Alpha Satellite Insertion Close to an Ancestral Centromeric Region.
Alpha Satellite Insertion Close to an Ancestral Centromeric Region.
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DOI：
10.1093/molbev/msab244
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发表时间：
2021-12-09
影响因子：
10.7
通讯作者：
Reymond A
中科院分区：
文献类型：
--
作者：
Giannuzzi G;Logsdon GA;Chatron N;Miller DE;Reversat J;Munson KM;Hoekzema K;Bonnet-Dupeyron MN;Rollat-Farnier PA;Baker CA;Sanlaville D;Eichler EE;Schluth-Bolard C;Reymond A
人类着丝粒主要由α卫星DNA组成，按等级组织为高阶重复序列（HORs）。α卫星动力学表现为着丝粒阵列中的序列均质化及其转移到其他着丝粒位置，例如，在新着丝粒成熟期间。我们发现在产前非整倍体诊断荧光原位杂交从头插入α卫星DNA从着丝粒染色体18（D18 Z1）到细胞带15 q26。尽管被CENP-B结合，但该位点没有获得着丝粒功能，如缺乏收缩和缺乏CENP-A结合所证明的。插入与2.8 kbp缺失相关，可能发生在父系生殖系中。该位点富含长末端重复序列，距离2000 - 2500万年前人类和猿的共同祖先中着丝粒祖先播种并变得不活跃的位置约10 Mbp。T2 T-CHM 13人类基因组组装的长读段作图揭示了插入来自染色体18着丝粒12-mer HOR阵列的特定区域，其中单体大小遵循规则模式。重排没有直接破坏任何基因或预测的调控元件，也没有改变周围区域的甲基化状态，这与载体中不存在表型结果一致。这种情况表明，一种可能罕见但新的结构变异，我们称之为“阿尔法卫星插入”。它也扩大了我们的知识alphoid DNA动力学和传达的可能性，alphoid阵列可以重新定位附近的退化着丝粒位点。
Human centromeres are mainly composed of alpha satellite DNA hierarchically organized as higher-order repeats (HORs). Alpha satellite dynamics is shown by sequence homogenization in centromeric arrays and by its transfer to other centromeric locations, for example, during the maturation of new centromeres. We identified during prenatal aneuploidy diagnosis by fluorescent in situ hybridization a de novo insertion of alpha satellite DNA from the centromere of chromosome 18 (D18Z1) into cytoband 15q26. Although bound by CENP-B, this locus did not acquire centromeric functionality as demonstrated by the lack of constriction and the absence of CENP-A binding. The insertion was associated with a 2.8-kbp deletion and likely occurred in the paternal germline. The site was enriched in long terminal repeats and located ∼10 Mbp from the location where a centromere was ancestrally seeded and became inactive in the common ancestor of humans and apes 20–25 million years ago. Long-read mapping to the T2T-CHM13 human genome assembly revealed that the insertion derives from a specific region of chromosome 18 centromeric 12-mer HOR array in which the monomer size follows a regular pattern. The rearrangement did not directly disrupt any gene or predicted regulatory element and did not alter the methylation status of the surrounding region, consistent with the absence of phenotypic consequences in the carrier. This case demonstrates a likely rare but new class of structural variation that we name “alpha satellite insertion.” It also expands our knowledge on alphoid DNA dynamics and conveys the possibility that alphoid arrays can relocate near vestigial centromeric sites.
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影响因子：
48
作者：
Cheng H;Concepcion GT;Feng X;Zhang H;Li H
通讯作者：
Li H
影响因子：
4.4
作者：
ALEXANDROV, IA;MASHKOVA, TD;YUROV, YB
通讯作者：
YUROV, YB
影响因子：
10.7
作者：
Cellamare，A.;Catacchio，C. R.;Ventura，M.
通讯作者：
Ventura，M.
影响因子：
12.3
作者：
Cantsilieris, Stuart;Sunkin, Susan M.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
5.8
作者：
Li, Heng
通讯作者：
Li, Heng