Strong Association of De Novo Copy Number Mutations with Autism

Sebat, J., Lakshmi, B., Malhotra, D., Troge, J. E., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J. T., Leotta, A., Pai, D., Zhang, R., Lee, Y. H., Hicks, J. B., Spence, S. J., Lee, A. T., Puura, K., Lehtimaki, T., Ledbetter, D., Gregersen, P. K., Bregman, J., Sutcliffe, J. S., Jobanputra, V., Chung, W., Warburton, D., King, M. C., Skuse, D., Geschwind, D. H., Gilliam, T. C., Ye, K., Wigler, M. H. (2007) Strong Association of De Novo Copy Number Mutations with Autism. Science, 316 (5823). pp. 445-449.

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URL: http://www.ncbi.nlm.nih.gov/pubmed/17363630
DOI: 10.1126/science.1138659

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 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) 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.

Item Type: Paper
Subjects: diseases & disorders > mental disorders > personality disorders > autism
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants
CSHL Authors:
Communities: CSHL labs > Hicks lab
CSHL labs > Wigler lab
CSHL labs > Krasnitz lab
CSHL labs > Sebat lab
Depositing User: CSHL Librarian
Date Deposited: 03 Nov 2011 18:37
Last Modified: 31 Mar 2014 16:07
PMCID: PMC2993504
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23136

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