A model-based approach to characterize individual inbreeding at both global and local genomic scales
A model-based approach to characterize individual inbreeding at both global and local genomic scales
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DOI：
10.1111/mec.14324
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发表时间：
2017-10-01
影响因子：
4.9
通讯作者：
Gautier, M.
中科院分区：
文献类型：
--
作者：
Druet, T.;Gautier, M.
近亲繁殖是由相关个体的交配引起的，并且可能与降低的适应性有关，因为它将有害的变体聚集在一个个体中。一般来说，近亲繁殖是针对由假定不相关的祖先组成的任意基础种群进行估计的。我们在此提出了一种基于模型的方法来估计和表征个体近亲繁殖在全球和本地基因组尺度，假设个人基因组是一个马赛克的同源血统（HBD）和非HBD段。HBD片段可能起源于追溯到过去不同时期的祖先，定义了不同的年龄相关类。HBD片段的长度呈指数分布，具有类别特异性参数，反映了较老来源的近亲繁殖平均产生较短的观察到的纯合标记。该模型是在一个隐马尔可夫模型框架，使用标记等位基因频率，遗传距离，基因分型错误率和观察到的基因型序列。请注意，基因分型错误，低倍测序或基因型测序数据很容易适应这个框架。基于推理模型下的模拟，我们证明了全基因组近交系数和模型参数的准确估计。此外，当模拟几个近亲繁殖类时，如果它们的年龄足够不同，则模型捕获它们。补充分析，无论是在更现实的模型下模拟的数据集，还是在人类、狗和羊的真实的数据上，都说明了该方法的应用范围，以及它如何揭示种群中最近的人口统计学历史（例如，最近的瓶颈或创始人效应）。该方法还可以清楚地识别极端近亲交配产生的个体。
Inbreeding results from the mating of related individuals and may be associated with reduced fitness because it brings together deleterious variants in one individual. In general, inbreeding is estimated with respect to an arbitrary base population consisting of ancestors that are assumed unrelated. We herein propose a model-based approach to estimate and characterize individual inbreeding at both global and local genomic scales by assuming the individual genome is a mosaic of homozygous-by-descent (HBD) and non-HBD segments. The HBD segments may originate from ancestors tracing back to different periods in the past defining distinct age-related classes. The lengths of the HBD segments are exponentially distributed with class-specific parameters reflecting that inbreeding of older origin generates on average shorter stretches of observed homozygous markers. The model is implemented in a hidden Markov model framework that uses marker allele frequencies, genetic distances, genotyping error rates and the sequences of observed genotypes. Note that genotyping errors, low-fold sequencing or genotype-by-sequencing data are easily accommodated under this framework. Based on simulations under the inference model, we show that the genomewide inbreeding coefficients and the parameters of the model are accurately estimated. In addition, when several inbreeding classes are simulated, the model captures them if their ages are sufficiently different. Complementary analyses, either on data sets simulated under more realistic models or on human, dog and sheep real data, illustrate the range of applications of the approach and how it can reveal recent demographic histories among populations (e.g., very recent bottlenecks or founder effects). The method also allows to clearly identify individuals resulting from extreme consanguineous matings.