Abstract
The ultimate goal of QTL studies is to find causative mutations, which requires additional expression studies. Given the limited amount of time and funds, the smart option is to identify the most important QTL with minimal effort. A cost-effective solution is to genotype only those animals with high or low phenotypic values or DNA-pools of these individuals. A two-stage genotyping strategy was applied on samples in the tails of the distribution of breeding values. The tail-analysis approach identified eight out of the 19 QTL in the first stage, explaining about half of 98% of the genetic variance. Four additional QTL with small effects were found in the second stage. The two-stage genotyping strategy with selective genotyping detected regions with highly significant QTL useful for further fine-mapping. The large reduction in costs allows for follow-up expression and functional studies.
Highlights
BackgroundDiscovery and subsequent validation of causative mutations affecting complex traits require identification and fine-mapping of QTL followed by expression and functional studies
The ultimate goal of QTL studies is to find causative mutations, which requires additional expression studies
Disadvantages to genotyping tails or pools are the number of traits that can be studied with the selected genotypes, separate high/low tails or pools have to be made for each trait, and non-optimal use of haplotype information
Summary
Discovery and subsequent validation of causative mutations affecting complex traits require identification and fine-mapping of QTL followed by expression and functional studies. A cost-effective strategy is to reduce genotyping costs by only genotyping individuals with high and low phenotypic values, or to genotype pools of these individuals. Korol et al [4] improved on the latter method by studying fractioned DNA pooling. Wang et al [5] improved on statistical methods developed by Dekkers [6] for interpretation of results obtained by DNA pooling. Commercial breeding pedigrees present a situation where phenotypes are abundant, across many generations. In such a situation, selective genotyping is an important step in setting up a cost effective QTL study. The objective is to identify major segregating QTL in a simulated pig-type pedigree with minimal effort both in terms of genotyping and analysis
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