高通量基因测序技术在自然流产胎儿绒毛染色体的核型分析

目的 探讨自然妊娠与辅助生殖助孕(ART)流产组织胎儿绒毛染色体异常情况.方法 采用高通量测序技术对364例流产组织进行染色体核型分析,并根据染色体非显带核型对三体核型进行分组,将其分为A、B、C、D、E、F、G 7组.结果 ①绒毛染色体总异常发生率为48. 90％(178/ 364),自然妊娠组绒毛染色体异常发生率显著高于ART组(52. 85％ vs 40. 68％)(P=0. 033);异常核型以三体型最多见,占65. 17％ ,染色体微缺失/微重复次之,占15. 73％ ;② ART组<35岁与≥35岁胚停组织绒毛染色体异常发生率差异无统计学意义,自然妊娠组两者间差异有统计学意义(P=0.005);③流产组织中女性胚胎异常核型占总异常核型的46. 89％,男性胚胎占53. 11％,两者差异有统计学意义(P=0.007);④ART组以复发性流产最常见,占60. 00％;⑤自然流产组织中胚胎异常核型主要分布于E组和G组,男胚A组异常核型显著多于女胚(P=0.007).结论 高通量测序在自然流产绒毛组织染色体核型分析中有较高的应用价值,有助于判断早期流产的遗传学病因,为再次妊娠遗传学咨询提供服务.

Application of next-generation sequencing technique in chromosome karyotype analysis of spontaneous abortion villi

Objective To investigate the occurrence of chromosomal abnormalities in spontaneous abortion villi derived from both natural pregnancy (NP) and assisted reproductive technology (ART). Methods Chromosome karyotype analysis of fetal villi were carried out in 364 cases of abortion women through high-throughput sequencing technology, and the trisomy was grouped into A, B, C, D, E, F, G seven groups according to the karyotype of nonbanding chromosome. Results ① Of the 364 cases, abnormal karyotypes were identified in 178 cases (48. 90％ ), and the incidence of chromosomal abnormalities in NP group was significantly higher than ART group (52. 85％ vs 40. 68％ ) (P =0. 033). Moreover, trisomy was the most frequent abnormal karyotype (65. 17％ ), followed by the copy number variation (15. 73％ );② There was no significant difference in incidences of chromosomal abnormality between <35 years and ≥35 years in ART group, while which showed significant difference in NC group (P =0. 005);③ There were significant difference in incidence of chromosomal abnormality between female embryos and male embryos (46. 89％ vs 53. 11％, P=0. 007);④ Recurrent spontaneous abortion was the most common cause of infertility in ART group, and the incidence of villi chromosomal abnormality was up to 60. 00％;⑤ Chromosomal abnormalities in both female and male embryos were mainly distributed in group E and group G, while chromosomal abnormality of A group in male embryos were significantly more than female (P =0. 007). Conclusion Numerical abnormalities of chromosomes are the most important cause of early spontaneous abortion, and karyotype analysis of the villus is helpful for identifying the cause of abortion and could provide some valuable information for genetic counselling of next pregnancy.