AutDB: A gene reference resource for autism research

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Nucleic Acids Research (Impact Factor: 9.11). 12/2008; 37(Database issue):D832-6. DOI: 10.1093/nar/gkn835
Source: PubMed


Recent advances in studies of Autism Spectrum Disorders (ASD) has uncovered many new candidate genes and continues to do so
at an accelerated pace. To address the genetic complexity of ASD, we have developed AutDB (, a publicly available web-portal for on-going collection, manual annotation and visualization of genes linked to the disorder.
We present a disease-driven database model in AutDB where all genes connected to ASD are collected and classified according
to their genetic variation: candidates identified from genetic association studies, rare single gene mutations and genes linked
to syndromic autism. Gene entries are richly annotated for their relevance to autism, along with an in-depth view of their
molecular functions. The content of AutDB originates entirely from the published scientific literature and is organized to
optimize its use by the research community. The main focus of this resource is to provide an up-to-date, annotated list of
ASD candidate genes in the form of reference dataset for interrogating molecular mechanisms underlying the disorder. Our model
for consolidated knowledge representation in genetically complex disorders could be replicated to study other such disorders.

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Available from: Sharmila Banerjee-Basu
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    • "These data suggest that Kdm5c loss leads to different functional consequences depending on the brain area. To determine whether genes associated with neurodevelopmental disorders significantly overlap with the mis-regulated genes in Kdm5c-KO brain, we performed LR path analyses using curated lists of genes that are associated with IDs (Gardiner, 2015), ASDs (Basu et al., 2009), and schizophrenia (Fromer et al., 2014). Although many of these genes overlapped with mis-regulated genes in the KO brains, we did not find statistically significant enrichment in either the amygdala or the frontal cortex (p = 0.37 $0.93; "
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    ABSTRACT: Mutations in a number of chromatin modifiers are associated with human neurological disorders. KDM5C, a histone H3 lysine 4 di- and tri-methyl (H3K4me2/3)-specific demethylase, is frequently mutated in X-linked intellectual disability (XLID) patients. Here, we report that disruption of the mouse Kdm5c gene recapitulates adaptive and cognitive abnormalities observed in XLID, including impaired social behavior, memory deficits, and aggression. Kdm5c-knockout brains exhibit abnormal dendritic arborization, spine anomalies, and altered transcriptomes. In neurons, Kdm5c is recruited to promoters that harbor CpG islands decorated with high levels of H3K4me3, where it fine-tunes H3K4me3 levels. Kdm5c predominantly represses these genes, which include members of key pathways that regulate the development and function of neuronal circuitries. In summary, our mouse behavioral data strongly suggest that KDM5C mutations are causal to XLID. Furthermore, our findings suggest that loss of KDM5C function may impact gene expression in multiple regulatory pathways relevant to the clinical phenotypes.
    Full-text · Article · Jan 2016 · Cell Reports
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    • "We performed ultradeep sequencing on DNA from postmortem cerebral cortical and/or cerebellar brain samples from 55 ASD cases, 50 neurotypical controls, and 17 cases with suspected ASD or related diagnoses (Figure 1A; see Table S1 available online ). In order to achieve the high coverage necessary to sensitively detect somatic mosaic mutations, we used a targeted panel of 78 ASD candidate genes showing dominant or X-linked inheritance (see Supplemental Experimental Procedures) (Basu et al., 2009; Betancur, 2011; O'Roak et al., 2012). We achieved 5473 average coverage, with 95.7% of the analyzable target regions covered by R100 reads and 48.2% covered by R1,000 reads, providing sensitivity to detect somatic mutations in these genes to a level of z5% alternate allele frequency (AAF). "
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    ABSTRACT: Single nucleotide variants (SNVs), particularly loss-of-function mutations, are significant contributors to autism spectrum disorder (ASD) risk. Here we report the first systematic deep sequencing study of 55 postmortem ASD brains for SNVs in 78 known ASD candidate genes. Remarkably, even without parental samples, we find more ASD brains with mutations that are protein-altering (26/55 cases versus 12/50 controls, p = 0.015), deleterious (16/55 versus 5/50, p = 0.016), or loss-of-function (6/55 versus 0/50, p = 0.028) compared to controls, with recurrent deleterious mutations in ARID1B, SCN1A, SCN2A, and SETD2, suggesting these mutations contribute to ASD risk. In several cases, the identified mutations and medical records suggest syndromic ASD diagnoses. Two ASD and one Fragile X premutation case showed deleterious somatic mutations, providing evidence that somatic mutations occur in ASD cases, and supporting a model in which a combination of germline and/or somatic mutations may contribute to ASD risk on a case-by-case basis.
    Full-text · Article · Dec 2015 · Neuron
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    • "The role of TOP2B in neural development suggests it may be involved in neurodevelopmental disorders such as autism and schizophrenia. Genes associated with TOP2B peaks and genes on or near loci implicated in autism or schizophrenia (Basu et al., 2009;De Rubeis et al., 2014; Schizophrenia Working Group of the PsychiatricGenomics Consortium, 2014), have been compared, see Venn diagram in Fig. 4, the genes are listed in Table S2. TOP2B 2 peaks from untreated cells are associated with three genes (CNTN4, IMMP2L and SATB2) implicated in both autism and schizophrenia whilst TOP2B 2 peaks from E2-treated cells are associated with five genes (CNTN4, IMMP2L, EPC, SMG6 and CACNA1C). "
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    ABSTRACT: We report the whole genome ChIP seq for human TOP2B from MCF7 cells. Using three different peak calling methods, regions of binding were identified in the presence or absence of the nuclear hormone estradiol, as TOP2B has been reported to play a role in ligand-induced transcription. TOP2B peaks were found across the whole genome, 50% of the peaks fell either within a gene or within 5 kb of a transcription start site. TOP2B peaks coincident with gene promoters were less frequently associated with epigenetic features marking active promoters in estradiol treated than in untreated cells. Significantly enriched transcription factor motifs within the DNA sequences underlying the peaks were identified. These included SP1, KLF4, TFAP2A, MYF, REST, CTCF, ESR1 and ESR2. Gene ontology analysis of genes associated with TOP2B peaks found neuronal development terms including axonogenesis and axon guidance were significantly enriched. In the absence of functional TOP2B there are errors in axon guidance in the zebrafish eye. Specific heparin sulphate structures are involved in retinal axon targeting. The glycosaminoglycan biosynthesis-heparin sulphate/heparin pathway is significantly enriched in the TOP2B gene ontology analysis, suggesting changes in this pathway in the absence of TOP2B may cause the axon guidance faults.
    Full-text · Article · Oct 2015 · Biology Open
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