单胞胎双胞胎的基因组,表观基因组和RNA序列对多发性硬化症不一致
Sergio E Baranzini1, Joann Mudge, Jennifer C van Velkinburgh
1Department of Neurology, University of California at San Francisco, San Francisco, California 94143, USA. sebaran@cgl.ucsf.edu
Nature
|April 30, 2010
概括
患有多发性硬化症 (MS) 的同卵双胞胎没有显著的遗传或表观遗传差异,挑战了环境因素单独导致疾病不一致的想法. 这项研究对双胞胎基因组和表观基因组进行了测序,以了解MS患者的自然与培养对比.
科学领域:
- 遗传学 遗传学 是一个
- 免疫学 免疫学 免疫学
- 神经科学是一个神经科学.
背景情况:
- 单胞胎 (同卵) 双胞胎对于研究遗传与环境对多发性硬化症 (MS) 等疾病的影响至关重要.
- 传统上,同卵双胞胎的多发性硬化病不一致性表明环境因素起着重要作用.
- 最近的发现表明同卵双胞胎之间的潜在遗传和表观遗传变异,质疑这种模式.
研究的目的:
- 调查多发性硬化症不一致的单胞胎双胞胎对中的遗传,表观遗传和转录组差异.
- 确定这些差异是否可以解释同卵双胞胎在MS发育中观察到的不一致性.
主要方法:
- 一个MS不一致的同卵双胞胎对的全基因组测序.
- 来自三个MS异调的同卵双胞胎对的CD4 (((+) 淋巴细胞的RNA转录组和表观基因组测序.
- 对单核酸多态 (SNP),插入删除多态,HLA单元型,拷贝数变异和DNA甲基化模式的分析.
主要成果:
- 同胞双胞胎之间没有发现可再生的遗传差异 (SNP,indels).
- 没有观察到HLA单元型,MS敏感性SNP,副本数变异或基因表达的显著差异.
- 在双胞胎之间检测到最小的表观遗传差异 (DNA甲基化),远远少于无关个人或不同组织之间的差异.
结论:
- 该研究没有发现遗传,表观遗传或转录组差异的证据,可以解释同卵双胞胎中MS疾病的不一致性.
- 这些发现挑战了在MS病变发生过程中对同卵双胞胎研究的传统解释.
- 这项研究提供了第一个报告的女性,双胞胎和自身免疫疾病个体基因组序列.
相关概念视频
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