在RET增强剂中的一个常见的性别依赖突变是赫施普朗格病风险的基础
Eileen Sproat Emison1, Andrew S McCallion, Carl S Kashuk
1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature
|April 15, 2005
概括
在RET基因中一个常见的遗传变异显著增加了赫施普朗格病 (HSCR) 的风险. 这种在增强器区域发现的低透率变异解释了这种罕见疾病的复杂遗传模式.
科学领域:
- 遗传学 是一个遗传学.
- 基因组学就是基因组学.
- 发展生物学 发展生物学
背景情况:
- 赫施普隆病 (HSCR) 是一种复杂的遗传性疾病.
- 在RET基因的罕见突变有助于HSCR风险.
- 鉴定遗传性疾病的常见遗传变异是具有挑战性的.
研究的目的:
- 为了确定与希尔施普朗格病 (HSCR) 易感性相关的常见遗传变异.
- 为了研究非编码变异在HSCR病原发生中的作用.
- 了解HSCR复杂的继承模式.
主要方法:
- 基于家庭的关联研究,以确定疾病间隔.
- 对比和功能性基因组分析以优先考虑遗传元素.
- 在体外测试以评估RET变体的增强剂活性.
主要成果:
- 在intron 1中,一个常见的非编码的RET变体与HSCR有显著的关联.
- 这种变体位于保存增强剂中,比罕见的等位基因增加20倍的风险.
- 该变种显著降低了体外增强剂活性,并表现出低透率,在男性和女性中具有差异性影响.
结论:
- 常见的,低透率的变种可以成为常见和罕见的遗传性疾病的基础.
- 调节元件中的非编码变体在希尔施普朗格病病因学中起着至关重要的作用.
- 关联研究有效地识别了复杂遗传疾病的风险变异.
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