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

The 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.