Identification of chromosomal abnormalities in miscarriages by CNV-Seq.

IF 1.3 4区生物学 Q4 GENETICS & HEREDITY

Molecular Cytogenetics Pub Date : 2024-02-18 DOI:10.1186/s13039-024-00671-7

Yuqi Shao, Saisai Yang, Lin Cheng, Jie Duan, Jin Li, Jiawei Kang, Fang Wang, Juan Liu, Fang Zheng, Jianhong Ma, Yuanzhen Zhang

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引用次数: 0

Abstract

Objective: The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies.

Methods: This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs).

Results: Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein-protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages.

Conclusion: Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.

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通过 CNV-Seq 鉴定流产中的染色体异常。

研究目的本研究的主要目的是分析通过拷贝数变异测序（CNV-Seq）检测到的流产中的染色体异常，确定与流产相关的潜在途径或基因，并为后续妊娠的生育健康提供指导：本研究共纳入 580 例流产病例，通过 CNV-Seq 分析其配对的临床信息和染色体检测结果。结果：在 580 例流产病例中，有 3 例病例的染色体检测结果与临床信息不符：在 580 例流产病例中，有 3 例因母体细胞污染而被排除，357 例染色体结果显示异常，其余 220 例正常，阳性检出率为 61.87%（357/577）。在 357 个流产病例中，发现了 470 个变异，其中 65.32%（307/470）为致病变异。在所有发现的变异中，251 个为染色体数目异常，219 个为结构异常。随着孕妇年龄的增长，数字异常的比例增加，但结构异常的比例下降。京都基因和基因组百科全书》的通路和基因本体分析显示，pCNVs 区域基因富集了 11 条通路和 636 个生物过程。对226个剂量敏感基因进行的蛋白-蛋白相互作用分析表明，TP53、CTNNB1、UBE3A、EP300、SOX2、ATM和MECP2可能对流产的发生有重要影响：结论：我们的研究提供了染色体异常导致流产的证据，并强调了微缺失或重复在导致流产方面的重要性。在 pCNVs 区域发现的重要基因可能是导致流产的原因，这需要进一步验证。

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.