Identification of chromosomal abnormalities in miscarriages by CNV-Seq
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. Method...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Molecular Cytogenetics |
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| Online Access: | https://doi.org/10.1186/s13039-024-00671-7 |
| _version_ | 1797273105778868224 |
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| author | Yuqi Shao Saisai Yang Lin Cheng Jie Duan Jin Li Jiawei Kang Fang Wang Juan Liu Fang Zheng Jianhong Ma Yuanzhen Zhang |
| author_facet | Yuqi Shao Saisai Yang Lin Cheng Jie Duan Jin Li Jiawei Kang Fang Wang Juan Liu Fang Zheng Jianhong Ma Yuanzhen Zhang |
| author_sort | Yuqi Shao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:38:50Z |
| format | Article |
| id | doaj.art-72384a310523490db2d181319683c33a |
| institution | Directory Open Access Journal |
| issn | 1755-8166 |
| language | English |
| last_indexed | 2024-03-07T14:38:50Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cytogenetics |
| spelling | doaj.art-72384a310523490db2d181319683c33a2024-03-05T20:27:22ZengBMCMolecular Cytogenetics1755-81662024-02-0117111010.1186/s13039-024-00671-7Identification of chromosomal abnormalities in miscarriages by CNV-SeqYuqi Shao0Saisai Yang1Lin Cheng2Jie Duan3Jin Li4Jiawei Kang5Fang Wang6Juan Liu7Fang Zheng8Jianhong Ma9Yuanzhen Zhang10Department of Obstetrics, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics, Zhongnan Hospital of Wuhan UniversityHubei Clinical Research Center for Prenatal Diagnosis and Birth HealthDepartment of Obstetrics, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics, Zhongnan Hospital of Wuhan UniversityHubei Clinical Research Center for Prenatal Diagnosis and Birth HealthDepartment of Obstetrics, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics, Zhongnan Hospital of Wuhan UniversityAbstract 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.https://doi.org/10.1186/s13039-024-00671-7Chromosomal abnormalitiesCopy number variantsMiscarriageCNV-Seq |
| spellingShingle | Yuqi Shao Saisai Yang Lin Cheng Jie Duan Jin Li Jiawei Kang Fang Wang Juan Liu Fang Zheng Jianhong Ma Yuanzhen Zhang Identification of chromosomal abnormalities in miscarriages by CNV-Seq Molecular Cytogenetics Chromosomal abnormalities Copy number variants Miscarriage CNV-Seq |
| title | Identification of chromosomal abnormalities in miscarriages by CNV-Seq |
| title_full | Identification of chromosomal abnormalities in miscarriages by CNV-Seq |
| title_fullStr | Identification of chromosomal abnormalities in miscarriages by CNV-Seq |
| title_full_unstemmed | Identification of chromosomal abnormalities in miscarriages by CNV-Seq |
| title_short | Identification of chromosomal abnormalities in miscarriages by CNV-Seq |
| title_sort | identification of chromosomal abnormalities in miscarriages by cnv seq |
| topic | Chromosomal abnormalities Copy number variants Miscarriage CNV-Seq |
| url | https://doi.org/10.1186/s13039-024-00671-7 |
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