染色体易位携带者的胚胎基因组拷贝数变异分析

Embryonic genome copy number variation analysis of chromosomaltranslocation carriers

目的探讨染色体易位对胚胎染色体组成的影响,分析平衡易位携带者胚胎染色体减数分裂的分离特点。方法研究纳入柳州市妇幼保健院2018年1月至2019年11月在本中心进行第三代辅助生殖患者,共收集140个PGT-SR周期病例,其中相互易位96个周期,罗氏易位44个周期。通过二代测序平台分析胚胎植入前遗传学检测周期中染色体易位携带者胚胎拷贝数变异情况,比较不同携带者性别、不同易位及染色体类型及不同断裂点位置下胚胎染色体的非整倍体情况及分离特点。结果相互易位携带者胚胎染色体异常率(81.8%)明显高于罗氏易位携带者(65.7%),差异有统计学意义(χ^(2)=29.300,P<0.001),在相互易位和罗氏易位携带者中,女方携带者胚胎染色体异常比率分别为85.7%和84.7%,均高于男方携带者(78.9%和58.1%),且差异有统计学意义(P<0.05)。在胚胎异常染色体来源的分析中,相互易位携带者胚胎产生亲缘易位异常染色体比例(32.9%)明显高于罗氏易位携带者(17.1%),差异有统计学意义(χ^(2)=17.082,P<0.001),而罗氏易位携带者比相互易位更容易产生非亲缘易位的染色体异常(50.8%VS 27.1%,χ^(2)=34.917,P<0.001)。在相互易位和罗氏易位中,男方易位携带者胚胎非亲缘易位的染色体异常(33.0%和59.8%)均明显高于女方携带者(20.0%和35.2%)。女方易位携带者更易发生2∶2邻近-2和3∶1分离,相互易位携带者中,有近端着丝粒染色体参与的携带者,其胚胎发生3∶1分离的概率要高于非近端着丝粒参与组,而断裂点是否位于染色体末端,胚胎的异常率则均差异无统计学意义。结论胚胎染色体的组成与易位类型及携带者性别相关,近端着丝粒染色体和断裂点位置与配子分离方式相关,但不影响胚胎整倍体的比例。

Objective To explore the influence factors of chromosome translocation on embryo chromosome composition,and analyze the separation characteristics of meiosis in balanced translocation carriers.Methods The study included patients who underwent third-generation assisted reproduction in our center in Liuzhou Maternity&Child Healthcare Hospital from January 2018 to November 2019.A total of 140 PGT-SR cycles were collected,including 96 cycles of mutual translocation and 44 cycles of Roche translocation.The embryo copy number variation of chromosomal translocation carriers in the preimplantation genetic testing cycle was analyzed by next-generation sequencing platform.The aneuploidy and segregation characteristics of embryonic chromosomes under different carrier genders,different translocations and chromosome types,and different breakpoint positions were compared.Results The chromosomal abnormality rate in the carriers of reciprocal(81.8%)was significantly higher than Robertsonian(65.7%),and the difference was statistically significant(χ^(2)=29.300,P<0.001).Compared with male carriers,there was an increase in the rate of abnormalities of female carriers(85.7%vs 78.9%for reciprocal translocations,and 84.7%vs 58.1%for Robertsonian translocations),and the difference was statistically significant(P<0.05).The proportion of embryos with translocation-related abnormality of reciprocal carriers(32.9%)was significantly higher than Robertsonian translocations carriers(17.1%,χ^(2)=17.082,P<0.001).Roche translocation carriers were more likely to have unrelated translocation chromosomal abnormalities than reciprocal translocations(50.8%vs 27.1%,χ^(2)=34.917,P<0.001).In reciprocal translocation and Roche translocation,the chromosomal abnormalities of unrelated translocation embryos in male translocation carriers(33.0%and 59.8%)were significantly higher than those in female carriers(20.0%and 35.2%).Female translocation carriers are more prone to 2∶2 adjacent-2 and 3∶1 segregation.Among the reciprocal translocation carriers,carriers with acrocentric chromosomes are more likely to have 3∶1 segregation in embryos.There was no significant difference in the abnormal rate of embryos in the non-acrocentric participation group,and whether the breakpoint was located at the end of the chromosome.Conclusion The types of parental translocation and gender of carrier have certain effect on the composition of embryonic chromosomes.The presence of acrocentric chromosomes and terminal breakpoints were related to the segregation modes in blastocysts,but not the proportion of embryo euploidy.