在CACNA1C精神分裂症位点的多态重复的结构
Raquel Moya1, Xiaohan Wang2,3, Richard W Tsien2,3
1Institute for Systems Genetics, New York University School of Medicine, New York, NY 10016.
在CACNA1C基因中的遗传变异.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 在CACNA1C基因的内部3的遗传变异与神经精神疾病如精神分裂症有关.
- 分析因果变异是具有挑战性的,因为附近的变量数串重复 (VNTR).
研究的目的:
- 调查CACNA1C内部3 VNTR.的结构多样性和种群变异性.
- 了解VNTR等位基因,基因表达和神经精神疾病风险之间的关系.
主要方法:
- 利用来自78个不同个体的155个长时间读取的基因组组合.
- 根据重复单元差异将VNTR序列分为7个结构性等位基因 (类型).
- 分析了与全基因组关联研究 (GWAS) 变异的链接不平衡,并评估了基因表达.
主要成果:
- 确定了7个结构VNTR等位基因 (类型),其中一些通过重复相关,而另一些则显示早期分歧.
- 发现了罕见的,分离的VNTR类型,主要在非洲祖先的个体中.
- 在风险单元型和精神分裂GWAS变体之间建立了完全的链接不平衡,与减少CACNA1C大脑表达相关.
结论:
- 人类特异性CACNA1C内3 VNTR中的序列变异影响基因表达.
- 在神经精神病GWAS的关键位置特征了新的VNTR基因.
- VNTR多态性早于早期人类的出现,并影响与大脑功能相关的基因调节.
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