Fine Mapping and Evolution of a QTL Region on Cattle Chromosome 3

Abstract

Using genotypes obtained from the offspring of three half sib families, paternal and maternal haplotypes of the offspring were reconstructed in addition to the six sire haplotypes. A 9.7 Mbp haplotype block likely to be identical by descent was identified in sires, S1 and S2. This shared haplotype block was found to be associated with high milk yield in families, F1 and F2, confirming previous studies. Maternal haplotypes of offspring were then used to define linkage disequilibrium (LD) within the QTL critical region. There were 15 LD blocks found to be shared among all three sires, covering 0.5 Mbp within the 9.7 Mbp region. These regions may contain QTL alleles carried by all three sires. Fst analysis and integrated haplotype scores (iHS) identified signatures of selection in a 3 Mbp subregion of the QTL critical region. For genes located in the QTL critical region, functions were predicted on the basis of human gene annotation. To identify orthologous genomic regions containing candidate genes, a bioinformatics tool, SyntenyTracker was developed. Within the QTL critical region, eight genes with well established functions related to metabolism, membrane transport or mammary gland function were identified. These results show that the combination of a high density marker map, haplotype analysis, characterization of LD, and identification of genomic regions and nucleotides under selection is a powerful approach for QTL fine mapping.