AutDB: a platform to decode the genetic architecture of autism

Abstract

AutDB is a deeply annotated resource for exploring the impact of genetic variations associated with autism spectrum disorders (ASD). First released in 2007, AutDB has evolved into a multi-modular resource of diverse types of genetic and functional evidence related to ASD. Current modules include: Human Gene, which annotates all ASD-linked genes and their variants; Animal Model, which catalogs behavioral, anatomical and physiological data from rodent models of ASD; Protein Interaction (PIN), which builds interactomes from direct relationships of protein products of ASD genes; and Copy Number Variant (CNV), which catalogs deletions and duplications of chromosomal loci identified in ASD. A multilevel data-integration strategy is utilized to connect the ASD genes to the components of the other modules. All information in this resource is manually curated by expert scientists from primary scientific publications and is referenced to source articles. AutDB is actively maintained with a rigorous quarterly data release schedule. As of June 2017, AutDB contains detailed annotations for 910 genes, 2197 CNV loci, 1060 rodent models and 38 296 PINs. With its widespread use by the research community, AutDB serves as a reference resource for analysis of large datasets, accelerating ASD research and potentially leading to targeted drug treatments. AutDB is available at http://autism.mindspec.org/autdb/Welcome.do.

PAK2 Haploinsufficiency Results in Synaptic Cytoskeleton Impairment and Autism-Related Behavior

“…Autism spectrum disorders (ASD), characterized by abnormal social interaction and communication and restricted interests and repetitive behaviors, are a group of complex neurodevelopmental disorders (Christensen et al, 2016;de la Torre-Ubieta et al, 2016). To date, >800 ASD-related genes have been included in the database AutDB (Pereanu et al, 2018), suggesting the extreme genetic heterogeneity of this disease (Bi et al, 2012;Jeste and Geschwind, 2014;Li et al, , 2017. However, the molecular etiologies of these genes in ASD have been demonstrated only in limited animal models Deriziotis et al, 2014;Huang et al, 2014;Katayama et al, 2016;Liu et al, 2016;Orosco et al, 2014;Peç a et al, 2011;Peñ agarikano et al, 2011;Schoch et al, 2017;Wang et al, 2016), leaving the challenge of translating autism genetics to clinical applications (Vorstman et al, 2017).…”

Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins

“…The preferential effect on large mRNAs is likely mediated by direct FMR1 binding, because the average size of target proteins common to both this study and (7) was 1841 amino acids. Furthermore, genes linked to autism as a group are significantly longer than average (16,20).…”

FMRP activates the translation of large autism/intellectual disability proteins and stimulates N-end rule E3 ligase Poe/UBR4 production within puromycin-sensitive RNP particles

“…In order to determine whether characteristics of transcripts encoded by ASD/ID genes distinguish them from other neuronally-expressed genes, we examined general properties of all transcripts expressed in the juvenile mouse cortex (Das Sharma et al 2019). We classified SFARI Class I and Class II (Abrahams et al 2013;Pereanu et al 2017) autism genes as "ASD genes" and found that they differ from other neuronally-expressed genes in several ways. (1) ASD/ID genes as a group encode proteins much larger than average.…”