Nantong Municipal Maternal and Child Health Hospital, Nantong 226010, China.
Shanghai Qianbei Medical Technology Co., Ltd., Shanghai 201612, China.
Comb Chem High Throughput Screen. 2022;25(9):1462-1473. doi: 10.2174/1386207324666210628115715.
Spontaneous abortion is a common disease in obstetrics and reproduction.
This study aimed to screen candidate pathogenic genes for spontaneous abortion using whole-exome sequencing.
Genomic DNA was extracted from abortion tissues of spontaneous abortion patients and sequenced using the Illumina HiSeq2500 high-throughput sequencing platform. Whole exome sequencing was performed to select harmful mutations, including SNP and insertion and deletion sites, associated with spontaneous abortion. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and gene fusion analyses were performed. MUC3A and PDE4DIP were two novel mutation genes that were screened and verified by PCR in abortion tissues of patients.
A total of 83,633 SNPs and 13,635 Indel mutations were detected, of which 29172 SNPs and 3093 Indels were screened as harmful mutations. The 7 GO-BP, 4 GO-CC, 9 GO-MF progress, and 3 KEGG pathways were enriched in GO and KEGG pathway analyses. A total of 746 gene fusion mutations were obtained, involving 492 genes. MUC3A and PDE4DIP were used for PCR verification because of their high number of mutation sites in all samples.
There are extensive SNPs and Indel mutations in the genome of spontaneous abortion tissues, and the effect of these gene mutations on spontaneous abortion needs further experimental verification.
自然流产是妇产科常见的疾病。
本研究旨在通过全外显子组测序筛选自然流产的候选致病基因。
从自然流产患者的流产组织中提取基因组 DNA，使用 Illumina HiSeq2500 高通量测序平台进行测序。进行全外显子组测序以选择与自然流产相关的有害突变，包括 SNP 和插入缺失位点。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析和基因融合分析。筛选并通过 PCR 在患者流产组织中验证 MUC3A 和 PDE4DIP 这两个新的突变基因。
共检测到 83633 个 SNPs 和 13635 个 Indel 突变，其中 29172 个 SNPs 和 3093 个 Indels 被筛选为有害突变。GO 和 KEGG 通路富集分析中，有 7 个 GO-BP、4 个 GO-CC、9 个 GO-MF 进程和 3 个 KEGG 通路被富集。共获得 746 个基因融合突变，涉及 492 个基因。由于所有样本中突变位点数量较多，因此选择 MUC3A 和 PDE4DIP 进行 PCR 验证。
自然流产组织的基因组中存在广泛的 SNPs 和 Indel 突变，这些基因突变对自然流产的影响需要进一步的实验验证。
