An intron is any nucleotide sequence within a gene that is removed by RNA splicing during maturation of the final RNA product. The term intron refers to both the DNA sequence within a gene and the sequence in RNA transcripts. Sequences that are joined together in the final mature RNA after RNA splicing are exons. Introns are found in the genes of most organisms and many viruses, and can be located in a range of genes, including those that generate proteins, ribosomal RNA. When proteins are generated from intron-containing genes, RNA splicing takes place as part of the RNA processing pathway that follows transcription, the word intron is derived from the term intragenic region, i. e. a region inside a gene. Introns were first discovered in protein-coding genes of adenovirus, and were identified in genes encoding transfer RNA. Introns are now known to occur within a variety of genes throughout organisms. The frequency of introns within different genomes is observed to vary widely across the spectrum of biological organisms, in contrast, the mitochondrial genomes of vertebrates are entirely devoid of introns, while those of eukaryotic microorganisms may contain many introns.
A particularly extreme case is the Drosophila dhc7 gene containing a ≥3.6 Mb intron, splicing of all intron-containing RNA molecules is superficially similar, as described above. However, different types of introns were identified through the examination of intron structure by DNA sequence analysis, together with genetic and they appear to be related to group II introns, and possibly to spliceosomal introns. Nuclear pre-mRNA introns are characterized by specific intron sequences located at the boundaries between introns and exons and these sequences are recognized by spliceosomal RNA molecules when the splicing reactions are initiated. Apart from these three short conserved elements, nuclear pre-mRNA intron sequences are highly variable, nuclear pre-mRNA introns are often much longer than their surrounding exons. Transfer RNA introns that depend upon proteins for removal occur at a location within the anticodon loop of unspliced tRNA precursors. The exons are linked together by a protein, the tRNA splicing ligase.
Note that self-splicing introns are found within tRNA genes. Group I and group II introns are found in genes encoding proteins, transfer RNA, following transcription into RNA, group I and group II introns make extensive internal interactions that allow them to fold into a specific, complex three-dimensional architecture. While introns do not encode protein products, they are integral to gene expression regulation, some introns themselves encode functional RNAs through further processing after splicing to generate noncoding RNA molecules. Alternative splicing is widely used to generate multiple proteins from a single gene, some introns play essential roles in a wide range of gene expression regulatory functions such as non-sense mediated decay and mRNA export
Glycerol /ˈɡlɪsərɒl/ is a simple polyol compound. It is a colorless, viscous liquid that is sweet-tasting, the glycerol backbone is found in all lipids known as triglycerides. It is widely used in the industry as a sweetener and humectant. Glycerol has three groups that are responsible for its solubility in water and its hygroscopic nature. Although achiral, glycerol is prochiral with respect to reactions of one of the two primary alcohols, thus, in substituted derivatives, the stereospecific numbering labels each carbon as either sn-1, sn-2, or sn-3. Glycerol is generally obtained from plant and animal sources where it occurs as triglycerides, triglycerides are esters of glycerol with long-chain carboxylic acids. Approximately 950,000 tons per year are produced in the United States and it was projected in 2006 that by the year 2020, production would be six times more than demand. Glycerol from triglycerides is produced on a scale, but the crude product is of variable quality. It can be purified, but the process is expensive, some glycerol is burned for energy, but its heat value is low.
High purity glycerol is obtained by distillation, vacuum is helpful due to the high boiling point of glycerol. Although usually not cost-effective, glycerol can be produced by various routes from propylene and this epichlorohydrin is hydrolyzed to give glycerol. Chlorine-free processes from propylene include the synthesis of glycerol from acrolein, because of the large-scale production of biodiesel from fats, where glycerol is a waste product, the market for glycerol is depressed. Thus, synthetic processes are not economical, owing to oversupply, efforts are being made to convert glycerol to synthetic precursors, such as acrolein and epichlorohydrin. In food and beverages, glycerol serves as a humectant and sweetener and it is used as filler in commercially prepared low-fat foods, and as a thickening agent in liqueurs. Glycerol and water are used to preserve certain types of plant leaves, as a sugar substitute, it has approximately 27 kilocalories per teaspoon and is 60% as sweet as sucrose.
It does not feed the bacteria that form plaques and cause dental cavities, as a food additive, glycerol is labeled as E number E422. It is added to icing to prevent it from setting too hard, as used in foods, glycerol is categorized by the Academy of Nutrition and Dietetics as a carbohydrate. The U. S. Food and Drug Administration carbohydrate designation includes all caloric macronutrients excluding protein, glycerol is used in medical and personal care preparations, mainly as a means of improving smoothness, providing lubrication, and as a humectant
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 sequence in RNA transcripts. In RNA splicing, introns are removed and exons are joined to one another as part of generating the mature messenger RNA. Just as the set of genes for a species constitutes the genome. This definition was made for protein-coding transcripts that are spliced before being translated. Although unicellular eukaryotes such as yeast have either no introns or very few, 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. The large variation in 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, on average,5.48 exons per gene, the average exon encoded 30-36 amino acids.
While the longest exon in the genome is 11555 bp long. A single-nucleotide exon has been reported from the Arabidopsis genome, in protein-coding genes, the exons include both the protein-coding sequence and the 5′- and 3′-untranslated regions. Often the first exon includes both the 5′-UTR and the first part of the sequence, but exons containing only regions of 5′-UTR or 3′-UTR occur in some genes. Some non-coding RNA transcripts have exons and introns, 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. Exonization is the creation of a new exon, as a result of mutations in introns, Exon trapping or gene trapping is a molecular biology technique that exploits the existence of the intron-exon splicing to find new genes. The first exon of a trapped gene splices into the exon that is contained in the insertional DNA and this new exon contains the ORF for a reporter gene that can now be expressed using the enhancers that control the target gene. A scientist knows that a new gene has been trapped when the gene is expressed.
This has become a technique in developmental biology. Morpholino oligos can be targeted to prevent molecules that regulate splicing from binding to pre-mRNA, exitron Exon shuffling Interrupted gene Intron mRNA Untranslated region Gilbert W. Statistical features of human exons and their flanking regions, prediction of exact boundaries of exons
In biology, a mutation is the permanent alteration of the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA or other genetic elements. Mutations may result from insertion or deletion of segments of DNA due to mobile genetic elements, mutations may or may not produce discernible changes in the observable characteristics of an organism. Mutations play a part in normal and abnormal biological processes including, evolution and the development of the immune system. The genomes of RNA viruses are based on RNA rather than DNA, the RNA viral genome can be double stranded or single stranded. In some of these viruses replication occurs quickly and there are no mechanisms to check the genome for accuracy and this error-prone process often results in mutations. Mutation can result in different types of change in sequences. Mutations in genes can either have no effect, alter the product of a gene, mutations can occur in nongenic regions. Mutations can involve the duplication of large sections of DNA, usually through genetic recombination and these duplications are a major source of raw material for evolving new genes, with tens to hundreds of genes duplicated in animal genomes every million years.
Most genes belong to larger families of shared ancestry, known as homology. Here, protein domains act as modules, each with a particular and independent function, that can be mixed together to produce genes encoding new proteins with novel properties. For example, the eye uses four genes to make structures that sense light. Another advantage of duplicating a gene is that this increases engineering redundancy, other types of mutation occasionally create new genes from previously noncoding DNA. Changes in chromosome number may involve even larger mutations, where segments of the DNA within chromosomes break and rearrange. For example, in the Homininae, two fused to produce human chromosome 2, this fusion did not occur in the lineage of the other apes. Sequences of DNA that can move about the genome, such as transposons, make up a fraction of the genetic material of plants and animals. For example, more than a million copies of the Alu sequence are present in the genome. Another effect of these mobile DNA sequences is that when they move within a genome, they can mutate or delete existing genes, nonlethal mutations accumulate within the gene pool and increase the amount of genetic variation.
The abundance of some changes within the gene pool can be reduced by natural selection, while other more favorable mutations may accumulate
Anthracyclines are a class of drugs used in cancer chemotherapy extracted from Streptomyces bacterium Streptomyces peucetius var. caesius. These compounds are used to treat cancers, including leukemias, breast, uterine, bladder cancer. The anthracyclines are among the most effective anticancer treatments ever developed and are effective against more types of cancer than any class of chemotherapeutic agents. Their main adverse effect is cardiotoxicity, which limits their usefulness. Use of anthracyclines has shown to be significantly associated with cycle 1 severe or febrile neutropenia. The first anthracycline discovered was daunorubicin, which is produced naturally by Streptomyces peucetius, doxorubicin was developed shortly after, and many other related compounds have followed, although few are in clinical use. Anthracyclines are used to various cancers and as of 2012 were among the most commonly used chemotherapeutic agents. Doxorubicin and its derivative, are used in breast cancer, childhood solid tumors, soft tissue sarcomas, daunorubicin is used to treat acute lymphoblastic or myeloblastic leukemias, and its derivative, idarubicin is used in multiple myeloma, non-Hodgkins lymphomas, and breast cancer.
Inhibition of topoisomerase II enzyme, preventing the relaxing of supercoiled DNA, some sources say that topoisomerase II inhibitors prevent topoisomerase II turning over which is needed for dissociation of topoisomerase II from its nucleic acid substrate. In other words, topoisomerase II inhibitors stabilise the topoisomerase II complex after it has broken the DNA chain and this leads to topoisomerase II mediated DNA-cleavage, producing DNA breaks. Iron-mediated generation of oxygen radicals that damage the DNA, proteins. Induction of histone eviction from chromatin that deregulates DNA damage response, the cardiotoxicity often presents as ECG changes and arrhythmias, or as a cardiomyopathy leading to heart failure. This cardiotoxicity is related to a cumulative lifetime dose. A patients lifetime dose is calculated during treatment, and anthracycline treatment is usually stopped upon reaching the maximum dose of the particular anthracycline. There exists evidence that the effect of cardiotoxicity increases in long-term survivors, in addition to staying below the cumulative doses, various prevention measures may be employed by the oncologist in order to reduce the risk of cardiotoxicity.
Cardiac monitoring are recommended at 3,6, and 9 months, longer infusion rates will result in a reduced plasma level and a much lower left ventricular peak concentration. At least one study found lower verbal memory performance on tests of immediate. Daunorubicin was first isolated from streptomyces early in the 1960s by groups in Italy and France, doxorubicin was discovered after a strain of Streptomyces was mutated to produce different compounds
A base pair is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the blocks of the DNA double helix. Dictated by specific hydrogen bonding patterns, Watson-Crick base pairs allow the DNA helix to maintain a regular helical structure that is dependent on its nucleotide sequence. The complementary nature of this structure provides a backup copy of all genetic information encoded within double-stranded DNA. Many DNA-binding proteins can recognize specific base pairing patterns that identify particular regulatory regions of genes, intramolecular base pairs can occur within single-stranded nucleic acids. The size of a gene or an organisms entire genome is often measured in base pairs because DNA is usually double-stranded. Hence, the number of base pairs is equal to the number of nucleotides in one of the strands. The haploid human genome is estimated to be about 3.2 billion bases long and to contain 20, a kilobase is a unit of measurement in molecular biology equal to 1000 base pairs of DNA or RNA.
The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, in comparison, the total mass of the biosphere has been estimated to be as much as 4 TtC. Hydrogen bonding is the interaction that underlies the base-pairing rules described above. Appropriate geometrical correspondence of hydrogen donors and acceptors allows only the right pairs to form stably. Purine-pyrimidine base pairing of AT or GC or UA results in proper duplex structure, the only other purine-pyrimidine pairings would be AC and GT and UG, these pairings are mismatches because the patterns of hydrogen donors and acceptors do not correspond. The GU pairing, with two bonds, does occur fairly often in RNA. Higher GC content results in higher melting temperatures, it is, therefore, on the converse, regions of a genome that need to separate frequently — for example, the promoter regions for often-transcribed genes — are comparatively GC-poor. GC content and melting temperature must be taken into account when designing primers for PCR reactions, the following DNA sequences illustrate pair double-stranded patterns.
By convention, the top strand is written from the 5 end to the 3 end and this is due to their isosteric chemistry. One common mutagenic base analog is 5-bromouracil, which resembles thymine, most intercalators are large polyaromatic compounds and are known or suspected carcinogens. Examples include ethidium bromide and acridine, an unnatural base pair is a designed subunit of DNA which is created in a laboratory and does not occur in nature
Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds.
Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture.
He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
A locus in genetics is the position on a chromosome. Each chromosome carries many genes, humans estimated haploid protein coding genes are 19, 000-20,000, a variant of the similar DNA sequence located at a given locus is called an allele. The ordered list of known for a particular genome is called a gene map. Gene mapping is the process of determining the locus for a biological trait. The chromosomal locus of a gene might be written 3p22.1, here 3 means chromosome 3, p means p-arm. And 22 refers to region 2, band 2 and this is read as two two, not as twenty-two. So the entire locus is read as three P two two point one, the cytogenetic bands are counting from the centromere out toward the telomeres. A range of loci is specified in a similar way. For example, the locus of gene OCA1 may be written 11q1. 4-q2.1, meaning it is on the arm of chromosome 11. The ends of a chromosome are labeled pter and qter, a centisome is defined as 1% of a chromosome length. Chromosomal translocation Cytogenetic notation Karyotype Null allele Michael, R.
Cummings, California, Brooks/Cole Overview at ornl. gov Chromosome Banding and Nomenclature from NCBI
Amino acids are organic compounds containing amine and carboxyl functional groups, along with a side chain specific to each amino acid. The key elements of an acid are carbon, oxygen. About 500 amino acids are known and can be classified in many ways, in the form of proteins, amino acids comprise the second-largest component of human muscles and other tissues. Outside proteins, amino acids perform critical roles in such as neurotransmitter transport. In biochemistry, amino acids having both the amine and the acid groups attached to the first carbon atom have particular importance. They are known as 2-, alpha-, or α-amino acids and they include the 22 proteinogenic amino acids, which combine into peptide chains to form the building-blocks of a vast array of proteins. These are all L-stereoisomers, although a few D-amino acids occur in bacterial envelopes, as a neuromodulator, twenty of the proteinogenic amino acids are encoded directly by triplet codons in the genetic code and are known as standard amino acids.
The other two are selenocysteine, and pyrrolysine and selenocysteine are encoded via variant codons, for example, selenocysteine is encoded by stop codon and SECIS element. N-formylmethionine is generally considered as a form of methionine rather than as a separate proteinogenic amino acid, codon–tRNA combinations not found in nature can be used to expand the genetic code and create novel proteins known as alloproteins incorporating non-proteinogenic amino acids. Many important proteinogenic and non-proteinogenic amino acids play critical roles within the body. Nine proteinogenic amino acids are called essential for humans because they cannot be created from other compounds by the human body, others may be conditionally essential for certain ages or medical conditions. Essential amino acids may differ between species, because of their biological significance, amino acids are important in nutrition and are commonly used in nutritional supplements and food technology. Industrial uses include the production of drugs, biodegradable plastics, the first few amino acids were discovered in the early 19th century.
In 1806, French chemists Louis-Nicolas Vauquelin and Pierre Jean Robiquet isolated a compound in asparagus that was subsequently named asparagine, cystine was discovered in 1810, although its monomer, remained undiscovered until 1884. Glycine and leucine were discovered in 1820, usage of the term amino acid in the English language is from 1898. Proteins were found to yield amino acids after enzymatic digestion or acid hydrolysis, in the structure shown at the top of the page, R represents a side chain specific to each amino acid. The carbon atom next to the group is called the α–carbon. Amino acids containing an amino group bonded directly to the alpha carbon are referred to as amino acids
A gene is a locus of DNA which is made up of nucleotides and is the molecular unit of heredity. The transmission of genes to an offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes, genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions, genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotypical traits, usage of the term having a gene typically refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection or survival of the fittest of the alleles, the concept of a gene continues to be refined as new phenomena are discovered. For example, regulatory regions of a gene can be far removed from its coding regions, some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs.
The existence of discrete inheritable units was first suggested by Gregor Mendel, from 1857 to 1864, in Brno, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas, although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured the distinction between genotype and phenotype, charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan and genesis / genos. Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction, de Vries called these units pangenes, after Darwins 1868 pangenesis theory. In 1909 the Danish botanist Wilhelm Johannsen shortened the name to gene, advances in understanding genes and inheritance continued throughout the 20th century.
Deoxyribonucleic acid was shown to be the repository of genetic information by experiments in the 1940s to 1950s. In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics, in 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene, the gene for Bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing, an automated version of the Sanger method was used in early phases of the Human Genome Project. The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the evolutionary synthesis
For example, at a specific base position in the human genome, the base C may appear in most individuals, but in a minority of individuals, the position is occupied by base A. There is a SNP at this base position, and the two possible nucleotide variations - C or A - are said to be alleles for this base position. SNPs underlie differences in our susceptibility to disease, a range of human diseases, e. g. sickle-cell anemia, β-thalassemia. The severity of illness and the way our body responds to treatments are manifestations of genetic variations, for example, a single base mutation in the APOE gene is associated with a higher risk for Alzheimers disease. A single-nucleotide variant is a variation in a single nucleotide without any limitations of frequency, a somatic single nucleotide variation may be called a single-nucleotide alteration. Single-nucleotide polymorphisms may fall within coding sequences of genes, non-coding regions of genes, SNPs within a coding sequence do not necessarily change the amino acid sequence of the protein that is produced, due to degeneracy of the genetic code.
SNPs in the region are of two types and nonsynonymous SNPs. Synonymous SNPs do not affect the sequence while nonsynonymous SNPs change the amino acid sequence of protein. The nonsynonymous SNPs are of two types and nonsense, SNPs that are not in protein-coding regions may still affect gene splicing, transcription factor binding, messenger RNA degradation, or the sequence of non-coding RNA. Gene expression affected by type of SNP is referred to as an eSNP. Association studies can determine whether a variant is associated with a disease or trait. A tag SNP is a representative single-nucleotide polymorphism in a region of the genome with high linkage disequilibrium, tag SNPs are useful in whole-genome SNP association studies in which hundreds of thousands of SNPs across the entire genome are genotyped. Haplotype mapping, sets of alleles or DNA sequences can be clustered so that a single SNP can identify many linked SNPs, linkage Disequilibrium, a term used in population genetics, indicates non-random association of alleles at two or more loci, not necessarily on the same chromosome.
It refers to the phenomenon that SNP allele or DNA sequence which are together in the genome tend to be inherited together. LD is affected by two parameters, 1) The distance between the SNPs, other factors, like genetic recombination and mutation rate, can determine SNP density. There are variations between populations, so a SNP allele that is common in one geographical or ethnic group may be much rarer in another. Within a population, SNPs can be assigned a minor allele frequency — the lowest allele frequency at a locus that is observed in a particular population and this is simply the lesser of the two allele frequencies for single-nucleotide polymorphisms. Variations in the DNA sequences of humans can affect how humans develop diseases and respond to pathogens, drugs, vaccines, SNPs are critical for personalized medicine