Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089, USA.
Nature. 2010 Jun 3;465(7298):627-31. doi: 10.1038/nature08800. Epub 2010 Mar 24.
Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases, genome-wide association (GWA) studies have, owing to advances in genotyping and sequencing technology, become an obvious general approach for studying the genetics of natural variation and traits of agricultural importance. They are particularly useful when inbred lines are available, because once these lines have been genotyped they can be phenotyped multiple times, making it possible (as well as extremely cost effective) to study many different traits in many different environments, while replicating the phenotypic measurements to reduce environmental noise. Here we demonstrate the power of this approach by carrying out a GWA study of 107 phenotypes in Arabidopsis thaliana, a widely distributed, predominantly self-fertilizing model plant known to harbour considerable genetic variation for many adaptively important traits. Our results are dramatically different from those of human GWA studies, in that we identify many common alleles of major effect, but they are also, in many cases, harder to interpret because confounding by complex genetics and population structure make it difficult to distinguish true associations from false. However, a-priori candidates are significantly over-represented among these associations as well, making many of them excellent candidates for follow-up experiments. Our study demonstrates the feasibility of GWA studies in A. thaliana and suggests that the approach will be appropriate for many other organisms.
尽管全基因组关联 (GWA) 研究最初是由人类遗传学家提出的,作为解决寻找常见人类疾病遗传基础这一具有挑战性问题的潜在解决方案,但由于基因分型和测序技术的进步,它已经成为研究自然变异和农业重要性状遗传基础的一种明显的通用方法。当存在近交系时,它们特别有用,因为一旦这些系被基因分型,就可以多次表型分析,从而可以(而且非常具有成本效益)在许多不同的环境中研究许多不同的性状,同时复制表型测量值以减少环境噪声。在这里,我们通过对拟南芥中的 107 个表型进行 GWA 研究,展示了这种方法的强大功能,拟南芥是一种分布广泛、主要自花授粉的模式植物,已知对许多适应性重要性状具有相当大的遗传变异。我们的结果与人类 GWA 研究的结果大不相同,因为我们确定了许多具有主要影响的常见等位基因,但它们在许多情况下也更难解释,因为复杂的遗传和群体结构的混杂使得很难将真正的关联与虚假关联区分开来。然而,这些关联中也明显过度代表了先验候选物,使其中许多成为后续实验的绝佳候选物。我们的研究表明 GWA 研究在拟南芥中的可行性,并表明该方法将适用于许多其他生物体。