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.

A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.

Abstract: The t(11;18) (q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. We previously identified a YAC clone y789F3, which includes the breakpoint at 18q21 in a MALT lymphoma patient. BAC and PAC contigs were constructed on the YAC, and BAC 193f9 was found to encompass the breakpoint region. In the present study, we further narrowed down the breakpoint region at 18q21 in five MALT lymphoma patients by means of FISH and Southern blot analyses using the plasmid contig constructed from BAC 193f9. The breakpoints at 18q21 in three of the five MALT lymphoma patients were found to be clustered approximately within the 20 kb region. By using exon amplification and cDNA library screening, we identified a novel cDNA spanning the breakpoint region that exhibited aberrant mRNA signals in four of the five MALT lymphoma patients. The nucleotide sequence predicted an 813 amino acid protein that shows significant sequence similarity to the CD22beta and laminin 5 alpha3b subunit. We refer to the gene encoding this transcript as MALT1 (Mucosa-Associated Lymphoid Tissue lymphoma translocation gene 1). The alteration of MALT1 by translocation strongly suggests that this gene plays an important role in the pathogenesis of MALT lymphoma.

A new view of transcriptome complexity and regulation through the lens of local splicing variations

Abstract: Alternative splicing (AS) can critically affect gene function and disease, yet mapping splicing variations remains a challenge. Here, we propose a new approach to define and quantify mRNA splicing in units of local splicing variations (LSVs). LSVs capture previously defined types of alternative splicing as well as more complex transcript variations. Building the first genome wide map of LSVs from twelve mouse tissues, we find complex LSVs constitute over 30% of tissue dependent transcript variations and affect specific protein families. We show the prevalence of complex LSVs is conserved in humans and identify hundreds of LSVs that are specific to brain subregions or altered in Alzheimer's patients. Amongst those are novel isoforms in the Camk2 family and a novel poison exon in Ptbp1, a key splice factor in neurogenesis. We anticipate the approach presented here will advance the ability to relate tissue-specific splice variation to genetic variation, phenotype, and disease.

Universal PCR primers for S7 ribosomal protein gene introns in fish.

Abstract: Lessa (1992) introduced intron-targeted PCR, in which a noncoding intron was amplified using primers designed from highly conserved exon sequences. Introns appear to harbour a much greater degree of genetic polymorphism within and between species than exons. On the other hand, length and nucleotide sequence of exons, and exonÐintron arrangement can be highly conserved between considerably distant animal taxa. These characteristics may allow us to design sets of primers based on exon sequences to amplify flanking intron regions. Such sets of primers might function in very distant species. This study introduces two pairs of primer sets which were designed for amplifying the 1st and 2nd introns of the S7 ribosomal protein gene in fish. These primers were applied to distant fish species in order to determine their universality, and polymorphism in the amplified fragments was investigated. The DNA sequence data of the S7 ribosomal protein gene of puffer fish (Fugu rubripes), frog (Xenopus laevis) and human were derived from Cecconi et al. (1996), Mariottini et al. (1993) and Annilo et al. (1995), respectively. Exons 1, 2 and 3 of these species were aligned to determine conserved sequence regions. Because exon 1 of humans showed very poor homology with exon 1 of other species, data from puffer fish and frog were used for aligning exon 1. By contrast, highly conserved regions among these distant species were observed in exons 2 and 3. Two sets of primers were designed from the conserved sequence regions. The primer sequences to amplify the 1st intron (RP1) were 5'-TGGCCTCTTCCTTGGCCGTC-3' (S7RPEX1F) and 5'-AACTCGTCTGGCTTTTCGCC-3' (S7RPEX2R), and those for the 2nd intron (RP2) were 5'-AGCGCCAAAATAGTGAAGCC-3' (S7RPEX2F) and 5'-GCCTTCAGGTCAGAGTTCAT-3' (S7RPEX3R). The PCR reaction mixture contained 0.2 U of Taq DNA polymerase (Perkin Elmer Cetus), 0.2 mM of each dNTP, 1 μL of the manufacturerOs supplied 10× buffer, 2 mM MgCl2, 10 pmol of each primer and 10Ð50 ng of template DNA, in a final volume of 10 μL. Amplification was carried out with an initial denaturation at 95 iC for 1 min, followed by 30 cycles of amplification (denaturation at 95 iC for 30 s, annealing at 60 iC for 1 min and extension at 72 iC for 2 min, with a final extension at 72 iC for 10 min). PCR products and those digested by endonuclease were electrophoresed on a 2.5% agarose gel (Biogel) in TBE buffer (50 mM Tris, 1 mM EDTA, and 48.5 mM boric acid). Using the standard phenolÐchloroform method, crude DNA was extracted from frozen or ethanol-preserved muscles of chum salmon (Onchorhyncus keta), tuna (Thunnus spp.) and puffer fish (Fugu rubripes), each of which belonged to a different order. Results from PCR amplifications of RP1 and RP2 are shown in Fig. 1, where amplification of a single fragment was eminent in all species. Amplified fragments of salmon, tuna and puffer fish were all different in length with respect to each other, while no length difference was observed among eight tuna species (data not shown). A battery of 4-bp cutter endonucleases was applied to PCR products of yellowfin tuna (Thunnus albacares) in order to investigate intraspecific restriction site polymorphism. P R I M E R N O T E S 1255

Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors.

Abstract: PURPOSE: Activating mutations of the KIT juxtamembrane region are the most common genetic events in gastrointestinal stromal tumors (GISTs) and have been noted as independent prognostic factors. The impact of KIT mutation in other regions, such as the extracellular or kinase domains, is not well-defined and fewer than 30 cases have been published to date. EXPERIMENTAL DESIGN: One hundred twenty GISTs, confirmed by KIT immunoreactivity, were evaluated for the presence of KIT exon 9, 11, 13, and 17 mutations. The relation between the presence/type of KIT mutation and clinicopathological factors was analyzed using Fisher's exact test and log-rank test. RESULTS: Forty-four % of the tumors were located in the stomach, 47% in the small bowel, 6% in the rectum, and 3% in the retroperitoneum. Overall, KIT mutations were detected in 78% of patients as follows: 67% in exon 11, 11% in exon 9, and none in exon 13 or 17. The types of KIT exon 11 mutations were heterogeneous and clustered in the classic "hot spot" at the 5' end of exon 11. Seven % of cases showed internal tandem duplications (ITD) at the 3' end of exon 11, in a region that we designate as a second hot spot for KIT mutations. Interestingly, these cases were associated with: female predominance, stomach location, occurrence in older patients, and favorable outcome. There were significant associations between exon 9 mutations and large tumor size (P < 0.001) and extragastric location (P = 0.02). Ten of these 13 patients with more than 1-year follow-up have developed recurrent disease. CONCLUSIONS: Most KIT-expressing GISTs show KIT mutations that are preferentially located within the classic hot spot of exon 11. In addition, we found an association between a second hot spot at the 3'end of exon 11, characterized by ITDs, and a subgroup of clinically indolent gastric GISTs in older females. KIT exon 9 mutations seem to define a distinct subset of GISTs, located predominantly in the small bowel and associated with an unfavorable clinical course.