Exons
Alternative Splicing
Introns
Base Sequence
Molecular Sequence Data
RNA Splicing
Amino Acid Sequence
RNA Splice Sites
Mutation
RNA, Messenger
Polymerase Chain Reaction
Cloning, Molecular
RNA Precursors
Pedigree
Polymorphism, Single-Stranded Conformational
DNA
Protein Isoforms
DNA, Complementary
Sequence Homology, Nucleic Acid
Transcription, Genetic
Sequence Analysis, DNA
Genes
Point Mutation
Promoter Regions, Genetic
Restriction Mapping
DNA Primers
Chromosome Mapping
Codon, Nonsense
Frameshift Mutation
Sequence Alignment
Alleles
Mutation, Missense
Blotting, Southern
Dystrophin
Polymorphism, Genetic
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Genomic Library
Gene Deletion
Gene Expression Regulation
Tight binding of the 5' exon to domain I of a group II self-splicing intron requires completion of the intron active site. (1/14753)
Group II self-splicing requires the 5' exon to form base pairs with two stretches of intronic sequence (EBS1 and EBS2) which also bind the DNA target during retrotransposition of the intron. We have used dimethyl sulfate modification of bases to obtain footprints of the 5' exon on intron Pl.LSU/2 from the mitochondrion of the alga Pylaiella littoralis, as well as on truncated intron derivatives. Aside from the EBS sites, which are part of the same subdomain (ID) of ribozyme secondary structure, three distant adenines become either less or more sensitive to modification in the presence of the exon. Unexpectedly, one of these adenines in subdomain IC1 is footprinted only in the presence of the distal helix of domain V, which is involved in catalysis. While the loss of that footprint is accompanied by a 100-fold decrease in the affinity for the exon, both protection from modification and efficient binding can be restored by a separate domain V transcript, whose binding results in its own, concise footprint on domains I and III. Possible biological implications of the need for the group II active site to be complete in order to observe high-affinity binding of the 5' exon to domain I are discussed. (+info)A premature termination codon interferes with the nuclear function of an exon splicing enhancer in an open reading frame-dependent manner. (2/14753)
Premature translation termination codon (PTC)-mediated effects on nuclear RNA processing have been shown to be associated with a number of human genetic diseases; however, how these PTCs mediate such effects in the nucleus is unclear. A PTC at nucleotide (nt) 2018 that lies adjacent to the 5' element of a bipartite exon splicing enhancer within the NS2-specific exon of minute virus of mice P4 promoter-generated pre-mRNA caused a decrease in the accumulated levels of P4-generated R2 mRNA relative to P4-generated R1 mRNA, although the total accumulated levels of P4 product remained the same. This effect was seen in nuclear RNA and was independent of RNA stability. The 5' and 3' elements of the bipartite NS2-specific exon enhancer are redundant in function, and when the 2018 PTC was combined with a deletion of the 3' enhancer element, the exon was skipped in the majority of the viral P4-generated product. Such exon skipping in response to a PTC, but not a missense mutation at nt 2018, could be suppressed by frame shift mutations in either exon of NS2 which reopened the NS2 open reading frame, as well as by improvement of the upstream intron 3' splice site. These results suggest that a PTC can interfere with the function of an exon splicing enhancer in an open reading frame-dependent manner and that the PTC is recognized in the nucleus. (+info)Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences. (3/14753)
Splicing enhancers are RNA sequences required for accurate splice site recognition and the control of alternative splicing. In this study, we used an in vitro selection procedure to identify and characterize novel RNA sequences capable of functioning as pre-mRNA splicing enhancers. Randomized 18-nucleotide RNA sequences were inserted downstream from a Drosophila doublesex pre-mRNA enhancer-dependent splicing substrate. Functional splicing enhancers were then selected by multiple rounds of in vitro splicing in nuclear extracts, reverse transcription, and selective PCR amplification of the spliced products. Characterization of the selected splicing enhancers revealed a highly heterogeneous population of sequences, but we identified six classes of recurring degenerate sequence motifs five to seven nucleotides in length including novel splicing enhancer sequence motifs. Analysis of selected splicing enhancer elements and other enhancers in S100 complementation assays led to the identification of individual enhancers capable of being activated by specific serine/arginine (SR)-rich splicing factors (SC35, 9G8, and SF2/ASF). In addition, a potent splicing enhancer sequence isolated in the selection specifically binds a 20-kDa SR protein. This enhancer sequence has a high level of sequence homology with a recently identified RNA-protein adduct that can be immunoprecipitated with an SRp20-specific antibody. We conclude that distinct classes of selected enhancers are activated by specific SR proteins, but there is considerable sequence degeneracy within each class. The results presented here, in conjunction with previous studies, reveal a remarkably broad spectrum of RNA sequences capable of binding specific SR proteins and/or functioning as SR-specific splicing enhancers. (+info)Substrate specificities of SR proteins in constitutive splicing are determined by their RNA recognition motifs and composite pre-mRNA exonic elements. (4/14753)
We report striking differences in the substrate specificities of two human SR proteins, SF2/ASF and SC35, in constitutive splicing. beta-Globin pre-mRNA (exons 1 and 2) is spliced indiscriminately with either SR protein. Human immunodeficiency virus tat pre-mRNA (exons 2 and 3) and immunoglobulin mu-chain (IgM) pre-mRNA (exons C3 and C4) are preferentially spliced with SF2/ASF and SC35, respectively. Using in vitro splicing with mutated or chimeric derivatives of the tat and IgM pre-mRNAs, we defined specific combinations of segments in the downstream exons, which mediate either positive or negative effects to confer SR protein specificity. A series of recombinant chimeric proteins consisting of domains of SF2/ASF and SC35 in various combinations was used to localize trans-acting domains responsible for substrate specificity. The RS domains of SF2/ASF and SC35 can be exchanged without effect on substrate specificity. The RNA recognition motifs (RRMs) of SF2/ASF are active only in the context of a two-RRM structure, and RRM2 has a dominant role in substrate specificity. In contrast, the single RRM of SC35 can function alone, but its substrate specificity can be influenced by the presence of an additional RRM. The RRMs behave as modules that, when present in different combinations, can have positive, neutral, or negative effects on splicing, depending upon the specific substrate. We conclude that SR protein-specific recognition of specific positive and negative pre-mRNA exonic elements via one or more RRMs is a crucial determinant of the substrate specificity of SR proteins in constitutive splicing. (+info)Identification of DNA polymorphisms associated with the V type alpha1-antitrypsin gene. (5/14753)
alpha1-Antitrypsin (alpha1-AT) is a highly polymorphic protein. The V allele of alpha1-AT has been shown to be associated with focal glomerulosclerosis (FGS) in Negroid and mixed race South African patients. To identify mutations and polymorphisms in the gene for the V allele of alpha1-AT in five South African patients with FGS nephrotic syndrome DNA sequence analysis and restriction fragment length polymorphisms of the coding exons were carried out. Four of the patients were heterozygous for the BstEII RFLP in exon III [M1(Val213)(Ala213)] and one patient was a M1(Ala213) homozygote. The mutation for the V allele was identified in exon II as Gly-148 (GGG)-->Arg (AGG) and in all patients was associated with a silent mutation at position 158 (AAC-->AAT). The patient who was homozygous for (Ala213) also had a silent mutation at position 256 in exon III (GAT-->GAC) which was not present in any of the other four patients. Although the V allele of alpha1-AT is not associated with severe plasma deficiency, it may be in linkage disequilibrium with other genes on chromosome 14 that predispose to FGS. Furthermore, the associated silent mutation at position 158 and the Ala213 polymorphism are of interest, as these could represent an evolutionary intermediate between the M1(Ala213) and M1(Val213) subtypes. (+info)Promoter and exon-intron structure of the protein kinase C gene from the marine sponge Geodia cydonium: evolutionary considerations and promoter activity. (6/14753)
We report the gene structure of a key signaling molecule from a marine sponge, Geodia cydonium. The selected gene, which codes for a classical protein kinase C (cPKC), comprises 13 exons and 12 introns; the introns are, in contrast to those found in cPKC from higher Metazoa, small in size ranging from 93 nt to 359 nt. The complete gene has a length of 4229 nt and contains exons which encode the characteristic putative regulatory and catalytic domains of metazoan cPKCs. While in the regulatory domain only one intron is in phase 0, in the catalytic domain most introns are phase 0 introns, suggesting that the latter only rarely undergo module duplication. The 5'-flanking sequence of the sponge cPKC gene contains a TATA-box like motif which is located 35-26 nt upstream from the start of the longest sequenced cDNA. This 5'-flanking sequence was analyzed for promoter activity. The longest fragment (538 nt) was able to drive the expression of luciferase in transient transfections of NIH 3T3 fibroblasts; the strong activity of the sponge promoter was found to be half the one displayed by the SV40 reference promoter. Deletion analysis demonstrates that the AP4 site and the GC box which is most adjacent to the TATA box are the crucial elements for maximal promoter activity. The activity of the promoter is not changed in 3T3 cells which are kept serum starved or in the presence of a phorbol ester. In conclusion, these data present the phylogenetically oldest cPKC gene which contains in the 5'-flanking region a promoter functional in the heterologous mammalian cell system. (+info)Expression of novel alternatively spliced isoforms of the oct-1 transcription factor. (7/14753)
Analysis of the alternatively spliced isoforms of the human and mouse oct-1 genes, combined with their exon-intron structure, show a high level of evolutionary conservation between these two species. The differential expression of several oct-1 isoforms was examined by reverse transcription-polymerase chain reaction performed on the 3' region of the murine oct-1 cDNA. Variations in the relative levels and patterns of expression of the isoforms were found among different tissues. Three novel isoforms originating from the 3'-distal region of oct-1, were isolated and sequenced: Two were derived from testis, and one from myeloma cells. Splicing out of different exons as revealed in the structure of these isoforms results in reading frameshifts that presumably lead to the expression of shortened Oct-1 proteins, with distinct C-terminal tails. Altogether, six out of the eight known murine oct-1 isoforms may have distinct C-termini, implying that these multiple tails have different functional roles in cellular differentiation and physiology. (+info)The alphaE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells. (8/14753)
The acquisition of invasiveness is a crucial step in the malignant progression of cancer. In cancers of the colon and of other organs the E-cadherin/catenin complex, which is implicated in homotypic cell-cell adhesion as well as in signal transduction, serves as a powerful inhibitor of invasion. We show here that one allele of the alphaE-catenin (CTNNA1) gene is mutated in the human colon cancer cell family HCT-8, which is identical to HCT-15, DLD-1 and HRT-18. Genetic instability, due to mutations in the HMSH6 (also called GTBP) mismatch repair gene, results in the spontaneous occurrence of invasive variants, all carrying either a mutation or exon skipping in the second alphaE-catenin allele. The alphaE-catenin gene is therefore, an invasion-suppressor gene in accordance with the two-hit model of Knudsen for tumour-suppressor genes. (+info)Exons are the coding regions of DNA that remain in the mature, processed mRNA after the removal of non-coding intronic sequences during RNA splicing. These exons contain the information necessary to encode proteins, as they specify the sequence of amino acids within a polypeptide chain. The arrangement and order of exons can vary between different genes and even between different versions of the same gene (alternative splicing), allowing for the generation of multiple protein isoforms from a single gene. This complexity in exon structure and usage significantly contributes to the diversity and functionality of the proteome.
Alternative splicing is a process in molecular biology that occurs during the post-transcriptional modification of pre-messenger RNA (pre-mRNA) molecules. It involves the removal of non-coding sequences, known as introns, and the joining together of coding sequences, or exons, to form a mature messenger RNA (mRNA) molecule that can be translated into a protein.
In alternative splicing, different combinations of exons are selected and joined together to create multiple distinct mRNA transcripts from a single pre-mRNA template. This process increases the diversity of proteins that can be produced from a limited number of genes, allowing for greater functional complexity in organisms.
Alternative splicing is regulated by various cis-acting elements and trans-acting factors that bind to specific sequences in the pre-mRNA molecule and influence which exons are included or excluded during splicing. Abnormal alternative splicing has been implicated in several human diseases, including cancer, neurological disorders, and cardiovascular disease.
Introns are non-coding sequences of DNA that are present within the genes of eukaryotic organisms, including plants, animals, and humans. Introns are removed during the process of RNA splicing, in which the initial RNA transcript is cut and reconnected to form a mature, functional RNA molecule.
After the intron sequences are removed, the remaining coding sequences, known as exons, are joined together to create a continuous stretch of genetic information that can be translated into a protein or used to produce non-coding RNAs with specific functions. The removal of introns allows for greater flexibility in gene expression and regulation, enabling the generation of multiple proteins from a single gene through alternative splicing.
In summary, introns are non-coding DNA sequences within genes that are removed during RNA processing to create functional RNA molecules or proteins.
A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
RNA splicing is a post-transcriptional modification process in which the non-coding sequences (introns) are removed and the coding sequences (exons) are joined together in a messenger RNA (mRNA) molecule. This results in a continuous mRNA sequence that can be translated into a single protein. Alternative splicing, where different combinations of exons are included or excluded, allows for the creation of multiple proteins from a single gene.
An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.
RNA splice sites are specific sequences on the pre-messenger RNA (pre-mRNA) molecule where the splicing process occurs during gene expression in eukaryotic cells. The pre-mRNA contains introns and exons, which are non-coding and coding regions of the RNA, respectively.
The splicing process removes the introns and joins together the exons to form a mature mRNA molecule that can be translated into a protein. The splice sites are recognized by the spliceosome, a complex of proteins and small nuclear RNAs (snRNAs) that catalyze the splicing reaction.
There are two main types of splice sites: the 5' splice site and the 3' splice site. The 5' splice site is located at the junction between the 5' end of the intron and the 3' end of the exon, while the 3' splice site is located at the junction between the 3' end of the intron and the 5' end of the exon.
The 5' splice site contains a conserved GU sequence, while the 3' splice site contains a conserved AG sequence. These sequences are recognized by the snRNAs in the spliceosome, which bind to them and facilitate the splicing reaction.
Mutations or variations in RNA splice sites can lead to abnormal splicing and result in diseases such as cancer, neurodegenerative disorders, and genetic disorders.
A mutation is a permanent change in the DNA sequence of an organism's genome. Mutations can occur spontaneously or be caused by environmental factors such as exposure to radiation, chemicals, or viruses. They may have various effects on the organism, ranging from benign to harmful, depending on where they occur and whether they alter the function of essential proteins. In some cases, mutations can increase an individual's susceptibility to certain diseases or disorders, while in others, they may confer a survival advantage. Mutations are the driving force behind evolution, as they introduce new genetic variability into populations, which can then be acted upon by natural selection.
DNA Mutational Analysis is a laboratory test used to identify genetic variations or changes (mutations) in the DNA sequence of a gene. This type of analysis can be used to diagnose genetic disorders, predict the risk of developing certain diseases, determine the most effective treatment for cancer, or assess the likelihood of passing on an inherited condition to offspring.
The test involves extracting DNA from a patient's sample (such as blood, saliva, or tissue), amplifying specific regions of interest using polymerase chain reaction (PCR), and then sequencing those regions to determine the precise order of nucleotide bases in the DNA molecule. The resulting sequence is then compared to reference sequences to identify any variations or mutations that may be present.
DNA Mutational Analysis can detect a wide range of genetic changes, including single-nucleotide polymorphisms (SNPs), insertions, deletions, duplications, and rearrangements. The test is often used in conjunction with other diagnostic tests and clinical evaluations to provide a comprehensive assessment of a patient's genetic profile.
It is important to note that not all mutations are pathogenic or associated with disease, and the interpretation of DNA Mutational Analysis results requires careful consideration of the patient's medical history, family history, and other relevant factors.
Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.
Polymerase Chain Reaction (PCR) is a laboratory technique used to amplify specific regions of DNA. It enables the production of thousands to millions of copies of a particular DNA sequence in a rapid and efficient manner, making it an essential tool in various fields such as molecular biology, medical diagnostics, forensic science, and research.
The PCR process involves repeated cycles of heating and cooling to separate the DNA strands, allow primers (short sequences of single-stranded DNA) to attach to the target regions, and extend these primers using an enzyme called Taq polymerase, resulting in the exponential amplification of the desired DNA segment.
In a medical context, PCR is often used for detecting and quantifying specific pathogens (viruses, bacteria, fungi, or parasites) in clinical samples, identifying genetic mutations or polymorphisms associated with diseases, monitoring disease progression, and evaluating treatment effectiveness.
Molecular cloning is a laboratory technique used to create multiple copies of a specific DNA sequence. This process involves several steps:
1. Isolation: The first step in molecular cloning is to isolate the DNA sequence of interest from the rest of the genomic DNA. This can be done using various methods such as PCR (polymerase chain reaction), restriction enzymes, or hybridization.
2. Vector construction: Once the DNA sequence of interest has been isolated, it must be inserted into a vector, which is a small circular DNA molecule that can replicate independently in a host cell. Common vectors used in molecular cloning include plasmids and phages.
3. Transformation: The constructed vector is then introduced into a host cell, usually a bacterial or yeast cell, through a process called transformation. This can be done using various methods such as electroporation or chemical transformation.
4. Selection: After transformation, the host cells are grown in selective media that allow only those cells containing the vector to grow. This ensures that the DNA sequence of interest has been successfully cloned into the vector.
5. Amplification: Once the host cells have been selected, they can be grown in large quantities to amplify the number of copies of the cloned DNA sequence.
Molecular cloning is a powerful tool in molecular biology and has numerous applications, including the production of recombinant proteins, gene therapy, functional analysis of genes, and genetic engineering.
RNA precursors, also known as primary transcripts or pre-messenger RNAs (pre-mRNAs), refer to the initial RNA molecules that are synthesized during the transcription process in which DNA is copied into RNA. These precursor molecules still contain non-coding sequences and introns, which need to be removed through a process called splicing, before they can become mature and functional RNAs such as messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), or transfer RNAs (tRNAs).
Pre-mRNAs undergo several processing steps, including 5' capping, 3' polyadenylation, and splicing, to generate mature mRNA molecules that can be translated into proteins. The accurate and efficient production of RNA precursors and their subsequent processing are crucial for gene expression and regulation in cells.
I must clarify that the term "pedigree" is not typically used in medical definitions. Instead, it is often employed in genetics and breeding, where it refers to the recorded ancestry of an individual or a family, tracing the inheritance of specific traits or diseases. In human genetics, a pedigree can help illustrate the pattern of genetic inheritance in families over multiple generations. However, it is not a medical term with a specific clinical definition.
Single-Stranded Conformational Polymorphism (SSCP) is not a medical condition but rather a laboratory technique used in molecular biology and genetics. It refers to the phenomenon where a single-stranded DNA or RNA molecule can adopt different conformations or shapes based on its nucleotide sequence, even if the difference in the sequence is as small as a single base pair change. This property is used in SSCP analysis to detect mutations or variations in DNA or RNA sequences.
In SSCP analysis, the denatured single-stranded DNA or RNA sample is subjected to electrophoresis on a non-denaturing polyacrylamide gel. The different conformations of the single-stranded molecules migrate at different rates in the gel, creating multiple bands that can be visualized by staining or other detection methods. The presence of additional bands or shifts in band patterns can indicate the presence of a sequence variant or mutation.
SSCP analysis is often used as a screening tool for genetic diseases, cancer, and infectious diseases to identify genetic variations associated with these conditions. However, it has largely been replaced by more sensitive and accurate methods such as next-generation sequencing.
Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.
Protein isoforms are different forms or variants of a protein that are produced from a single gene through the process of alternative splicing, where different exons (or parts of exons) are included in the mature mRNA molecule. This results in the production of multiple, slightly different proteins that share a common core structure but have distinct sequences and functions. Protein isoforms can also arise from genetic variations such as single nucleotide polymorphisms or mutations that alter the protein-coding sequence of a gene. These differences in protein sequence can affect the stability, localization, activity, or interaction partners of the protein isoform, leading to functional diversity and specialization within cells and organisms.
Complementary DNA (cDNA) is a type of DNA that is synthesized from a single-stranded RNA molecule through the process of reverse transcription. In this process, the enzyme reverse transcriptase uses an RNA molecule as a template to synthesize a complementary DNA strand. The resulting cDNA is therefore complementary to the original RNA molecule and is a copy of its coding sequence, but it does not contain non-coding regions such as introns that are present in genomic DNA.
Complementary DNA is often used in molecular biology research to study gene expression, protein function, and other genetic phenomena. For example, cDNA can be used to create cDNA libraries, which are collections of cloned cDNA fragments that represent the expressed genes in a particular cell type or tissue. These libraries can then be screened for specific genes or gene products of interest. Additionally, cDNA can be used to produce recombinant proteins in heterologous expression systems, allowing researchers to study the structure and function of proteins that may be difficult to express or purify from their native sources.
A sequence deletion in a genetic context refers to the removal or absence of one or more nucleotides (the building blocks of DNA or RNA) from a specific region in a DNA or RNA molecule. This type of mutation can lead to the loss of genetic information, potentially resulting in changes in the function or expression of a gene. If the deletion involves a critical portion of the gene, it can cause diseases, depending on the role of that gene in the body. The size of the deleted sequence can vary, ranging from a single nucleotide to a large segment of DNA.
Sequence homology in nucleic acids refers to the similarity or identity between the nucleotide sequences of two or more DNA or RNA molecules. It is often used as a measure of biological relationship between genes, organisms, or populations. High sequence homology suggests a recent common ancestry or functional constraint, while low sequence homology may indicate a more distant relationship or different functions.
Nucleic acid sequence homology can be determined by various methods such as pairwise alignment, multiple sequence alignment, and statistical analysis. The degree of homology is typically expressed as a percentage of identical or similar nucleotides in a given window of comparison.
It's important to note that the interpretation of sequence homology depends on the biological context and the evolutionary distance between the sequences compared. Therefore, functional and experimental validation is often necessary to confirm the significance of sequence homology.
Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.
During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.
Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.
DNA Sequence Analysis is the systematic determination of the order of nucleotides in a DNA molecule. It is a critical component of modern molecular biology, genetics, and genetic engineering. The process involves determining the exact order of the four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - in a DNA molecule or fragment. This information is used in various applications such as identifying gene mutations, studying evolutionary relationships, developing molecular markers for breeding, and diagnosing genetic diseases.
The process of DNA Sequence Analysis typically involves several steps, including DNA extraction, PCR amplification (if necessary), purification, sequencing reaction, and electrophoresis. The resulting data is then analyzed using specialized software to determine the exact sequence of nucleotides.
In recent years, high-throughput DNA sequencing technologies have revolutionized the field of genomics, enabling the rapid and cost-effective sequencing of entire genomes. This has led to an explosion of genomic data and new insights into the genetic basis of many diseases and traits.
A gene is a specific sequence of nucleotides in DNA that carries genetic information. Genes are the fundamental units of heredity and are responsible for the development and function of all living organisms. They code for proteins or RNA molecules, which carry out various functions within cells and are essential for the structure, function, and regulation of the body's tissues and organs.
Each gene has a specific location on a chromosome, and each person inherits two copies of every gene, one from each parent. Variations in the sequence of nucleotides in a gene can lead to differences in traits between individuals, including physical characteristics, susceptibility to disease, and responses to environmental factors.
Medical genetics is the study of genes and their role in health and disease. It involves understanding how genes contribute to the development and progression of various medical conditions, as well as identifying genetic risk factors and developing strategies for prevention, diagnosis, and treatment.
A point mutation is a type of genetic mutation where a single nucleotide base (A, T, C, or G) in DNA is altered, deleted, or substituted with another nucleotide. Point mutations can have various effects on the organism, depending on the location of the mutation and whether it affects the function of any genes. Some point mutations may not have any noticeable effect, while others might lead to changes in the amino acids that make up proteins, potentially causing diseases or altering traits. Point mutations can occur spontaneously due to errors during DNA replication or be inherited from parents.
Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.
Restriction mapping is a technique used in molecular biology to identify the location and arrangement of specific restriction endonuclease recognition sites within a DNA molecule. Restriction endonucleases are enzymes that cut double-stranded DNA at specific sequences, producing fragments of various lengths. By digesting the DNA with different combinations of these enzymes and analyzing the resulting fragment sizes through techniques such as agarose gel electrophoresis, researchers can generate a restriction map - a visual representation of the locations and distances between recognition sites on the DNA molecule. This information is crucial for various applications, including cloning, genome analysis, and genetic engineering.
DNA primers are short single-stranded DNA molecules that serve as a starting point for DNA synthesis. They are typically used in laboratory techniques such as the polymerase chain reaction (PCR) and DNA sequencing. The primer binds to a complementary sequence on the DNA template through base pairing, providing a free 3'-hydroxyl group for the DNA polymerase enzyme to add nucleotides and synthesize a new strand of DNA. This allows for specific and targeted amplification or analysis of a particular region of interest within a larger DNA molecule.
Chromosome mapping, also known as physical mapping, is the process of determining the location and order of specific genes or genetic markers on a chromosome. This is typically done by using various laboratory techniques to identify landmarks along the chromosome, such as restriction enzyme cutting sites or patterns of DNA sequence repeats. The resulting map provides important information about the organization and structure of the genome, and can be used for a variety of purposes, including identifying the location of genes associated with genetic diseases, studying evolutionary relationships between organisms, and developing genetic markers for use in breeding or forensic applications.
A nonsense codon is a sequence of three nucleotides in DNA or RNA that does not code for an amino acid. Instead, it signals the end of the protein-coding region of a gene and triggers the termination of translation, the process by which the genetic code is translated into a protein.
In DNA, the nonsense codons are UAA, UAG, and UGA, which are also known as "stop codons." When these codons are encountered during translation, they cause the release of the newly synthesized polypeptide chain from the ribosome, bringing the process of protein synthesis to a halt.
Nonsense mutations are changes in the DNA sequence that result in the appearance of a nonsense codon where an amino acid-coding codon used to be. These types of mutations can lead to premature termination of translation and the production of truncated, nonfunctional proteins, which can cause genetic diseases or contribute to cancer development.
A frameshift mutation is a type of genetic mutation that occurs when the addition or deletion of nucleotides in a DNA sequence is not divisible by three. Since DNA is read in groups of three nucleotides (codons), which each specify an amino acid, this can shift the "reading frame," leading to the insertion or deletion of one or more amino acids in the resulting protein. This can cause a protein to be significantly different from the normal protein, often resulting in a nonfunctional protein and potentially causing disease. Frameshift mutations are typically caused by insertions or deletions of nucleotides, but they can also result from more complex genetic rearrangements.
In genetics, sequence alignment is the process of arranging two or more DNA, RNA, or protein sequences to identify regions of similarity or homology between them. This is often done using computational methods to compare the nucleotide or amino acid sequences and identify matching patterns, which can provide insight into evolutionary relationships, functional domains, or potential genetic disorders. The alignment process typically involves adjusting gaps and mismatches in the sequences to maximize the similarity between them, resulting in an aligned sequence that can be visually represented and analyzed.
An allele is a variant form of a gene that is located at a specific position on a specific chromosome. Alleles are alternative forms of the same gene that arise by mutation and are found at the same locus or position on homologous chromosomes.
Each person typically inherits two copies of each gene, one from each parent. If the two alleles are identical, a person is said to be homozygous for that trait. If the alleles are different, the person is heterozygous.
For example, the ABO blood group system has three alleles, A, B, and O, which determine a person's blood type. If a person inherits two A alleles, they will have type A blood; if they inherit one A and one B allele, they will have type AB blood; if they inherit two B alleles, they will have type B blood; and if they inherit two O alleles, they will have type O blood.
Alleles can also influence traits such as eye color, hair color, height, and other physical characteristics. Some alleles are dominant, meaning that only one copy of the allele is needed to express the trait, while others are recessive, meaning that two copies of the allele are needed to express the trait.
A missense mutation is a type of point mutation in which a single nucleotide change results in the substitution of a different amino acid in the protein that is encoded by the affected gene. This occurs when the altered codon (a sequence of three nucleotides that corresponds to a specific amino acid) specifies a different amino acid than the original one. The function and/or stability of the resulting protein may be affected, depending on the type and location of the missense mutation. Missense mutations can have various effects, ranging from benign to severe, depending on the importance of the changed amino acid for the protein's structure or function.
Southern blotting is a type of membrane-based blotting technique that is used in molecular biology to detect and locate specific DNA sequences within a DNA sample. This technique is named after its inventor, Edward M. Southern.
In Southern blotting, the DNA sample is first digested with one or more restriction enzymes, which cut the DNA at specific recognition sites. The resulting DNA fragments are then separated based on their size by gel electrophoresis. After separation, the DNA fragments are denatured to convert them into single-stranded DNA and transferred onto a nitrocellulose or nylon membrane.
Once the DNA has been transferred to the membrane, it is hybridized with a labeled probe that is complementary to the sequence of interest. The probe can be labeled with radioactive isotopes, fluorescent dyes, or chemiluminescent compounds. After hybridization, the membrane is washed to remove any unbound probe and then exposed to X-ray film (in the case of radioactive probes) or scanned (in the case of non-radioactive probes) to detect the location of the labeled probe on the membrane.
The position of the labeled probe on the membrane corresponds to the location of the specific DNA sequence within the original DNA sample. Southern blotting is a powerful tool for identifying and characterizing specific DNA sequences, such as those associated with genetic diseases or gene regulation.
Dystrophin is a protein that provides structural stability to muscle fibers. It is an essential component of the dystrophin-glycoprotein complex, which helps maintain the integrity of the sarcolemma (the membrane surrounding muscle cells) during muscle contraction and relaxation. Dystrophin plays a crucial role in connecting the cytoskeleton of the muscle fiber to the extracellular matrix, allowing for force transmission and protecting the muscle cell from damage.
Mutations in the DMD gene, which encodes dystrophin, can lead to various forms of muscular dystrophy, including Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). In DMD, a severe form of the disease, genetic alterations typically result in little or no production of functional dystrophin, causing progressive muscle weakness, wasting, and degeneration. In BMD, a milder form of the disorder, partially functional dystrophin is produced, leading to less severe symptoms and later onset of the disease.
Genetic polymorphism refers to the occurrence of multiple forms (called alleles) of a particular gene within a population. These variations in the DNA sequence do not generally affect the function or survival of the organism, but they can contribute to differences in traits among individuals. Genetic polymorphisms can be caused by single nucleotide changes (SNPs), insertions or deletions of DNA segments, or other types of genetic rearrangements. They are important for understanding genetic diversity and evolution, as well as for identifying genetic factors that may contribute to disease susceptibility in humans.
Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a laboratory technique used in molecular biology to amplify and detect specific DNA sequences. This technique is particularly useful for the detection and quantification of RNA viruses, as well as for the analysis of gene expression.
The process involves two main steps: reverse transcription and polymerase chain reaction (PCR). In the first step, reverse transcriptase enzyme is used to convert RNA into complementary DNA (cDNA) by reading the template provided by the RNA molecule. This cDNA then serves as a template for the PCR amplification step.
In the second step, the PCR reaction uses two primers that flank the target DNA sequence and a thermostable polymerase enzyme to repeatedly copy the targeted cDNA sequence. The reaction mixture is heated and cooled in cycles, allowing the primers to anneal to the template, and the polymerase to extend the new strand. This results in exponential amplification of the target DNA sequence, making it possible to detect even small amounts of RNA or cDNA.
RT-PCR is a sensitive and specific technique that has many applications in medical research and diagnostics, including the detection of viruses such as HIV, hepatitis C virus, and SARS-CoV-2 (the virus that causes COVID-19). It can also be used to study gene expression, identify genetic mutations, and diagnose genetic disorders.
Sequence homology, amino acid, refers to the similarity in the order of amino acids in a protein or a portion of a protein between two or more species. This similarity can be used to infer evolutionary relationships and functional similarities between proteins. The higher the degree of sequence homology, the more likely it is that the proteins are related and have similar functions. Sequence homology can be determined through various methods such as pairwise alignment or multiple sequence alignment, which compare the sequences and calculate a score based on the number and type of matching amino acids.
A genomic library is a collection of cloned DNA fragments that represent the entire genetic material of an organism. It serves as a valuable resource for studying the function, organization, and regulation of genes within a given genome. Genomic libraries can be created using different types of vectors, such as bacterial artificial chromosomes (BACs), yeast artificial chromosomes (YACs), or plasmids, to accommodate various sizes of DNA inserts. These libraries facilitate the isolation and manipulation of specific genes or genomic regions for further analysis, including sequencing, gene expression studies, and functional genomics research.
Gene deletion is a type of mutation where a segment of DNA, containing one or more genes, is permanently lost or removed from a chromosome. This can occur due to various genetic mechanisms such as homologous recombination, non-homologous end joining, or other types of genomic rearrangements.
The deletion of a gene can have varying effects on the organism, depending on the function of the deleted gene and its importance for normal physiological processes. If the deleted gene is essential for survival, the deletion may result in embryonic lethality or developmental abnormalities. However, if the gene is non-essential or has redundant functions, the deletion may not have any noticeable effects on the organism's phenotype.
Gene deletions can also be used as a tool in genetic research to study the function of specific genes and their role in various biological processes. For example, researchers may use gene deletion techniques to create genetically modified animal models to investigate the impact of gene deletion on disease progression or development.
'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.
A phenotype is the physical or biochemical expression of an organism's genes, or the observable traits and characteristics resulting from the interaction of its genetic constitution (genotype) with environmental factors. These characteristics can include appearance, development, behavior, and resistance to disease, among others. Phenotypes can vary widely, even among individuals with identical genotypes, due to differences in environmental influences, gene expression, and genetic interactions.
Exon
Exon (disambiguation)
Exon skipping
Arthur Exon
Nat Exon
Exon shuffling
Exon trapping
Exon junction complex
Tandem exon duplication
J. James Exon
Exon-Florio Amendment
Philip of Exon
Exon-intron database
Trans-Spliced Exon Coupled RNA End Determination
Netrin receptor DCC
TMEM125
CFAP206
HLA-A
Helicase, POLQ-like
C17orf75
ACOT1
TEX9
Uncharacterized protein C15orf32
SHLD1
TEKTIP1
Pseudoachondroplasia
Basic leucine zipper and W2 domain-containing protein 2
JETLAG gene
ACOT11
GLS2
Exon - Wikipedia
exon Archives - Liliputing
Structure and novel exons of the human tau gene
Mel Exon | Media Trust
Absence of specific alternatively spliced exon of CD44 in macrophages prevents colitis | Mucosal Immunology
028599 - TLR5[fl] (TLR5 floxed exon 4) Strain Details
Organization of Genes: Introns, Exons & Regulatory Elements | Biology | JoVE
SimpleChIP® Human DNAJB9 Exon 1 Primers | Cell Signaling Technology
Capmatinib for MET Exon 14-Mutated NSCLC
FDA grants accelerated approval to mobocertinib for metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations...
Recurrent BRCA2 exon 3 deletion in Assyrian families | Journal of Medical Genetics
Paper: Initial exon sequencing of putatively acid-neutralizing basic proline rich proteins (AADR Annual Meeting (March 21-24,...
Colony EXON Flatland Folding Tire (Black) (20' / 406 ISO) (1.75') - Dan's Comp
EvC Forum: Exons v. Introns Creationist Challenge
PPT - Exon skipping/inclusion PowerPoint Presentation, free download - ID:3965866
Dryad | Data -- Insecticide resistance mediated by an exon skipping event
JCI - Identification of a novel exonic mutation at -13 from 5' splice site causing exon skipping in a girl with mitochondrial...
SeCore® DRB1 Locus Exon Kit Thank You | Thermo Fisher Scientific - US
Tepotinib Shows Activity in Advanced NSCLC with a MET Exon 14
Frontiers | Transport Granules Bound with Nuclear Cap Binding Protein and Exon Junction Complex Are Associated with...
"Alternative first exon splicing regulates subcellular distribution of " by Hwa-Young Kim and Vadim Gladyshev
Two Case Reports of Rare BRAF Mutations in Exon 11 and Exon 15 with Discussion of Potential Treatment Options | Case Reports in...
Entrada Therapeutics Shares New Data on ENTR-601-44 Exon Skipping Therapy - Parent Project Muscular Dystrophy
Oncogene- and drug resistance-associated alternative exon usage in acute myeloid leukemia (AML) - Laboratoire de Biologie et...
Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing | Protocol ...
Exon Junction Complexes Suppress Spurious Splice Sites to Safeguard Transcriptome Integrity - Kölner...
WCLC 2022: Study discloses clinical-relevant intertumoural heterogeneity of NSCLC driven by MET exon 14 skipping - ecancer
Exon, NF et al. (2005): Paleontology age profile (datum list) of ODP Hole 189-1172A
Exon number from Ensembl ID
Silent variant in F8:c.222G|T (p.Thr74Thr) causes a partial exon skipping in a patient with mild hemophilia A | Lund University...
Gene28
- An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. (wikipedia.org)
- The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. (wikipedia.org)
- Across all eukaryotic genes in GenBank, there were (in 2002), on average, 5.48 exons per protein coding gene. (wikipedia.org)
- Mature mRNAs originating from the same gene need not include the same exons, since different introns in the pre-mRNA can be removed by the process of alternative splicing. (wikipedia.org)
- Exon trapping or 'gene trapping' is a molecular biology technique that exploits the existence of the intron-exon splicing to find new genes. (wikipedia.org)
- The first exon of a 'trapped' gene splices into the exon that is contained in the insertional DNA. (wikipedia.org)
- This new exon contains the ORF for a reporter gene that can now be expressed using the enhancers that control the target gene. (wikipedia.org)
- DBASS3/5 Exitron Exon-intron database Exon shuffling Interrupted gene Outron Twintron Untranslated region (UTR) Gilbert W (February 1978). (wikipedia.org)
- The restriction analysis and partial sequencing of the gene shows that it contains (1) four alternatively spliced exons previously described in rodent and bovine but not in human tau cDNAs and (2) two CpG islands, one associated with the promoter region, the other with exon 9. (nih.gov)
- SimpleChIP ® Human DNAJB9 Exon 1 Primers contain a mix of forward and reverse PCR primers that are specific to exon 1 of the human DnaJ homolog subfamily B member 9 gene. (cellsignal.com)
- Patients with MET exon 14 skipping mutations or MET amplifications, according to the gene copy number in tumor tissue, were enrolled. (onclive.com)
- When we compare the gene between vertebrate species and look for conserved sequence we find that there are strong signals of sequence conservation that line up with the exons. (evcforum.net)
- The gene encoding the insect nicotinic acetylcholine receptor (nAChR) α6 subunit, target of the bio-insecticide spinosad, is one example of this and expands protein diversity via alternative splicing of mutually exclusive exons. (datadryad.org)
- Our results demonstrate that the intrinsic capacity of the α6 gene to generate transcript diversity via alternative splicing can be readily exploited during the evolution of resistance and identifies exon skipping as a molecular alteration conferring insecticide resistance. (datadryad.org)
- We identified a novel exonic mutation which causes exon skipping in the mitochondrial acetoacetyl-CoA thiolase (T2) gene from a girl with T2 deficiency (GK07). (jci.org)
- At the gene level, a C to T transition causing Gln272 to termination codon (Q272STOP) was identified within exon 8, 13 bp from the 5' splice site of intron 8 in the paternal allele. (jci.org)
- I am not familiar with the Gtex portal, but looks like they really count all the exons of a gene no matter from which transcript they come. (biostars.org)
- Here we report a silent variant found in exon 2 in the F8 gene in a 47-year-old patient with a previous von Willebrand disease (VWD) type 1 diagnosis. (lu.se)
- I want to download the sequences of all the exons for each human gene. (biostars.org)
- my bed file is not in bed12 and each exon is in a separate row (though the name column of the bed file is the gene ID). (biostars.org)
- Comparison of our mouse exon-skipping events to previously detected human exon-skipping events on chromosome 22 by Hide et al.2001, has revealed that mouse and human exon-skipping events were never observed together within an orthologous gene-pair. (uwc.ac.za)
- Although the transcript identity between mouse and human orthologous transcripts were high (greater than 80% sequence identity), the exon order in these gene-pairs may be different between mouse and human orthologous genes. (uwc.ac.za)
- Our conclusion that the mouse exon-skipping frequency may be lower than the human estimate remains to be tested with a larger mouse multi-exon gene set. (uwc.ac.za)
- How can we get the exon co-ordinates of the variants from MAF file (Mutation Annotation Format), if we have chromosome location of the genes and gene symbol. (bioconductor.org)
- Emerging therapeutic approaches include gene transfer therapy using adeno-associated virus (AAV) vectors, and exon skipping agents. (nova.edu)
- However, researchers have found that DNA variations outside the exons can affect gene activity and protein production and lead to genetic disorders--variations that whole exome sequencing would miss. (medlineplus.gov)
- These primers amplify approximately 495 bp of exons and introns at the 5' end of the β-tubulin gene. (cdc.gov)
- A 133 bp fragment, spanning exon 11 of the APC gene was amplified, and Rsal digestion of the PCR product defined the alleles as either homozygous 133 bp (Rsa(-/-)) or 87 and 46 bp (Rsa(+/+)) fragments, and heterozygous (Rsa(+/-)) exhibiting the three fragments. (who.int)
Mutations15
- Exonization is the creation of a new exon, as a result of mutations in introns. (wikipedia.org)
- Among patients with non-small cell lung cancer and MET exon 14 skipping mutations, an overall response rate of approximately 41% has been seen. (onclive.com)
- What we learned is that this drug elicits meaningful responses in patients who harbor MET exon 14 skipping mutations. (onclive.com)
- I would consider identifying MET exon 14 skipping mutations up front and using this drug in the first line. (onclive.com)
- The key takeaways for me are this is an exciting advance for the field and is another drug that can and should be used for patients with MET exon 14 skipping mutations. (onclive.com)
- On September 15, 2021, the Food and Drug Administration granted accelerated approval to mobocertinib (Exkivity, Takeda Pharmaceuticals, Inc.) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. (fda.gov)
- Approval was based on Study 101, an international, non-randomized, open-label, multicohort clinical trial (NCT02716116) which included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. (fda.gov)
- NSCLC patients with MET exon 14 skipping mutations are typically 70 years of age or older. (esmo.org)
- In their article, published in the NEJM, they reported the results in patients with MET exon 14 skipping mutations. (esmo.org)
- The authors concluded that their results show that the selective MET inhibitor tepotinib has durable clinical activity in patients with NSCLC with MET mutations associated with exon 14 skipping. (esmo.org)
- Imatinib in systemic mastocytosis: a phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature. (qxmd.com)
- Resistance to imatinib has been recurrently reported in systemic mastocytosis (SM) carrying exon 17 KIT mutations. (qxmd.com)
- We evaluated the efficacy and safety of imatinib therapy in 10 adult SM patients lacking exon 17 KIT mutations, 9 of which fulfilled criteria for well-differentiated SM (WDSM). (qxmd.com)
- Absence of exon 17 KIT mutations was confirmed in highly-purified BM MCs by peptide nucleic acid-mediated PCR, while mutations involving other exons were investigated by direct sequencing of purified BM MC DNA. (qxmd.com)
- Because most known mutations that cause disease occur in exons, whole exome sequencing is thought to be an efficient method to identify possible disease-causing mutations. (medlineplus.gov)
Genes20
- Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome. (wikipedia.org)
- In humans, like protein coding mRNA, most non-coding RNA also contain multiple exons In protein-coding genes, the exons include both the protein-coding sequence and the 5′- and 3′-untranslated regions (UTR). (wikipedia.org)
- Often the first exon includes both the 5′-UTR and the first part of the coding sequence, but exons containing only regions of 5′-UTR or (more rarely) 3′-UTR occur in some genes, i.e. the UTRs may contain introns. (wikipedia.org)
- However, these sorts of definitions only cover protein-coding genes, and omit those exons that become part of a non-coding RNA or the untranslated region of an mRNA. (wikipedia.org)
- Examination of human tau mRNA indicates that the human cerebrocortical splicing pattern differs from that previously reported for the murine and bovine tau mRNAs, despite conserved exon organization in all three genes. (nih.gov)
- Genes themselves consist of protein-coding exons and non-coding introns. (jove.com)
- Because longer genes encode longer BPRPs, we investigated the possibility of exon sequencing BPRP alleles encoded by PRB1 and PRB2. (umich.edu)
- Just for clarity, exons are segments of eukaryotic genes that are stitched together to make a mature mRNA molecule that is then translated into protein. (evcforum.net)
- Many genes increase coding capacity by alternate exon usage. (datadryad.org)
- Several alternative splicing surveys have confirmed the frequent occurrence of exon skipping in human genes. (uwc.ac.za)
- However, the occurrence of exon skipping in mouse genes has not yet been extensively examined. (uwc.ac.za)
- Recent improvements in mouse genome sequencing have permitted the current study to explore the occurrence of exon skipping in mouse genes orthologous to human genes on chromosome 22. (uwc.ac.za)
- A low number (5/72 multi-exon genes) of mouse exon-skipped genes were captured through alignments of mouse ESTs to mouse genomic contigs. (uwc.ac.za)
- Exon-skipping events in two mouse exon-skipped genes (GNB1L, SMARCB1) appear to affect biological processes such as electron and protein transport. (uwc.ac.za)
- These factors resulted in a large number (112/269) of mouse transcripts lacking matches to mouse genomic contigs and nearly half (12/25) of the mouse multi-exon genes, which have matching Ensembl transcript identifiers, have under-predicted exons. (uwc.ac.za)
- However, when compared to a higher estimate (52/347) of exon skipping in human genes for chromosome 22 produced under similar conditions by Hide et al.2001, it is possible that our mouse exon-skipping frequency may be lower than the human frequency. (uwc.ac.za)
- However, the mouse exon-skipping frequency may represent the highest estimate that can be obtained given that the current number (87) of mouse genes orthologous to chromosome 22 in Ensembl (v1 30th Jan. 2002) does not deviate significantly from our total number (72) of mouse multi-exon genes. (uwc.ac.za)
- Certain combinations of common variants in exon 3 of OPN1LW and OPN1MW, the genes encoding the apo- protein of the long- and middle-wavelength sensitive cone photoreceptor visual pigments in humans , induce splicing defects and have been associated with dyschromatopsia and cone dysfunction syndromes . (bvsalud.org)
- In BASE, reporters also refer to Affymetrix Probeset ID but reporters can be used to describe genes, transcripts, exons or any other sequence entity of biological relevance. (lu.se)
- Reporters are used to represent genes, transcripts, exons and therefore come in their thousands. (lu.se)
MRNA8
- Splicing can be experimentally modified so that targeted exons are excluded from mature mRNA transcripts by blocking the access of splice-directing small nuclear ribonucleoprotein particles (snRNPs) to pre-mRNA using Morpholino antisense oligos. (wikipedia.org)
- Introns are excised once the sequence is transcribed to mRNA, leaving only exons to code for proteins. (jove.com)
- Sequencing of the α6 subunit cDNA from spinosad selected and unselected strains of T. absoluta revealed all Taα6 transcripts of the selected strain were devoid of exon 3, with comparison of genomic DNA and mRNA revealing this is a result of exon skipping. (datadryad.org)
- This substitution was thought to alter the secondary structure of T2 pre-mRNA around exon 8 and thus impede normal splicing. (jci.org)
- Here we report a class of mRNA granules in human neuronal processes that are enriched in the nuclear cap-binding protein complex (CBC) and exon junction complex (EJC) core components, Y14 and eIF4AIII. (frontiersin.org)
- In addition to the cis -elements in its 3′UTR and trans -acting factor Staufen, posterior localization of oskar mRNA requires deposition of exon junction complex (EJC) in its first exon through splicing ( Hachet and Ephrussi, 2004 ). (frontiersin.org)
- Here, we find that many aberrant exonic SS are efficiently silenced by the exon junction complex (EJC), a multi-protein complex that is deposited on spliced mRNA near the exon-exon junction. (uni-koeln.de)
- Current DMD therapeutics use phosphorordiamidate morpholino oligomers (PMO) to skip over the frame-shifting exon during the splicing of the dystrophin pre-mRNA, resulting in translation of a truncated dystrophin protein product. (gene-tools.com)
NSCLC5
- In patients with advanced non-small cell lung cancer (NSCLC) with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. (esmo.org)
- A study presented today at the IASLC World Conference on Lung Cancer 2022 in Vienna disclosed the clinical-relevant intertumoural heterogeneity of non-small cell lung cancer (NSCLC) driven by MET exon 14 skipping. (ecancer.org)
- MET exon 14 skipping, as a rare driver for non-small cell lung cancer (NSCLC), can be successfully targeted by MET specific tyrosine kinase inhibitors (TKI) like savolitinib, tepotinib, and capmatinib. (ecancer.org)
- Recent clinical trials of MET selective TKIs displayed encouraging clinical efficacy but nearly half of NSCLC patients with MET exon 14 skipping did not benefit from MET-TKI treatment, which indicated biological heterogeneity in NSCLCs driven by METex14 skipping. (ecancer.org)
- En este video, el Dr. Rodríguez nos actualiza sobre objetivos moleculares emergentes en NSCLC: fusiones RET, MET, KRAS, inserciones del exón 20 de EFGR. (cancergrace.org)
Antisense-mediated exon1
- She was also involved in mouse studies to develop antisense-mediated exon skipping therapies for DMD. (exonskipping.nl)
Skip1
- Thus, in the study presented here, fifty-four individuals constituted a group comparable to DMD patients by exon 45 skip. (institut-myologie.org)
Deletion2
- To test the hypothesis that miR-146a is inhibitory to exon skipping dystrophin restoration, we generated a novel DMD double knockout mouse model with body-wide miR-146a deletion ( 146aX mice) and administered an exon 51 skipping PMO into the tibialis anterior (TA) muscles of mdx52 and 146aX mice. (gene-tools.com)
- These data demonstrate genetic deletion of miR-146a is sufficient to increase dystrophin rescue via exon skipping. (gene-tools.com)
Introns and exons2
- Importantly, between these beginning and end points lie areas called introns and exons, both of which are reflected in the RNA product. (jove.com)
- How does ID/creationism explain this pattern where introns and exons diverge as we move through these species? (evcforum.net)
Transcript3
- I am not sure what you mean by "exon Numer" but I guess it is the rank (position of exon in a transcript, starting with 1 for the first one, even if not coding). (biostars.org)
- Sanger sequencing of the patient's cDNA after nested polymerase chain reaction showed that the patient had both a normal transcript containing exons 1-4 and a defect transcript lacking exon 2. (lu.se)
- The capture of mouse exon-skipping events may increase as the quality and quantity of mouse genomic and transcript sequences improves. (uwc.ac.za)
Transcripts6
- Some non-coding RNA transcripts also have exons and introns. (wikipedia.org)
- Because an exon can have different ranks in different transcripts. (biostars.org)
- But the rank of this exon is 2 for both protein coding transcripts of SOD1. (biostars.org)
- The issue you have with more sequences and exons is most likely due to alternative transcripts. (biostars.org)
- Main factors contributing towards the low detection of mouse exon-skipping events include the lack of mouse transcripts matching to mouse genomic sequences and the under-prediction of mouse exons. (uwc.ac.za)
- Applying minigene assays for all observed exon 3 haplotypes in the patients , we demonstrated that the novel exon 3 haplotype L-I-V-V-A induces a strong but incomplete splicing defect with 3-5% of residual correctly spliced transcripts. (bvsalud.org)
Ensembl1
- Given an Ensembl exon ID, how can I determine the exon number? (biostars.org)
Exome2
- Methods: All exons of PRB1 and PRB2 from 8 healthy adults were sequenced using an Illumina HiSeq 2000 (100 bp paired sequencing readouts with TruSeq™ Exome Enrichment Kit). (umich.edu)
- Together, all the exons in a genome are known as the exome, and the method of sequencing them is known as whole exome sequencing. (medlineplus.gov)
Sequences2
- The role of exon sequences in the splicing mechanism is indicated by the exon skipping which occurred with an exonic mutation. (jci.org)
- Then I tried to download directly Exon sequences, but the number of sequences was again larger the the number of exons should be and moreover several exon ids correspond to the same sequence. (biostars.org)
Dystrophin4
- While exon skipping therapies are promising, their potential has not been fully realized as increases in dystrophin protein have been minimal and highly variable in clinical trials. (gene-tools.com)
- In dystrophin-deficient mice we find that co-injection of an exon skipping PMO with miR-146a but not a control sequence reduces the extent of dystrophin positive fibers. (gene-tools.com)
- Our data suggests that antagomiR-mediated inhibition of miR-146a or other dystrophin targeting miRNAs could be a viable exon skipping DMD co-therapy and warrants further research. (gene-tools.com)
- Even though exon skipping agents produce a smaller dystrophin protein, they effectively preserve a significant portion of its function. (nova.edu)
Proteins2
- Since this RNA will be used to generate proteins, exons are denoted as coding regions, whereas introns are another example of non-coding material. (jove.com)
- DNA and RNA sequencing analyses suggested that exon skipping did not result from genetic alterations in intronic or exonic cis-regulatory elements, but rather was associated with a single epigenetic modification downstream of exon 3a, and quantitative changes in the expression of trans-acting proteins that have known roles in the regulation of alternative splicing. (datadryad.org)
Therapies1
- Exon skipping agents have clinical advantages over traditional therapies, such as corticosteroids, because they slow the progression of DMD in addition to relieving symptoms. (nova.edu)
Insertions1
- CD44 is a transmembrane molecule appearing in numerous isoforms generated by insertions of alternatively spliced variant exons ( CD44v ) and having various binding partners. (nature.com)
Defect1
- Exon 3 Haplotype-Associated Splicing Defect in Patients with X-Linked Cone Dysfunction. (bvsalud.org)
Duchenne3
- Entrada Therapeutics has shared new data from a preclinical study evaluating ENTR-601-44 , an exon-skipping therapy set to target individuals with Duchenne amenable to exon 44 skipping. (parentprojectmd.org)
- The company announced new non-human primate (NHP) data demonstrating durability of response through 12 weeks for ENTR-601-44, an EEV-conjugated phosphorodiamidate morpholino oligomer (PMO) for the potential treatment of people with Duchenne muscular dystrophy (DMD) who are exon 44 skipping amenable. (parentprojectmd.org)
- Duchenne muscular dystrophy: Current treatment and emerging exon skipp" by Grant Patterson, Haley Conner et al. (nova.edu)
Clinical1
- This study disclosed the clinical-relevant intertumoural heterogeneity of NSCLCs driven by MET exon 14 skipping. (ecancer.org)
Organization1
- The cryo-electron microscopy structure reveals domain organization and structural details of the Nf1 exon 23a splicing 3 isoform 2 in a closed, self-inhibited, Zn-stabilized state and an open state. (nature.com)
Genome5
- 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. (wikipedia.org)
- While the longest exon in the human genome is 11555 bp long, several exons have been found to be only 2 bp long. (wikipedia.org)
- A single-nucleotide exon has been reported from the Arabidopsis genome. (wikipedia.org)
- The low frequency of mouse exon skipping on chromosome 22 cannot be extrapolated to represent a genome-wide estimate due to the small number of observed mouse exon-skipping events. (uwc.ac.za)
- These pieces, called exons, are thought to make up 1 percent of a person's genome. (medlineplus.gov)
Promoter1
- Among them a promoter, exons, introns, and regulatory elements, which together help to determine protein expression in a cell. (jove.com)
CDNA1
- The paternal allele was associated with exon 8 skipping at the cDNA level. (jci.org)
Findings1
- The findings from the VISION study validate MET exon 14 skipping mutation as a therapeutic target and emphasize the importance of routine testing for these MET alterations by liquid or tissue biopsy. (esmo.org)
Primers3
- SimpleChIP ® Human DNAJB9 Exon 1 Primers were tested on DNA isolated from cross-linked cells using the SimpleChIP ® Plus Enzymatic Chromatin IP Kit (Magnetic Beads) #9005. (cellsignal.com)
- PCR product melting curves were obtained for real-time PCR reactions performed using SimpleChIP ® Human DNAJB9 Exon 1 Primers. (cellsignal.com)
- Exons 2 and 3 of the HLA-B locus were amplified with locus specific primers and the amplified DNA was arrayed onto seven replicate nylon membranes and immobilized by UV cross-linking. (cdc.gov)
Content1
- can do what you want, if you supply a reference fasta and corresponding gtf or bed file of all exons ( http://bedtools.readthedocs.io/en/latest/content/tools/getfasta.html) . (biostars.org)
Therapeutic1
- It is then possible to compare groups of patients benefiting from a therapeutic jump from exon 45 or 51 with a corresponding BMD group, the idea being to have a predictive tool for the expected functional improvement. (institut-myologie.org)
Partial1
- In vivo splicing experiments revealed that the exonic mutation caused partial skipping of exon 8. (jci.org)
Expression2
- See Exon Expression on the GTEx portal . (biostars.org)
- All mouse, skipped exons were observed to have ubiquitous tissue expression. (uwc.ac.za)
Inclusion1
- Inclusion of exon 23a is found in most human tissues but predominately skipped in neurons of the central nervous system 3 , and variation of the isoform 1/2 splicing ratio leads to disturbed neuronal differentiation 11 . (nature.com)
Human2
- As we can see, there is a lot of similarity between human and rhesus introns, but as we get to frogs and fish towards the bottom of the group the only similarities we find are in the exons. (evcforum.net)
- Exon skipping cosegregated with spinosad resistance in survival bioassays, and functional characterization of this alteration using modified human nAChR α7, a model of insect α6, demonstrated that exon 3 is essential for receptor function and hence spinosad sensitivity. (datadryad.org)
Alternative2
Methods1
- Methods: We assessed DNA methylation at three CpG sites in the NOS2 exon 1 from blood from 201 welders. (cdc.gov)
Data4
- Discussion on the FDA approval of capmatinib, a MET inhibitor, as treatment for patients with MET exon 14-mutated non-small cell lung cancer based on data demonstrated by the GEOMETRY mono-1 study. (onclive.com)
- The new data from a preclinical study evaluating ENTR-601-44 for the potential treatment of DMD, show robust exon 44 skipping in NHP biceps through 12 weeks following a single intravenous (IV) infusion, demonstrating durability of response (See Figure 1). (parentprojectmd.org)
- These data build on a previously reported NHP study indicating robust exon 44 skipping across different muscle groups at 7 days following a single IV infusion. (parentprojectmd.org)
- I talked to a colleague who sees these exon-peak events in some of his data depending on what protein or transcription factor he's after. (seqanswers.com)
Patterns1
- Hi Pogaora, We observed the same exon enriched peak patterns in our ChIP-seq datasets. (seqanswers.com)
Patients3
- Capmatinib is a MET TKI [tyrosine kinase inhibitor] with very high affinity and excellent CNS [central nervous system] penetrance, so this is a huge step forward for our patients with MET exon 14 skipping non-small cell lung cancer. (onclive.com)
- Le pourcentage de CD44 dans les lymphocytes T périphériques était significativement plus élevé chez les patients que chez les témoins, comme détecté par la cytométrie en flux. (who.int)
- En outre, il y avait une aug- mentation significative de la forme soluble du c-kit dans le sérum des patients atteints de pemphigus vulgaire actif par rapport aux témoins. (who.int)
Found1
- We have found that in a lot of cases we see peaks lining up with exons. (seqanswers.com)
Represent1
- The boxes represent the exons and the lines between the boxes are the introns. (evcforum.net)
Species1
- The challenge for ID/creationists in this thread is to explain the divergence of exons and introns as measured by sequence comparisons between species. (evcforum.net)
Larger1
- The first thing I noticed is that the number of exons is almost twice larger then the number I see on the Wiki. (biostars.org)