Strong Association of De Novo Copy Number Mutations with Autism.

@article{citeulike:1237323, abstract = {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.}, address = {Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.}, author = {Sebat, Jonathan and Lakshmi, B. and Malhotra, Dheeraj and Troge, Jennifer and Lese-Martin, Christa and Walsh, Tom and Yamrom, Boris and Yamrom, Boris and Yoon, Seungtai and Krasnitz, Alex and Kendall, Jude and Leotta, Anthony and Pai, Deepa and Zhang, Ray and Lee, Yoon-Ha H. and Hicks, James and Spence, Sarah J. J. and Lee, Annette T. T. and Puura, Kaija and Lehtim\"{a}ki, Terho and Ledbetter, David and Gregersen, Peter K. K. and Bregman, Joel and Sutcliffe, James S. S. and Jobanputra, Vaidehi and Chung, Wendy and Warburton, Dorothy and King, Mary-Claire C. and Skuse, David and Geschwind, Daniel H. H. and Conrad and Ye, Kenny and Wigler, Michael }, citeulike-article-id = {1237323}, doi = {http://dx.doi.org/10.1126/science.1138659}, issn = {1095-9203}, journal = {Science}, keywords = {autism, genetics, quals}, month = {March}, number = {5823}, pages = {445--449}, posted-at = {2007-09-10 07:45:11}, priority = {0}, title = {Strong Association of De Novo Copy Number Mutations with Autism.}, url = {http://dx.doi.org/10.1126/science.1138659}, volume = {316}, year = {2007} }

TY - JOUR ID - citeulike:1237323 L3 - citeulike-article-id:1237323 TI - Strong Association of De Novo Copy Number Mutations with Autism. JF - Science VL - 316 IS - 5823 SP - 445 EP - 449 AD - Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. SN - 1095-9203 N2 - 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. KW - autism KW - genetics KW - quals AU - Sebat, Jonathan AU - Lakshmi, B AU - Malhotra, Dheeraj AU - Troge, Jennifer AU - Lese-Martin, Christa AU - Walsh, Tom AU - Yamrom, Boris AU - Yamrom, Boris AU - Yoon, Seungtai AU - Krasnitz, Alex AU - Kendall, Jude AU - Leotta, Anthony AU - Pai, Deepa AU - Zhang, Ray AU - Lee, Yoon-Ha AU - Hicks, James AU - Spence, Sarah AU - Lee, Annette AU - Puura, Kaija AU - Lehtimäki, Terho AU - Ledbetter, David AU - Gregersen, Peter AU - Bregman, Joel AU - Sutcliffe, James AU - Jobanputra, Vaidehi AU - Chung, Wendy AU - Warburton, Dorothy AU - King, Mary-Claire AU - Skuse, David AU - Geschwind, Daniel AU - Conrad AU - Ye, Kenny AU - Wigler, Michael PY - 2007/03/15/ UR - http://dx.doi.org/10.1126/science.1138659 ER -