Use of linkage disequilibrium for quantitative trait loci mapping in livestock.

摘要

The goal of quantitative trait loci (QTL) mapping in livestock is to find genes underlying traits of economic importance for genetic improvement through marker assisted selection (MAS). The studies presented in this thesis address several important issues in QTL detection and fine mapping using candidate gene analysis and linkage disequilibrium (LD) mapping using high density genotyping. Tests for candidate genes in F2 populations for QTL mapping were developed and evaluated. Results show that the extensive between-breed LD that is present in a cross can result in significant associations for candidate genes at considerable distances from the QTL. Tests that removed the impact of between-breed LD were not powerful in detecting candidate genes closely linked to the QTL, unless the candidate gene was the QTL. Therefore, candidate gene tests in QTL mapping populations must be interpreted with caution. Effectiveness of QTL mapping and MAS using LD in outbred populations depends on the extent of LD between markers and QTL which can differ between populations. Nine measures of LD between multi-allelic markers were evaluated as predictors of usable LD when LD is generated by drift. A standardized chi-square statistic (chi 2') was found to be the best predictor of usable LD of multi-allelic markers with QTL, while three other measures ( c2df , r2 and D*) were found to be good predictors of usable LD of single nucleotide polymorphisms (SNPs) with QTL. The effect of various factors on power and precision of QTL detection was evaluated and power and precision of regression- and identical by descent (IBD)-based LD mapping methods were compared. Power and precision of QTL detection increased with sample size, marker density and QTL effect. *D x Single marker regression had similar or greater power and precision than other regression models. For IBD methods, fitting a 4-SNP haplotype, in general, resulted in relatively high power and the greatest mapping precision among the haplotype sizes. Single marker regression was comparable to the 4-SNP IBD method. The results for the haplotype regression and the IBD method assume that haplotypes are known, which would not be true in practice. This will obviously reduce power of these methods. Thus, for rapid initial screening, QTL can be detected and mapped by regression on SNP genotypes without recovering haplotypes with adequate sample size. LD mapping using high density genotyping in outbred populations is a promising method for QTL detection and fine mapping, and would result in markers that can immediately be implemented for MAS.