RESUMO
Impaired reciprocal social interaction is one of the core features of autism. While its determinants are complex, one biomolecular pathway that clearly influences social behavior is the arginine-vasopressin (AVP) system. The behavioral effects of AVP are mediated through the AVP receptor 1a (AVPR1a), making the AVPR1a gene a reasonable candidate for autism susceptibility. We tested the gene's contribution to autism by screening its exons in 125 independent autistic probands and genotyping two promoter polymorphisms in 65 autism affected sibling pair (ASP) families. While we found no nonconservative coding sequence changes, we did identify evidence of linkage and of linkage disequilibrium. These results were most pronounced in a subset of the ASP families with relatively less severe impairment of language. Thus, though we did not demonstrate a disease-causing variant in the coding sequence, numerous nontraditional disease-causing genetic abnormalities are known to exist that would escape detection by traditional gene screening methods. Given the emerging biological, animal model, and now genetic data, AVPR1a and genes in the AVP system remain strong candidates for involvement in autism susceptibility and deserve continued scrutiny.
Assuntos
Transtorno Autístico/genética , Receptores de Vasopressinas/genética , Transtorno Autístico/epidemiologia , Códon/genética , Análise Mutacional de DNA , Éxons/genética , Saúde da Família , Ligação Genética , Predisposição Genética para Doença , Testes Genéticos , Genótipo , Humanos , Transtornos da Linguagem/epidemiologia , Transtornos da Linguagem/genética , Desequilíbrio de Ligação , Escore Lod , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Irmãos , Estados UnidosRESUMO
Eighteen families informative for c-Harvey-ras-1 and INS DNA markers were tested for linkage to unipolar depression and alcoholism. No evidence of linkage was found between these DNA markers and the disorders observed in the families. This study fails to replicate the Old Order Amish Study and suggests that a significant degree of genetic heterogeneity may be present among psychiatric disorders.
