부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1399-0004.2007.00858.x Byline: MH Shen (a), K Mantripragada (b), JP Dumanski (c,d), I Frayling (a), M Upadhyaya (a) Keywords: array CGH; DNA microarray; molecular diagnosis; mutation detection; NF1 Abstract: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disease caused by various types of mutations in the NF1 gene. We have previously developed a locus-specific DNA microarray for detection of copy number changes at the NF1 locus by comparative genomic hybridization (CGH) analysis. The original array contains 183 probes pooled from 444 polymerase chain reaction (PCR) products. In the current work, we have used 493 probes derived from single PCR products (200-998 bp in size) to construct a higher resolution array with a smaller average probe size for molecular diagnosis of NF1. This has improved the average resolution from 12.6 kb in the previous array to 4.5 kb in the current version. The performance of the newly constructed microarray was validated with 14 well-characterized NF1 mutations for CGH analysis. These mutations represent deletions from [proportional to]7 kb to over 2 Mb in size. Using this array, we examined a total of 55 NF1 patients for copy number changes at the NF1 locus, detecting deletions in four of them. These results demonstrate that a locus-specific microarray constructed from single PCR products can efficiently detect copy number changes at the NF1 locus, providing a simple method for the molecular diagnosis of NF1. Author Affiliation: (a)All Wales Laboratory Genetics Service, Institute of Medical Genetics, University Hospital of Wales, Cardiff, UK (b)Institute of Medical Genetics, Cardiff University, Cardiff, UK (c)Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden (d)Department of Genetics, University of Alabama at Birmingham (UAB), Medical School, Birmingham, AL, USA Article History: Received 21 March 2007, revised and accepted for publication 17 May 2007 Article note: Ming Hong Shen, All Wales Laboratory Genetics Service, Institute of Medical Genetics, University Hospital of Wales, Cardiff CF14 4XN, UK., Tel.: 0044 29 20744042; fax: 0044 2920 747603; e-mail: shenmh@cf.ac.uk