A genome-wide study of Hardy-Weinberg equilibrium with next generation sequence data.
A genome-wide study of Hardy-Weinberg equilibrium with next generation sequence data.
复制标题
DOI：
10.1007/s00439-017-1786-7
复制
发表时间：
2017-06
期刊：
影响因子：
5.3
通讯作者：
Weir B
中科院分区：
文献类型：
--
作者：
Graffelman J;Jain D;Weir B
Hardy-Weinberg平衡的统计检验在过去一直是检测基因分型错误的重要工具，并且在下一代序列数据的质量控制中仍然很重要。在本文中，我们使用常染色体和X染色体变异的精确测试程序来分析1000个基因组计划的完整染色体。我们发现，对于所有的染色体来说，不平衡的速度大大超过了可能仅凭偶然而预期的速度。在大约60%的病例中，观察到的不平衡是由于杂合子过量所致。我们认为，大多数过剩的不平衡可以通过测序问题来解释，以及可以解释异常杂合性的假设机制。我们报告了6号染色体上MHC区域、着丝粒两侧区域和端着丝粒染色体p臂的较高不平衡率。我们还检测到了远距离单倍型和附带高度不平衡的区域。我们报告不平衡与阅读深度有关，具有极端阅读深度的变体更有可能失去平衡。在节段性复制和简单串联重复区域，不平衡率高出11倍。具有显著不平衡的变异被认为集中在这些区域。对于下一代序列数据，Hardy-Weinberg不平衡似乎是拷贝数变异的一个主要指标。本文的在线版本(doi：10.1007/s00439-0171786-7)包含补充材料，授权用户可以使用。
Statistical tests for Hardy–Weinberg equilibrium have been an important tool for detecting genotyping errors in the past, and remain important in the quality control of next generation sequence data. In this paper, we analyze complete chromosomes of the 1000 genomes project by using exact test procedures for autosomal and X-chromosomal variants. We find that the rate of disequilibrium largely exceeds what might be expected by chance alone for all chromosomes. Observed disequilibrium is, in about 60% of the cases, due to heterozygote excess. We suggest that most excess disequilibrium can be explained by sequencing problems, and hypothesize mechanisms that can explain exceptional heterozygosities. We report higher rates of disequilibrium for the MHC region on chromosome 6, regions flanking centromeres and p-arms of acrocentric chromosomes. We also detected long-range haplotypes and areas with incidental high disequilibrium. We report disequilibrium to be related to read depth, with variants having extreme read depths being more likely to be out of equilibrium. Disequilibrium rates were found to be 11 times higher in segmental duplications and simple tandem repeat regions. The variants with significant disequilibrium are seen to be concentrated in these areas. For next generation sequence data, Hardy–Weinberg disequilibrium seems to be a major indicator for copy number variation. The online version of this article (doi:10.1007/s00439-017-1786-7) contains supplementary material, which is available to authorized users.