Institut Pasteur, Human Evolutionary Genetics, Department of Genomes and Genetics, Paris, France.
Ann N Y Acad Sci. 2010 Dec;1214:1-17. doi: 10.1111/j.1749-6632.2010.05856.x.
Detecting whether and how natural selection has targeted regions of the human genome represents a complementary strategy for identifying functionally important loci and variants involved in disease resistance and adaptation to the environment. In contrast with most complex diseases or traits, the genetic architecture of most Mendelian traits is relatively well established. Most mutations associated with Mendelian disease-related traits are highly penetrant and kept at low population frequencies because of the effects of purifying selection. However, this is not always the case. Here, we review several examples of Mendelian mutations-associated with various disease conditions or other traits of anthropological interest-that have increased in frequency in the human population as a result of past positive selection. These examples clearly illustrate the value of a population genetics approach to unravel the biological mechanisms that have been central to our past and present survival against the selective pressures imposed by diseases and other environmental factors.
检测自然选择是否以及如何针对人类基因组的区域，代表了一种识别功能重要基因座和与疾病抗性和环境适应相关变异体的互补策略。与大多数复杂疾病或特征不同，大多数孟德尔特征的遗传结构相对明确。与孟德尔疾病相关特征相关的大多数突变具有高度外显率，由于纯化选择的影响，其在人群中的频率保持较低。然而，情况并非总是如此。在这里，我们回顾了几种与各种疾病状况或其他人类学感兴趣的特征相关的孟德尔突变的例子，这些突变由于过去的正向选择而在人类群体中的频率增加。这些例子清楚地说明了群体遗传学方法的价值，这种方法可以揭示生物学机制，这些机制一直是我们过去和现在抵御疾病和其他环境因素带来的选择压力的关键。
