Thompson E A, Neel J V
Department of Statistics, University of Washington, Seattle 98195, USA.
Am J Hum Genet. 1997 Jan;60(1):197-204.
Allelic disequilibrium between closely linked genes is a common observation in human populations and often gives rise to speculation concerning the role of selective forces. In a previous treatment, we have developed a population model of the expected distribution of rare variants (including private polymorphisms) in Amerindians and have argued that, because of the great expansion of Amerindian numbers with the advent of agriculture, most of these rare variants are of relatively recent origin. Many other populations have similar histories of striking recent expansions. In this treatment, we demonstrate that, in consequence of this fact, a high degree of linkage disequilibrium between two nonhomologous alleles <0.5 cM apart is the "normal" expectation, even in the absence of selection. This expectation is enhanced by the previous subdivision of human populations into relatively isolated tribes characterized by a high level of endogamy and inbreeding. We also demonstrate that the alleles associated with a recessive disease phenotype are expected to exist in a population in very variable frequencies: there is no need to postulate positive selection with respect to the more common disease-associated alleles for such entities as phenylketonuria or cystic fibrosis.
紧密连锁基因之间的等位基因不平衡在人类群体中是常见现象，常常引发关于选择力作用的猜测。在之前的论述中，我们构建了一个关于美洲印第安人中稀有变异（包括私有多态性）预期分布的群体模型，并指出，由于农业出现后美洲印第安人口数量大幅增长，这些稀有变异大多起源相对较近。许多其他群体也有类似的近期显著扩张历史。在本论述中，我们证明，鉴于这一事实，即使在没有选择的情况下，两个相距<0.5厘摩的非同源等位基因之间高度的连锁不平衡也是“正常”预期。人类群体先前细分为以高度近亲通婚和近亲繁殖为特征的相对隔离部落，这增强了这种预期。我们还证明，与隐性疾病表型相关的等位基因在群体中的频率预计会非常多变：对于苯丙酮尿症或囊性纤维化等疾病，无需假定对更常见的疾病相关等位基因存在正选择。
