罕见变异修饰器分析确定了SEC24D中的变异,这些变异与面腔裂亚型相关
Sarah W Curtis1, Jenna C Carlson2,3, Terri H Beaty4
1Department of Human Genetics, Emory University, Atlanta, GA, 30322, USA.
Human genetics
|September 7, 2023
概括
在SEC24D中,罕见的遗传变异与裂唇 (CL) 相关,但不与裂唇和 palatal (CLP) 相关. 这些变异可能会通过改变基因调节来影响面发育,从而导致面面裂异质.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 发展生物学 发展生物学
- 儿科研究 儿科研究
背景情况:
- 耳鼻裂 (OFC) 是一种常见的出生缺陷,具有已知的遗传影响.
- 以前的研究集中在常见的遗传变异或针对罕见的变异.
- 在OFC亚型中,罕见的全基因组遗传变异的作用仍未得到充分研究.
研究的目的:
- 调查罕见遗传变异对不同OFC表型的贡献.
- 为了区分裂唇 (CL) 和裂唇和 palatal (CLP) 之间的遗传修饰剂.
主要方法:
- 利用了加布里埃拉·米勒儿童第一儿科研究计划的全基因组测序数据.
- 进行基因负担分析,比较了CL和CLP病例.
- 在SEC24D中分析了与面增强剂重叠的变异,以及对转录因子结合部位 (TFBS) 的潜在影响.
主要成果:
- 与CLP病例相比,在CL病例中观察到SEC24D罕见变异负担显著增加 (p=6.86x10−7).
- 在SEC24D中同义变体重叠了一个已知的面增强器.
- 预计这些变异会破坏包括Pax1在内的9个转录因子的结合点,并为包括Pax6和Pax9.9在内的23个转录因子创建结合点.
结论:
- 罕见的遗传变异有助于在口面裂中观察到的表型异质性.
- 调控变异,特别是在像SEC24D这样的基因内,可能在OFC发展中发挥功能作用.
- 对监管变化的进一步调查是有必要的,以了解OFCs的遗传风险因素.
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