Grhl2的非编码插入突变会导致基因过度表达和多种结构异常,包括口腔裂,脊柱裂和脑
Zoe Crane-Smith1, Sandra C P De Castro1, Evanthia Nikolopoulou1
1Developmental Biology and Cancer Department, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK.
Human molecular genetics
|June 26, 2023
概括
在Grainhead-like 2 (Grhl2) 中的调控突变会导致小鼠的神经管缺陷 (NTD) 和面腔裂. 这些发现表明Grhl2调节可能会影响人类面异常和NTD.
科学领域:
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
- 遗传异常是一种先天性异常.
背景情况:
- 耳面裂 (CL/P) 和神经管缺陷 (NTD) 是常见的先天性异常,其遗传基础尚未完全理解.
- 在CL/P,NTD和相关疾病之间共享的遗传风险因素尚不清楚.
- 假设调节突变有助于这些疾病的遗传性.
研究的目的:
- 为了调查 orofacial 裂和神经管缺陷的遗传基础.
- 探索调节突变在先天性异常中的作用.
- 识别与面和神经管缺陷相关的致病基因和突变.
主要方法:
- 在轴性缺陷 (Axd) 鼠标模型中进行全基因组测序.
- 在Grhl2调节区域内对逆转移子插入的分析.
- 在人类NTD和口腔裂病例中研究GRHL2上游变体.
主要成果:
- 过度的Grhl2表达会导致脊椎NTD和部缺陷,包括中线裂唇和口,面骨异常和小鼠脑.
- 在Axd小鼠中发现了一种4kb的LTR逆转移子插入,破坏了Grhl2非编码调节区域.
- 在GRHL2上游区域的罕见或新型变异在少数人类NTD和口腔裂变病例中被发现.
结论:
- 影响Grhl2调节的突变会导致一系列发育缺陷,包括NTD和口腔裂.
- 这些发现意味着Grhl2调节突变作为人类面异常和NTD的潜在贡献者.
- 需要对GRHL2调节进行进一步的研究,以了解并潜在地治疗这些先天性疾病.
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