Performance of Markov chain-Monte Carlo approaches for mapping genes in oligogenic models with an unknown number of loci.
Markov chain-Monte Carlo (MCMC) techniques for multipoint mapping of quantitative trait loci have been developed on nuclear-family and extended-pedigree data. These methods are based on repeated sampling-peeling and gene dropping of genotype vectors and random sampling of each of the model parameters from their full conditional distributions, given phenotypes, markers, and other model parameters. We further refine such approaches by improving the efficiency of the marker haplotype-updating algorithm and by adopting a new proposal for adding loci. Incorporating these refinements, we have performed an extensive simulation study on simulated nuclear-family data, varying the number of trait loci, family size, displacement, and other segregation parameters. Our simulation studies show that our MCMC algorithm identifies the locations of the true trait loci and estimates their segregation parameters well-provided that the total number of sibship pairs in the pedigree data is reasonably large, heritability of each individual trait locus is not too low, and the loci are not too close together. Our MCMC algorithm was shown to be significantly more efficient than LOKI (Heath 1997) in our simulation study using nuclear-family data.
Lee
J K
JK
Department of Health Evaluation Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. jaeklee@virginia.edu
Thomas
D C
DC
D000465:Algorithms; D002874:Chromosome Mapping / Q000379:methods*; D020090:Chromosome Segregation; D003198:Computer Simulation; D005191:Family Characteristics; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008297:Male; D008390:Markov Chains; D008957:Models, Genetic; D009010:Monte Carlo Method; D009679:Nuclear Family; D010375:Pedigree; D019683:Penetrance; D019655:Quantitative Trait, Heritable; D011995:Recombination, Genetic / Q000235:genetics; D013997:Time Factors
D005819:Genetic Markers