Allele-Specific Regulation of the Candidate Autism Liability Gene by the Enhancer Variant rs4925102 ().

() is a dosage-sensitive gene that causes autistic phenotypes when deleted or duplicated. Observations from clinical cases and animal models also suggest that changes of expression levels contribute to autism. Previously, we used a bioinformatic approach to identify several single nucleotide polymorphisms (SNPs) located within the 5'-region of that correlate with mRNA expression in the human brain.

RNA binding motif protein 10 suppresses lung cancer progression by controlling alternative splicing of eukaryotic translation initiation factor 4H.

Background: RNA splicing defects are emerging molecular hallmarks of cancer. The gene encoding splicing factor RNA binding motif protein 10 (RBM10) has been found frequently mutated in various types of cancer, particularly lung adenocarcinoma (LUAD), but how RBM10 affects cancer pathogenesis remains to be determined. Moreover, the functional roles and clinical significance of RBM10 mutation-associated splicing events in LUAD are largely unknown.

A multiple coefficient of determination-based method for parsing SNPs that correlate with mRNA expression.

In this study, we present a novel, multiple coefficient of determination (R)-based method for parsing SNPs located within the chromosomal neighborhood of a gene into semi-independent families, each of which corresponds to one or more functional variants that regulate transcription of the gene. Specifically, our method utilizes a matrix equation framework to calculate R values for SNPs within a chromosome region of interest (ROI) based upon the choices of 1-4 "index" SNPs (iSNPs) that serve as proxies for underlying regulatory variants. Exhaustive testing of sets of 1-4 candidate iSNPs identifies iSNP models that best account for estimated R values derived from single-variable linear regression analysis of correlations between mRNA expression and genotypes of individual SNPs.

Functional analysis of novel DEAF1 variants identified through clinical exome sequencing expands DEAF1-associated neurodevelopmental disorder (DAND) phenotype.

Deformed epidermal autoregulatory factor-1 (DEAF1), a transcription factor essential for central nervous system and early embryonic development, has recently been implicated in a series of intellectual disability-related neurodevelopmental anomalies termed, in this study, as DEAF1-associated neurodevelopmental disorder (DAND). We identified six potentially deleterious DEAF1 variants in a cohort of individuals with DAND via clinical exome sequencing (CES) and in silico analysis, including two novel de novo variants: missense variant c.634G > A p.

Autoregulation of RBM10 and cross-regulation of RBM10/RBM5 via alternative splicing-coupled nonsense-mediated decay.

Mutations in the spliceosomal RNA binding protein RBM10 cause TARP syndrome and are frequently observed in lung adenocarcinoma (LUAD). We have previously shown that RBM10 enhances exon skipping of its target genes, including its paralog RBM5. Here, we report that RBM10 negatively regulates its own mRNA and protein expression and that of RBM5 by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD).