在Fcgr3中的复制数多态性使大鼠和人类易患球炎
Timothy J Aitman1, Rong Dong, Timothy J Vyse
1Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Imperial College, London W12 0NN, UK. t.aitman@csc.mrc.ac.uk
Nature
|February 17, 2006
概括
在Fcgr3基因中基因复制数的变化影响了老鼠和人类对球炎的易感性. 这一发现突显了基因组的可塑性.
科学领域:
- 分子遗传学 分子遗传学
- 基因组学就是基因组学.
- 免疫学 免疫学 免疫学
背景情况:
- 鉴定复杂特征的基因和理解真核生物基因组进化是关键的挑战.
- 基因拷贝数变异 (CNV) 导致基因组差异和表型变异.
- CNV被认为是基因组进化和表型多样性的驱动因素.
研究的目的:
- 调查Fcgr3基因拷贝数变异对免疫介导的质膜炎易感性的作用.
- 探索复杂表型和疾病易感性中的基因组可塑性的进化意义.
主要方法:
- 定位克隆被用来识别大鼠中淋巴结膜炎的遗传决定因素.
- 在老鼠和人类群体中对Fcgr3基因正统和副本数量的比较分析.
- 关联研究将FCGR3B拷贝数与人类自身免疫性疾病中的淋巴结核炎联系起来.
主要成果:
- 在Wistar京都大鼠中,与巨细胞过度活跃和质炎相关的,大鼠特有的Fcgr3对应物 (Fcgr3-rs) 的丧失.
- 人类FCGR3B基因的低拷贝数与全身性红斑狼患者的血球炎有关.
- 在老鼠和人类中,Fcgr3基因CNV是免疫介导病敏感性的决定因素.
结论:
- 在Fcgr3中的基因复制数多态性使得哺乳动物物种的免疫媒介病易发.
- 这项研究为基因组可塑性在复杂的表型和疾病易感性进化中的作用提供了直接证据.
- 免疫系统基因的CNV可能有助于人类常见疾病的遗传基础.
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