儿童癌症对人类基因库的进化影响
Ulrik Kristoffer Stoltze1,2,3, Jon Foss-Skiftesvik4,5, Thomas van Overeem Hansen6,7
1Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Blegdamsvej 9, Copenhagen, The Capital Region, Denmark. ulrik.kristoffer.stoltze@regionh.dk.
Nature communications
|February 29, 2024
概括
儿童癌症基因表现出强烈的自然选择,变种比预期的要少. 这表明影响儿童癌症风险的遗传因素正处于显著的进化压力之下.
科学领域:
- 人口遗传学 人口遗传学
- 人类遗传学 人类遗传学
- 癌症基因组学 癌症基因组学
背景情况:
- 预计与儿童死亡率增加相关的生殖系病原体变异在自然选择下存在.
- 了解这些选择性压力可以揭示儿童癌症的遗传结构.
研究的目的:
- 研究自然选择对与儿科癌症倾向综合征 (pCPS) 相关的基因的影响.
- 分析儿科和成人队伍的生殖系遗传数据,以识别选择性约束下的基因.
主要方法:
- 对公开可用的4,574名患有癌症的儿童和141,456名成年人的生殖系遗传元数据的分析.
- 利用了整个外体序列 (WES),整个基因组序列 (WGS) 和基因组数据.
- 评估了85个pCPS基因和23个与双风险相关的基因的突变约束.
主要成果:
- 儿科癌症倾向综合征 (pCPS) 基因受到高度限制,仅观察到四分之一的预期功能丧失变体.
- 六个基因 (ELP1,GPR161,VHL,SDHA/B/C) 显示缺乏突变约束,质疑他们的儿科透性或严重性.
- 在23个双基因风险基因中的2个 (DIS3L2,MSH2) 显示出显著的约束,这表明儿童癌症的潜在单基因风险.
结论:
- 人口遗传数据提供了自然选择对遗传性儿童癌症的实证证据.
- 这种选择对当今人类基因库产生了重大影响.
- 这些发现强调了进化压力在理解儿童癌症遗传学的重要性.
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