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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Linkage disequilibrium in human populations
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Linkage disequilibrium in human populations

机译：人口中的连锁不平衡

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Whereas the human linkage map appears on limited evidence to be constant over populations, maps of linkage disequilibrium (LD) vary among populations that differ in gene history. The greatest difference is between populations of sub-Saharan origin and populations remotely derived from Africa after a major bottleneck that reduced their heterozygosity and altered their Malecot parameters, increasing the intercept M that reflects association in founders and decreasing the exponential decline ε. Variation among populations within this ethnic dichotomy is much smaller. These observations validate use of a cosmopolitan LD map based on a sizeable sample representing a large population reliably typed for markers at high density. Then an LD map for a region or isolate within an ethnic group may be created by fitting the sample LD to the cosmopolitan map, estimating Malecot parameters simultaneously. The cosmopolitan map scaled by ε recovers 95% of the information that a local map at the same density gives and therefore more than the information in a low-resolution local map. Relative to a Eurasian cosmopolitan map the scaling factors are estimated to be 0.82 for isolates of European descent, 1.53 for Yorubans, and 1.74 for African Americans. These observations are consistent with a common bottleneck (perhaps but not necessarily speciation) ≈173,500 years ago, if the bottleneck associated with migration out of Africa was 100,000 years ago. Eurasian populations (especially isolates with numerous cases) are efficient for genome scans, and populations of recent African origin (such as African Americans) are efficient for identification of causal polymorphisms within a candidate sequence.
机译：人类连锁图谱在有限的证据上似乎在整个种群中是恒定的，而连锁不平衡图谱（LD）在基因历史不同的人群中也有所不同。最大的差异在于撒哈拉以南地区的人口与非洲的远距离人口之间的重大瓶颈，这降低了他们的杂合度并改变了他们的Malecot参数，增加了反映创始人间联系的截距M并减小了指数递减ε。在这种种族二分法内，人口之间的差异要小得多。这些观察结果验证了基于大样本的大都会LD图的使用，该样本代表了可靠地为高密度标记输入的大量种群。然后，可以通过将样本LD拟合到世界地图，同时估计Malecot参数，来创建族群内某个区域或孤立人群的LD图。按ε缩放的大都会地图可恢复95％相同密度的本地地图提供的信息，因此比低分辨率本地地图中的信息要多。相对于欧亚大都会地图，比例缩放因子对于欧洲人后裔而言估计为0.82，对于日罗巴人来说为1.53，对于非洲裔美国人则为1.74。这些观察结果与大约173,500年前的常见瓶颈（也许但不一定是物种形成）一致，如果与从非洲迁出有关的瓶颈是100,000年前。欧亚种群（尤其是许多病例的分离株）对于基因组扫描非常有效，而最近来自非洲的种群（例如非裔美国人）对于识别候选序列中的因果多态性也非常有效。

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