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. (April 2007) Strong Association of De Novo Copy Number Mutations with Autism. Science, 316 (5823). pp. 445-449.
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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: | 20 April 2007 |
| Date Deposited: | 03 Nov 2011 18:37 |
| Last Modified: | 31 Mar 2014 16:07 |
| PMCID: | PMC2993504 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/23136 |
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