Fine-mapping of quantitative trait loci by identity by descent in outbred populations: Application to milk production in dairy cattle

We previously mapped a quantitative trait locus (QTL) affecting milk produc tion to bovine chromosome 14, To refine the map position of this QTL, we ha ve increased the density of the genetic map of BTA14q11-16 by addition of n ine microsatellites and three single nucleotide polymorphisms. Fine-mapping of the QTL was accomplished by a two-tiered approach. In the first phase, we identified seven sires heterozygous "Qq" for the QTL by marker-assisted segregation analysis in a Holstein-Friesian pedigree comprising 1,158 indiv iduals. In a second phase, we genotyped the seven selected sires for the ne wly developed high-density marker map and searched for a shared haplotype f lanking an hypothetical, identical-by-descent QTL allele with large substit ution effect. The seven chromosomes increasing milk fat percentage were ind eed shown to carry a common chromosome segment with an estimated size of 5 cM predicted to contain the studied QTL, The same haplotype was shown to be associated with increased fat percentage in the general population as well , providing additional support in favor of the location of the QTL within t he corresponding interval.