全基因组检测自闭症中扩展的双重DNA重复
Brett Trost1,2, Worrawat Engchuan1,2, Charlotte M Nguyen1,2,3
1Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Nature
|July 28, 2020
概括
双重DNA重复扩展在自闭症谱系障碍 (ASD) 中很常见,有助于其遗传原因和复杂性. 这些扩展与神经和发育基因有关, 影响认知能力.
科学领域:
- 基因组学与遗传学
- 神经发育障碍
- 人类遗传学
背景情况:
- 双重DNA重复,当扩展时,已知是40多种单一性疾病的原因.
- 在复杂的遗传障碍中,如自闭症谱系障碍 (ASD) 中,双重重复扩张的作用和异质性仍然在很大程度上未被探索.
- 对于理解它们对复杂疾病的贡献至关重要.
研究的目的:
- 在患有自闭症谱系障碍 (ASD) 的个体和人口对照中调查协同DNA重复的全基因组特征 (2-20根基对动机).
- 识别与基因相关的并联重复扩张,这种扩张在一般人群中很少见,但在自闭症患者中更为普遍.
- 探索这些罕见的并列重复扩展与像智商和自闭症适应能力这样的表型特征的关联.
主要方法:
- 对2-20个基因对的图案长度的双重重复的全基因组分析
- 17,231个自闭症家庭的基因组与人口对照组的双重重复特征的比较.
- 与未受影响的兄弟姐妹相比,在自闭症患者中明显更为普遍的双重重复扩张的统计分析.
主要成果:
- 在整个基因组中观察到大量的重复模式大小和序列.
- 在对照组中,2,588个位点表现出罕见的与基因相关的并列重复扩张,但在自闭症患者中明显更为常见,特别是在神经发育和心血管/肌肉相关基因的编码和拼接区域.
- 在ASD患者中,罕见的并列重复扩张发现在23. 3%的儿童中,对照组为20. 7%,估计为ASD风险贡献了2. 6%,并且与智商和适应能力的降低有关.
结论:
- 双重DNA重复扩展是自闭症谱系障碍 (ASD) 的遗传病因的一个重要因素.
- 这些扩展有助于自闭症的表型复杂性,包括与较低的认知和适应功能相关联.
- 该研究确定了FGF14和CACNB1等基因的新型ASD连接重复扩张,以及已知的DMPK和FXN等疾病基因.
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