父亲遗传的 cis-regulatory 结构变异与自闭症有关
William M Brandler1,2,3,4, Danny Antaki1,2,3,5, Madhusudan Gujral1,2,3
1Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
Science (New York, N.Y.)
|April 21, 2018
概括
在 cis 调节元件 (CRE-SVs) 中罕见的遗传结构变异可能使儿童易患自闭症谱系障碍 (ASD). 父亲遗传的CRE-SV向受影响的后代呈现优势传播,这表明非编码变体在ASD病因学中的作用.
科学领域:
- 遗传学
- 神经发育障碍
- 基因组医学
背景情况:
- 自闭症谱系障碍 (ASD) 具有复杂的遗传基础,特定基因的新突变起着已知的作用.
- 遗传性结构变异对自闭症风险的贡献,特别是在 cis 调节元素 (CRE-SV) 中,仍然不太清楚.
研究的目的:
- 调查该假设的罕见遗传结构变异在cis-regulatory元素 (CRE-SVs) 贡献自闭症的遗传病因.
- 评估受自闭症影响的家庭中CRE-SV的自然选择和传播扭曲的证据.
主要方法:
- 在2600个自闭症家庭的9274名受试者中进行了全基因组测序.
- 分析的重点是CRE-SV在发起者和未翻译地区的消耗和传播模式.
- 使用了发现队列 (829个家庭) 和独立复制队列 (1771个家庭).
主要成果:
- 发现结构变异在促进体和变异不耐受基因的未翻译区域内已经枯竭.
- 与未受影响的兄弟姐妹相比,从父亲遗传的CRE-SV对ASD受影响的后代具有优越的传播.
- 在独立的队列中成功复制了父亲CRE-SV的这种联系.
结论:
- 罕见的遗传非编码变异,特别是CRE-SV,被认为是自闭症的潜在诱导因素.
- 父亲对CRE-SVs的遗传似乎在ASD易感性中起着重要作用.
- 这些发现突显了自闭症谱系障碍遗传性非编码变异的重要性.
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