Whole population, genome-wide mapping of hidden relatedness
Whole population, genome-wide mapping of hidden relatedness
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DOI：
10.1101/gr.081398.108
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发表时间：
2009-02-01
期刊：
影响因子：
7
通讯作者：
Pe'er, Itsik
中科院分区：
文献类型：
--
作者：
Gusev, Alexander;Lowe, Jennifer K.;Pe'er, Itsik
我们提出了GERMLINE，一个强大的算法，用于识别段共享指示最近的共同祖先对个人之间。与具有可比目标的方法不同，GERMLINE与样本数量呈线性关系，能够分析大型队列的全基因组数据。我们的方法是基于一个字典的单倍型，是用来有效地发现短的个人之间的精确匹配。然后，我们扩大这些匹配使用动态规划，以确定长，几乎相同的片段共享，这是相关性的指示。我们使用GERMLINE全面调查隐藏的相关性，无论是在HapMap，以及在密集型岛屿人口的3000人。我们验证了GERMLINE与其他方法在处理数据时是一致的，并且也有利于更大规模研究的分析。我们通过展示隐藏相关性的精确分析的新应用来支持这些结果，用于（1）鉴定和解决定相错误和（2）暴露多态性缺失，否则难以检测。这一发现得到了检测到的缺失与来自独立数据库的其他证据的一致性以及GERMLINE未使用的荧光强度统计分析的支持。
We present GERMLINE, a robust algorithm for identifying segmental sharing indicative of recent common ancestry between pairs of individuals. Unlike methods with comparable objectives, GERMLINE scales linearly with the number of samples, enabling analysis of whole-genome data in large cohorts. Our approach is based on a dictionary of haplotypes that is used to efficiently discover short exact matches between individuals. We then expand these matches using dynamic programming to identify long, nearly identical segmental sharing that is indicative of relatedness. We use GERMLINE to comprehensively survey hidden relatedness both in the HapMap as well as in a densely typed island population of 3000 individuals. We verify that GERMLINE is in concordance with other methods when they can process the data, and also facilitates analysis of larger scale studies. We bolster these results by demonstrating novel applications of precise analysis of hidden relatedness for (1) identification and resolution of phasing errors and (2) exposing polymorphic deletions that are otherwise challenging to detect. This finding is supported by concordance of detected deletions with other evidence from independent databases and statistical analyses of fluorescence intensity not used by GERMLINE.