Robust QTL fine mapping by applying a quantitative transmission disequilibrium test to the Mendelian sampling term.

In many farm animal populations, high-density single nucleotide polymorphism (SNP) genotypes are becoming available on a large scale, and routine estimation of breeding values is implemented for a multiplicity of traits. We propose to apply the basic principle of the quantitative transmission disequilibrium test (QTDT) to estimated Mendelian sampling terms. A two-step procedure is suggested, where in the first step additive breeding values are estimated with a mixed linear model and the Mendelian sampling terms are calculated from the estimated breeding values. In the second step, the QTDT is applied to these estimated Mendelian sampling terms. The resulting test is expected to yield significant results if the SNP is in sufficient linkage disequilibrium and linkage with quantitative trait loci (QTL). This principle is illustrated with a simulated data set comprising 4665 individuals genotyped for 6000 SNP and 15 true QTL. Thirteen of the fifteen QTL were significant on a genome-wide 0.1% error level. Results for the empirical power are derived from repeated samples of 1000 and 3000 genotyped individuals, respectively. General properties and potential extensions of the methodology are indicated. Owing to its computational simplicity and speed, the suggested procedure is well suited to scan whole genomes with high-density SNP coverage in samples of substantial size and for a multiplicity of different traits.