Moncrieffe Halima, Prahalad Sampath, Thompson Susan D
aDivision of Rheumatology and the Center for Autoimmune Disease Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio bDivision of Pediatric Rheumatology, Department of Pediatrics and Genetics,, Emory University School of Medicine, Atlanta, Georgia, USA.
Curr Opin Rheumatol. 2014 Sep;26(5):579-84. doi: 10.1097/BOR.0000000000000094.
In juvenile idiopathic arthritis (JIA), there are now more than 25 regions represented by single nucleotide polymorphisms that show strong genetic associations. The causal variants and corresponding functions have not yet been defined for the majority of these regions. Here, we review current JIA association findings and the recent progress in the annotation of noncoding portion of the human genome as well as the new technologies necessary to apply this knowledge to JIA association findings.
An international collaboration was able to amass sufficient numbers of JIA and control samples to identify significantly robust genetic associations for JIA. The Encyclopedia of DNA Elements project and the National Institutes of Health (NIH) Roadmap Epigenetics Program have now annotated more than 80% of the noncoding genome, important in understanding the impact of risk loci, the majority of which fall outside of protein coding regions. Recent technological advances in high throughput sequencing, chromatin structure determination, transcription factor and enhancer binding site mapping and genome editing will likely provide a basis for understanding JIA genetic risk.
Understanding the role of genetic variation in the cause of JIA will provide insight for disease mechanism and may explain disease heterogeneity between JIA subtypes and between autoimmune diseases in general.
在幼年特发性关节炎（JIA）中，目前有超过25个由单核苷酸多态性代表的区域显示出强烈的遗传关联。这些区域中的大多数的因果变异和相应功能尚未明确。在此，我们综述当前JIA的关联研究结果，以及人类基因组非编码部分注释的最新进展，以及将这些知识应用于JIA关联研究结果所需的新技术。
一项国际合作能够收集到足够数量的JIA和对照样本，以确定JIA显著稳健的遗传关联。DNA元件百科全书计划和美国国立卫生研究院（NIH）表观遗传学路线图计划现已注释了超过80%的非编码基因组，这对于理解风险位点的影响很重要，其中大多数位于蛋白质编码区域之外。高通量测序、染色质结构测定、转录因子和增强子结合位点定位以及基因组编辑等近期技术进展可能为理解JIA遗传风险提供基础。
了解遗传变异在JIA病因中的作用将为疾病机制提供见解，并可能解释JIA亚型之间以及一般自身免疫性疾病之间的疾病异质性。
