整体外体测序识别了印尼人具有裂的有害变体
Emmanuel Aladenika1,2, Ani Maskoen3, Waheed Awotoye1
1Iowa Institute for Oral Health Research, University of Iowa, Iowa City, IA, USA.
概括
在MMACHC,SOS1,TULP4和MTHFD1L基因中的罕见遗传变异与印尼人的非综合征性口腔口腔裂有关. 这项研究突出了MMACHC的重点.
科学领域:
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
- 头骨面部异常 头骨面部异常
背景情况:
- 非综合征性口腔口腔裂 (nsOFC) 是遗传和环境因素之间的复杂相互作用的结果.
- 以前的研究已经涉及几种基因在nsOFC的发展,但罕见和新型变体的作用仍然未经探索.
- 了解nsOFC的遗传结构对于诊断和潜在的治疗干预至关重要.
研究的目的:
- 调查印尼nsOFC患者已知的裂相关基因中罕见和新型遗传变异的贡献.
- 识别特定变异并预测它们对蛋白质结构和功能的功能影响.
- 探索MMACHC基因在nsOFC发展中的作用.
主要方法:
- 整体外基因组测序 (WES) 在6名印尼人身上进行了nsOFC.
- 变种被确定,注释,并根据新奇性和稀有性进行过 (小等位基因频率 [MAF] <1%).
- 有害变异被优先考虑,并使用生物信息学工具 (Polyphen,SIFT,CADD) 和HOPE算法预测它们的功能影响.
主要成果:
- 在四个面基因中发现了罕见的有害变异:MMACHC (rs371937044),SOS1 (rs190222208),TULP4 (rs199583035) 和MTHFD1L (rs143492706).
- 以前与小鼠模型中的面部裂相关的MMACHC基因,在一个只有非综合征裂 palatal (nsCPO) 的个体中显示出一种罕见的变异 (MAF = 0.00011).
- 在TULP4和SOS1中确定的变体的MAF分别为0.067和0.00045,而MTHFD1L的MAF分别为0.0044.
结论:
- 这项研究提供了进一步的证据,支持TULP4,SOS1,MTHFD1L和MMACHC基因参与nsOFC的病因.
- 这项研究是第一个将MMACHC基因与人类nsOFC发育有关的研究.
- 这些发现有助于更深入地了解 orofacial 裂的遗传基础,并可能为未来的遗传查和咨询提供信息.
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