| Summary: | 碩士 === 國立陽明大學 === 公共衛生研究所 === 92 === In the post-genome era, disease gene mapping using dense genetic markers has become an important tool for dissecting complex inheritable diseases. Locating disease susceptibility genes using DNA pooling experiments is an economical alternative to those involving individual genotyping. The foundation of a successful pooling association test is a precise and accurate estimation of allele frequency. In this paper, we propose some new adjustment methods, based on the concept of ratio estimator, that correct for preferential amplification of nucleotides when estimating the allele frequency of single nucleotide polymorphisms. We also discuss the sample size, the estimation of coefficient of linkage disequilibrium and new association test when calibrating unequal allelic amplification. Complete the whole pipeline of disease-gene mapping using a DNA pooling design.
We have conducted simulation studies to assess the performance of different adjustment procedures and find that our proposed adjustments are more reliable with respect to the estimation bias and root mean squared error compared with current approach (Hoogendoorn et al. 2000). The improved performance not only benefits the estimation of allele frequency but leads to more powerful disease gene mapping. An authentic data set from National Genotyping Center Core is used for illustration of the proposed methods.
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