Thu, 21 Aug 2008 15:34:52 BST CiteULike: mrkrause Sebat http://www.citeulike.org/user/mrkrause/author/Sebat CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/mrkrause/article/1237323 <i>Science, Vol. 316, No. 5823. (15 March 2007), pp. 445-449.</i><br /><br />We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (2%) of patients with an affected first-degree relative, and in 2 out of 196 (1.0%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized. Strong Association of De Novo Copy Number Mutations with Autism. Jonathan Sebat B Lakshmi Dheeraj Malhotra Jennifer Troge Christa Lese-Martin Tom Walsh Boris Yamrom Boris Yamrom Seungtai Yoon Alex Krasnitz Jude Kendall Anthony Leotta Deepa Pai Ray Zhang Yoon-Ha Lee James Hicks Sarah Spence Annette Lee Kaija Puura Terho Lehtimäki David Ledbetter Peter Gregersen Joel Bregman James Sutcliffe Vaidehi Jobanputra Wendy Chung Dorothy Warburton Mary-Claire King David Skuse Daniel Geschwind Conrad Kenny Ye Michael Wigler doi:10.1126/science.1138659 Science, Vol. 316, No. 5823. (15 March 2007), pp. 445-449. 2007-04-19T17:15:36-00:00 2007 Science 1095-9203 316 5823 445 449 autism genetics quals http://www.citeulike.org/user/mrkrause/article/108658 <i>Science, Vol. 305, No. 5683. (23 July 2004), pp. 525-528.</i><br /><br />The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease. Large-Scale Copy Number Polymorphism in the Human Genome Jonathan Sebat B Lakshmi Jennifer Troge Joan Alexander Janet Young Par Lundin Susanne Maner Hillary Massa Megan Walker Maoyen Chi Nicholas Navin Robert Lucito John Healy James Hicks Kenny Ye Andrew Reiner Conrad Gilliam Barbara Trask Nick Patterson Anders Zetterberg Michael Wigler doi:10.1126/science.1098918 Science, Vol. 305, No. 5683. (23 July 2004), pp. 525-528. 2005-03-01T18:53:00-00:00 2004 Science 305 5683 525 528 copy_number genetics quals