Version

V. 5.2 (LINKAGE) / 4.1P (FASTLINK) installed in CORONA

Description

The LINKAGE package consists of a series of programs for maximum likelihood estimation of recombination rates, calculation of lod score tables, and analysis of genetic risks.

The analysis programs are divided into two groups. First, general pedigrees with marker and disease loci data analysis (mlink, ilink, linkmap, lodscore), and second, three-generation families and codominant marker loci analysis primarily to construct genetic maps from data on reference families (cilink, cmap).

The input to the LINKAGE programs consists of pedigree and genotypic data, combined to locus description, recombination rates, and gene order information. Prior to analysis, the pedigree and genotypic data must be processed by a series of preparatory programs that accompany the analytic programs in the LINKAGE package.

In addition, the LINKAGE package contains "shell," or interface, programs to control the use of the analytic programs (makeped, preplink, lcp, lsp, lrp). The speed of the routines has been significantly improved by rewriting the programs in C (FASTLINK) instead of Pascal (LINKAGE). At CSC, mlink, ilink, linkmap, lodscore and unknown are FASTLINK versions.

Usage

Programs are installed in CORONA (corona.csc.fi).

To add all installed linkage programs to you path in CORONA, type:

'use genemap'

The LINKAGE package includes following programs:

1. makeped: converts a raw pedigree file to a file including sib pointers

2. preplink: creates a parameter file

3. unknown: infers possible genotypes and mating combinations for parents with unknown genotypes (FASTLINK version)

4. mlink: calculates lod scores and risk with two of more loci (FASTLINK version)

5. ilink: estimates parameters (recombination fractions, allele frequencies ...) (FASTLINK version)

6. lodscore: for two locus data, almost identical to ilink (FASTLINK version)

7. linkmap: calculates location scores of one locus against a fixed map of other loci (FASTLINK version)

8. lcp: the linkage control program

9. lsp: modifies parameter and pedigree files

10. lrp: the linkage report program

Running the LINKAGE programs requires the following steps:

1. Input pedigree and genotypic data (makeped)

2. Description of loci (preplink)

3. Analysis (lcp, pedin)

4. Reports -- optional -- (lrp)

or

1. Input pedigree and genotypic data (makeped)

2. Description of loci (preplink)

3. Modify files -- optional -- (lsp)

4. Genotype checking (unknown)

5. Analysis (ilink, mlink, or linkmap)

6. Reports -- optional -- (lrp)

Batch jobs

When large data sets are analyzed the LINKAGE runs should be submitted for batch processing.

Steps for a bach job

1. create a LINKAGE batch file with lcp e.q. pedin

2. create a batch control file e.g. ajo1

3. submit the bach control file for execution 'qsub ajo1'

The batch control file should look like:

#!/bin/csh
# QSUB -q prime
# QSUB -lt 28800
# QSUB -eo
# QSUB -o raportti
use linkage
cd $HOME/linkage
pedin

It is assumed here that you have all your data files and 'pedin'-file in directory 'linkage'. You will see the output messages in a file called 'raportti' and final results in 'final.out' as usual. If 8h (28800 s) is not enough for the task to finish use

# QSUB -lt 90000

You can monitor the status of your batch job by typing:

nqeq | grep 'userid' --- where 'userid' is your user ID.

For more information about the batch jobs see 'Metakoneen käyttöopas' or 'CSC User's guide'. See also online information about batch jobs / eräajot.

Documentation

A HTML version of the manual is available from Rockefeller University.

More information can be found from the 'Handbook of human genetic linkage' by J. Terwilliger and J. Ott. The Johns Hopkins University Press.

Documentation about FASTLINK (not a user's guide!) is available in HTML.

References

Published research assisted by this software should always cite:

G. M. Lathrop, J.-M. Lalouel, C. Julier, and J. Ott, Strategies for Multilocus Analysis in Humans, PNAS 81(1984), pp. 3443-3446.

G. M. Lathrop and J.-M. Lalouel, Easy Calculations of LOD Scores and Genetic Risks on Small Computers, American Journal of Human Genetics, 36(1984), pp. 460-465.

G. M. Lathrop, J.-M. Lalouel, and R. L. White, Construction of Human Genetic Linkage Maps: Likelihood Calculations for Multilocus Analysis, Genetic Epidemiology 3(1986), pp. 39-52.

R. W. Cottingham Jr., R. M. Idury, and A. A. Schaffer, Faster Sequential Genetic Linkage Computations, American Journal of Human Genetics, 53(1993), pp. 252-263.

A. A. Schaffer, S. K. Gupta, K. Shriram, and R. W. Cottingham, Jr., Avoiding Recomputation in Genetic Linkage Analysis, Human Heredity, 4(1994), pp. 225-37.

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