对131个人类大脑的体质突变分析揭示了与衰老相关的超变性
Taejeong Bae1, Liana Fasching2, Yifan Wang1
1Department of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
概括
大多数人的大脑都很少有体质突变, 但有些人会出现数百种突变, 自闭症大脑在发育过程中具有影响MEIS转录因子的特定突变.
科学领域:
- 神经遗传学
- 基因组医学
- 发展神经科学
背景情况:
- 在受孕后发生的体质突变或DNA变化会在整个生命中积累在人类的大脑细胞中.
- 了解这些突变在健康和患病的大脑中的模式和影响对于神经科学和医学至关重要.
研究的目的:
- 综合分析不同类型的人类大脑的体变异,包括神经类型的个体和图雷特综合征,精神分裂症和自闭症患者.
- 调查体质突变负担,特定遗传变异和神经发育障碍,特别是自闭症谱系障碍之间的关联.
主要方法:
- 131个人类大脑的全基因组测序以高深度 (> 200 ×) 来检测单核酸突变和结构变异.
- 对突变模式的分析,包括超变性,与年龄相关,与癌症相关的基因,克隆扩张和重复.
- 在患有自闭症的大脑中识别特定的突变类型和受影响的调节元素,重点是转录因子结合动机.
主要成果:
- 大多数大脑表现出20-60个体质突变,而大约6%表现出数百个,与年龄和癌症相关基因突变相关.
- 在5%的大脑中观察到体质重复,这表明在发育过程中发生基因突变.
- 患有自闭症的大脑显示增强器区域的突变,为MEIS (骨髓外宫病毒整合部位) 转录因子产生结合动机,这表明在大脑发育过程中对基因调节的作用.
结论:
- 人类大脑的体质突变格局有很大差异,其中有一部分与衰老和癌症相关的超变性.
- 发育过程对健康和患病的大脑都有助于体质重复.
- 在与自闭症相关的大脑突变中发现的MEIS转录因子失调突出了导致该疾病发病的潜在机制.
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