单细胞DNA测序揭示了人类胚胎囊中染色体异常的高发病率
Effrosyni A Chavli1, Sjoerd J Klaasen2,3, Diane Van Opstal4
1Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
The Journal of clinical investigation
|January 4, 2024
概括
染色体马赛克在人类胚胎中很常见,即使是那些看起来正常的胚胎. 先进的单细胞测序揭示了当前植入前遗传检测方法忽略的广泛异常.
科学领域:
- 生殖生物学 生殖生物学
- 遗传学 是一个遗传学.
- 胚胎学 胚胎学
背景情况:
- 状体,一个偏离正常的染色体数,导致早期怀孕损失.
- 染色体马赛克主义,即胚胎内存在多种不同类型的核型,源于线粒错误.
- 目前用于植入前遗传测试的大量DNA测序方法对马赛克的检测值有限.
研究的目的:
- 通过单细胞全基因组测序,准确评估人类胚胎细胞中的染色体马赛克.
- 为了比较单细胞测序与大量DNA测序的灵敏度,以检测马赛克主义.
主要方法:
- 从55个多余的胚胎囊中分离出托菲克托皮 (TE) 和内细胞质 (ICM).
- 应用单细胞全基因组测序 (scKaryo-Seq) 在1057个单细胞上.
- 在单细胞水平上对数值和结构染色体异常的分析.
主要成果:
- 在82%的优质胚胎囊中检测到马赛克主义.
- 大多数检测到的异常影响胚胎内不到20%的细胞.
- 在69%的胚胎中发现了结构异常,可能与复制压力有关.
- 大量DNA测序可能会将这些胚胎错误地归类为正常.
结论:
- 染色体马赛克主义在人类胚芽细胞中非常普遍.
- 与当前的临床方法相比,单细胞测序为检测马赛克主义提供了更高的灵敏度.
- 马赛克主义的高患病率挑战了目前用于体积的植入前遗传检测协议.
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