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Genetics of Infectious and Inflammatory Diseases: Overlapping Discoveries from Association and Exome-Sequencing Studies

机译:传染病和炎症性疾病的遗传学:来自关联和exome测序研究的重叠发现

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Genome technologies have defined a complex genetic architecture in major infectious, inflammatory, and autoimmune disorders. High density marker arrays and Immunochips have powered genome-wide association studies (GWAS) that have mapped nearly 450 genetic risk loci in 22 major inflammatory diseases, including a core of common genes that play a central role in pathological inflammation. Whole-exome and whole-genome sequencing have identified more than 265 genes in which mutations cause primary immunodeficiencies and rare forms of severe inflammatory bowel disease. Combined analysis of inflammatory disease GWAS and primary immunodeficiencies point to shared proteins and pathways that are required for immune cell development and protection against infections and are also associated with pathological inflammation. Finally, sequencing of chromatin immunoprecipitates containing specific transcription factors, with parallel RNA sequencing, has charted epigenetic regulation of gene expression by proinflammatory transcription factors in immune cells, providing complementary information to characterize morbid genes at infectious and inflammatory disease loci.
机译:基因组技术在主要传染病,炎症和自身免疫障碍中定义了复杂的遗传建筑。高密度标志物阵列和免疫噬粒具有动力基因组 - 宽协会研究(GWAS),其在22种主要炎症疾病中映射了近450个遗传风险基因座,其中包括在病理炎症中发挥着核心作用的常见基因的核心。全极端和全基因组测序鉴定了超过265个基因,其中突变引起初级免疫缺乏和稀有形式的严重炎症肠疾病。炎症性疾病GWAS和初级免疫缺乏对免疫细胞发育和免疫感染保护所需的共用蛋白质和途径的综合分析,以及病理炎症。最后,含有特异性转录因子的染色质免疫沉淀物的测序,具有平行RNA测序的初炎转录因子在免疫细胞中的基因表达的图表表观调节,提供了互补的信息,以表征传染病和炎症性疾病的病态基因。

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