在先天性心脏病中,基因组蛋白修饰基因的新突变是先天性心脏病
Samir Zaidi1, Murim Choi, Hiroko Wakimoto
1Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nature
|May 14, 2013
概括
调节染色体标记的基因中的de novo突变导致严重的先天性心脏病 (CHD). 关键发育基因中的这些遗传变化解释了大约10%的严重心血管疾病病例.
科学领域:
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 先天性心脏病 (CHD) 是最常见的出生缺陷,影响0.8%的新生儿.
- 慢性心血管疾病的零星发生和降低生殖能力表明新突变的作用.
- 了解CHD的遗传基础对于诊断和治疗至关重要.
研究的目的:
- 研究重症冠状动脉疾病中新突变的发生率和影响.
- 为了确定涉及到心血管疾病发展的特定基因和途径.
- 确定新突变对严重心脏病病的病因学的贡献.
主要方法:
- 362个患有严重心血管疾病的父子三组和264个对照组的外体序列测序.
- 在发育中的心脏中表达的基因中对蛋白质改变的de novo突变的分析.
- 研究调节基因基因突变的基因基因甲基化 (H3K4,H3K27) 和H2BK120无处不在.
主要成果:
- 与对照组相比,在心血管疾病病例中观察到蛋白质改变新突变 (OR=7.5) 的显著过多.
- 基因突变丰富的基因涉及到组织素甲基化 (H3K4,H3K27) 和H2BK120无处不在.
- 这些表观遗传调节者的新突变共同导致约10%的严重心血管疾病病例.
结论:
- 控制染色体标记的基因的新突变与严重心血管疾病的发病有关.
- 这些发现强调了表观遗传失调在先天性心脏发育中的作用.
- 识别这些突变可以了解心血管疾病的遗传结构和潜在的治疗点.
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