Extreme enrichment of VNTR-associated polymorphicity in human subtelomeres: genes with most VNTRs are predominantly expressed in the brain.
Extreme enrichment of VNTR-associated polymorphicity in human subtelomeres: genes with most VNTRs are predominantly expressed in the brain.
复制标题
DOI：
10.1038/s41398-020-01060-5
复制
发表时间：
2020-11-02
影响因子：
6.8
通讯作者：
Holstege H
中科院分区：
文献类型：
--
作者：
Linthorst J;Meert W;Hestand MS;Korlach J;Vermeesch JR;Reinders MJT;Holstege H
人类基因组含有许多结构变体（SV），由于它们的重复性质，目前在短读全基因组测序方法中探索不足。使用单分子实时（SMRT）长读段测序技术与EPCON-Unzip相结合，我们生成了一名115岁荷兰认知健康女性的二倍体基因组的从头组装。我们将该组件与先前发表的两个单倍体组件（CHM 1和CHM 13）和GRCh 38参考基因组相结合，使用基于图形的多基因组比对器REVEAL创建了五个独立人类单倍型中发生的SV的概要。在这五种单倍型中，我们检测到31，680个常染色质SV（>50 bp）。其中，约62%由具有“可变数目串联重复”（VNTR）的重复序列组成，约10%是移动的元件（Alu、L1和SVA），而其余变体是倒位和插入缺失。我们观察到GC含量>60%且重复模式长于15 bp的VNTR在亚端粒区域（染色体臂末端的5 Mb内）富集21倍。VNTR长度可以扩展到超过与受损基因转录相关的临界长度。包含大多数VNTR的基因，其中PTPRN 2和DLGAP 2是最突出的例子，被发现主要在大脑中表达，并与各种神经系统疾病相关。重复诱导的变异代表了人类基因组中相当大的一部分遗传变异，应该包括在与表型性状相关的遗传因素的研究中，特别是与神经系统疾病相关的遗传因素。我们提供了超级百岁老人基因组的长和短读段序列数据，以及在5种人类单倍型中鉴定的SV的概要。
The human genome harbors numerous structural variants (SVs) which, due to their repetitive nature, are currently underexplored in short-read whole-genome sequencing approaches. Using single-molecule, real-time (SMRT) long-read sequencing technology in combination with FALCON-Unzip, we generated a de novo assembly of the diploid genome of a 115-year-old Dutch cognitively healthy woman. We combined this assembly with two previously published haploid assemblies (CHM1 and CHM13) and the GRCh38 reference genome to create a compendium of SVs that occur across five independent human haplotypes using the graph-based multi-genome aligner REVEAL. Across these five haplotypes, we detected 31,680 euchromatic SVs (>50 bp). Of these, ~62% were comprised of repetitive sequences with ‘variable number tandem repeats’ (VNTRs), ~10% were mobile elements (Alu, L1, and SVA), while the remaining variants were inversions and indels. We observed that VNTRs with GC-content >60% and repeat patterns longer than 15 bp were 21-fold enriched in the subtelomeric regions (within 5 Mb of the ends of chromosome arms). VNTR lengths can expand to exceed a critical length which is associated with impaired gene transcription. The genes that contained most VNTRs, of which PTPRN2 and DLGAP2 are the most prominent examples, were found to be predominantly expressed in the brain and associated with a wide variety of neurological disorders. Repeat-induced variation represents a sizeable fraction of the genetic variation in human genomes and should be included in investigations of genetic factors associated with phenotypic traits, specifically those associated with neurological disorders. We make available the long and short-read sequence data of the supercentenarian genome, and a compendium of SVs as identified across 5 human haplotypes.
登录
查看更多内容
影响因子：
12.7
作者：
De Roeck A;Duchateau L;Van Dongen J;Cacace R;Bjerke M;Van den Bossche T;Cras P;Vandenberghe R;De Deyn PP;Engelborghs S;Van Broeckhoven C;Sleegers K;BELNEU Consortium
通讯作者：
BELNEU Consortium
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
4.2
作者：
den Dunnen, Wilfred F. A.;Brouwer, Wiebo H.;Holstege, Gert
通讯作者：
Holstege, Gert
影响因子：
48
作者：
Chin, Chen-Shan;Peluso, Paul;Schatz, Michael C.
通讯作者：
Schatz, Michael C.
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--