TY - JOUR. T1 - Intron/exon structure of the human gene for the muscle isozyme of glycogen phosphorylase. AU - Burke, J.. AU - Hwang, P.. AU - Anderson, L.. AU - Lebo, R.. AU - Gorin, Fredric A. AU - Fletterick, R.. PY - 1987. Y1 - 1987. N2 - The intron/exon organization of the human gene for glycogen phosphorylase has been determined. The segments of the polypeptide chain that corresponds to the 19 exons of the gene are examined for relationships between the three-dimensional structure to the protein and gene structure. Only weak correlations are observed between domains of phosphorylase and exons. The nucleotide binding domains that are found in phosphorylase and other glycolytic enzymes are examined for relationships between exons of the genes and structures of the domains. When mapped to the three-dimensional structures, the intron/exon boundaries are shown to be widely distributed in this family of protein domains.. AB - The intron/exon organization of the human gene for glycogen ...
To test the quality of the new algorithm, several well-known genes with clusters of mutually exclusive exons with different characteristics were analysed (Figure 3). The first test case is the cytoplasmic dynein heavy chain from Schistosoma mansoni (Sm DHC1). Dynein heavy chains belong to the longest genes in eukaryotes encoding 4000 - 5000 residues and are spread over several dozens of exons. The mutually exclusive exon is clearly identified in the middle of the gene, encoding split codons at the 3- and 5-end of the exon. The query exon and the candidate exon have identical lengths and show strong homology. Based on the multiple sequence alignment of more than 2000 DHCs these exons are mutually exclusive and not constitutive or differentially included. The second case represents the muscle myosin heavy chain gene from the waterflea Daphnia magna[19]. The arthropod muscle myosin heavy chain genes contain several clusters of mutually exclusive exons to fine tune the mechanochemical ...
Alternative exon usage (AEU) is an important component of gene regulation. Exon expression platforms allow the detection of associations between AEU and phenotypes such as cancer. Numerous studies have identified associations between gene expression and the brain cancer glioblastoma multiforme (GBM). The few consistent gene expression biomarkers of GBM that have been reported may be due to the limited consideration of AEU and the analytical approaches used. The objectives of this study were to develop a model that accounts for the variations in expression present between the exons within a gene and to identify AEU biomarkers of GBM survival. The expression of exons corresponding to 25,403 genes was related to the survival of 250 individuals diagnosed with GBM in a training data set. Genes exhibiting AEU in the training data set were confirmed in an independent validation data set of 78 patients. A hierarchical mixed model that allows the consideration of covariation between exons within a gene and of
Background The contribution of alternative splicing and isoform expression to cellular response is emerging as an area of considerable interest, and the newly developed exon arrays allow for systematic study of these processes. We use this pilot study to report on the feasibility of exon array implementation looking to replace the 3 in vitro transcription expression arrays in our laboratory. Results Peripheral blood mononuclear cells form healthy donors were activated using phytohemagglutinin, IL2 and ionomycin and harvested at 5 points over a 7 day period. Flow cytometry measured cell cycle events and the Affymetrix exon array platform was used to identify the gene expression and alternate exon usage changes. Gene expression changes were noted in a total of 2105 transcripts, and alternate exon usage identified in 472 transcript clusters. There was an overlap of 263 transcripts which showed both differential expression and alternate exon usage over time. Gene ontology enrichment analysis showed ...
This track shows the genomic locations of the probesets and probes from the Affymetrix Exon array. This array was designed to interrogate every known and putative exon in the human genome. For the design of this array, Affymetrix compiled evidence of expression from sources including well-annotated genes such as RefSeq, genomic alignments of mRNA and EST sequences, gene predictions, exon predictions, and regions that are syntenic to conserved regions in related species. Using this evidence, Affymetrix designed a probeset for each known or putative exon. While some of these regions might never be transcribed, the goal is to obtain a comprehensive measurement of transcription in the human genome. In most cases, this array contains one probeset per exon. However, whenever this design-time evidence suggested that some exon had alternative splice sites, the exon was subdivided into two or more regions, and one probeset was designed for each region (where possible). The array contains no probesets for ...
This study addresses two important aspects of TMPRSS2-ERG expression in prostate cancer. First of all, a remarkable difference in expression characteristics was detected between TMPRSS2(exon 1) and TMPRSS2(exon 1)-ERG transcripts on the one hand and TMPRSS2(exon 0) and TMPRSS2(exon 0)-ERG transcripts on the other hand. Secondly, the clinical data indicated a more favorable prognosis for prostate cancer patients expressing TMPRSS2(exon 0)-ERG transcripts.. It is estimated that almost half of all genes in the human genome contain more than one first exon as an important mechanism to regulate gene expression (19). Here, we showed that TMPRSS2 transcripts starting at exon 0 were much more prostate specific than those starting at exon 1 (Fig. 1B) and that the expression level of transcripts containing exon 0 was much more variable (Fig. 1D). TMPRSS2 exon 0 is located in a retroviral repeat element, ERVL-B4 (Fig. 1A). This repeat does not contain a standard long terminal repeat promoter element; ...
An additional nicety would be to somehow work in a preference for 5 exons. For example, lets say a gene has 3 exons and, with the expression data, all 3 exons are equally expressed. Id like to selectively get the first 2 exons. Ive started learning Galaxy and was able to import BED files for UCSC exons (as in the Galaxy 101 tutorial) and a BED file for Affy microarray expression data. (I tried also importing the Burge RNA-seq track as BED but couldnt get it to work). I did an inner join on genomic sequences to join the expression data with the exons and sorted them from most expressed to least. But how do I sort within genes? That is, how do I get the top 2 exons per gene (highest expressing exons per gene) and, if there are more than 2 with equally high expression, how do I preferentially get the 5` exons? Im also open to ways to do this without using Galaxy, etc. I want to do this for an entire genome, so I figured it would be good to have a Galaxy workflow, which I could then apply to ...
Exon shuffling was first introduced in 1978 when Walter Gilbert discovered that the existence of introns could play a major role in the evolution of proteins. It was noted that recombination within introns could help assort exons independently and that repetitive segments in the middle of introns could create hotspots for recombination to shuffle the exonic sequences. However, the presence of these introns in eukaryotes and absence in prokaryotes created a debate about the time in which these introns appeared. Two theories arose: the introns early theory and the introns late theory. Supporters of the introns early theory believed that introns and RNA splicing were the relics of the RNA world and therefore both prokaryotes and eukaryotes had introns in the beginning. However, prokaryotes eliminated their introns in order to obtain a higher efficiency, while eukaryotes retained the introns and the genetic plasticity of the ancestors. On the other hand, supporters of the introns late theory ...
DNA microarrays and RNAseq are complementary methods for studying RNA molecules. Current computational methods to determine alternative exon usage (AEU) using such data require impractical visual inspection and still yield high false-positive rates. Integrated Gene and Exon Model of Splicing (iGEMS) adapts a gene-level residuals model with a gene size adjusted false discovery rate and exon-level analysis to circumvent these limitations. iGEMS was applied to two new DNA microarray datasets, including the high coverage Human Transcriptome Arrays 2.0 and performance was validated using RT-qPCR. First, AEU was studied in adipocytes treated with (n = 9) or without (n = 8) the anti-diabetes drug, rosiglitazone. iGEMS identified 555 genes with AEU, and robust verification by RT-qPCR (∼90%). Second, in a three-way human tissue comparison (muscle, adipose and blood, n = 41) iGEMS identified 4421 genes with at least one AEU event, with excellent RT-qPCR verification (95%, n = 22). Importantly, iGEMS ...
TY - JOUR. T1 - Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene. AU - Fukumura, Kazuhiro. AU - Kato, Ayako. AU - Jin, Yui. AU - Ideue, Takashi. AU - Hirose, Tetsuro. AU - Kataoka, Naoyuki. AU - Fujiwara, Toshinobu. AU - Sakamoto, Hiroshi. AU - Inoue, Kunio. PY - 2007/8/1. Y1 - 2007/8/1. N2 - Fox-1 is a regulator of tissue-specific splicing, via binding to the element (U)GCAUG in mRNA precursors, in muscles and neuronal cells. Fox-1 can regulate splicing positively or negatively, most likely depending on where it binds relative to the regulated exon. In cases where the (U)GCAUG element lies in an intron upstream of the alternative exon, Fox-1 protein functions as a splicing repressor to induce exon skipping. Here we report the mechanism of exon skipping regulated by Fox-1, using the hF1γ gene as a model system. We found that Fox-1 induces exon 9 skipping by repressing splicing of the downstream intron 9 ...
Due to the inclusive nature of our genome-wide exon microarrays, we are able to discover novel alternative splicing patterns in addition to monitoring known splicing events. As technology allows for smaller feature sizes, it will be possible to include larger numbers of probes per array, thereby increasing the feasibility of large-scale non-biased designs. Microarray designs that are more inclusive and less dependent on current genome annotations will ultimately aid in the development of tools that are designed to annotate, rather than the other way around. For example, recent work using a similar design concept based on the mouse genome was able to refine gene boundaries using co-regulation of exons across many different tissue types [43]. However, our data suggest that there is a large amount of expression outside of well annotated exons. Reliance on any one single exon prediction algorithm or sequence content source will likely result in incomplete coverage.. Exon microarrays represent a huge ...
Genemark = Bio::Tools::Genemark-,new(-file =, result.Genemark); # filehandle: $Genemark = Bio::Tools::Genemark-,new( -fh =, \*INPUT ); # parse the results # note: this class is-a Bio::Tools::AnalysisResult which implements # Bio::SeqAnalysisParserI, i.e., $Genemark-,next_feature() is the same while($gene = $Genemark-,next_prediction()) { # $gene is an instance of Bio::Tools::Prediction::Gene, which inherits # off Bio::SeqFeature::Gene::Transcript. # # $gene-,exons() returns an array of # Bio::Tools::Prediction::Exon objects # all exons: @exon_arr = $gene-,exons(); # initial exons only @init_exons = $gene-,exons(Initial); # internal exons only @intrl_exons = $gene-,exons(Internal); # terminal exons only @term_exons = $gene-,exons(Terminal); # singleton exons: ($single_exon) = $gene-,exons(); } # essential if you gave a filename at initialization (otherwise the file # will stay open) $Genemark-,close ...
Dopamine D4 receptor exon III genotype influence on the auditory evoked novelty P3.: The functional implications of the dopamine D4 receptor gene (DRD4) exon II
Comparative analysis of exon/intron organization of genes and their resulting protein structures is important for understanding evolutionary relationships between species, rules of protein organization, and protein functionality. We present SEDB, the Structural Exon Database, with a web interface, an application which allows users to retrieve the exon/intron organization of genes and map the location of the exon boundaries and intron phase onto a multiple structural alignment. SEDB is linked with Friend, an integrated analytical multiple sequence/structure viewer, which allows simultaneous visualization of exon boundaries on structure and sequence alignments. With SEDB researchers can study the correlations of gene structure with the properties of the encoded three-dimensional protein structures across eukaryotic organisms ...
The properties of genotype-phenotype landscapes are crucial for understanding evolution but are not characterized for most traits. Here, we present a ,95% complete local landscape for a defined molecular function-the alternative splicing of a human exon (FAS/CD95 exon 6, involved in the control of apoptosis). The landscape provides important mechanistic insights, revealing that regulatory information is dispersed throughout nearly every nucleotide in an exon, that the exon is more robust to the effects of mutations than its immediate neighbours in genotype space, and that high mutation sensitivity (evolvability) will drive the rapid divergence of alternative splicing between species unless it is constrained by selection. Moreover, the extensive epistasis in the landscape predicts that exonic regulatory sequences may diverge between species even when exon inclusion levels are functionally important and conserved by selection ...
Protein tyrosine phosphatase CD45 is a key player in T-cell receptor signaling and lymphocyte development. Differential expression of multiple CD45 isoforms resulting from the alternative splicing of exons A, B, and C, which encode part of the extracellular domain, is an important feature of CD45 expression. We report a novel isoform that results from the alternative splicing of a previously undiscovered exon between the constitutively spliced exon 3 and the alternatively spliced exon A. This 123-bpâ€:#x0093:long exon encodes 41 amino acids and is unlikely to undergo te extensive glycosylation seen for the regions encoded by exons A, B, and C. Reverse transcriptase polymerase chain reaction demonstrates that this isoform is expressed in human peripheral blood mononuclear cells and cell lines of lymphoid origin, but with a clearly different pattern to that of the isoforms caused by exons A, B, and C, implying a different regulatory mechanism.
The recently released Exon arrays differ from the previous 3 arrays in terms of the number, placement and annotational confidence of oligonucleotide probes. As a result, new methods that take advantage of Exon array design features can improve gene-level expression estimates. In this manuscript we propose a strategy for computing gene expression indices on Exon arrays that combines a probe-specific background correction with a probe selection procedure. Analysis of independent SAGE data demonstrates that A/P calls generated from the MAT background model offer substantial improvements. This improvement is likely due to both the increased number of probes per gene and the improvement of the MAT background model over the default Affymetrix background correction. Furthermore, we observed that Exon array gene expression indices show a high degree of correlation between human and mouse orthologs.. This work represents a step in the continued development of accurate gene-level expression estimates ...
Although unicellular eukaryotes such as yeast have either no introns or very few, metazoans and especially vertebrate genomes have a large fraction of non-coding DNA. For instance, in the human genome only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA.[5] This can provide a practical advantage in omics-aided health care (such as precision medicine) because it makes commercialized whole exome sequencing a smaller and less expensive challenge than commercialized whole genome sequencing. The large variation in genome size and C-value across life forms has posed an interesting challenge called the C-value enigma. Across all eukaryotic genes in GenBank there were (in 2002), on average, 5.48 exons per gene. The average exon encoded 30-36 amino acids.[6] While the longest exon in the human genome is 11555 bp long, several exons have been found to be only 2 bp long.[7] A single-nucleotide exon has been reported from the Arabidopsis ...
patients (13% of all patients), while exon 45 and 53 skipping would both individually be applicable to 8% of the patients (Aartsma-Rus et al. 2009a). AONs to skip each individual exon have been identified and theoretically exon skipping would be applicable to 80% of deletions, 91% of small mutations and 73% of duplications, or 83% of all patients (Table 5.2).. However, mutations in the essential cysteine-rich domain invariably cause DMD, regardless of whether deletions are in-frame or out-of-frame (Aartsma-Rus et al. 2006b). Thus, for patients with mutations in the part of the transcripts that encodes the cysteine-rich domain (exons 64-70, Fig. 5.1) exon skipping will in all likelihood not be beneficial. Since there are two N-terminal actin-binding domains, and a third domain located in the central rod domain (Fig. 5.1), there is more flexibility for deletions affecting one or two actin-binding domains, as the additional domains retain some of the functionality (Aartsma-Rus et al. 2006b). ...
Detection of exon junctions in single cells within the tissue environment is possible by using only one ZZ probe uniquely designed on the specific exon junction of interest. For an example of the detection of a sequence with specific exon skipping, METΔ14 (Frampton GM et al, Cancer Discovery, 2015; Awad MM et al, J Clin Oncol, 2016) where 3 probes are designed (image 1): one control probe designed for an exon junction present in all MET transcripts (exon junction 12/13), one probe designed for the exon junction with exon 14 (exon junction 14/15), and one probe designed for the exon junction with exon 14 skipping (exon junction 13/15). Figure 2 shows an example of the BaseScope™ assay used for the detection of METΔ14 in cell lines ...
Tumor-predominant splice isoforms were identified during comparative in silico sequence analysis of EST clones, suggesting that global aberrant alternative pre-mRNA splicing may be an epigenetic phenomenon in cancer. We used an exon expression array to perform an objective, genome-wide survey of glioma-specific splicing in 24 GBM and 12 nontumor brain samples. Validation studies were performed using RT-PCR on glioma cell lines, patient tumor and nontumor brain samples. In total, we confirmed 14 genes with glioma-specific splicing; seven were novel events identified by the exon expression array (A2BP1, BCAS1, CACNA1G, CLTA, KCNC2, SNCB, and TPD52L2). Our data indicate that large changes (| 5-fold) in alternative splicing are infrequent in gliomagenesis (| 3% of interrogated RefSeq entries). The lack of splicing changes may derive from the small number of splicing factors observed to be aberrantly expressed. While we observed some tumor-specific alternative splicing, the number of genes showing exclusive
Abstract: Cultured muscle cells from DMD patients carrying duplications were transfected with AONs targeting the duplicated exons, and the dystrophin RNA and protein were analyzed.For two brothers with an exon 44 duplication, skipping was, even at suboptimal transfection conditions, so efficient that both exons 44 were skipped, thus generating, once more, an out-of-frame transcript. In such cases, one may resort to multi-exon skipping to restore the reading frame, as is shown here by inducing skipping of exon 43 and both exons 44. By contrast, in cells from a patient with an exon 45 duplication we were able to induce single exon 45 skipping, which allowed restoration of wild type dystrophin. The correction of a larger duplication (involving exons 52 to 62), by combinations of AONs targeting the outer exons, appeared problematic due to inefficient skipping and mistargeting of original instead of duplicated exons.The correction of DMD duplications by exon skipping depends on the specific exons ...
An exon is any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature messenger RNA. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome. The term exon derives from the expressed region and was coined by American biochemist Walter Gilbert in 1978: The notion of the cistron… must be replaced by that of a transcription unit containing regions which will be lost from the mature messenger - which I suggest we call introns (for intragenic regions) - alternating with regions which will be expressed - exons. This definition was originally made for protein-coding transcripts that are spliced before being translated. The term later ...
The Fgf2 gene is expressed in the brain neuroepithelium during embryonic development and in astroglial cells throughout life. Previous knockout studies suggested that FGF2 plays a role in the proliferation of neural progenitors in the embryonic cerebral cortex. These studies exclusively used knockout alleles lacking the Fgf2 exon 1. However, the description of putative alternative exons located downstream from the canonical exon 1 raised the possibility that alternatively spliced transcripts may compensate for the lack of the canonical exon 1 in the Fgf2 -/- mice. We generated and characterized a new line of Fgf2 knockout mice lacking the expression of exon 3, which is conserved in all Fgf2 transcripts and contains essential heparin and receptor binding interfaces. The expression of Fgf2 exon 3 was prevented by inserting a transcriptional STOP cassette in the Fgf2 genomic locus. These mice demonstrate a phenotype in the adult neocortex characterized by decreased density and number of cortical excitatory
Author: Britanova, O. et al.; Genre: Journal Article; Published in Print: 2002-07; Keywords: cortex; transcription factor; subtraction; Sey; reeler; mutant|br/|; Title: The mouse Laf4 gene: Exon/intron organization, cDNA sequence, alternative splicing, and expression during central nervous system development
mzef = Bio::Tools::MZEF-,new(-file =, result.mzef); # filehandle: $mzef = Bio::Tools::MZEF-,new( -fh =, \*INPUT ); # to indicate that the sequence was reversed prior to feeding it to MZEF # and that you want to have this reflected in the strand() attribute of # the exons, as well have the coordinates translated to the non-reversed # sequence $mzef = Bio::Tools::MZEF-,new( -file =, result.mzef, -strand =, -1 ); # parse the results # note: this class is-a Bio::Tools::AnalysisResult which implements # Bio::SeqAnalysisParserI, i.e., $genscan-,next_feature() is the same while($gene = $mzef-,next_prediction()) { # $gene is an instance of Bio::Tools::Prediction::Gene # $gene-,exons() returns an array of # Bio::Tools::Prediction::Exon objects # all exons: @exon_arr = $gene-,exons(); # internal exons only @intrl_exons = $gene-,exons(Internal); # note that presently MZEF predicts only internal exons! } # essential if you gave a filename at initialization (otherwise the file # will stay open) ...
In human pre-mRNA splicing, infrequent errors occur resulting in erroneous splice products as shown in a genome-wide approach. One characteristic subgroup consists of products lacking one cassette exon. The noise in the splicing process, represented by those misspliced products, can be increased by cold shock treatment or by inhibiting the nonsense mediated decay. Here, we investigated whether the splicing noise frequency increases with age in vivo in peripheral bloods cells or in vitro in cultured and aged fibroblasts from healthy donors. Splicing noise frequency was measured for four erroneously skipped NF1 exons and one exon of RABAC1, AATF and PCGF2 by RT-qPCR. Measurements were validated in cultured fibroblasts treated with cold shock or puromycin. Intragenic but not interpersonal differences were detected in splicing noise frequencies in vivo in peripheral blood cells of 11 healthy donors (15 y-85 y) and in in vitro senescent fibroblasts from three further donors. No correlation to the age of the
While, characterizing the hAT1R gene it was demonstrated that ≥4 alternatively spliced hAT1R mRNAs were transcribed in human tissues (Figure 1).33,34 The hAT1R mRNA splice variants were composed of the following exons: exons 1 and 4; exons 1, 2, and 4; exons 1, 3, and 4; and exons 1, 2, 3, and 4; therefore, alternatively spliced hAT1R mRNAs differ only in the inclusion or exclusion of exon 2 and/or 3 (reviewed in Reference 37).. Splice variants that harbor exon 2 are functionally interesting because they contain 2 upstream AUG start codons (Figure 1),34,38 which are predicted to generate upstream ORFs (uORFs) of different lengths. PCR analysis demonstrated that hAT1R mRNA splice variants, which included exon 2 (ie, exons 1, 2, and 4), were composed of ≥30% of the total hAT1R mRNA transcripts expressed in a given tissue; this suggests that this splice variant is physiologically important.34,38-40 Curnow et al34 and Warnecke et al38 demonstrated that the presence of exon 2 inhibited the ...
The genetic change was a single base (G) insertion in exon 25 of the cardiac MyBP-C gene on chromosome 11, which resulted in a sequence suitable to serve as a 5′ splice donor site (AG GTGGG). This mutation was also recently reported in a nonrelated family of the same ethnic group in North America.10 We showed that the mutation resulted in the loss of 40 bp at the 3′ end of exon 25 in mRNA extracted from affected myocardial tissue. This loss resulted in a premature translational stop, which was then predicted to result in a truncated protein of 95 kDa and the loss of the C-terminal binding sites for myosin heavy chain and titin.20 A reading shift would also occur if mRNA splicing were unaffected by the inserted G in exon 25. In this case, the shift resulting from the additional G would lead to a premature stop 40 residues away from the 3′ terminal of codon 792. However, such mutated mRNA was not observed (data not shown).. The shortened 95-kDa MyBP-C protein was not detected in ...
Abstract Background To date, exon capture has largely been restricted to species with fully sequenced genomes, which has precluded its applicat
DNA is made up of different units called nucleotides. There are a variety of four different nucleotides that make up the polymer that is DNA[1]. DNA consists of two different regions, one being exons and the other introns. The regions of exons in the DNA consist of fewer nucleotides than the regions of introns and are the regions that code for proteins[2]. It is also now thought that enhancer sequences for regulation of gene transcription is not just found in introns but also exons.[3]. Exons are the coding regions of a gene and are separated by regions of introns; they are copied during transcription (along with introns) to produce pre-mRNA[4] ...
OBJECTIVE: To investigate the expression of the familial Mediterraneanfever (FMF) gene (MEFV) in human synovial fibroblasts. METHODS: MEFVmessenger RNA in synovial fibroblasts, chondrocytes, and peripheral bloodleukocytes (PBLs) was analyzed by semiquantitative and real-timepolymerase chain reaction and ribonuclease protection assay. Thesubcellular localization of pyrin, the MEFV product, was determined intransfected synovial fibroblasts and HeLa cells with plasmids encodingpyrin isoforms. Native pyrin was detected with an antipyrin antibody.RESULTS: MEFV was expressed in synovial fibroblasts, but not inchondrocytes. Four alternatively spliced transcripts were identified: anextension of exon 8 (exon 8ext) resulting in a frameshift that predicts atruncated protein lacking exons 9 and 10, the addition of an exon (exon4a) predicting a truncated protein at exon 5, the in-frame substitution ofexon 2a for exon 2, and the previously described removal of exon 2 (exon2Delta). Exon 8ext transcripts ...
The classification of human gene sequences into exons and introns is a difficult problem in DNA sequence analysis. In this paper, we define a set of features, called the simple Z (SZ) features, which is derived from the Z-curve features for the recognition of human exons and introns. The classification results show that SZ features, while fewer in numbers ~three in total!, can preserve the high recognition rate of the original nine Z-curve features. Since the size of SZ features is one-third of the Z-curve features, the dimensionality of the feature space is much smaller, and better recognition efficiency is achieved. If the stop codon feature is used together with the three SZ features, a recognition rate of up to 92% for short sequences of length ,140 bp can be obtained ...
Exon definition, (in Britain) one of four yeomen of the guard who act as commanding officers in the absence of higher authority. See more.
The complete exon size and distribution pattern in the gene for the alpha 1 chain of human type IV collagen was determined. Clones covering 145 kilobases (kb) of genomic DNA including 100 kb of the gene itself as well as 25 kb upstream and 20 kb downstream of the gene sequences, respectively, were isolated from lambda phage and cosmid libraries. The overall gene structure was determined by endonuclease restriction mapping and R-loop analyses and all exon sizes by nucleotide sequencing. The characterized clones contained all the coding sequences except for exon 2 whose sequence was determined after its amplification by the polymerase chain reaction. There were four gaps in the intron sequences; the exact size of the gene is unknown. The entire gene is at least 100 kb in size and contains 52 exons whose size distribution is completely different from that of the genes for fibrillar collagens. In the -Gly-X-Y- coding region there are three exons of 99, 90, and 45 base pairs (bp) each and two exons ...
Hi everyone, I need a bed file containing starts and ends of the exons, gene name and number of the exon - but just for the canonical transcript - because I dont want to have the regions repeated. I tried UCSC Table browser and BioMart but non of them gives me exactly what I need.. Using UCSC I can get canonical transcripts (but at the same time I couldnt get starts and ends of the exon altogether with the gene name).. Using BioMart I can get starts and ends of the exons altogether with the gene name, but I cant find how to choose the canonical transcripts and thats why the regions are repeated as seen below in the case of NUS1P3:. ...
Digital processing of a nucleotide sequence requires it to be mapped to a numerical sequence in which the choice of nucleotide to numeric mapping affects how well its biological properties can be preserved and reflected from nucleotide domain to numerical domain. Digital spectral analysis of nucleotide sequences unfolds a period-3 power spectral value which is more prominent in an exon sequence as compared to that of an intron sequence. The success of a period-3 based exon and intron classification depends on the choice of a threshold value. The main purposes of this article are to introduce novel codes for 1-sequence numerical representations for spectral analysis and compare them to existing codes to determine appropriate representation, and to introduce novel thresholding methods for more accurate period-3 based exon and intron classification of an unknown sequence. The main findings of this study are summarized as follows: Among sixteen 1-sequence numerical representations, the K-Quaternary Code I
Digital processing of a nucleotide sequence requires it to be mapped to a numerical sequence in which the choice of nucleotide to numeric mapping affects how well its biological properties can be preserved and reflected from nucleotide domain to numerical domain. Digital spectral analysis of nucleotide sequences unfolds a period-3 power spectral value which is more prominent in an exon sequence as compared to that of an intron sequence. The success of a period-3 based exon and intron classification depends on the choice of a threshold value. The main purposes of this article are to introduce novel codes for 1-sequence numerical representations for spectral analysis and compare them to existing codes to determine appropriate representation, and to introduce novel thresholding methods for more accurate period-3 based exon and intron classification of an unknown sequence. The main findings of this study are summarized as follows: Among sixteen 1-sequence numerical representations, the K-Quaternary Code I
In this work, organization, expression and function of the human Peroxisomal Testis-specific 1 (PXT1) gene were investigated. The mRNA of the human PXT1 gene doesnt contain two exons as known so far, but five exons. The expression of three putative upstream exons was confirmed in this work. The results of the qualitative and quantitative real-time PCR show that the exon 1 consists of three variously spliced units (exons 1a, 1b and 1c). The human PXT1 gene is subjected to alternative splicing, of which exons 1b, 1c, 2 and 4 are concerned, which was shown by sequence analysis. In total, six transcripts were identified. The additional exons have an impact on the protein structure due to the extension of the ORF coding for 51 amino acids previously to 134 now. In the longer protein the BH3 interacting domain (BID) is detected which has a known proapoptotic function. Due to the alternatively spliced exon 4 and the resulting frameshift a truncated protein exists and in its mRNA a premature stop codon ...
Nous montrons lutilisation de la puce exon dAffymetrix pour lanalyse simultanée de lexpression des gènes et de la variation disoformes. Nous avons utilisé les échantillons dARN du cerveau et des tissus de référence qui ont été antérieurement utilisés dans létude du consortium MicroArray Quality Control (MAQC). Nous démontrons une forte concordance de la quantification de lexpression des gènes entre trois plateformes dexpression populaires à savoir la puce exon dAffymetrix, la puce Illumina et la puce U133A dAffymetrix. Plus intéressant nous montrons que la majorité des discordances entre les trois plateformes résulterait des positions différentes des sondes à travers les plateformes et que les variations disoforme exactes ne peuvent être identifiées que par la puce exon. Nous avons détecté avec succès, entre les tissus de référence et ceux du cerveau, une centaine de cas dévènements dépissage alternatif. La puce exon est requise dans lanalyse de ...
Aims to balance the goal of giving the complete picture of possible coding exons, with the need to stay grounded in terms of the verifiability of the actual function of the sequences it collects. Thus it relies on the ENSEMBLs annotation of known (known here being the actual annotation term used, hence the quotes) human exons as the anchor for the search and for the results presentation. To these, ExoLocator adds the search for ostensibly missing exons in orthologous protein pairs across species, using an extensive computational pipeline to narrow down the search region for the candidate exons and find a suitable template in the other species, as well as state-of-the-art implementations of pairwise alignment algorithms. The resulting complements of exons are organized in a way currently unique to ExoLocator: multiple sequence alignments, both on the nucleotide and on the peptide levels, clearly indicating the exon boundaries. The alignments can be inspected in the web-embedded viewer, downloaded or
Author Summary Changes in gene regulation have long been known to play important roles in both innate and adaptive immune responses. While transcriptional responses to infection have been well-characterized, much less is known about the extent to which co-transcriptional mechanisms of mRNA processing are involved in the regulation of immune defenses. In this study, we sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infection. Using primary human macrophages derived from whole blood samples from 60 individuals, we sequenced mRNA both before and after infection with two live bacteria. We show that immune responses to infection are accompanied by pervasive changes in mRNA isoform usage, with systematic shifts towards increased cassette exon inclusion and shortening of Tandem 3 UTRs post-infection. These patterns are conserved in nonhuman primates, supporting their functional importance across evolutionary time. Complementary microRNA
Author Summary Changes in gene regulation have long been known to play important roles in both innate and adaptive immune responses. While transcriptional responses to infection have been well-characterized, much less is known about the extent to which co-transcriptional mechanisms of mRNA processing are involved in the regulation of immune defenses. In this study, we sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infection. Using primary human macrophages derived from whole blood samples from 60 individuals, we sequenced mRNA both before and after infection with two live bacteria. We show that immune responses to infection are accompanied by pervasive changes in mRNA isoform usage, with systematic shifts towards increased cassette exon inclusion and shortening of Tandem 3 UTRs post-infection. These patterns are conserved in nonhuman primates, supporting their functional importance across evolutionary time. Complementary microRNA
Does anyone have any information on these exons. I know exon skipping is not an option because of the complexity of these exons but that is where my knowledge…
Like CB1R, the CB2R coding region is contained in a single exon and is flanked by upstream noncoding exons in human, mouse, and, debatably, rat. Human CB2R consists of three exons alternatively transcribed and spliced to yield isoforms CB2A and -B (Liu et al., 2009). CB2B, the first cloned cDNA, is transcribed from a promoter proximal to exon2 and expressed most highly in immune cells and tissues. The more recently identified CB2A contains exon1 and exon3 and is generated from a promoter 5′ proximal to exon1. In contrast to CB2B, CB2A is most highly expressed in testis and shows some expression in the brain.. Mouse CB2R similarly consists of three exons alternatively transcribed by two promoters (Onaivi et al., 2006; Liu et al., 2009). In contrast to humans, however, both CB2A and CB2B are expressed predominantly in the spleen (Liu et al., 2009). Rat CB2R gene structure seems more complex than that of human and mouse, although findings are conflicting. In Fig. 1, we present findings by Liu et ...
1. In the context of a new mammalian model organism recently sequenced and annotated, gene YFG has 3 introns and 4 exons. Databases show that there are 3 different lengths of cDNA sequences associated with Gene YFG. One of these cDNA sequences has three out of four exons plus additional nucleotide sequence at the 3 end of the cDNA. This part codes for an extra 123 amino acids. Annotated gene UB2, appears immediately downstream of YFG. UB2 has a single exon coding for 123 amino acids matching the cDNA. There is no cDNA in your database encoding for a UB2 gene with these 123 amino acids at the N-terminus ...
antibody-antibodies.com is the marketplace for research antibodies. Find the right antibody for your research needs. The identification of a new alternative exon with highly restricted tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. Comparison of all 10 variable exons between mouse, human, and rat.
RNA modification must be performed in order to form the various proteins needed for eukaryotes to function. RNA modification generates mature RNA. Through RNA modification, a eukaryotic cell can use fewer variations in base pairs of the genetic code (DNA and RNA) while creating proteins with diverse functions. One of the most common methods employed by eukaryotes is to use spliceosomes to cleave out introns (intervening sequences/ non coding proteins) of the pre-RNA, leaving only exons (expressed sequences/coding proteins). Cutting out the intron segments allows for the possibility of exon to rearrangement. Spicing all exons together is called mature mRNA.. Whats the advantage of spitting genes? Exons are segments that coding proteins and give proteins specific functions. This leads to the concept of exon shuffling. Exons shuffling is the rearrangement of the exons in the mRNA. These mRNA will come up with different types of proteins with different functions, binding sites, and catalytic sites. ...
Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show intragenic deletions ranging from one to several exons of the DMD gene and leading to a premature stop codon. Other deletions that maintain the translational reading frame of the gene result in the milder Becker muscular dystrophy (BMD) form of the disease. Thus the opportunity to transform a DMD phenotype into a BMD phenotype appeared as a new treatment strategy with the development of antisense oligonucleotides technology, which is able to induce an exon skipping at the pre-mRNA level in order to restore an open reading frame. Because the DMD gene contains 79 exons, thousands of potential transcripts could be produced by exon skipping and should be investigated. The conventional approach considers skipping of a single exon. Here we report the comparison of single- and multiple-exon skipping strategies based on bioinformatic analysis. By using the Universal Mutation Database (UMD)-DMD, we predict that an optimal multiexon
Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1F region (GR-1F) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1F methylation (52 loci) was quantified ... read more using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) ...
We used differential scanning calorimetry (DSC) and circular dichroism (CD) to investigate thermal unfolding of recombinant fibroblast isoforms of alpha-tropomyosin (Tm) in comparison with that of smooth muscle Tm. These two nonmuscle Tm isoforms 5a and 5b differ internally only by exons 6b/6a, and they both differ from smooth muscle Tm by the N-terminal exon 1b which replaces the muscle-specific exons 1a and 2a. We show that the presence of exon 1b dramatically decreases the measurable calorimetric enthalpy of the thermal unfolding of Tm observed with DSC, although it has no influence on the alpha-helix content of Tm or on the end-to-end interaction between Tm dimers. The results suggest that a significant part of the molecule of fibroblast Tm (but not smooth muscle Tm) unfolds noncooperatively, with the enthalpy no longer visible in the cooperative thermal transitions measured. On the other hand, both DSC and CD studies show that replacement of muscle exons 1a and 2a by nonmuscle exon 1b not ...
To explore exonic variants in possibly associated with gout susceptibility, we sequenced all exons of in 480 gout cases and 480 controls of Japanese male6 and conducted an association analysis (see online supplementary furniture S1 and S2), followed by a replication study on 924 gout instances and 2113 settings (see online supplementary number S1). In two recognized variants with small allele rate of recurrence (MAF) >0.5%, only rs117371763 (c.1129C>T; p.Arg377Cys [R377C]) was significantly associated with gout susceptibility after Bonferroni correction (p=0.014). The significant association between rs117371763 and gout susceptibility was replicated, and our meta-analysis showed a significant protecting effect of rs117371763 on gout susceptibility (OR=0.67; 95% CI 0.53 to 0.85; pmeta=7.810-4) (table 1). In addition, a quantitative trait locus analysis focusing on SUA levels in 3208 individuals (observe online supplementary table S3) showed the small allele of rs117371763 significantly decreases ...
The object isnt able to load since the IDs are different. Same is the case with exons and transcripts ids. Upon looking into the .ctab files, the exons, introns, transcripts differ across Control- Sample. But are same across the 3 controls. And they are same across the 5 samples. It is like so- Controls: exon 442247, introns 366654, transcripts 181466. Samples: exon 686514, introns 416565, transcripts 247538. The exons, introns, transcripts differ only between the two conditions. Hence, I am not able to progress from here. Can anyone please help me with as to why this is occuring? Why would the exons, introns, transcripts id be different for control & sample, since both control and sample RNA are collected from human patients. Please add a note on how I can solve this issue.. Any help is much appreciated.. ...
Four separate CETP gene mutations have been published previously. Of the four mutations, the intron 14 donor splice site mutation4 and the Asp442-to-Gly mutation in exon 1528 are both known to be very common in the Japanese population.7 8 9 10 29 The other two mutations, the Gln309-to-Stop mutation in exon 1026 and a 1-bp insertion in intron 14,7 are probably sporadic mutations. Except for the Asp442-to-Gly mutation that causes partial CETP deficiency, the other three seemed to have null allelic effects, although exact mechanisms underlying the null effects have not been studied. In the present study, we demonstrated that the primary abnormality due to the intron 14 donor splice site mutation is the exon skipping of mRNA, which decreases the level of mRNA and produces a truncated protein that should be degraded intracellularly. These observations clearly explain the molecular basis of the complete CETP deficiency found not only in patients with the common intron 14 splicing mutation but also in ...
Transcription factor binding to enhancer elements is critical for proper gene regulation. Enhancers are often found in noncoding sequences in close proximity to the gene that they regulate and sometimes even on another chromosome; however, whether they are also found in exons, the coding regions of DNA, is unclear. Birnbaum et al. analyzed 25 mouse and human enhancer-associated ChIP-seq data sets in order to identify enhancer peaks that overlap exons and found regulatory transcription factor binding to exonic regions. In fact, in mice, roughly 7% of enhancer peaks overlapped coding exons. Mutation of these elements in zebrafish and mouse enhancer assays showed that although exonic sequences are necessary, they are not sufficient for full enhancer function. Absence of an exon-encoded enhancer, however, did have functional consequences. Thus, exonic sequences may function in the regulation of nearby genes. Moreover, phenotypes seen in genetic knockout animals may be the result of not only the lack ...
Saitta B., Wang Y.-M., Renkart L., Zhang R.-Z., Pan T.-C., Timpl R., Chu M.-L.. The alpha 1(VI) and alpha 2(VI) chains, two of the three constituent chains of type VI collagen, are highly similar in size and domain structure. They are encoded by single-copy genes residing in close proximity on human chromosome 21. To study the evolution of the type VI collagen genes, we have isolated and characterized genomic clones coding for the triple-helical domains of the human alpha 1(VI) and alpha 2(VI) chains, which consist of 336 and 335 amino acid residues, respectively. Nucleotide sequencing indicates that, in both genes, the exons are multiples of 9 bp in length (including 27, 36, 45, 54, 63, and 90 bp) except for those encoding for regions with triple-helical interruptions. In addition, the introns are positioned between complete codons. The most predominant exon size is 63 bp, instead of 54 bp as seen in the fibrillar collagen genes. Of particular interest is the finding that the exon structures of ...
Author(s): Ji, Xinjun; Park, Juw Won; Bahrami-Samani, Emad; Lin, Lan; Duncan-Lewis, Christopher; Pherribo, Gordon; Xing, Yi; Liebhaber, Stephen A | Abstract: Alternative splicing (AS) is a robust generator of mammalian transcriptome complexity. Splice site specification is controlled by interactions of cis-acting determinants on a transcript with specific RNA binding proteins. These interactions are frequently localized to the intronic U-rich polypyrimidine tracts (PPT) located 5 to the majority of splice acceptor junctions. αCPs (also referred to as polyC-binding proteins (PCBPs) and hnRNPEs) comprise a subset of KH-domain proteins with high affinity and specificity for C-rich polypyrimidine motifs. Here, we demonstrate that αCPs promote the splicing of a defined subset of cassette exons via binding to a C-rich subset of polypyrimidine tracts located 5 to the αCP-enhanced exonic segments. This enhancement of splice acceptor activity is linked to interactions of αCPs with the U2 snRNP complex and
The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of ...
How to trace exon number in genome sequence? - posted in Molecular Biology: Hi, I am working on a fusion oncogene (BCR-ABL) causing blood cancer. The problem is that I dont exactly know the product size of my pcr product (amplifying the fusion-oncogene). I know the exons of both genes involved (e13 & 14 of BCR) and (a2 of ABL1) in the chromosomal translocation. but when I try to trace these exons in ensemble sequence I get confused. as there are many small exons not shown i...
This page is badly in need of updating - some of the links are probably broken. A complete redesign wouldnt hurt either. But I have tendonitis, so it wont happen for a while. This is a collection of NPR stories on the Telecommunications bill and Exon Communications Decency Act. These links were organized by me, Steve Rhodes. I have nothing to do with NPR. Im just a listener. You can also listen to the debate on the Senate Floor over Exon and Gingrichs statement against Exon. To listen to any of the audio on this page, you need a free beta verstion of the RealAudio player for the Mac or Windows. There is also more information on Exon. ...
Chromatin firm affects substitute splicing and prior studies show that exons possess increased nucleosome occupancy weighed against their flanking introns. splice site, but U1 pairing had not been needed for U1 snRNA improvement of transcription. General, these results claim that splicing make a difference chromatin business. Introduction Alternate splicing (AS) enhances transcriptome and proteome variety, especially in mammals, and latest analyses estimation that over 95% of human being multi-exon genes make on the other hand spliced transcripts [1]. Until lately, whether an exon was on the other hand or constitutively spliced was thought to be exclusively affected by sequences in the pre-mRNA, such as for example those determining exon/intron limitations, and by binding of splicing regulatory protein [2]. It has become apparent, nevertheless, that transcription by RNA polymerase II (RNAPII) and chromatin framework contribute to option splicing rules [3], [4]. Nucleosome placing may be ...
In this study, we demonstrate that Dscam endodomain variants are dynamically and differentially expressed in the developing Drosophila CNS. This conclusion derives from: (1) the analysis of Dscam transcript compositions by RT-PCR, (2) the localization of specific Dscam endodomains by depleting the alternatives via RNAi against exon 19, exon 23, or the unique exon-exon junctions derived from skipping of exon 19 or exon 23 (Fig. 2), and (3) the direct visualization of Dscam+19 using Ab19 as opposed to labeling all the Dscam isoforms with Ab18 (Fig. 3). Postembryonic neuronal morphogenesis uses Dscam variants lacking exons 19 and 23 (Fig. 4C), while Dscam+19 plays a more important role in the wiring of embryonic neural tracts (Fig. 4F). Skipping exon 19 prevents accumulation of Dscams in neuronal cell bodies, implicating a mechanism for regulating Dscam protein targeting by the alternative splicing of exon 19 (Figs. 6, 7). In addition, exon 23 is dispensable for most Dscam-dependent neuronal ...
A fundamental aspect of the independent birth theory is the ability to find complete genes in a string of random DNA in the primordial pond. Because of the length of an average gene, the probability of finding just one unsplit (prokaryote) gene in any amount of DNA is very, very small, even if we consumed all of the mass in the universe when making the DNA. However, when a gene is split into numerous exons, the gene can be found in a far shorter, and very manageable length of random DNA. In fact, almost any gene can be found in a small amount of random DNA -- if the gene is split into exons. [Reference: Independent Birth of Organisms, Chapter 7, pages 223 - 253]. Furthermore, because of codon and amino acid degeneracies, the probability of finding a split gene that codes for a particular protein function is even higher in a reasonable amount of DNA. [Reference: pages 254 - 266]. This search engine demonstrates how easily a complete gene composed of exons (or words) can be found in a random ...
Exon Property Pte Ltd, a franchisee of Century 21 Singapore, is set by its Key Executive Officer (KEO), Eddy Lau.. Eddy Lau started his real estate career in 1993, from an associate realtor to associate director within a short period of 2 years. As a veteran in the real estate industry for over the last 2 decades, he won numerous top achiever award from various real estate agencies before setting up Exon Property Pte Ltd.. All salespersons in Exon Property have at least 3 years of experience is real estate. And our international project team, set up in the year 2008, has successfully marketed properties from Malaysia, Thailand, UK, USA & Australia across to investors in the region.. Today, as CENTURY 21 Exon Property Pte Ltd, we are part of the largest real estate sales organisation in the world.. ...
In the current study, we report on differences in outcome based on EGFR genotype after treatment with gefitinib or erlotinib in patients with NSCLC. A total of 36 eligible patients with EGFR mutations were identified. Of these, 32 (89%) patients had either an exon 19 deletion (n = 22) or the L858R point mutation (n = 10). This is the second study to compare patients with exon 19 deletions with those harboring an L858R point mutation and provides important independent validation to earlier observations (35). In a previously reported study, Riely et al. analyzed 34 NSCLC patients with either an exon 19 deletion (n = 23) or an L858R mutation (n = 11). Of these, 22 were treated with gefitinib and 12 were treated with erlotinib. The baseline characteristics of the patients in both studies are remarkably similar with respect to age, gender, smoking status, tumor histology, performance status, number of prior chemotherapy regimens, and EGFR-TKI administered.. Although the radiographic response rate in ...
Objective The innate immune component TRIM5α has the ability to restrict retrovirus infection in a species-specific manner. TRIM5α of some primate species restricts infection by HIV-1, while huTRIM5α lacks this specificity. Previous studies have suggested that certain polymorphisms in huTRIM5 may enhance or impair the proteins affinity for HIV-1. This study investigates the role of TRIM5 polymorphisms in resistance/susceptibility to HIV-1 within the Pumwani sex worker cohort in Nairobi, Kenya. A group of women within this cohort remain HIV-1 seronegative and PCR negative despite repeated exposure to HIV-1 through active sex work. Design A 1 kb fragment of Trim5alpha gene, including exon 2, from 1032 women enrolled in the Pumwani sex worker cohort was amplified and sequenced. SNPs and haplotypes were compared between HIV-1 positive and resistant women. Methods The TRIM5 exon 2 genomic fragment was amplified, sequenced and genotyped. Pypop32-0.6.0 was used to determine SNP and haplotype ...
MAGOH (mago homolog, exon junction complex core component), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
RefSeq Summary (NM_002117): HLA-C belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Over one hundred HLA-C alleles have been described [provided by RefSeq, Jul 2008 ...
For each BAM, we use samtools to retrieve the reads in the region(s)) of interest. The reads are then filtered with samjs (https://github.com/lindenb/jvarkit/wiki/SamJS) to only keep the reads carrying an intron-exon junction at the desired location(s). Basically, the javascript-based filter loops over the CIGAR string of the read, computes the genomic interval skipped when the cigar operator is a deletion or a skipped region/intron. The read is printed if it describes the new intron-exon junction ...
Gene identification studies, centred on a region of overlapping loss of heterozygosity in breast tumours within band 1p31.1, lead to the characterisation of LPHH1, a novel human 7TM gene. The coding sequence of LPHH1 extends over a 60 kb region and comprises in excess of 28 exons. Alternative splicing occurs minimally at five positions, four of which are within the coding sequence. The fifth region of alternative splicing occurs at the extreme 5 end of the transcript. A clear tissue specific bias in alternative exon selection is observed to some degree at all five positions, including the extreme 5 region, which raises the possibility of multiple and perhaps tissue specific promoters. One such putative promoter region, which appears to be utilised predominantly in breast cancer cells, has been identified. LPHH1 is highly evolutionarily conserved, with the simplest (19 exon) gene product being 95% identical between human and rat. Comparison of the alternatively spliced exons between three ...
Data_Sheet_2_Widespread Separation of the Polypyrimidine Tract From 3′ AG by G Tracts in Association With Alternative Exons in Metazoa and Plants.zip
Data_Sheet_1_Widespread Separation of the Polypyrimidine Tract From 3′ AG by G Tracts in Association With Alternative Exons in Metazoa and Plants.zip
RosBREEDSNP_SNP_AC_27071636_Lg15_02084_MAF30_187884_exon1, RosBREEDSNP_SNP_AC_27071636_Lg15_02084_MAF30_187884_exon1 (genetic_marker) Malus x ...
RosBREEDSNP_SNP_TC_45022535_Lg15_ACS_MAF50_1618441_exon1, RosBREEDSNP_SNP_TC_45022535_Lg15_ACS_MAF50_1618441_exon1 (genetic_marker) Malus x ...
Background: CD36 is a multiligand receptor involved in various metabolic pathways, including cellular uptake of long-chain fatty acids. Defect function or expression of CD36 can result in dyslipidemia or insulin resistance. We have previously shown that CD36 expression is female-predominant in rat liver. In the present study, hormonal and nutritional regulation of hepatic CD36 expression was examined in male and female rats. Since alternative transcription start sites have been described in murine and human Cd36, we investigated whether alternative CD36 transcripts are differentially regulated in rat liver during these conditions.. Results: Sequence information of the rat Cd36 5-UTR was extended, showing that the gene structure of Cd36 in rat is similar to that previously described in mouse with at least two alternative first exons. The rat Cd36 exon 1a promoter was sequenced and found to be highly similar to murine and human Cd36. We show that alternative first exon usage is involved in the ...
Fig. 4 shows the amino acid sequences of the predicted proteins of AtFpg-1, -1a, -2, -3, and -4. Exons 1, 2, 3, 5, 6, and 7 were entirely conserved in all the Arabidopsis cDNA clones. The polypeptide chains encoded by exons 1, 5, 6,and 7 represent the major conserved regions between Arabidopsis and bacterial FPGs , showing between 29 and 54% identity between Arabidopsis and E. coli amino acid sequences. The N-terminal sequence of exon 1 and the lysine of exon 5 (K155) of E. coli FPG have been associated with the active site. The predicted amino acid sequence coded by exon 1 shows a surprising relationship to a sequence from DNA photolyase, another DNA repair enzyme but one quite unrelated to FPG (Fig. 5). If this relates to DNA binding, it might explain how AtFPG-2, which lacks the C-terminal DNA-binding region present in AtFPG-1 (or the zinc-finger of E. coli FPG) might have the DNA cleavage activities measured by Gao and Murphy (Photochem. Photobiol., in press). The optional exons are exon 4 ...
Recent studies suggest that ANRIL expression mediates susceptibility to CAD1 via CDKN2B.2 We used fluorescently-labelled whole-blood RNA, from 20 healthy volunteers genotyped for the CAD-risk-SNP rs2891168, to probe custom-designed Agilent tiling expression microarrays. Raw data were normalized to probe GC content and housekeeping genes. We found that ANRIL exons 1-4 were more abundantly expressed in blood than 5-20, with exons 6, 8, 9, 20 showing low expression. We derived a set of training tiling probes from HUVEC cells in which ANRIL expression was attenuated using siRNA against exons 13 and 19. ANRIL expression (probes in exons 5,6,8,13,16,18,19) was reduced by at least 50% and CDKN2B expression (probes in exons 1,2) increased, with no effect on CDKN2A. We confirmed these data using real-time QPCR. Using the tiling probe training-set, a probe in exon 16 of ANRIL showed a CAD genotype-specific difference in expression (p,0.001), with the risk-allele lower, and probes in exon 2 of CDKN2B ...
This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been ...
This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been ...
By means of alternative splicing in two of its nine exons (exons 3 and 6), the RDL gene encodes four distinct polypeptides (Fig. 1A), all of which are expressed (ffrench-Constant and Rocheleau, 1993). Three splice variants (RDLac, RDLbd, and RDLab) have been cloned and functionally expressed (Hosie and Sattelle, 1996a). Residues that vary in exon 3 lie upstream to loop D of the GABA binding site and near the equivalent positions of known determinants of agonist potency in GABAA receptors of vertebrates. Alternative splicing occurs in other ligand-gated ion channels (Villarroel, 1999) and has been shown to affect agonist sensitivity in glycine receptors (Miller et al., 2004). It is noteworthy that alternative splicing of the D. melanogaster nicotinic acetylcholine receptor subunit Dα6 (Grauso et al., 2002) also occurs in exon 3, which aligns to exon 3 of RDL. The exon 6 alternatively spliced residues of RDL lie in loops F and C (Fig. 1B) and exon 6 splicing affects the expressed receptors ...
This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been ...
We read with great interest the recent paper by Beer and Sahin-Tóth1 addressing the missing heritability observed in approximately 60% of German cases of chronic pancreatitis.2 These authors opined that discovery studies tend to focus on exons and exon-intron boundaries and may thus miss many intronic variants.1 This premise seems eminently reasonable, given the generally much larger size of intronic sequences as compared with the coding sequences of protein-coding genes. However, there is a trade-off here. On the one hand, larger sequence size means larger target size for mutation, and hence the greater the number of mutations that could be missed if intronic sequences were not screened. On the other hand, to be of pathological significance, an intronic mutation must either create a new functional splicing donor or acceptor site or alternatively impact a functional sequence motif responsible for regulating splicing (eg, an intronic splicing enhancer), which depends upon many additional ...
This study demonstrates that some FTDP-17 mutations alter the MT-binding properties of tau, and others alter the ratio of 4R/3R tau isoforms. Intronic mutations (for example, in the DDPAC kindred) presumably alter 4R/3R tau ratios by weakening a stem-loop structure at the 5′ splice site of exon 10, which normally inhibits the inclusion of exon 10 into tau mRNA (5). How the N279K mutation increases 4Rtau production is less clear. Because the N279K mutation does not alter the binding of tau to MTs or decrease the ability of tau to promote MT assembly, the selective aggregation of 4Rtau into filamentous lesions probably results from overproduction of 4Rtau proteins by increasing the inclusion of exon 10 into more tau mRNAs. Presumably, this mutation could act by altering an exon-splicing enhancer (ESE) sequence in exon 10 (15). At the nucleotide level, the N279K mutation changes the normal sequence of TAAGAA to GAAGAA, a potential GAR (where R is a purine) ESE motif (6). These ESE sequences have ...
Alternative Isoform Detection Using Exon Arrays: 10.4018/978-1-60566-076-9.ch015: Eukaryotic genes have the ability to produce several distinct products from a single genomic locus. Recent developments in microarray technology allow
Methods. The human GNB1 locus extends from base 1812355 (5 end) to 1706589 (3 end) in the genomic sequence of chromosome 1p (NCBI). The gene has 12 exons. There is an open reading frame in exons 3 to 11 with a coding sequence corresponding to the human cDNA sequence of the β-subunit of rod transducin (accession number BC004186) [6]. This human cDNA sequence encodes a polypeptide with a sequence identical to the β-subunit of rod transducin in both cattle (accession number BC105260) and mice (accession number NM_008142) [5-7]. We developed PCR-based methods to amplify individually each of the 12 exons of the human GNB1 gene. The primers used for PCR are in Table 1. Each set of primers amplified an entire exon as well as 10 to 72 bp of flanking intron DNA or untranslated region. We amplified the individual exonic fragments from genomic leukocyte DNA from 185 unrelated patients with ADRP. These patients came from families with at least two affected generations with RP; many families had three or ...
The CD19 antigen, expressed on most B-cell acute lymphoblastic leukemias (B-ALL), can be targeted with chimeric antigen receptor-armed T cells (CART-19), but relapses with epitope loss occur in 10% to 20% of pediatric responders. We detected hemizygous deletions spanning the CD19 locus and de novo frameshift and missense mutations in exon 2 of CD19 in some relapse samples. However, we also discovered alternatively spliced CD19 mRNA species, including one lacking exon 2. Pull-down/siRNA experiments identified SRSF3 as a splicing factor involved in exon 2 retention, and its levels were lower in relapsed B-ALL. Using genome editing, we demonstrated that exon 2 skipping bypasses exon 2 mutations in B-ALL cells and allows expression of the N-terminally truncated CD19 variant, which fails to trigger killing by CART-19 but partly rescues defects associated with CD19 loss. Thus, this mechanism of resistance is based on a combination of deleterious mutations and ensuing selection for alternatively ...
flataustralia posted a photo of the new Colony Exon flatland tires. As you can clearly see the maximum pressure is 110 PSI and there was probably no way to write that even bigger ;-) They come as 20 x 1.75 and should be a great addition to the Colony Exon flatland range. More details are yet to be announced ...
Sen. J. James Exon (D-Neb.), 63, has been hospitalized after complaining of stomach pains, his office said today.Mark Bowen, Exons press secretary, said doctors at Bethesda Naval Hospital have
Lynch syndrome patients are susceptible to colorectal and endometrial cancers owing to inactivating germline mutations in mismatch repair genes, including MSH2 (ref. 1). Here we describe patients from Dutch and Chinese families with MSH2-deficient tumors carrying heterozygous germline deletions of the last exons of TACSTD1, a gene directly upstream of MSH2 encoding Ep-CAM. Due to these deletions, transcription of TACSTD1 extends into MSH2. The MSH2 promoter in cis with the deletion is methylated in Ep-CAM positive but not in Ep-CAM negative normal tissues, thus revealing a correlation between activity of the mutated TACSTD1 allele and epigenetic inactivation of the corresponding MSH2 allele. Gene silencing by transcriptional read-through of a neighboring gene in either sense, as demonstrated here, or antisense direction, could represent a general mutational mechanism. Depending on the expression pattern of the neighboring gene that lacks its normal polyadenylation signal, this may cause either
Schramm, A, Schowe, B, Fielitz, K, Heilmann, M, Martin, M, Marschall, T, … Schulte, J.H. (2012). Exon-level expression analyses identify MYCN and NTRK1 as major determinants of alternative exon usage and robustly predict primary neuroblastoma outcome. British Journal of Cancer, 107, 1409-1417 ...