RT Journal Article SR Electronic T1 C11 Copy number variation in Huntington's disease JF Journal of Neurology, Neurosurgery & Psychiatry JO J Neurol Neurosurg Psychiatry FD BMJ Publishing Group Ltd SP A19 OP A19 DO 10.1136/jnnp.2010.222588.11 VO 81 IS Suppl 1 A1 A Vittori A1 F Giorgini A1 F T Outeiro A1 E J Hollox YR 2010 UL http://jnnp.bmj.com/content/81/Suppl_1/A19.2.abstract AB Background A copy number variant is a DNA segment containing an increased or decreased number of copies in comparison with a reference genome. Copy number variation (CNV) contributes significantly to genomic diversity, representing the most prevalent type of structural variation in the human genome. In several cases, CNV causes disease by altering gene dosage or by indirect alteration of gene expression. Several studies have been focusing on investigating the role of CNVs in nervous system disorders such as Parkinson's disease and Alzheimer's disease. Aim The aim of the present study was to investigate CNV and association with variable adult age of onset (AAO) of Huntington's disease. Several candidate genes have been identified that may show CNV and are candidates for involvement in neurological disease. These candidates were identified from published proteomic and genetic analysis, unpublished yeast genetic interaction studies or candidate scanning of the literature. Thus we are analysing the copy number of these genes in HD cohorts to assess whether there is an association with variation of AAO. We are assessing CNV using the Parologue Ratio Test (PRT), which employs quantitative duplex PCR. Primers are designed to precisely amplify a portion of the variable region and an unlinked reference region with no variation in copy number. We are currently analysing several CNVs in candidate genes by PRT on a cohort of HD patients to evaluate possible correlations between this variation and the AAO of HD. Any influence of CNV on AAO will be validated using functional assays in mammalian cell culture.