Strong Association of De Novo Copy Number Mutations with Autism

Overview

Journal Science

Specialty Science

Date 2007 Mar 17

PMID 17363630

Citations 1342

Authors

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 Lehtimaki

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

Michael Wigler

Affiliations

Soon will be listed here.

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.

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