Identity by descent in population data

摘要 两个人的DNA被认为是相同的血统时，个人继承了它从一个共享的 祖先，如曾祖父母。血统同一性（IBD）发生在相对较长的片段中， 当共同的祖先生活在大约过去的50代中时，有数百万个碱基对。 由于50代前的祖先可以有许多后代，因此有可能找到 IBD发生在许多对个体之间，但没有已知的关系。 该提案的目标是开发IBD细分市场的三个新应用程序。 第一个应用是估计重组率。在基因组中，转化率各不相同， 为了进行许多其他的遗传分析，必须估计这些比率。我们将开发方法 使用IBD片段从群体样本数据中估计重组率。我们还将开发 方法来严格比较IBD为基础的重组图谱人群。我们估计 在不同人群中的重组率，我们将调查基因组的区域， 人口之间存在差异。 第二个应用是估计性别特定的人口统计学史。男性和女性可以有 不同的有效人口规模，由于不同的变异，在繁殖成功，和男性和 女性的移徙率往往不同。我们将开发方法来估计性别特异性有效性 通过比较X染色体上IBD片段的比率（其是 对女性历史加权）和常染色体（男性和女性之间的权重相等）。 女性历史）。这项工作将提高我们对历史动态的理解， 人口。 第三个应用是分析最近的积极选择。选定的区域可以通过查找 IBD水平升高。我们将开发统计方法来估计选择的强度， 选择模式和所选变体的频率。我们知道，选择在不同的 地理区域，由于不同的病原体和其他环境暴露，我们将分析 不同的人群，以目录选定的地区，以及他们如何在人群之间的差异。

Abstract Two individuals’ DNA is said to be identical by descent when the individuals inherited it from a shared ancestor such as a great-grandparent. Identity by descent (IBD) occurs in relatively long segments of several million base pairs when the shared ancestor lived within approximately the past 50 generations. Since ancestors from 50 generations ago can have many descendants, it is possible to find segments of IBD between many pairs of individuals without known relationships. The goal of this proposal is to develop three new applications of IBD segments. The first application is estimating recombination rates. Recombination rates vary across the genome, and the rates must be estimated in order to perform many other genetic analyses. We will develop methods that use IBD segments to estimate recombination rates from population sample data. We will also develop methods to rigorously compare IBD-based recombination maps across populations. We will estimate recombination rates in different human populations, and we will investigate regions of the genome where there are differences between populations. The second application is estimating sex-specific demographic history. Males and females can have different effective population sizes due to differing variability in reproductive success, and males and females often have different rates of migration. We will develop method to estimate sex-specific effective population sizes and mutation rates by comparing rates of IBD segments on the X chromosome (which is weighted towards female history) and the autosomes (which are equally weighted between male and female histories). This work will improve our understanding of the historical dynamics that have shaped populations. The third application is analyzing recent positive selection. Selected regions can be found by looking for elevated levels of IBD. We will develop statistical methodology to estimate the strength of selection, the mode of selection, and the frequency of the selected variants. We know that selection differs across geographic regions due to different pathogens and other environmental exposures, and we will analyze diverse populations to catalog selected regions and how they differ between populations.