Chromosomal structural abnormalities are now being studied as a result of the completion of the Human Genome Project. much of the structural variation in the genome has gone unrecognised until recently. Deletions and duplications of DNA strands of between a few hundred base pairs and several million base pairs (copy number variants) are widespread. Human genomic variation, as single nucleotide substitutions has been catalogued since the completion of the draft human genome sequence in 2000. The HapMap project, which by 2007 had documented more than 3 ·1 million single nucleotide polymorphisms (SNPs) and their inter-relation, has underpinned subsequent successful genome-wide association studies. Since 2007, genome-wide association studies based on single nucleotide polymorphisms show replicated associations to several common diseases. Some copy number variants explain rare, previously uncharacterised disorders, and they are now expected to explain some of the genetic contribution to common diseases. This review by Wain et al reviews current work to map copy number variants and discusses the of further understanding human health and disease.
Large deletions, duplications, and other structural rearrangements have a role in the aetiology of specific diseases (genomic disorders)
In addition intermediate scale structural variation, caused by a variable number of copies of a particular DNA segment are referred to as copy number variants. The influence of these on disease aetiology is now being studied.
The potential role of copy number variation in complex diseases, includes susceptibility to autism, shizophrenia, Crohn’s disease, psoriasis,” systemic lupus erythematosus. amyotrophic lateral sclerosis, and HIV-l . Such variation has also been associated with vertical transmission of HIV-l, and the progression and response to treatment of HIV-l/ AIDS.
Some of these associations could be false positives, others have had either technical validation or replication of findings in different study populations, or both. These validated associations are probably a direct or an indirect result of changes to the copy number of the relevant genomic sequence.
The location, size, and boundaries (breakpoints) of these variants documented in public databases have been very imprecise, although the new generation of maps of copy number variants are providing much improvement. Scalable methods to characterise copy number variation in association studies have been inexact. In this Review, Wain et al introduce copy number variation, examine advances in our understanding, and discuss the inferences that can be reasonably drawn from association studies of copy number variation.
Wain et al 2009genomic number variation, human health and disease. Lancet vol 374 pp 340-350

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