Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Eur J Immunol. 2012 Aug;42(8):1969-76. doi: 10.1002/eji.201242601.
Copy number variation, namely regions of the genome that can be either deleted or duplicated in a variable way, has emerged as an important source of genetic variance in the human genome. Genes with immunological functions are particularly prone to copy number variation, in part because this is a mechanism to expand the recognition repertoire; however, immunological genes not directly involved in immune recognition are also copy number variable but, despite the link between immunological function and copy number variation, very few copy number variants (CNVs) have been found to be associated with autoimmune diseases, even in recent large genome-wide CNV-association studies. Nonetheless, CNVs in FCGR3B, DEFB4, CCL3L1, C4A/B and NCF1 have been suggested to be associated with autoimmune diseases, although there is conflicting evidence in all cases. The reasons for the lack of definitive data on CNV-autoimmunity associations, as well as the technical challenges for the field are the focus of this review.
拷贝数变异，即基因组中可以以可变方式缺失或重复的区域，已成为人类基因组中遗传变异的一个重要来源。具有免疫功能的基因特别容易发生拷贝数变异，部分原因是这是一种扩展识别范围的机制；然而，与免疫识别不直接相关的免疫基因也存在拷贝数变异，但尽管免疫功能和拷贝数变异之间存在联系，即使在最近的大型全基因组拷贝数变异关联研究中，也很少发现与自身免疫性疾病相关的拷贝数变异（CNVs）。尽管如此，FCGR3B、DEFB4、CCL3L1、C4A/B 和 NCF1 中的 CNVs 已被认为与自身免疫性疾病相关，但在所有情况下都存在相互矛盾的证据。缺乏关于 CNV-自身免疫关联的明确数据的原因以及该领域的技术挑战是本综述的重点。
