Assessment of SNP streak statistics using gene drop simulation with linkage disequilibrium.
We describe methods and programs for simulating the genotypes of individuals in a pedigree at large numbers of linked loci when the alleles of the founders are under linkage disequilibrium. Both simulation and estimation of linkage disequilibrium models are shown to be feasible on a genome wide scale. The methods are applied to evaluate the statistical significance of streaks of loci at which sets of related individuals share a common allele. The effects of properly allowing for linkage disequilibrium are shown to be important as they explain many of the large observations. This is illustrated by reanalysis of a previously reported linkage of prostate cancer to chromosome 1p23.
Thomas
Alun
A
Department of Biomedical Informatics, University of Utah, USA. alun@genepi.med.utah.edu
D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011381:Programming Languages; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D014589:Utah / Q000453:epidemiology