Exon

About: Exon is a research topic. Over the lifetime, 38308 publications have been published within this topic receiving 1745408 citations. The topic is also known as: exons.

Genomic variants in exons and introns: identifying the splicing spoilers

Abstract: When genome variants are identified in genomic DNA, especially during routine analysis of disease-associated genes, their functional implications might not be immediately evident. Distinguishing between a genomic variant that changes the phenotype and one that does not is a difficult task. An increasing amount of evidence indicates that genomic variants in both coding and non-coding sequences can have unexpected deleterious effects on the splicing of the gene transcript. So how can benign polymorphisms be distinguished from disease-associated splicing mutations?

Regulation of insulin-like growth factor I gene expression by growth hormone.

Abstract: Recombinant clones containing exon 3 of the insulin-like growth factor I (IGF-I) gene were isolated from a mouse genomic library. These sequences were used to generate an RNA probe, which was used in a solution hybridization assay to quantitate IGF-I mRNA in various murine tissues as a function of growth hormone status. The liver is the major site of IGF-I synthesis and the level of IGF-I mRNA is regulated about 10-fold by growth hormone in the growth hormone-deficient lit/lit mouse. Nuclear run-on assays were used to show that growth hormone regulation is manifested in part at the transcriptional level. Growth hormone also affects the size distribution of hepatic IGF-I mRNAs. Pancreas showed the highest non-hepatic expression, but every tissue analyzed contained some IGF-I mRNA. Expression was not growth hormone-dependent in most non-hepatic tissues.

Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction

Abstract: Through a large-scale case-control association study using 52,608 haplotype-based single nucleotide polymorphism (SNP) markers, we identified a susceptible locus for myocardial infarction (MI) on chromosome 22q12.1. Following linkage disequilibrium (LD) mapping, haplotype analyses revealed that six SNPs in this locus, all of which were in complete LD, showed markedly significant association with MI (chi2=25.27, P=0.0000005; comparison of allele frequency, 3,435 affected individuals versus 3,774 controls, in the case of intron 1 5,338 C>T; rs2331291). Within this locus, we isolated a complete cDNA of a novel gene, designated myocardial infarction associated transcript (MIAT). MIAT has five exons, and in vitro translation assay showed that MIAT did not encode any translational product, indicating that this is likely to be a functional RNA. In vitro functional analyses revealed that the minor variant of one SNP in exon 5 increased transcriptional level of the novel gene. Moreover, unidentified nuclear protein(s) bound more intensely to risk allele than non-risk allele. These results indicate that the altered expression of MIAT by the SNP may play some role in the pathogenesis of MI.

Frequent alternative splicing of human genes.

Abstract: Alternative splicing can produce variant proteins and expression patterns as different as the products of different genes, yet the prevalence of alternative splicing has not been quantified. Here the spliced alignment algorithm was used to make a first inventory of exon-intron structures of known human genes using EST contigs from the TIGR Human Gene Index. The results on any one gene may be incomplete and will require verification, yet the overall trends are significant. Evidence of alternative splicing was shown in 35% of genes and the majority of splicing events occurred in 5' untranslated regions, suggesting wide occurrence of alternative regulation. Most of the alternative splices of coding regions generated additional protein domains rather than alternating domains.