在ASIP形状的人体色素中插入SVA逆转移素的序列
Nolan Kamitaki1,2,3,4,5,6, Margaux L A Hujoel7,8,9, Ronen E Mukamel7,8,9
1Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. nolan_kamitaki@hms.harvard.edu.
Nature genetics
|July 24, 2024
概括
在ASIP基因中的逆转移体插入会影响人类皮肤色素和癌症风险. 在几千年的时间里,一种特定的SVA插入可能减少了欧洲人群的色素.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 人类进化人类进化
- 基因组学就是基因组学.
背景情况:
- 逆转移体构成了人类基因组的重要组成部分,但它们在人类特征变异和进化中的作用尚未得到充分研究.
- 阿古蒂信号蛋白 (ASIP) 在哺乳动物色素化中起着至关重要的作用.
研究的目的:
- 研究逆转移素插入对人类色素和特征变异的影响.
- 探索ASIP基因中SVA逆转移体插入的进化史和功能后果.
主要方法:
- 使用英国生物库数据进行全基因组关联研究 (n=169,641).
- 在ASIP基因中分析SVA逆转移素插入多态性.
- 在皮肤组织中的ASIP基因表达分析.
- 扩展的哈普罗型同胞性分析以推断随着时间的推移而发生的等位基频率变化.
主要成果:
- 在ASIP内体中,一种特定的SVA逆转移素插入多态性与欧洲人群中皮肤颜色更浅和皮肤癌风险增加有很强的相关性.
- 这种插入与ASIP表达的2.2倍增加有关.
- 该机制涉及一个上游的SVA元件,通过非生产性拼接导致ASIP缺功,多态插入减轻了这一问题.
- 在过去的几千年里,插入等位基因在欧洲人群中的频率有所增加.
结论:
- 一系列的逆转移素插入显著影响了人类的色素,导致全物种的增加,随后局部下降.
- 逆转移子动态,特别是ASIP基因中的SVA插入,是人类表型进化的重要因素.
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