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METHODS FOR ASSOCIATING QUANTITATIVE TRAITS WITH ALLELES IN SIBLING PAIRS
METHODS FOR ASSOCIATING QUANTITATIVE TRAITS WITH ALLELES IN SIBLING PAIRS
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机译：双性对中等位基因与数量性状的关联方法
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摘要
Identifying the genetic components of complex diseases is one of the most important goals of the human genome project. These diseases and their underlying risk factors are often better described by quantitative phenotypes than by an arbitrary distinction between affected and unaffected individuals. Association studies are able to identify genetic loci contributing to these quantitative trait loci directly at the cost of requiring large population sizes. Studies of sib pair populations have been suggested to increase power when populations are stratified, and tests on pooled DNA may reduce the experimental burden, but these approaches have been analyzed primarily in the context of affected/unaffected disease phenotypes. Disclosed herein are efficient methods for QTL mapping using DNA pooled from sib pairs. A preferred test using a single set of pools is to select unrelated sibs with extreme phenotypic values, requiring a population size approximately 1.5Xlarger than for individual genotyping. A preferred strategy overall, with a population size requirement only 1.24Xlarger than for individual genotyping, is a combined test of DNA pooled according to sib-difference phenotypic values. The optimal pooling fraction is 27 % and is insensitive to all model parameters including allele frequency, inheritance mode, and the magnitude of the QTL effect.
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