Clinical OMICs - Issue 8 - (Page 19)

Image © fotohunter/iStock The growth of genomic medicine has cast a spotlight on the need for higher-resolution technologies for chromosomal analysis. been used as the definitive diagnostic test for microdeletion/duplication disorders such as Williams syndrome and 22q11.2 deletion (DiGeorge/ velocardiofacial) syndrome, as well as submicroscopic chromosomal rearrangements involving the subtelomeric regions that cause congenital abnormalities and developmental disabilities. FISH however, can only detect deletions or duplications of regions specifically targeted by the probe used and which are larger than the probe. The technique, therefore, may miss small deletions. Copy Number Variation As copy number variation (CNV) has been increasingly recognized as playing a role in such human diseases as obesity, heart disease, cancer, autism, and schizophrenia, and as a major cause of structural variation in the genome, the need for higher-resolution technologies for chromosomal analysis has emerged. CNVs involve both duplications and deletions of www.clinicalomics.com sequences that typically range in relatively rare variants that are much length from 1,000-5,000,000 base longer than CNPs, ranging in size from pairs, in many cases below the cyto- hundreds of thousands of base pairs genetic level of resolution. to over 1 million base pairs in length. Based on the length of the affected Also known as microdeletions and sequence, scientists assign CNVs microduplications, these large and to one of two main categories. The rare structural variants occur disprofirst includes copy number polymor- portionately in patients with mental phisms (CNPs), found retardation, developcommonly in the genmental delay, schizoCNV has been eral population, at phrenia, and autism, an overall frequency suggesting to some increasingly recognized of greater than 1%. scientists that their as playing a role in CNPs are typically appearance in such such human diseases as small (most are less patients has led to obesity, heart disease, than 10 kilobases in speculation that large cancer, autism, and length), and they are and rare CNVs may schizophrenia. often enriched for be more important in genes that encode neurocognitive disproteins important in drug detoxifica- eases than other forms of inherited tion and immunity. CNPs associated mutations, including single nucleowith immune response genes have tide substitutions. recently been associated with suscepCNVs, which result from larger-scale tibility to complex genetic diseases, genomic events such as deletions, including psoriasis, Crohn's disease, duplications, inversions, and transloand glomerulonephritis. cations, occur more commonly than The second class of CNVs includes (continued on next page) August 13, 2014 Clinical OMICs 19 http://www.clinicalomics.com

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Clinical OMICs - Issue 8