A perspective on epistasis: Limits of models displaying no main effect
A perspective on epistasis: Limits of models displaying no main effect
复制标题
DOI：
10.1086/338759
复制
发表时间：
2002-02-01
影响因子：
9.8
通讯作者：
Reich, T
中科院分区：
文献类型：
--
作者：
Culverhouse, R;Suarez, BK;Reich, T
人类基因组草案序列的完成以及快速的单核苷酸 - 多态性生成型技术的希望导致呼吁放弃链接研究，以支持基因组进行关联的基因组扫描。但是，存在大量的遗传模型，这种方法将失败：纯粹的上皮模型在任何敏感性基因座中均无添加剂或优势变化。结果，如果单独检查基因座，传统的关联方法（例如案例/对照，测量的基因型和传播/不平衡测试[TDT]）将无力。在本文中，我们研究了这类模型，划定了两，三和四位式纯粹纯粹信世物模型的遗传确定和复发风险的范围。我们的研究表明，尽管这些模型没有引起添加剂或优势差异，但确实会导致受影响的SIB之间的等位基因共享增加。因此，用于连锁的基因组扫描可以检测具有易感基因座的基因组子区域。我们还讨论了单位分析方法的一些简单的多焦点扩展，包括TDT的条件形式。
The completion of a draft sequence of the human genome and the promise of rapid single-nucleotide-polymorphism-genotyping technologies have resulted in a call for the abandonment of linkage studies in favor of genome scans for association. However, there exists a large class of genetic models for which this approach will fail: purely epistatic models with no additive or dominance variation at any of the susceptibility loci. As a result, traditional association methods (such as case/control, measured genotype, and transmission/disequilibrium test [TDT]) will have no power if the loci are examined individually. In this article, we examine this class of models, delimiting the range of genetic determination and recurrence risks for two-, three-, and four-locus purely epistatic models. Our study reveals that these models, although giving rise to no additive or dominance variation, do give rise to increased allele sharing between affected sibs. Thus, a genome scan for linkage could detect genomic subregions harboring susceptibility loci. We also discuss some simple multilocus extensions of single-locus analysis methods, including a conditional form of the TDT.