在新发罕见的EMX2变体中,会导致异常性性性性性性
Maria Stamou1, Miranda Tompkins2, Hannah Bow2
1Reproductive Endocrine Unit, Massachusetts General Hospital and the Center for Reproductive Medicine, Boston, MA.
概括
鉴定出EMX2基因是人类不孕症的一个原因. 罕见的EMX2变体与异形性性性性性 (IHH) 有关,而常见的变体与不孕症和其他疾病有关.
科学领域:
- 遗传学 遗传学 是一个
- 生殖生物学 生殖生物学
- 神经内分泌学神经内分泌学
背景情况:
- 人类不孕不育的遗传基础,特别是异形性形性形性形性形性形性形性形性形性形性形性形性形 (IHH),在很大程度上是未知的.
- IHH的特点是发生性腺激素释放激素 (GnRH) 缺乏,导致生殖发育受损.
- 识别致病基因对于理解不孕症病原和开发诊断至关重要.
研究的目的:
- 识别与人类不孕症相关的新型基因.
- 调查新型变体在异形性形性形性形性形性形性形性形性 (IHH) 中的作用.
- 探索候选基因在GnRH神经元发育和迁移中的功能.
主要方法:
- 在142个具有IHH的父试验三组中进行了外体序列测序和de novo变体分析.
- 在大型生物银行队列中对常见的EMX2变异进行关联研究 (N = 65,253).
- 在体外研究中使用器官类型的探索剂,在体内研究中使用Emx2淘汰赛小鼠模型来评估GnRH神经元迁移.
主要成果:
- 发现EMX2基因在IHH患者中既含有罕见的de novo副本数和单核酸变异 (CNV和SNV).
- 罕见的新型EMX2变体与IHH,发育延迟和听力损失有关.
- 常见的EMX2变种与不孕不育,帕金森病和听力损失有关. Emx2敲除/敲除损害了GnRH细胞迁移.
结论:
- 确定EMX2是一种涉及人类不孕症的新型基因.
- 新变种分析是一种强大的方法,用于发现像IHH这样的复杂疾病背后的基因.
- EMX2在GnRH神经元的发育和迁移中发挥着关键作用,对生殖功能至关重要.
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