转录因子DNA结合变异的遗传学
Bart Deplancke1, Daniel Alpern1, Vincent Gardeux1
1Laboratory of Systems Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne and Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Cell
|July 30, 2016
概括
非编码DNA的遗传变异通过改变转录因子 (TF) -DNA结合来影响特征. 然而,大多数结合性变异来自于超出简单动机变化的机制,揭示了人类特征的复杂遗传基础.
科学领域:
- 基因组学和分子生物学
- 表观遗传学和基因调控
背景情况:
- 复杂的特征相关遗传变异常常存在于非编码的调节区域.
- 这些变异已知会破坏转录因子 (TF) - DNA结合基因,影响基因表达.
- 可变的TF-DNA相互作用越来越被认为是表型变异的关键驱动因素.
研究的目的:
- 总结理解TF-DNA结合变异的范式转变.
- 对基因变异驱动的TF-DNA结合变异性提出的机制进行审查.
- 讨论解剖复杂特征和疾病易感性的非编码变体的影响.
主要方法:
- 对TF-DNA结合事件的最新全基因组研究的审查.
- 综合了有关TF-DNA结合变异的机制的发现.
- 对非编码变体分析的生物医学影响的讨论.
主要成果:
- 大多数可变的TF-DNA结合事件不是由TF结合动机内的直接序列改变引起的.
- 这表明驱动TF-DNA结合变异的分子机制比以前更复杂.
- 局部,近位或远位遗传变异可以影响TF-DNA结合.
结论:
- 了解TF-DNA结合变异对于解释个体间的表型变异至关重要.
- 这些机制的复杂性挑战了分析非编码变体的传统方法.
- 需要进一步研究以阐明这些机制及其在复杂特征和疾病中的作用.
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