Linkage, Association, and Gene-Expression Analyses Identify CNTNAP2 as an Autism-Susceptibility Gene

Alarcon, M., Abrahams, B. S., Stone, J. L., Duvall, J. A., Perederiy, J. V., Bomar, J. M., Sebat, J., Wigler, M. H., Martin, C. L., Ledbetter, D. H., Nelson, S. F., Cantor, R. M., Geschwind, D. H. (January 2008) Linkage, Association, and Gene-Expression Analyses Identify CNTNAP2 as an Autism-Susceptibility Gene. Am J Hum Genet, 82 (1). pp. 150-159.

[thumbnail of Linkage,_Association,_and_Gene-Expression_Analyses_Identify_CNTNAP2_as_an_Autism-Susceptibility_Gene.pdf]

Download (829kB)
DOI: 10.1016/j.ajhg.2007.09.005


Autism is a genetically complex neurodevelopmental syndrome in which language deficits are a core feature. We describe results from two complimentary approaches used to identify risk variants on chromosome 7 that likely contribute to the etiology of autism. A two-stage association study tested 2758 SNPs across a 10 Mb 7q35 language-related autism QTL in AGRE (Autism Genetic Resource Exchange) trios[1] and [2] and found significant association with Contactin Associated Protein-Like 2 (CNTNAP2), a strong a priori candidate. Male-only containing families were identified as primarily responsible for this association signal, consistent with the strong male affection bias in ASD and other language-based disorders. Gene-expression analyses in developing human brain further identified CNTNAP2 as enriched in circuits important for language development. Together, these results provide convergent evidence for involvement of CNTNAP2, a Neurexin family member, in autism, and demonstrate a connection between genetic risk for autism and specific brain structures.

Item Type: Paper
Additional Information: DOI 10.1016/j.ajhg.2007.09.005
Subjects: diseases & disorders > congenital hereditary genetic diseases
diseases & disorders > mental disorders > personality disorders > autism
organism description > animal > gender > male
CSHL Authors:
Communities: CSHL labs > Wigler lab
CSHL labs > Sebat lab
Depositing User: CSHL Librarian
Date: January 2008
Date Deposited: 29 Aug 2011 20:49
Last Modified: 17 Nov 2016 16:52
PMCID: PMC2253955
Related URLs:

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving