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在1548个冰岛三组中,父母对人类生殖系新突变的影响
Hákon Jónsson1, Patrick Sulem1, Birte Kehr1
1deCODE genetics/Amgen Inc., 101 Reykjavik, Iceland.
Nature
|September 30, 2017
概括
父母的年龄对人类基因组测序的新突变有重大影响. 在特定的基因组区域中,母亲的年龄会增加突变集群,并改变突变类型,特别是C>G.
科学领域:
- 人类遗传学
- 进化生物学
- 基因组不稳定性
背景情况:
- 了解遗传变异的起源对于医学遗传学和进化研究至关重要.
- 新基因突变是人类序列多样性的主要来源.
- 父母的年龄和性别是影响突变率的已知因素.
研究的目的:
- 研究传染父母的年龄和性别如何影响新突变的发生率和特征.
- 确定受父母年龄影响的特定基因组区域和突变类型.
主要方法:
- 1,548名冰岛人的基因组测序,他们的父母,以及他们的子女的子集 (225) 到35×覆盖范围.
- 识别和确定超过108,000个de novo突变的原始基因 (单核酸多态和内基因).
- 对突变率,聚类,类型及其与父母年龄和基因组位置的相关性进行分析.
主要成果:
- 随着父母年龄的增长,新突变的发生率会增加,而父亲每年贡献的突变比母亲更多.
- 母亲年龄与突变群的增加和突变类型的转变有关,特别是更多的C>G突变.
- 与年龄相关的突变变化不均,像8p染色体这样的特定区域显示出明显更高的母体C>G突变率.
- 在特定区域的C>G变异是古老的,并且在灵长类动物中共享,这表明长期的进化过程.
结论:
- 父母的年龄,性别,突变类型和基因组位置相互作用形成人类序列的多样性.
- 特定的基因组区域表现出由母亲年龄影响的独特突变模式,表明局部突变过程.
- 观察到的序列多样性的模式具有进化根源,在人类和灵长类基因组中具有共同的特征.
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