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零分子突变的地形及其与人类疾病的相关性
Candace S Y Chan1,2,3, Ioannis Mouratidis3, Austin Montgomery3
1Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
零分子,短的DNA序列不在基因组中,可以通过突变出现. CpG二核酸和甲基化细胞因子是关键驱动因素,疾病突变更有可能产生零分子.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 人口遗传学 人口遗传学
背景情况:
- 零分子是缺少特定基因组的DNA序列,但可以通过突变产生的.
- 了解零分子形成的机制和基因组背景对于解释遗传变异和疾病至关重要.
- 单基因对突变,种群变异和病原性突变可能会导致nullomer的出现.
研究的目的:
- 为了全面描述人类潜在的零分子新兴单基对突变.
- 为了识别与nullomer出现相关的基因组特征和序列背景.
- 为了研究疾病相关突变和无分子形成之间的关系.
主要方法:
- 对人类基因组序列的生物信息分析.
- 单核酸变体的识别和分类.
- 在特定的基因组元素和序列背景下对突变的统计丰富分析.
主要成果:
- CpG二核酸和甲基化细胞因子是零分子出现的主要决定因素.
- 在调控元素 (转录开始/结束位点,拼接位点,TF结合位点) 和保存区域中,由零分子产生的突变得到了丰富.
- 重复显示了这些突变的位置丰富,与疾病相关的突变更有可能产生无基因体,而不是良性变异.
结论:
- 零分子的出现受特定的序列背景 (CpG,甲基化细胞因子) 和基因组位置的影响.
- 保护区域的突变,调节元件和Alu重复是零分子形成的热点.
- 病原性突变具有显著更高的倾向,以创建nullomers,这表明疾病发病和遗传查的含义.
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