Multiple-Marker Mapping for Selective DNA Pooling Within Large Families

Selective DNA pooling is a very powerful method for quantitative trait loci (QTL) mapping. It considerably reduces genotyping costs while maintaining high statistical power. Applied to a daughter design, milk samples of offspring with extreme phenotypic values for a trait of interest are assigned to high and low groups, respectively, and within each group the pooled DNA is used for densitometric estimation of allele frequencies in the 2 groups. A single-marker test for linkage between marker and QTL considers marker allele frequency differences between high and low groups. Single-marker across-sire test statistics are strongly affected by the number of sires that are heterozygous for a given marker and the QTL status (homozygous or heterozygous) of these sires, which decreases the accuracy of QTL mapping. Here we propose a simple method to deal with this problem by taking information from multiple linked markers into account. In particular, given the single-marker test statistics, a multiple-marker method was developed to predict test statistics for markers for which a sire was homozygous (or at any other location on the chromosome). Power and map resolution of the proposed method were assessed by simulation, and we show that for the same data set, multiple-marker mapping performed better than the commonly used single-marker analyses.