Genetics and Historical Demography of the Ashkenazim

描述（由申请人提供）：本研究的目的是测试长期存在的竞争假说，这些假说解释了为什么德系犹太人中导致疾病表型的突变如此普遍。该方法结合了理论和经验的方法。首先，一个德系犹太人的人口统计历史的计算机模型是从历史记录中构建的。遗传进化的模拟和概率所获得的观察到的遗传数据进行评估与蒙特卡罗程序。似然方法将用于区分模型的竞争假设和参数化。经验的方法包括调查了大量的微卫星位点，以及主要组织相容性复合体序列变异的几个人口被认为是代表欧洲的德系犹太人殖民化的各个阶段。这两个遗传数据集将被测试遗传瓶颈的可能性。如果发现瓶颈，并且其他数据与长期有效规模较低的人口统计模型一致，这表明选择在从小群体中去除有害突变方面可能效率低下。然而，如果没有瓶颈的证据，这表明最近人口的扩张可以大大增加有害突变的频率。

DESCRIPTION (provided by applicant): The purpose of this research is to test long-standing rival hypotheses that offer explanations for why there is such a high prevalence of mutations that cause disease phenotypes among the Ashkenazi Jews. The approach integrates a theoretical and empirical approach. First a computer model of Ashkenazi demographic history is constructed from historical records. Genetical evolution is simulated and probabilities of obtained observed genetic data are evaluated with a Monte Carlo procedure. A likelihood method will used to distinguish among competing hypotheses and parameterizations of models. The empirical approach consists of surveying a large number of microsatellite loci, as well as major histocompatibility complex sequence variation in several populations thought to represent the various stages of Ashkenazi colonization of Europe. These two genetic datasets will be tested for the possibility of a genetic bottleneck. If a bottleneck is found and other data are consistent with a demographic model of low long-term effective size, this suggests that selection can be inefficient at removing deleterious mutations from small populations. However, should there be no evidence for a bottleneck, this suggests that recent population's expansion can greatly increase the frequency of deleterious mutations.