Evans D M, Morris A P, Cardon L R, Sham P C
Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Behav Genet. 2006 Nov;36(6):947-50. doi: 10.1007/s10519-006-9087-2. Epub 2006 Jun 28.
Transmission distortion refers to deviation from the normal 50:50 transmission of alleles from parents to offspring. Identification of genomic regions which undergo distortion is necessary for the correct interpretation of linkage and association studies, since tests of linkage using affected relative pairs and family based tests of association will yield spurious results in the presence of transmission distortion. With the increasing availability of genome-wide high density SNP data (e.g. from the International HapMap project), identification of these loci is now a real possibility. Here we present an analytical formula which demonstrates that the power to detect transmission distortion is a simple function of the number of heterozygous parents in the sample and the level of distortion at the locus. Our results indicate that whilst it will be possible to identify loci undergoing major levels of distortion using tens or hundreds of trios, large sample sizes in the order of tens of thousands of trios will be necessary to detect minor levels of distortion with appreciable power. The corollary is that genome-wide searches are unlikely to identify loci where the level of distortion is small, although they may serve to identify interesting regions worthy of follow up.
传递失真指的是等位基因从亲代到子代的传递偏离正常的50:50比例。识别发生传递失真的基因组区域对于正确解释连锁和关联研究是必要的，因为在存在传递失真的情况下，使用患病亲属对进行连锁检验以及基于家系的关联检验会产生虚假结果。随着全基因组高密度SNP数据（例如来自国际人类基因组单体型图计划）的日益可得，现在识别这些位点成为了现实可能。在此我们给出一个解析公式，该公式表明检测传递失真的效能是样本中杂合亲代数量以及该位点失真水平的一个简单函数。我们的结果表明，虽然使用数十个或数百个三联体有可能识别出发生主要水平失真的位点，但要以可观的效能检测出轻微水平的失真，则需要数万数量级的大样本三联体。由此推论，全基因组搜索不太可能识别出失真水平较小的位点，尽管它们可能有助于识别值得后续研究的有趣区域。
