Sequence Analysis and Characterization of Active Human Alu Subfamilies Based on the 1000 Genomes Pilot Project.
Sequence Analysis and Characterization of Active Human Alu Subfamilies Based on the 1000 Genomes Pilot Project.
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DOI：
10.1093/gbe/evv167
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发表时间：
2015-08-29
影响因子：
3.3
通讯作者：
Batzer MA
中科院分区：
文献类型：
--
作者：
Konkel MK;Walker JA;Hotard AB;Ranck MC;Fontenot CC;Storer J;Stewart C;Marth GT;1000 Genomes Consortium;Batzer MA
1000基因组联盟的目标是表征人类基因组结构变异（SV），包括拷贝数变异的形式，如缺失、重复和插入。移动元件插入，特别是Alu元件，是人类基因组SV的主要贡献者。在项目的试点阶段，我们通过实验验证了645个（611个基因间和34个外显子靶向）多态“年轻”Alu插入事件，这些事件在人类参考基因组中缺失。在这里，我们报告了343个（322个独特的）最近的Alu插入事件的高分辨率测序，以及它们各自的目标位点重复，精确的基因组断点坐标，亚家族分配，分歧百分比和估计的a -富尾长度。所有测序的Alu基因座均来自AluY谱系，未发现涉及较老Alu家族（如AluJ和AluS）的反转录转位活性证据。AluYa5是目前人类谱系中最活跃的Alu亚家族，其次是AluYb8，还有许多其他的亚家族，包括三个新发现的亚家族，我们将其命名为AluYb7a3， AluYb8b1和AluYa4a1。该报告提供了来自人类个体基因组的322个独特的Alu变异的结构细节，总共增加了大约100 kb的基因组变异。许多Alu亚家族目前在人群中活跃，包括令人惊讶的AluY反转位。人类Alu亚家族表现出持续的进化，潜在的驱动因素萌发了新的Alu谱系。
The goal of the 1000 Genomes Consortium is to characterize human genome structural variation (SV), including forms of copy number variations such as deletions, duplications, and insertions. Mobile element insertions, particularly Alu elements, are major contributors to genomic SV among humans. During the pilot phase of the project we experimentally validated 645 (611 intergenic and 34 exon targeted) polymorphic “young” Alu insertion events, absent from the human reference genome. Here, we report high resolution sequencing of 343 (322 unique) recent Alu insertion events, along with their respective target site duplications, precise genomic breakpoint coordinates, subfamily assignment, percent divergence, and estimated A-rich tail lengths. All the sequenced Alu loci were derived from the AluY lineage with no evidence of retrotransposition activity involving older Alu families (e.g., AluJ and AluS). AluYa5 is currently the most active Alu subfamily in the human lineage, followed by AluYb8, and many others including three newly identified subfamilies we have termed AluYb7a3, AluYb8b1, and AluYa4a1. This report provides the structural details of 322 unique Alu variants from individual human genomes collectively adding about 100 kb of genomic variation. Many Alu subfamilies are currently active in human populations, including a surprising level of AluY retrotransposition. Human Alu subfamilies exhibit continuous evolution with potential drivers sprouting new Alu lineages.