Bodmer Walter, Bonilla Carolina
Cancer and Immunogenetics Laboratory, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
Nat Genet. 2008 Jun;40(6):695-701. doi: 10.1038/ng.f.136.
Here, we give a historical overview of the search for genetic variants that influence the susceptibility of an individual to a chronic disease, from RA Fisher's seminal work to the current excitement of whole-genome association studies (WGAS). We then discuss the concepts behind the identification of common variants as disease causal factors and contrast them to the basic ideas that underlie the rare variant hypothesis. The identification of rare variants involves the careful selection of candidate genes to examine, the availability of highly efficient resequencing techniques and the appropriate assessment of the functional consequences of the implicated variant. We believe that this strategy can be successfully applied at present in order to unravel the contribution of rare variants to the multifactorial inheritance of common diseases, which could lead to the implementation of much needed preventative screening schemes.
在此，我们将对寻找影响个体患慢性病易感性的基因变异进行历史概述，从RA·费希尔的开创性工作到当前全基因组关联研究（WGAS）的热潮。然后，我们将讨论将常见变异鉴定为疾病致病因素背后的概念，并将它们与稀有变异假说的基本观点进行对比。稀有变异的鉴定涉及仔细选择要检测的候选基因、高效重测序技术的可用性以及对相关变异功能后果的适当评估。我们相信，目前这种策略能够成功应用，以揭示稀有变异对常见疾病多因素遗传的贡献，这可能会促成急需的预防性筛查方案的实施。
