Strong association of de novo copy number mutations with autism.

Science 2007 Apr 15;316(5823):445-9. Epub 2007 Mar 15.

Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.1138659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993504PMC
April 2007
76 Reads

Publication Analysis

Top Keywords

copy number
12
associated autism
8
novo cnvs
8
genomic regions
8
novo copy
8
novo
5
00005 cnvs
4
autism 00005
4
cnvs associated
4
confirmed novo
4
identified 118
4
10% patients
4
118 10%
4
genotyping confirmed
4
patients sporadic
4
cnvs identified
4
situ hybridization
4
validated higher-resolution
4
higher-resolution cgh
4
regions validated
4

Similar Publications