EBD Blog

The Internet is a-buzz with the news of the study by Jonathan Sebat, B. Lakshmi, Dheeraj Malhotra, Jennifer Troge, Christa Lese-Martin, Tom Walsh, Boris Yamrom, Seungtai Yoon, Alex Krasnitz, Jude Kendall, Anthony Leotta, Deepa Pai, Ray Zhang, Yoon-Ha Lee, James Hicks, Sarah J Spence, Annette T. Lee, Kaija Puura, Terho Lehtimäki, David Ledbetter, Peter K. Gregersen, Joel Bregman, James S. Sutcliffe, Vaidehi Jobanputra, Wendy Chung, Dorothy Warburton, Mary-Claire King, David Skuse, Daniel H Geschwind, T. Conrad Gilliam, Kenny Ye, and Michael Wigler published yesterday in Sciencexpress. Sebat and colleagues compared the genes of children to the genes of their parents. They found that children with autism were much more likely to have genetic mutations that their parents didn’t have than were children who did not have autism.

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 (2%) of patients with an affected first-degree relative, and in 2 out of 196 (1.0%) 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.

One of the major sources of mutations of this sort is the gametes of the parents. As Leslie Feldman’s page on paternal age shows, older fathers’ sperm are more likely to carry mutations.

Sebat and colleagues are leaders in the study of copy number variation. They’ve done other work on copy number polymorphism in cancer as well as developing techniques and procedures widely used in the study of genetics. It’s wonderful that they’ve turned their focus to Autism. Link to Professor Sebat’s page at Cold Spring Harbor Lab.

Links:

• The press release from Cold Spring Harbor Labs;
• John Hamilton’s “Cause of Autism Narrowed Down to 100 Genes” on National Public Radio;
• Coverage by Edyta Zielinska in The Scientist (UK);
• “Study Finds Autism Key” by Jamie Talan of Newsday;
• Coverage by Tom Paulson in the Seattle (WA, US) Post Intelligencer;
• Results for a Google search of blogs for “autism sebat”;
• For good background information, see Flags and Lollipops entry on cnv.