Analysis of copy number variants detected by sequencing in spontaneous abortion.

IF 1.3 4区生物学 Q4 GENETICS & HEREDITY Molecular Cytogenetics Pub Date : 2024-05-20 DOI:10.1186/s13039-024-00683-3

Anhui Liu, Liyuan Zhou, Yazhou Huang, Dan Peng

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Abstract

Background: The incidence of spontaneous abortion (SA), which affects approximately 15-20% of pregnancies, is the most common complication of early pregnancy. Pathogenic copy number variations (CNVs) are recognized as potential genetic causes of SA. However, CNVs of variants of uncertain significance (VOUS) have been identified in products of conceptions (POCs), and their correlation with SA remains uncertain.

Results: Of 189 spontaneous abortion cases, trisomy 16 was the most common numerical chromosome abnormality, followed by monosomy X. CNVs most often occurred on chromosomes 4 and 8. Gene Ontology and signaling pathway analysis revealed significant enrichment of genes related to nervous system development, transmembrane transport, cell adhesion, and structural components of chromatin. Furthermore, genes within the VOUS CNVs were screened by integrating human placental expression profiles, PhyloP scores, and Residual Variance Intolerance Score (RVIS) percentiles to identify potential candidate genes associated with spontaneous abortion. Fourteen potential candidate genes (LZTR1, TSHZ1, AMIGO2, H1-4, H2BC4, H2AC7, H3C8, H4C3, H3C6, PHKG2, PRR14, RNF40, SRCAP, ZNF629) were identified. Variations in LZTR1, TSHZ1, and H4C3 may contribute to embryonic lethality.

Conclusions: CNV sequencing (CNV-seq) analysis is an effective technique for detecting chromosomal abnormalities in POCs and identifying potential candidate genes for SA.

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通过测序分析自然流产中检测到的拷贝数变异。

背景：自然流产（SA）的发生率约占妊娠的 15-20%，是妊娠早期最常见的并发症。致病性拷贝数变异（CNV）被认为是导致自然流产的潜在遗传原因。然而，在受孕产物（POC）中也发现了意义不明的变异（VOUS），但它们与 SA 的相关性仍不确定：结果：在189例自然流产病例中，16三体综合征是最常见的染色体数目异常，其次是X单体综合征。基因本体和信号通路分析表明，与神经系统发育、跨膜运输、细胞粘附和染色质结构成分有关的基因明显增多。此外，通过整合人类胎盘表达谱、PhyloP评分和残差不耐受评分（RVIS）百分位数，对VOUS CNVs中的基因进行了筛选，以确定与自然流产相关的潜在候选基因。结果发现了 14 个潜在候选基因（LZTR1、TSHZ1、AMIGO2、H1-4、H2BC4、H2AC7、H3C8、H4C3、H3C6、PHKG2、PRR14、RNF40、SRCAP、ZNF629）。LZTR1、TSHZ1和H4C3的变异可能会导致胚胎死亡：结论：CNV 测序（CNV-seq）分析是检测 POCs 染色体异常和鉴定 SA 潜在候选基因的有效技术。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cytogenetics GENETICS & HEREDITY-

CiteScore

2.60

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Cytogenetics encompasses all aspects of chromosome biology and the application of molecular cytogenetic techniques in all areas of biology and medicine, including structural and functional organization of the chromosome and nucleus, genome variation, expression and evolution, chromosome abnormalities and genomic variations in medical genetics and tumor genetics. Molecular Cytogenetics primarily defines a large set of the techniques that operate either with the entire genome or with specific targeted DNA sequences. Topical areas include, but are not limited to: -Structural and functional organization of chromosome and nucleus- Genome variation, expression and evolution- Animal and plant molecular cytogenetics and genomics- Chromosome abnormalities and genomic variations in clinical genetics- Applications in preimplantation, pre- and post-natal diagnosis- Applications in the central nervous system, cancer and haematology research- Previously unreported applications of molecular cytogenetic techniques- Development of new techniques or significant enhancements to established techniques. This journal is a source for numerous scientists all over the world, who wish to improve or introduce molecular cytogenetic techniques into their practice.