Identity by descent in population data

摘要 如果两个人从共同的一个人那里继承了DNA，那么两个人的DNA就被认为是相同的 祖先，如曾祖父母。血统认同(IBD)发生在相对较长的 当共同的祖先生活在大约50代人中时，有数百万个碱基对。 由于50代人以前的祖先可以有很多后代，所以有可能找到 多对没有已知关系的个体之间的IBD。 这项提案的目标是开发IBD细分市场的三个新应用。 第一个应用是估计重组率。重组率在基因组中各不相同，而且 为了进行许多其他的遗传分析，必须估计这些比率。我们将制定方法 他们使用IBD片段从人口样本数据中估计重组率。我们还将发展 方法严格比较不同人群间基于IBD的重组图谱。我们会估计 不同人群中的重组率，我们将研究基因组中 不同种群之间存在差异。 第二个应用是估计特定性别的人口史。男性和女性可以拥有 由于生殖成功的不同变异性而导致的不同的有效种群数量，以及雄性和 雌性通常有不同的迁徙速度。我们将开发方法来估计特定性别的有效性 通过比较X染色体上IBD片段的比率(这是 女性历史)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正面选择。可以通过查找以下内容找到选定的区域 IBD水平升高。我们将开发统计方法来估计遴选的力度， 选择模式，以及所选变种的频率。我们知道，不同国家的选择不同 由于不同的病原体和其他环境暴露而导致的地理区域，我们将分析 不同的人口，以编目选定的地区，以及不同人口之间的差异。

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.