在巨细胞中使用系统遗传学和基因环境相互作用来解开炎症反应
Luz D Orozco1, Brian J Bennett, Charles R Farber
1Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. ldorozco@mednet.ucla.edu
Cell
|October 30, 2012
概括
遗传变异会影响巨细胞的炎症反应. 这项研究确定了控制对细菌脂多糖 (LPS) 反应的关键基因和监管热点,为了解炎症疾病提供了资源.
科学领域:
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
- 系统生物学 系统生物学
背景情况:
- 巨细胞在许多常见疾病的炎症成分中起着至关重要的作用.
- 了解巨细胞炎症反应的遗传基础对于疾病研究至关重要.
研究的目的:
- 研究常见遗传变异对巨细胞对炎症刺激反应的影响.
- 确定控制巨细胞炎症途径的遗传位置和调节元件.
主要方法:
- 系统遗传学方法使用92个小鼠菌株的巨细胞中的全基因组转录水平.
- 巨细胞暴露于控制介质,细菌脂多糖 (LPS) 或氧化脂.
- 关联映射以确定表达定量特征位置 (eQTL) 和基因与环境相互作用,随后进行siRNA验证.
主要成果:
- 识别了成千上万的eQTL,基因与环境的相互作用,以及eQTL热点,特别是对于LPS反应.
- 验证了8号染色体上的eQTL热点,确定2310061C15Rik是巨细胞炎症反应的调节者.
- 创建一个公共数据库,以进一步研究炎症特征和基因调节.
结论:
- 常见的遗传变异显著塑造了巨细胞的炎症反应.
- 基因2310061C15Rik是巨细胞炎症反应的新型调节者.
- 生成的数据和数据库是研究炎症疾病和基因调节网络的宝贵资源.
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