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Distinguishing pedigree relationships via multi-way identity by descent sharing and sex-specific genetic maps

机译:通过血统分享和性别特异性遗传贴图通过多种方式确定谱系关系

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摘要

The proportion of samples with one or more close relatives in a genetic dataset increases rapidly with sample size, necessitating relatedness modeling and enabling pedigree-based analyses. Despite this, relatives are generally unreported and current inference methods typically detect only the degree of relatedness of sample pairs and not pedigree relationships. We developed CREST, an accurate and fast method that identifies the pedigree relationships of close relatives. CREST utilizes identity by descent (IBD) segments shared between a pair of samples and their mutual relatives, leveraging the fact that sharing rates among these individuals differ across pedigree configurations. Furthermore, CREST exploits the profound differences in sex-specific genetic maps to classify pairs as maternally or paternally related—e.g., paternal half-siblings—using the locations of autosomal IBD segments shared between the pair. In simulated data, CREST correctly classifies 91.5%–100% of grandparent-grandchild (GP) pairs, 80.0%–97.5% of avuncular (AV) pairs, and 75.5%–98.5% of half-siblings (HS) pairs compared to PADRE’s rates of 38.5%–76.0% of GP, 60.5%–92.0% of AV, 73.0%–95.0% of HS pairs. Turning to the real 20,032 sample Generation Scotland (GS) dataset, CREST identified seven pedigrees with incorrect relationship types or maternal/paternal parent sexes, five of which we confirmed as mistakes, and two with uncertain relationships. After correcting these, CREST correctly determines relationship types for 93.5% of GP, 97.7% of AV, and 92.2% of HS pairs that have sufficient mutual relative data; the parent sex in 100% of HS and 99.6% of GP pairs; and it completes this analysis in 2.8 h including IBD detection in eight threads.
机译:样品用与样品大小的基因数据集迅速增加的一个或多个近亲属,迫使相关性建模和实现基于系谱-分析的比例。尽管这样,亲戚一般是不报告和当前的推断方法通常只检测样本对,而不是血统关系的关联程度。我们开发了CREST,准确和快速的方法识别近亲血统关系。 CREST血统利用身份(IBD)的段的一对样品和它们的相互亲属之间共享,利用的事实是这些个体之间共享率跨越系谱结构不同。此外,CREST利用了性别 - 特异性的遗传图谱进行分类对作为母体或父本的深刻差异相关-如,父系半同胞-使用所述一对之间共享的常染色体IBD段的位置。在模拟数据,CREST相比,策略平台的正确分类91.5%-100%祖父母,孙子女(GP)对,80.0%-97.5母舅(AV)对%和75.5%-98.5的半同胞(HS)对% 38.5%率-76.0 GP的%,60.5%-92.0 AV的%,73.0%-95.0 HS对%。谈及真正的20032样本生成苏格兰(GS)的数据集,CREST确定了七个家系与不正确的关系类型或母亲/父本男女,其中五个,我们确认为失误和两个不确定的关系。纠正这些之后,CREST正确地确定用于GP的93.5%,AV的97.7%,并具有足够的相互相对的数据HS对92.2%的关系类型;在HS的100%,GP对99.6%的亲性;并完成了2.8 h包括在八个线程IBD检测这一分析。

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