非编码SNP的功能影响rs3741442 在 Orofacial 裂上的功能影响
N Funato1,2,3, S R F Twigg4,5
1Department of Signal Gene Regulation, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.
Journal of dental research
|May 12, 2025
概括
一种常见的出生缺陷,口腔裂 (OFC),可能与特定的遗传变异 (SNP rs3741442) 有关. 这种SNP影响了对皮肤发育至关重要的基因表达,并可能影响 palatogenesis.
科学领域:
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
- 遗传异常是一种先天性异常.
背景情况:
- 耳面裂 (OFC) 是一种常见的先天性异常,在各个族群中患病率各不相同.
- 全基因组关联研究 (GWAS) 已经确定了与非综合征性OFC (nsOFC) 相关的单核酸多态 (SNP),但潜在机制尚不清楚.
研究的目的:
- 在非综合征性口腔口腔裂 (nsOFC) 中研究跨基因SNP rs3741442的生物机制.
- 探索rs3741442在影响 palatogenesis 的基因表达调制中的作用.
主要方法:
- 利用表达量的特征位置 (eQTL) 分析来评估SNP对基因表达的影响.
- 使用表观遗传标记和in silico分析来优先考虑潜在的因果SNP.
- 使用CRISPR编辑细胞研究rs3741442风险等位基因对基因表达的功能影响.
- 研究了与不同SNP单基因结合的转录因子.
主要成果:
- 非编码SNP rs3741442对涉及外皮分化的上皮基因表现出cis-eQTL效应.
- 在东亚人群中普遍存在的rs3741442风险等位基因减少了邻近的KRT18和EIF4B的表达.
- 转录因子SP1与rs3741442.4的风险和非风险等位基因结合不同.
- rs3741442还证明了对TP63的跨eQTL作用,这是一种与综合征性OFC和牛皮相关的基因.
结论:
- 跨基因SNP rs3741442可能通过调节 palatogenesis期间的上皮基因表达来促进nsOFC.
- 这些发现突出了一个机制,即非编码的遗传变异通过基因调节来影响复杂的先天性异常.
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