在239个灵长类基因组中识别受约束的序列元素
Lukas F K Kuderna1, Jacob C Ulirsch1, Sabrina Rashid1
1Illumina Artificial Intelligence Laboratory, Illumina, San Diego, CA, USA.
Nature
|November 29, 2023
概括
研究人员通过分析239个物种, 确定了灵长类特有的调节性DNA元素. 这些元素对基因调节至关重要,与人类疾病有关,突出显示了最近的进化变化.
科学领域:
- 基因组学
- 进化生物学
- 人类遗传学
背景情况:
- 非编码DNA是人类基因调节和复杂疾病的关键.
- 进化序列约束有助于识别功能调节元素.
- 由于非编码DNA的快速演化和有限的基因组数据,对灵长类特定基因组元素的识别具有挑战性.
研究的目的:
- 特别是在灵长类动物中确定选择性约束下的人类调节元素.
- 了解近期进化在灵长类特异性调节序列中的作用.
主要方法:
- 构建了239种灵长类动物的全基因组对齐.
- 应用5%的错误发现率来识别受约束的监管要素.
- 验证了对基因表达的控制作用.
主要成果:
- 在灵长类动物中发现了111,318个DNase I过敏位和267,410个转录因子结合位.
- 这些元素对基因表达有调节作用.
- 对与基因表达,复杂特征和疾病相关的人类遗传变异进行了丰富.
结论:
- 监管序列中的近期进化事件显著地使灵长类与其他胎盘哺乳动物有所区别.
- 灵长类特定的约束性监管要素在功能上很重要,与人类健康有关.
- 这项研究为了解灵长类动物进化和人类疾病提供了宝贵的资源.
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