1.0
     0.0 0.5 << female followed by male penetrances

  Quantitative trait
Quantitative traits are described by a first line containing the quantitative code (0) and the number of alleles, and a second line with gene frequencies, as in the previous examples. These are followed by lines indicating the number of quantitative variables, genotypic means for each variable, a variance-covariance matrix, and a constant that gives the ratio of variance-covariance in heterozygotes to homozygotes. For a single quantitative variable, the format is:
     0 2 << quantitative variable code, number of alleles
     0.999 0.001 << gene frequencies
     1 << number of quantitative variables
     10.0 12.0 14.0 << genotypic means
     1.5 << variance
     1.0 << multiplier for heterozygote variance The genotypes are 1/1, 1/2 and 2/2, respectively, where allele 1 has the frequency 0.999. For two quantitative variables, the description is:
     0 2 << quantitative variable code, number of alleles
     0.999 0.001 << gene frequencies
     2 << number of liability classes
     10.0 12.0 14.0
    -10.0 0.0 10.0 << genotypic means
    1.5 10.0 100.0 << variance-covariance
    1.0 << multiplier for heterozyg. variance-covariance Only the upper triangle of the variance-covariance matrix is given; the order is V11, V12, V13 ... V22, V23 ... etc. Here, the variance of the first variable is 1.5, the covariance is 10.0, and the variance of the second variable is 100.0. When describing the "risk locus," the disease allele (risk allele) must be designated at the end of the locus description. For example:
     1 2 << affection status code, number of alleles
     0.999 0.001 << gene frequencies
     1 << number of liability classes
     0.0 1.0 1.0 << penetrances
     2 << risk allele

  Recombination Information
In addition to recombination rates, sex-differences and interference must be specified in this section. Sex-difference options are indicated by an integer variable that takes the following values:
0 | no sex-difference
1 | constant sex-difference (the ratio of female/male genetic distance is the same in all intervals)
2 | variable sex-difference (the female/male distance ratio can be different in each interval)
The interference option can take the following values:
0 | no interference
1 | interference without a mapping function
2 | user-specified mapping function
Interference (i.e. options 1 or 2) is allowed only in some analysis programs with three loci. The programs, as distributed, contain Kosambi interference as the user-specified mapping function. First, consider a case without interference. When the sex-difference is "0," one recombination rate is given for each of the nlocus-1 segments (see the complete example above). If the sex-difference option is "1," the male recombination rates are given on one line, and the female/male genetic distance is specified on the next line, e.g.:
     1 0 << sex difference, interference
     0.1 0.2 0.1 << male recombination
     2.0 << female/male ratio of genetic distance When the sex-difference option is "2", the male recombination rates are followed on the next line by female recombination rates:
     2 0 << sex difference, interference
     0.1 0.2 0.1 << male recombination
     0.2 0.1 0.2 << female recombination Interference can be specified for three loci. With the interference option 1, three recombination rates are given. These are the recombination rates between adjacent loci in the two segments and the recombination rate between the flanking loci. An example is:
     1 1 << sex difference, interference
     0.1 0.1 0.18 << male recombination
     2.0 << female/male ratio of genetic distance With the interference option 2, only the rates between the adjacent loci are provided:
     1 2 << sex difference, interference
     0.1 0.1 << male recombination
     2.0 << female/male ratio of genetic distance

  Program-specific information
The program-specific information consists of a series of lines at the end of the DATAFILE(1) describing which parameters should be varied iteratively by the analysis programs.

NOTES
The information contained herein was gleaned, often-times verbatim, from the LINKAGE User's Guide (http://linkage.rockefeller.edu/soft/linkage/) on the web by kind permission of Jurg Ott, Ph.D.

AUTHORS
Mark Lathrop and Jurg Ott.

This manual page was written by Elizabeth Barham <lizzy@soggytrousers.net> for the Debian GNU/Linux distribution.

WORLD-WIDE-WEB
http://linkage.rockefeller.edu/soft/linkage/ (http://linkage.rockefeller.edu/soft/linkage/)

SEE ALSO
LINKAGE(5), PEDFILE(5), ilink(1), linkmap(1), lodscore(1), mlink(1), and unknown(1).