BACK TO THE SUBJECT OF COPY NUMBER VARIATIONS IN SPORADIC AUTISM IN 10% OF THE OFFSPRING IN SEBAT AND WIGLER'S STUDY? IS IT DAD'S SPERM?

Genomics & Proteomics
Advantage Business Media





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.