Natural selection mapping of the warfarin-resistance gene
Natural selection mapping of the warfarin-resistance gene
复制标题
DOI：
10.1073/pnas.97.14.7911
复制
发表时间：
2000-07-05
影响因子：
11.1
通讯作者：
Wayne, RK
中科院分区：
文献类型：
--
作者：
Kohn, MH;Pelz, HJ;Wayne, RK
理论上，自然选择下的基因可以通过物理连锁位点的连锁不平衡（LD）和多态性的独特模式来揭示。然而，由于重组和突变的影响，LD模式在自然群体中的物理范围和持久性是不确定的。为了评估LD签名的选择，我们调查的变化，在26个微卫星位点跨越一个近似32厘米的区域，其中包括华法林耐药基因（RW）在5个野生大鼠种群的抗性水平在0和95%之间。我们发现，在抗性群体的微卫星位点的杂合子缺失的频率很高，和基因多样性（H）和抗性之间的负相关。与以前的研究相反，这些数据表明，在强烈的抗凝治疗期间，定向选择而不是超显性选择可能占主导地位。在高耐药人群中，广泛的LD观察到跨越约14%的大鼠1号染色体的染色体片段。相比之下，LD在一个中度耐药的人口更本地化，并结合似然比，允许分配Rw到一个2.2厘米的间隔。在这个基因组窗口内，诊断标记D1Rat219将91%的大鼠分配到正确的抗性类别。这些结果进一步表明，“自然选择作图”在外地人口可以检测和地图的主要健身相关基因，并质疑overdominance作为主要模式的选择抗凝剂耐药大鼠种群。
In theory, genes under natural selection can be revealed by unique patterns of linkage disequilibrium (LD) and polymorphism at physically linked loci. However, given the effects of recombination and mutation, the physical extent and persistence of LD patterns in natural populations is uncertain. To assess the LD signature of selection, we survey variation in 26 microsatellite loci spanning an approximate to 32-cM region that includes the warfarin-resistance gene (Rw) in five wild rat populations having resistance levels between 0 and 95%. We find a high frequency of heterozygote deficiency at microsatellite loci in resistant populations, and a negative association between gene diversity (H) and resistance. Contrary to previous studies, these data suggest that directional rather than overdominant selection may predominate during periods of intense anticoagulant treatment. In highly resistant populations, extensive LD was observed over a chromosome segment spanning approximate to 14% of rat chromosome 1. In contrast, LD in a moderately resistant population was more localized and, in conjunction with likelihood ratios, allowed assignment of Rw to a 2.2-cM interval. Within this genomic window, a diagnostic marker, D1Rat219, assigned 91% of rats to the correct resistance category. These results further demonstrate that "natural selection mapping" in field populations can detect and map major fitness-related genes, and question overdominance as the predominant mode of selection in anticoagulant-resistant rat populations.