7 documents found, page 1 of 1
Convergence of genes and cellular pathways dysregulated in autism spectrum diso...
Pinto, D.; Delaby, E.; Merico, D.; Barbosa, M.; Merikangas, A.; Klei, L; Thiruvahindrapuram, B.; Xu, X.; Ziman, R.; Wang, Z.; Vorstman, J.A.Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectua...
The impact of the metabotropic glutamate receptor and other gene family interac...
Hadley, D.; Wu, Z.L.; Kao, C.; Kini, A.; Mohamed-Hadley, A.; Thomas, K.; Vazquez, L.; Qiu, H.; Mentch, F.; Pellegrino, R.; Kim, C.; Connolly, J.Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs...
Individual common variants exert weak effects on the risk for autism spectrum d...
Anney, R.; Klei, L.; Pinto, D.; Almeida, J.; Bacchelli, E.; Baird, G.; Bolshakova, N.; Bölte, S.; Bolton, P.F.; Bourgeron, T.; Brennan, S.; Brian, J.While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stage...
Functional impact of global rare copy number variation in autism spectrum disor...
Pinto, D.; Pagnamenta, A.T.; Klei, L.; Anney, R.; Merico, D.; Regan, R.; Conroy, J.; Magalhaes, T.R.; Correia, C.; Abrahams, B.S.; Almeida, J.The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying ge...
Increased BDNF levels and NTRK2 gene association suggest a disruption of BDNF/T...
Correia, C.T.; Coutinho, A.M.; Sequeira, A.F.; Sousa, I.G.; Lourenço Venda, L.; Almeida, J.P.; Abreu, R.L.; Lobo, C.; Miguel, T.S.; Conroy, J.The brain-derived neurotrophic factor (BDNF), a neurotrophin fundamental for brain development and function, has previously been implicated in autism. In this study, the levels of BDNF in platelet-rich plasma were compared between autistic and control children, and the role of two genetic factors that might regulate this neurotrophin and contribute to autism etiology, BDNF and NTRK2, was examined. We found that...
A genome-wide scan for common alleles affecting risk for autism
Anney, R.; Klei, L.; Pinto, D.; Regan, R.; Conroy, J.; Magalhaes, T.R.; Correia, C.; Abrahams, B.S.; Sykes, N.; Pagnamenta, A.T.; Almeida, J.Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ...
Association of the alpha4 integrin subunit gene (ITGA4) with autism
Correia, C.; Coutinho, A.M.; Almeida, J.; Lontro, R.; Lobo, C.; Miguel, T.S.; Martins, M.; Gallagher, L.; Conroy, J.; Gill, M.; Oliveira, G.In the present work, we provide further evidence for the involvement of the integrin alpha-4 precursor gene (ITGA4) in the etiology of autism, by replicating previous findings of a genetic association with autism in various independent populations. The ITGA4 gene maps to the autism linkage region on 2q31-33 and is therefore a plausible positional candidate. We tested eight single nucleotide polymorphisms (SNPs)...