James Sutcliffe
Last active: 2/20/2014

Strong association of de novo copy number mutations with autism.

Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimäki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M
Science. 2007 316 (5823): 445-9

PMID: 17363630 · PMCID: PMC2993504 · DOI:10.1126/science.1138659

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.

MeSH Terms (22)

Asperger Syndrome Autistic Disorder Case-Control Studies Child Cytogenetic Analysis Female Gene Deletion Gene Dosage Gene Duplication Genetic Predisposition to Disease Genome, Human Germ-Line Mutation Humans In Situ Hybridization, Fluorescence Male Markov Chains Microsatellite Repeats Mutation Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis Parents Siblings

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