The genetics of human autoimmune disease: A perspective on progress in the field and future directions.
The genetics of human autoimmune disease: A perspective on progress in the field and future directions.
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DOI：
10.1016/j.jaut.2015.08.015
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发表时间：
2015-11
影响因子：
12.8
通讯作者：
Seldin MF
中科院分区：
文献类型：
--
作者：
Seldin MF
通过大规模的遗传研究，自身免疫性疾病遗传学的定义取得了显著进展。在过去十年中，使用高通量基因分型和适当的算法实施了全基因组方法，对数百种或某些疾病的数千例病例和对照进行了检查，以提供丰富的数据。这些研究已经确定了数百个非HLA位点，并进一步确定了易患不同自身免疫性疾病的HLA区域变异。这些鉴定遗传风险位点的研究也得到了基因表达研究进展的补充，包括表达数量性状位点（eQTL）的定义、染色质结构的各种改变，包括组蛋白标记、dna酶I敏感性、被抑制的染色质区域以及转录因子结合位点。这些信息的整合可以部分解释为什么特定的变异可以改变自身免疫表型的倾向。尽管我们的知识基础不完整，对遗传因素和可能的功能联系只有部分定义，但这一进展已经并将继续促进对免疫调节关键途径和关键变化的更好理解。在定义和理解功能变异方面的进展可能会导致新的治疗方法和个性化医疗，其中治疗方法是根据特定的分子表型和基因组改变来选择的。
Progress in defining the genetics of autoimmune disease has been dramatically enhanced by large scale genetic studies. Genome-wide approaches examining hundreds or for some diseases thousands of cases and controls have been implemented using high throughput genotyping and appropriate algorithms to provide a wealth of data over the last decade. These studies have identified hundreds of non-HLA loci as well as further defining HLA region variations that predispose to different autoimmune diseases. These studies to identify genetic risk loci are also complemented by progress in gene expression studies including definition of expression quantitative trait loci (eQTL), various alterations in chromatin structure including histone marks, DNase I sensitivity, repressed chromatin regions as well as transcript factor binding sites. Integration of this information can partially explain why particular variations can alter proclivity to autoimmune phenotypes. Despite our incomplete knowledge base with only partial definition of hereditary factors and possible functional connections, this progress has and will continue to facilitate a better understanding of critical pathways and critical changes in immunoregulation. Advances in defining and understanding functional variants potentially can lead to both novel therapeutics and personalized medicine in which therapeutic approaches are chosen based on particular molecular phenotypes and genomic alterations.