Linkage, Association, and Gene-Expression Analyses Identify CNTNAP2

详细信息    查看全文

• 作者：Maricela Alarcó ; n ; Brett S. Abrahams ; Jennifer L. Stone ; Jacqueline A. Duvall ; Julia V. Perederiy ; Jamee M. Bomar ; Jonathan Sebat ; Michael Wigler ; Christa L. Martin ; David H. Ledbetter ; Stanley F. Nelson ; Rita M. Cantor ; Daniel H. Geschwind
• 刊名：The American Journal of Human Genetics
• 出版年：2008
• 出版时间：10 January 2008
• 年：2008
• 卷：82
• 期：1
• 页码：150-159
• 全文大小：809 K

文摘

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.