SNPLINK: multipoint linkage analysis of densely distributed SNP data incorporating automated linkage disequilibrium removal

SUMMARY SNPLINK is a Perl script that performs full genome linkage analysis of high-density single nucleotide polymorphism (SNP) marker sets. The presence of linkage disequilibrium (LD) between closely spaced SNP markers can falsely inflate linkage statistics. SNPLINK removes LD from the marker sets in an automated fashion before carrying out linkage analysis. SNPLINK can compute both parametric and non-parametric statistics, utilizing the freely available Allegro and Merlin software. Graphical outputs of whole genome multipoint linkage statistics are provided allowing comparison of results before and after the removal of LD.

[1]  L Kruglyak,et al.  Parametric and nonparametric linkage analysis: a unified multipoint approach. , 1996, American journal of human genetics.

[2]  Daniel J Schaid,et al.  Comparison of microsatellites versus single-nucleotide polymorphisms in a genome linkage screen for prostate cancer-susceptibility Loci. , 2004, American journal of human genetics.

[3]  Eleftheria Zeggini,et al.  Whole-genome scan, in a complex disease, using 11,245 single-nucleotide polymorphisms: comparison with microsatellites. , 2004, American journal of human genetics.

[4]  N. Risch,et al.  A comparison of linkage disequilibrium measures for fine-scale mapping. , 1995, Genomics.

[5]  Leonid Kruglyak,et al.  The use of a genetic map of biallelic markers in linkage studies , 1997, Nature Genetics.

[6]  David M. Evans,et al.  Guidelines for genotyping in genomewide linkage studies: single-nucleotide-polymorphism maps versus microsatellite maps. , 2004, American journal of human genetics.

[7]  Richard S Houlston,et al.  Genomewide linkage searches for Mendelian disease loci can be efficiently conducted using high-density SNP genotyping arrays. , 2004, Nucleic acids research.

[8]  Lon R. Cardon,et al.  A first-generation linkage disequilibrium map of human chromosome 22 , 2002, Nature.

[9]  Daniel F. Gudbjartsson,et al.  Allegro, a new computer program for multipoint linkage analysis , 2000, Nature genetics.

[10]  P. Hedrick,et al.  Gametic disequilibrium measures: proceed with caution. , 1987, Genetics.

[11]  P. Deloukas,et al.  The impact of SNP density on fine-scale patterns of linkage disequilibrium. , 2004, Human molecular genetics.

[12]  Sanjay Shete,et al.  Ignoring linkage disequilibrium among tightly linked markers induces false-positive evidence of linkage for affected sib pair analysis. , 2004, American journal of human genetics.

[13]  Daniel J Schaid,et al.  Caution on pedigree haplotype inference with software that assumes linkage equilibrium. , 2002, American journal of human genetics.

[14]  Jeremy Heil,et al.  A 3.9-centimorgan-resolution human single-nucleotide polymorphism linkage map and screening set. , 2003, American journal of human genetics.

[15]  G. Abecasis,et al.  Merlin—rapid analysis of dense genetic maps using sparse gene flow trees , 2002, Nature Genetics.