Insertionally polymorphic sites of human endogenous retrovirus-K (HML-2) with long target site duplications.
Insertionally polymorphic sites of human endogenous retrovirus-K (HML-2) with long target site duplications.
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DOI：
10.1186/s12864-017-3872-6
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发表时间：
2017-06-27
期刊：
影响因子：
4.4
通讯作者：
Sugimura H
中科院分区：
文献类型：
--
作者：
Kahyo T;Yamada H;Tao H;Kurabe N;Sugimura H
人内源性逆转录病毒（HERV）属于LTR-逆转录转座子家族，其中完整的HERV序列包含位于每个末端的两个长末端重复序列（LTR）。完整的LTR具有高度保守的转录启动子和增强子序列，因此与传统的单核苷酸变异分析相比，HERV插入多态性分析有望为人类基因组变异提供更深入的见解。高通量测序技术正在发展，但HERV的全基因组研究在方法上具有挑战性，因此对HERV插入多态性和靶位点重复（TSD）的全面理解仍然是难以捉摸的。我们确定了5个人类特异性插入多态性位点的HERVK（HML-2），HERV亚组之一，通过提取HML-2缺失序列的基因组结构变异数据库，我们成功地表征，然后更新现有的目录HML-2插入多态性。在一个小的日本人口的基因组PCR分析确定的5个位点中的4个的插入多态性状态得到证实。对整合前位点的测序清楚地表明，位于7p21.2的HML-2位点具有250个碱基对（bp）的TSD，这是HML-2中最长的TSD之一。除了这5个位点外，还在6p25.2处鉴定了另一个非人特异性HML-2位点的插入多态性位点，其侧翼为111 bp的TSD，并且相应的ERV基因座也在非人灵长类动物的基因组中被注释。我们的分析表明存在HERV插入侧翼的非常规长TSD，包括那些长度高达250 bp。这表明逆转录病毒TSD的长度范围比以前考虑的要大，这可能有助于理解逆转录病毒整合如何在宿主基因组中发生。本文的在线版本（doi：10.1186/s12864-017-3872-6）包含补充材料，可供授权用户使用。
Human endogenous retroviruses (HERVs) belong to the LTR-retrotransposon family, where the complete HERV sequence contains two long terminal repeats (LTRs) located at each end. Intact LTRs possess highly conserved transcriptional promoter and enhancer sequences, so analyses of HERV insertional polymorphisms are expected to provide greater insights into human genomic variation compared with the conventional analysis of single nucleotide variations. High-throughput sequencing technology is developing but genome-wide investigations of HERVs are methodically challenging, and thus a comprehensive understanding of HERV insertional polymorphisms and target site duplications (TSDs) remains elusive. We identified five human-specific insertionally polymorphic sites in HERVK (HML-2), one of the HERV subgroups, by extracting HML-2-deleted sequences from the genomic structural variation database, which we successfully characterized and then updated the existing catalogue of HML-2 insertional polymorphisms. The insertionally polymorphic states were confirmed in a small Japanese population by genomic PCR analysis for four of the five sites identified. Sequencing of the preintegration sites clearly showed that the HML-2 site located at 7p21.2 had 250-base pair (bp) TSDs, which is one of the longest TSDs in HML-2. In addition to these five sites, another insertionally polymorphic site for a non-human-specific HML-2 site was also identified at 6p25.2, which was flanked by 111-bp TSDs and the corresponding ERV locus was also annotated in the genome of non-human primates. Our analysis demonstrated the existence of HERV insertions flanked by unconventionally long TSDs, including those with lengths as high as 250 bp. This suggests that the length range of retroviral TSDs is larger than considered previously, which might help to understand how retroviral integration occurs in the host genome. The online version of this article (doi:10.1186/s12864-017-3872-6) contains supplementary material, which is available to authorized users.