Copy number variation in the human genome and its implication in autoimmunity

Abstract

SummaryThe causes of autoimmune disease remain poorly defined. However, it is known that genetic factors contribute to disease susceptibility. Hitherto, studies have focused upon single nucleotide polymorphisms as both tools for mapping and as probable causal variants. Recent studies, using genome-wide analytical techniques, have revealed that, in the genome, segments of DNA ranging in size from kilobases to megabases can vary in copy number. These changes of DNA copy number represent an important element of genomic polymorphism in humans and in other species and may therefore make a substantial contribution to phenotypic variation and population differentiation. Furthermore, copy number variation (CNV) in genomic regions harbouring dosage-sensitive genes may cause or predispose to a variety of human genetic diseases. Several recent studies have reported an association between CNV and autoimmunity in humans such as systemic lupus, psoriasis, Crohn's disease, rheumatoid arthritis and type 1 diabetes. The use of novel analytical techniques facilitates the study of complex human genomic structures such as CNV, and allows new susceptibility loci for autoimmunity to be found that are not readily mappable by single nucleotide polymorphism-based association analyses alone.

Analysis of Immune Regulatory Genes' Copy Number Variants in Graves' Disease

“…However, recently it has been shown that copy number variants (CNVs) are also associated with complex diseases, including autoimmune diseases [reviewed in Ref. (10)]. CNVs are large DNA segments, ranging from kilobases to megabases, that are altered within the genome as a result of duplications, deletions, insertions, inversions, or complex combinations of rearrangements [reviewed in Ref.…”

Human gene copy number variation and infectious disease

“…Many of the immunity genes that show CNV have been investigated in the context of susceptibility 347 to autoimmune diseases (Olsson and Holmdahl 2012;Schaschl et al 2009). Perhaps the best-348 established is the CNV of complement C4 within the MHC region at chromosome 6p21.32.…”

Transcriptional immune response in mesenteric lymph nodes in pigs with different levels of resistance to Ascaris suum

“…The observed differences in FCGR1A expression could be due to variation in for instance a regulatory region; it is also possible that our marker is linked with a copy number variant of the FCGR1A gene (Hindorff et al 2009). In humans, there is a segmental duplication region on chromosome 1q23 which encompasses several low-affinity Fc gamma receptors, e.g., FCGR2A, FCGR2B, and FCGR3A (Schaschl et al 2009). This locus is located about 10 Mb from the human FCGR1A gene.…”