Genomic Patterns of Polymorphism in Primates

随着HapMap项目的完成和1000基因组计划的持续努力，近 DNA序列变异的全面目录不久将可供人类群体使用。 这些数据将是非常有用的，可以用来阐明形成 随着时间的推移而变化。为了帮助正确看待这些信息，这项研究建议收集大规模的 来自8个灵长类物种的广泛小组的序列多态数据。重要的是，该小组包括 对生物医学研究具有基本兴趣并拥有基因组测序项目的物种 已经完成或正在进行中。一个主要的目标是推断一些种群遗传的相对影响 对X染色体和常染色体产生不同影响的过程，例如种群的变化 大小和性别偏见的迁徙、自然选择(例如背景选择和正面定向选择)以及 性选择(即男性与女性生殖成功的差异较大)。要开发一种 比较框架，精选的8种灵长类物种代表了广泛的不同交配 策略和繁衍模式，包括一夫一妻制(如长臂猿)、单雄多雌 多个群体(大猩猩、猩猩、狒狒)和多雄多雌性群体(黑猩猩、狒狒、猕猴)。 为了理清人口和选择性因素的相对影响，这项研究的目标是一种组合 X染色体和常染色体上的300个基因区和非基因区。实验设计 采用DNA捕获阵列从每个物种的10个个体中提取1.8Mb的目标DNA。这个 然后，通过大规模并行测序，将目标DNA测序到覆盖深度的40-80倍 技术下一代序列数据的质量将通过与 用传统的Sanger方法对100kb的PCR扩增DNA进行测序。这项研究将会有所帮助 确定行为观察和形态测量在多大程度上可以预测 变异的基因组模式，以及自然选择在形成精细的遗传模式中所起的作用 可变性。这些信息也将作为人类变异的群体遗传学模型。 此外，这对于阐明影响服务物种遗传变异的因素也是至关重要的。 作为人类的主要生物医学模型。建立中性多态和连锁的基线水平 这些物种的不平衡将有助于两个候选基因研究的适当设计和分析。 以及全基因组关联研究，以确定复杂特征的遗传决定因素。

With the completion of the HapMap project and the ongoing efforts of the 1000 genomes project, a nearly comprehensive catalog of DNA sequence variants will soon become available for human populations. These data will be very informative for elucidating the historical forces that have shaped patterns of variation over time. To help put this information in perspective, this study proposes to gather large-scale sequence polymorphism data from a broad panel of eight primate species. Importantly, this panel includes species that are of fundamental interest to biomedical research and have genome sequencing projects that are completed or underway. A major goal is to infer the relative influence of a number of population genetic processes that differentially affect the X chromosome versus autosomes, such as changes in population size and sex-biased migration, natural selection (e.g., background and positive directional selection), and sexual selection (i.e., higher variance in male versus female reproductive success). To develop a comparative framework, the chosen set of 8 primate species represents a wide range of different mating strategies and dispersal patterns, including monogamous pairs (e.g., gibbons), single male multi-female groups (gorillas, orangutans, baboons), and multi-male multi-female groups (chimps, baboons, macaques). To disentangle the relative influence of demographic and selective forces, this study targets a combination of 300 genic and non-genic regions on the X chromosome and autosomes. The experimental design employs DNA capture arrays to enrich for 1.8 Mb of target DNA from 10 individuals from each species. The target DNA will then be sequenced to a depth of 40-80-fold coverage through massively parallel sequencing technology. The quality of the next generation sequence data will be assessed through comparison with 100 Kb of PCR-amplified DNA sequenced by conventional Sanger methodology. This study will help determine to what extent behavioral observations and morphological measurements are predictive of genomic patterns of variation, and what role natural selection plays in shaping fine-scale patterns of genetic variability. This information will also serve as a model for the population genetics of human variation. Moreover, it is essential for elucidating the factors that have affected genetic variation in species that serve as major biomedical models for humans. Establishing baseline levels of neutral polymorphism and linkage disequilibrium in these species will facilitate the proper design and analysis of both candidate gene studies and genome-wide association studies to identify the genetic determinants of complex traits.