Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses.
Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses.
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复发性流产中拷贝数变异和可能候选基因的表征
DOI：
10.3390/genes12020141
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发表时间：
2021-01-22
期刊：
影响因子：
3.5
通讯作者：
Zhu XY
中科院分区：
文献类型：
--
作者：
Sheng YR;Hou SY;Hu WT;Wei CY;Liu YK;Liu YY;Jiang L;Xiang JJ;Sun XX;Lei CX;Wang HL;Zhu XY
众所周知，胚胎染色体异常（染色体数量和结构）占早期妊娠损失的50%。然而，关于散发性流产（SA）和复发性流产（RPL）患者之间染色体异常的发生率和分布的潜在差异知之甚少，更不用说亚显微镜下拷贝数变异（CNVs）在这些情况下的作用了。本研究的目的是系统地评估胚胎染色体异常和CNVs在RPL病因学中的作用，并与SA进行比较。本研究采用单核苷酸多态性芯片（SNP-array）和CNV测序（CNV-seq）技术，对3年内1556例流产新鲜妊娠产物（POC）进行了研究，并进行了沿着功能富集分析。染色体异常率为57.52%（895/1556）。比较SA组和RPL组以及不同年龄组内染色体异常的发生率和分布。173例共检出346个CNVs，其中重复272个，缺失2个，重复伴缺失沿着72个。16q24.3和16p13.3的重复在RPL病例中明显更常见，因此被认为与RPL相关。有213个基因和131条信号通路分别被确定为潜在的RPL候选基因和信号通路，主要集中在6个功能类别。本研究的结果有助于提高我们对RPL病因的认识，并有助于建立一个基于人群的遗传标记诊断面板，用于筛查中国女性RPL。
It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.
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DOI：
10.1146/annurev-pathmechdis-012418-012743
发表时间：
2019-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
Deshmukh H;Way SS
通讯作者：
Way SS
影响因子：
1.3
作者：
Gao J;Liu C;Yao F;Hao N;Zhou J;Zhou Q;Zhang L;Liu X;Bian X;Liu J
通讯作者：
Liu J
影响因子：
4
作者：
Handrigan, Gregory Ryan;Chitayat, David;Rosenblum, Norman D.
通讯作者：
Rosenblum, Norman D.
影响因子：
--
作者：
Du, Yang;Zhu, Heng-cheng;Xiao, Cheng-cheng
通讯作者：
Xiao, Cheng-cheng
影响因子：
9.3
作者：
Jayasena, Channa N.;Radia, Utsav K.;Dhillo, Waljit S.
通讯作者：
Dhillo, Waljit S.