Orchestration of Neurodevelopmental Programs by RBFOX1

Bill, Brent R.; Lowe, Jennifer K.; DyBuncio, Christina T.; Fogel, Brent L.

doi:10.1016/b978-0-12-418700-9.00008-3

Cited by 70 publications

(65 citation statements)

References 67 publications

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“…It is reasonable to think that the length of a gene can be one of the factors that influence its probability of being interrupted when there is a chromosomal lesion or to mutate following point errors of DNA replication. Interestingly, for these genes mutations and clinical phenotypes have been described (27–29) and since their correlations with gene length do not yet appear to have been systematically studied to date, investigations in the field will be made easier by the systematic dataset we present here.…”

Section: Discussionmentioning

confidence: 99%

GeneBase 1.1: a tool to summarize data from NCBI gene datasets and its application to an update of human gene statistics

et al. 2016

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We release GeneBase 1.1, a local tool with a graphical interface useful for parsing, structuring and indexing data from the National Center for Biotechnology Information (NCBI) Gene data bank. Compared to its predecessor GeneBase (1.0), GeneBase 1.1 now allows dynamic calculation and summarization in terms of median, mean, standard deviation and total for many quantitative parameters associated with genes, gene transcripts and gene features (exons, introns, coding sequences, untranslated regions). GeneBase 1.1 thus offers the opportunity to perform analyses of the main gene structure parameters also following the search for any set of genes with the desired characteristics, allowing unique functionalities not provided by the NCBI Gene itself. In order to show the potential of our tool for local parsing, structuring and dynamic summarizing of publicly available databases for data retrieval, analysis and testing of biological hypotheses, we provide as a sample application a revised set of statistics for human nuclear genes, gene transcripts and gene features. In contrast with previous estimations strongly underestimating the length of human genes, a ‘mean’ human protein-coding gene is 67 kbp long, has eleven 309 bp long exons and ten 6355 bp long introns. Median, mean and extreme values are provided for many other features offering an updated reference source for human genome studies, data useful to set parameters for bioinformatic tools and interesting clues to the biomedical meaning of the gene features themselves.Database URL: http://apollo11.isto.unibo.it/software/

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Section: Discussionmentioning

confidence: 99%

GeneBase 1.1: a tool to summarize data from NCBI gene datasets and its application to an update of human gene statistics

et al. 2016

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“…RBFOX1 (or A2BP1 ) has been identified as disrupted by rare translocation or CNV in ASDs[111–113]. The encoded protein (FOX1) controls alternative splicing and transcription[114], including many other ASD candidate genes, and is thought to be a key regulator of neurodevelopment[115]. DISC1 , known for identification via rare structural variant in schizophrenia, has also been associated with ASDs[78,112,116,117].…”

Section: Discussionmentioning

confidence: 99%

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

et al. 2017

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Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02). We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10−16), with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway.

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“…RBFOX proteins have a single RRM, highly homologous among the three paralogs, and their binding sites are exceptionally highly conserved in sequence (UGCAUG) and position across vertebrate evolution (Sun et al 2012). Mutations or deletions in RBFOX1 and RBFOX3 are found in epilepsy patients (Bhalla et al 2004;Lal et al 2013a,b), whereas copy-number variations in RBFOX1 are associated with autism spectrum disorders and spinocerebellar ataxias (Bill et al 2013;Weyn-Vanhentenryck et al 2014). Mouse models with Rbfox KO or KD show extensive defects in neuronal and muscle physiology, suggesting that these proteins play key roles in normal development (Gehman et al 2011(Gehman et al , 2012.…”

Section: Rbfox2-rna Binding Protein Fox-2 Homologmentioning

confidence: 99%

Splicing-factor alterations in cancers

Anczuków

Krainer

2016

RNA

226

247

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Tumor-associated alterations in RNA splicing result either from mutations in splicing-regulatory elements or changes in components of the splicing machinery. This review summarizes our current understanding of the role of splicing-factor alterations in human cancers. We describe splicing-factor alterations detected in human tumors and the resulting changes in splicing, highlighting cell-type-specific similarities and differences. We review the mechanisms of splicing-factor regulation in normal and cancer cells. Finally, we summarize recent efforts to develop novel cancer therapies, based on targeting either the oncogenic splicing events or their upstream splicing regulators.

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Orchestration of Neurodevelopmental Programs by RBFOX1

Cited by 70 publications

References 67 publications

GeneBase 1.1: a tool to summarize data from NCBI gene datasets and its application to an update of human gene statistics

GeneBase 1.1: a tool to summarize data from NCBI gene datasets and its application to an update of human gene statistics

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

Splicing-factor alterations in cancers

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