Center for Human Genetics, Clemson University, Greenwood, SC, USA.
Department of Genetics and Biochemistry, Clemson University, Clemson, SC, USA.
Nat Rev Genet. 2024 Sep;25(9):639-657. doi: 10.1038/s41576-024-00711-3. Epub 2024 Apr 2.
Pleiotropy (whereby one genetic polymorphism affects multiple traits) and epistasis (whereby non-linear interactions between genetic polymorphisms affect the same trait) are fundamental aspects of the genetic architecture of quantitative traits. Recent advances in the ability to characterize the effects of polymorphic variants on molecular and organismal phenotypes in human and model organism populations have revealed the prevalence of pleiotropy and unexpected shared molecular genetic bases among quantitative traits, including diseases. By contrast, epistasis is common between polymorphic loci associated with quantitative traits in model organisms, such that alleles at one locus have different effects in different genetic backgrounds, but is rarely observed for human quantitative traits and common diseases. Here, we review the concepts and recent inferences about pleiotropy and epistasis, and discuss factors that contribute to similarities and differences between the genetic architecture of quantitative traits in model organisms and humans.
多效性（一种遗传多态性影响多种性状）和上位性（遗传多态性之间的非线性相互作用影响同一性状）是数量性状遗传结构的基本方面。最近在描述人类和模式生物群体中多态变异对分子和机体表型的影响方面的能力取得了进展，揭示了多效性的普遍性，以及包括疾病在内的数量性状之间意想不到的共同分子遗传基础。相比之下，模型生物中与数量性状相关的多态位点之间的上位性很常见，因此一个位点的等位基因在不同的遗传背景下有不同的作用，但在人类数量性状和常见疾病中很少观察到。在这里，我们回顾了多效性和上位性的概念和最近的推断，并讨论了导致模型生物和人类数量性状遗传结构相似和不同的因素。
