Structural variants exhibit widespread allelic heterogeneity and shape variation in complex traits
Structural variants exhibit widespread allelic heterogeneity and shape variation in complex traits
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DOI：
10.1038/s41467-019-12884-1
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发表时间：
2019-10-25
影响因子：
16.6
通讯作者：
Long, Anthony D.
中科院分区：
文献类型：
--
作者：
Chakraborty, Mahul;Emerson, J. J.;Long, Anthony D.
据推测，个体罕见的隐藏结构变异（SV）可以解释复杂性状变异的重要部分。在这里，我们从14个黑腹果蝇基因组组装中鉴定了超过20，000个常染色质SV，其中约40%是高特异性短读基因分型方法不可见的。SV是常见的，31.5%的二倍体个体在大于5kb的基因中携带一个SV，24%的二倍体个体在大于10kb的基因中携带多个SV。SV次要等位基因频率比氨基酸多态性更罕见，表明SV更有害。我们发现，一些功能重要的基因窝藏以前隐藏的结构变异可能会影响复杂的表型。此外，在与数量性状基因座相关的候选基因中，SV的比例过高。我们的结论是，SV是无处不在的，经常构成一个异质等位基因系列，并可以作为罕见的等位基因的大的影响。
It has been hypothesized that individually-rare hidden structural variants (SVs) could account for a significant fraction of variation in complex traits. Here we identified more than 20,000 euchromatic SVs from 14 Drosophila melanogaster genome assemblies, of which similar to 40% are invisible to high specificity short-read genotyping approaches. SVs are common, with 31.5% of diploid individuals harboring a SV in genes larger than 5kb, and 24% harboring multiple SVs in genes larger than 10kb. SV minor allele frequencies are rarer than amino acid poly-morphisms, suggesting that SVs are more deleterious. We show that a number of functionally important genes harbor previously hidden structural variants likely to affect complex phenotypes. Furthermore, SVs are overrepresented in candidate genes associated with quantitative trait loci mapped using the Drosophila Synthetic Population Resource. We conclude that SVs are ubiquitous, frequently constitute a heterogeneous allelic series, and can act as rare alleles of large effect.