Lee Wen-Chung, Yen Yu-Chun
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei.
Ann Hum Genet. 2003 Nov;67(Pt 6):580-8. doi: 10.1046/j.1529-8817.2003.00052.x.
Family-based studies of genetic association and linkage play a key role in mapping susceptibility genes of complex human diseases. Recent admixture between genetically differentiated populations can result in high levels of linkage disequilibrium even at far apart loci. This has been capitalized upon to reduce the burden of genotyping in a genomewide association scan. Here the authors describe an alternative approach for admixture mapping. The genome is divided into several non-overlapping intervals and the information of the markers in the same interval is integrated--the 'interval transmission/disequilibrium test' (ITDT). This method requires information in the form of the marker allele frequencies in the founding populations. However, computer simulations show that the performances of ITDT are hardly affected by imprecise allele-frequency information. Simulations also show that an interval-by-interval scan using ITDT perform much better than a conventional marker-by-marker scan using TDT, even under conditions where the admixture process occurred over many generations and the individuals in the admixed populations show considerable variation in admixture proportion. Hence the ITDT is a promising new genomewide scan method.
基于家系的基因关联和连锁研究在绘制复杂人类疾病的易感基因图谱中起着关键作用。遗传分化群体之间最近的混合甚至在相隔很远的基因座处也会导致高水平的连锁不平衡。这一点已被用于减轻全基因组关联扫描中的基因分型负担。在此，作者描述了一种用于混合作图的替代方法。将基因组划分为几个不重叠的区间，并整合同一区间内标记的信息——即“区间传递/不平衡检验”（ITDT）。该方法需要创始群体中标记等位基因频率形式的信息。然而，计算机模拟表明，ITDT的性能几乎不受不精确等位基因频率信息的影响。模拟还表明，即使在混合过程发生了许多代且混合群体中的个体在混合比例上表现出相当大差异的情况下，使用ITDT进行逐个区间扫描的效果也比使用TDT进行传统的逐个标记扫描要好得多。因此，ITDT是一种很有前景的新的全基因组扫描方法。
