MLINK is a program for calculation of lod scores and risk with two or more loci. Typically, two loci will be used for lod score calculations. Sometimes, however, it is useful to consider several completely linked marker loci with a disease locus when calculating lod scores .
MLINK is used with the accompanying program UNKNOWN. The calling order is:
UNKNOWN
MLINK
The input files for this suite of programs are:
PEDFILE
DATAFILE
The output files are:
UTFILE
STREAM
UNKNOWN produces temporary files called IPEDFILE and SPEEDFILE;
along with DATAFILE, these serve as input for MLINK.
If the program constant SCORE is set to "true," the program calculates lod scores; otherwise only the likelihood values are given. MLINK is distributed with SCORE set to "true."
The program-specific part of DATAFILE consists of a single line that contains the number of the recombination fraction to be varied, an increment for the recombination fraction, and a stopping value. The likelihood is evaluated for the initial recombination values, then the designated value is incremented and the likelihood recalculated if the incremented value is less than the final value. The incremental calculations are continued until the designated recombination is greater than the final value.
As an example, suppose that lod scores are calculated for two loci. If the following is the last line in DATAFILE:
1 0.1 0.5
the program will start with the initial recombination value,
specified in DATAFILE, and calculate with increments of 0.1 until
0.5 is surpassed. To calculate for increments of 0.01 stopping
at 0.2, this line should be:
1 0.01 0.2
For three loci, with the first two loci in the chromosome order
completely linked, a lod score
for linkage with the third locus
could be calculated with MLINK at increments of 0.05 with the
following line in DATAFILE:
1 0.05 0.5
Often different increments are desired in different regions of
the lod score table. This refinement can be achieved in MLINK by
adding additional lines at the end of DATAFILE. Each line
specifies a new starting recombination fraction, increment and
final value; the recombination to be varied is the same as
previously designated. Thus, the following two lines:
1 0.05 0.2
0.2 0.1 0.5
calculates the likelihood
with steps of 0.05 until reaching 0.2,
followed by steps of 0.1 until reaching 0.5.
If program constant SCORE is "true," the initial evaluation is made with the recombination to be varied at 0.5. For two-locus analysis, lod scores are calculated thereafter at each evaluation of the likelihood. With three or more loci, the 2 ln (likelihood) difference is calculated in place of the lod score. When the constant BYFAMILY is "true," the likelihood values are given for each family.
Comments: MLINK does not support sex-differences in the recombination
rates. Sex-differences can be included but only the male recombination
rate will be incremented.
MLINK allows the interference option 2 (user defined
mapping function)
but not option 1 (interference without a mapping function).