Structural variation, selection, and diversification of the NPIP gene family from the human pangenome.

IF 11.1 Q1 CELL BIOLOGY
Philip C Dishuck, Katherine M Munson, Alexandra P Lewis, Max L Dougherty, Jason G Underwood, William T Harvey, PingHsun Hsieh, Tomi Pastinen, Evan E Eichler
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引用次数: 0

Abstract

The NPIP gene family is among the most positively selected gene families in humans/apes and drives independent duplication in primate lineages. These duplications promote genetic instability, leading to recurrent disease-associated microduplication and microdeletion syndromes. Despite its importance, little is known about its function or variation in humans, as short-read sequencing cannot distinguish high-identity duplications. Using long-read assemblies of 169 human haplotypes, we find extreme variation in the content and organization of NPIP loci. We identify fixed and polymorphic paralogs and observe ongoing positive selection. With long-read RNA sequencing (RNA-seq), we create paralog-specific gene models, the majority of which were not previously documented, and observe paralog-specific tissue specificity. This analysis of an exceptionally dynamic gene family provides candidates for future functional study.

人类泛基因组NPIP基因家族的结构变异、选择和多样化。
NPIP基因家族是人类/类人猿中最积极选择的基因家族之一,并在灵长类谱系中驱动独立复制。这些重复促进遗传不稳定,导致复发性疾病相关的微重复和微缺失综合征。尽管它很重要,但人们对它在人类中的功能或变异知之甚少,因为短读测序无法区分高身份的重复。利用169个人类单倍型的长读序列,我们发现NPIP位点的内容和组织存在极大的差异。我们确定固定的和多态的类似物,并观察持续的积极选择。通过长读RNA测序(RNA-seq),我们创建了旁系特异性基因模型,其中大多数以前没有记录过,并观察了旁系特异性组织特异性。这种异常动态基因家族的分析为未来的功能研究提供了候选基因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
7.10
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