A hidden markov model combining linkage and linkage disequilibrium information for haplotype reconstruction and quantitative trait locus fine mapping.
Faithful reconstruction of haplotypes from diploid marker data (phasing) is important for many kinds of genetic analyses, including mapping of trait loci, prediction of genomic breeding values, and identification of signatures of selection. In human genetics, phasing most often exploits population information (linkage disequilibrium), while in animal genetics the primary source of information is familial (Mendelian segregation and linkage). We herein develop and evaluate a method that simultaneously exploits both sources of information. It builds on hidden Markov models that were initially developed to exploit population information only. We demonstrate that the approach improves the accuracy of allele phasing as well as imputation of missing genotypes. Reconstructed haplotypes are assigned to hidden states that are shown to correspond to clusters of genealogically related chromosomes. We show that these cluster states can directly be used to fine map QTL. The method is computationally effective at handling large data sets based on high-density SNP panels.
Druet
Tom
T
Unit of Animal Genomics, GIGA-Research and Department of Animal Production, Faculty of Veterinary Medicine, University of Liège, Belgium. tom.druet@ulg.ac.be
Georges
Michel
M
D002874:Chromosome Mapping / Q000379:methods; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium / Q000502:physiology*; D008297:Male; D008390:Markov Chains; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000502:physiology*