Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.
|Title||Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene.|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Alarcón, M, Abrahams BS, Stone JL, Duvall JA, Perederiy JV, Bomar JM, Sebat J, Wigler M, Martin CL, Ledbetter DH, Nelson SF, Cantor RM, Geschwind DH|
|Journal||American journal of human genetics|
|Date Published||2008 Jan|
|Keywords||Autistic Disorder, Brain, Child, Chromosomes, Human, Pair 7, Female, Gene Expression, Genetic Predisposition to Disease, Humans, Language Development, Male, Membrane Proteins, Nerve Tissue Proteins, Polymorphism, Single Nucleotide|
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 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.
|Alternate Journal||Am. J. Hum. Genet.|