标题：CNV-seq在流产物遗传学检测中的应用及相关基因的富集分析

      作者：李金玲 1，贾若 1，刘东东 2，柳爱华 1，李妍 3    1.沈阳市妇幼保健院遗传科，辽宁 沈阳 110000；2.北部战区总医院检验科，辽宁 沈阳 110016；3.沈阳市妇幼保健院产科，辽宁 沈阳 110000

      卷次： 2024年35卷4期

      【摘要】 目的 探讨基于二代测序的染色体拷贝数变异技术(CNV-seq)在流产物染色体异常检测中的应用效果和临床意义未明的CNVs变异在流产物病因中的作用。方法 选取2020年1月至2022年12月在沈阳市妇幼保健院因胚胎停育或自然流产，自愿行流产物分析的患者 178例，对绒毛或皮肤组织进行DNA提取和CNV-seq检测。对临床意义未明的CNVs变异涉及的基因进行富集分析。结果 178例流产物样本中，致病性CNVs 93例(93/178，52.25%)，其中染色体数目异常占46.63%，结构异常占5.62%。不同年龄段患者的致病性CNV与非致病性CNV差异有统计学意义(P=0.046)。染色体数目异常中45,X (16.87%)、69,XNN (12.05%)和 47,XN,+16 (12.05%)的发病率位列前三位，双重三体7例，三重三体1例，结构异常中共检出综合征10例。KEGG显著富集的是Pantothe-nate and CoA biosynthesis (P=0.001)，GO显著富集的是MHC class I protein binding I (GO: 0042288，P=9.04E-05)。结论 半数以上流产是由染色体异常引起的，CNV-seq利于发现罕见的综合征。对临床意义未明的CNVs涉及的基因进行富集可为寻找流产物标记基因提供新的思路。
      【关键词】 全基因组测序；拷贝数变异；流产物；富集分析
      【中图分类号】 R394 【文献标识码】 A 【文章编号】 1003—6350（2024）04—0537—05

Application of CNV-seq in genetic detection of abortive tissues and enrichment analysis of related genes.
LIJin-ling 1, JIA Ruo 1, LIU Dong-dong 2, LIU Ai-hua 1, LI Yan 3. 1. Department of Genetics, Shenyang Maternity and ChildHealth Hospital, Shenyang 110000, Liaoning, CHINA; 2. Department of Laboratory Medicine, General Hospital of NorthernTheater Command, Shenyang 110016, Liaoning, CHINA; 3. Department of Obstetrics, Shenyang Maternity and Child HealthHospital, Shenyang 110000, Liaoning, CHINA
【Abstract】 Objective To investigate the clinical application of copy number variation sequencing (CNV-seq)technology in the chromosome abnormality of abortive tissues in women with spontaneous abortion and the role of thevariant of uncertain significance (VOUS) of CNVs in the etiology of spontaneous abortion. Methods A total of 178 pa-tients who voluntarily underwent miscarriage analysis due to embryonic arrest or spontaneous abortion were selectedat Shenyang Maternal and Child Health Hospital from January 2020 to December 2022. The villus tissues or skin tis-sues were subjected to DNA extraction and CNV-seq. Enrichment analysis of genes involved in VOUS of CNVs wasperformed for the functional categories. Results Among the 178 samples, 93 (93/178, 52.25% ) were pathogenicCNVs, with 46.63% of chromosomal numerical abnormalities and 5.62% of structural abnormalities. There were sta-tistically significant differences in the pathogenic and non-pathogenic CNVs among different age groups (P=0.046).In chromosomal numerical abnormalities, 45,X (16.87%), 69,XNN (12.05%), and 47,XN,+16 (12.05%) were the mostfrequently, with 7 cases of double trisomy and 1 case of triple trisomy. In structural abnormalities, 10 cases of syn-drome were detected. KEGG showed that the most significant pathway was Pantothenate and CoA biosynthesis (P=0.001), and GO revealed that the most significant enrichment was MHC class I protein binding I (GO: 0042288, P=9.04E-05). Conclusion More than half of spontaneous abortion were attributable to chromosome abnormality, andCNV-seq is more conducive to the detection of rare syndromes. Enrichment of genes involved in VOUS of CNVs canprovide new ideas for searching for abortion marker genes.
      【Key words】 Whole genome sequencing; Copy number variations; Abortive tissues; Enrichment analysis