父母年龄和聚合物组成对短串重复de novo突变率的影响
Michael E Goldberg1,2, Michelle D Noyes1, Evan E Eichler1,3
1Department of Genome Sciences, University of Washington, 3720 15 Ave NE, Seattle, WA, 98195.
bioRxiv : the preprint server for biology
|January 8, 2024
概括
短串联重复 (STR) 突变率随着父亲和母亲的年龄增加而增加,挑战了聚合酶滑动模型. 静止细胞中的DNA损伤,而不仅仅是复制错误,可能是这些基因组变异的驱动因素.
科学领域:
- 遗传学 是一个遗传学.
- 基因组不稳定性 基因组不稳定性
- 人类的生殖线进化
背景情况:
- 短串联重复 (STRs) 是高度可变的基因组区域,具有快速的突变率.
- 传统上,在DNA复制过程中聚合酶滑动被认为是STR突变的主要驱动因素.
- 这种模型仅在父亲的血统中预测了年龄相关的突变率.
研究的目的:
- 调查父母年龄与STR突变率之间的关系.
- 探索超越聚合酶滑动驱动STR突变发生的替代机制.
- 分析STR核酸组成对两性突变率的影响.
主要方法:
- 与父亲和母亲年龄相关的STR突变率的分析.
- 通过不同STR核酸组合 (A/T与富含GC) 的突变模式进行比较.
- 对静止细胞中DNA损伤的证据的评估与复制滑动对比.
主要成果:
- STR突变率与父亲和母亲的年龄相关,这与经典模型相矛盾.
- 在已知的卵细胞突变热点之外观察到对STR突变的孕产妇年龄影响.
- 富含A/T的STR与母亲年龄的关联比富含GC的STR在母亲血统中更强.
结论:
- 静止细胞中的DNA损伤与聚合酶滑动一起,对STR突变有显著的贡献.
- 这些发现挑战了长期以来对复制滑动作为STR突变发生的唯一主导机制的信念.
- 父母年龄和STR序列组成在产生基因组变异性方面发挥着复杂的,性别特异性的作用.
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