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人类加速地区的突变扰乱了认知和社会行为
Ryan N Doan1, Byoung-Il Bae1, Beatriz Cubelos2
1Division of Genetics and Genomics, Manton Center for Orphan Disease Research, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.
Cell
|September 27, 2016
概括
人类加速区域 (HARs) 的罕见突变在5%的血缘病例中导致自闭症谱系障碍 (ASD). 这些HAR对神经发育和功能至关重要.
科学领域:
- 基因组学
- 进化生物学
- 神经科学
背景情况:
- 人类加速区域 (HAR) 是保存的基因组位点,在人类中显示出高度分歧,可能与人类特有的特征有关.
- 调节社会和行为特征的HAR突变可能会影响认知和社会障碍.
研究的目的:
- 研究HARs在人类发育中的功能作用及其对神经发育障碍的潜在贡献.
- 确定与自闭症谱系障碍 (ASD) 有关的特定HAR和相关基因.
主要方法:
- 全基因组和向的"HAR-ome"测序以识别罕见的双点突变.
- 染色体相互作用测序,大规模并行报告测试 (MPRA) 和转基因小鼠评估增强剂活性.
- 与对照人群相比,与ASD有血缘关系的个体的突变频率分析.
主要成果:
- 在来自血缘亲属家庭的自闭症患者中发现了罕见的双基HAR突变的显著过量,这表明5%的贡献.
- 在CUX1,PTBP2,GPC4和CDKL5等基因的活性增强剂中发现了与疾病相关的双基HAR突变.
- 这些基因与神经功能和/或自闭症有关.
结论:
- 特定的HAR对于正常的神经发育至关重要.
- 遗传证据支持HAR突变在自闭症发病过程中的作用.
- 哈尔的进化变化可能影响了人类的社会和认知行为.
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