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57-749: It is due to a specific gene mutation in which a guanine is changed to an adenine at position 20210 of the DNA of the prothrombin gene. Other blood clotting pathway mutations that increase the risk of clots include factor V Leiden . Prothrombin G20210A was identified in the 1990s. About 2% of Caucasians carry the variant, while it is less common in other populations. It is estimated to have originated in Caucasians about 24,000 years ago. The variant causes elevated plasma prothrombin levels ( hyperprothrombinemia ), possibly due to increased pre-mRNA stability. Prothrombin

114-436: A 5.23x-increased risk, and those with both factors a 6.35x risk. In a recommendation statement on venous thromboembolism, genetic testing for G20210A in adults that developed unprovoked venous thromboembolism was not advised, as was testing in asymptomatic family members related to G20210A carriers who in whom venous thromboembolism occurred. In those who develop venous thromboembolism, the results of thrombophilia tests (wherein

171-458: A C-terminal trypsin -like serine protease domain. Factor Xa with factor V as a cofactor leads to cleavage of the Gla and two Kringle domains (forming together a fragment called fragment 1.2) and leave thrombin, consisting solely of the serine protease domain. As is the case for all serine proteases , prothrombin is converted to active thrombin by proteolysis of an internal peptide bond, exposing

228-472: A SNP allele that is common in one geographical or ethnic group may be much rarer in another. However, this pattern of variation is relatively rare; in a global sample of 67.3 million SNPs, the Human Genome Diversity Project "found no such private variants that are fixed in a given continent or major region. The highest frequencies are reached by a few tens of variants present at >70% (and

285-539: A common consensus. The rs### standard is that which has been adopted by dbSNP and uses the prefix "rs", for "reference SNP", followed by a unique and arbitrary number. SNPs are frequently referred to by their dbSNP rs number, as in the examples above. The Human Genome Variation Society (HGVS) uses a standard which conveys more information about the SNP. Examples are: SNPs can be easily assayed due to only containing two possible alleles and three possible genotypes involving

342-447: A factor in the formation of the lupus anticoagulant (also known as antiphospholipid syndrome ). Hyperprothrombinemia can be caused by the G20210A mutation. Thrombin, a potent vasoconstrictor and mitogen , is implicated as a major factor in vasospasm following subarachnoid hemorrhage . Blood from a ruptured cerebral aneurysm clots around a cerebral artery , releasing thrombin. This can induce an acute and prolonged narrowing of

399-762: A few thousands at >50%) in Africa, the Americas, and Oceania. By contrast, the highest frequency variants private to Europe, East Asia, the Middle East, or Central and South Asia reach just 10 to 30%." 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. This is simply the lesser of the two allele frequencies for single-nucleotide polymorphisms. With this knowledge scientists have developed new methods in analyzing population structures in less studied species. By using pooling techniques

456-409: A good probability of a match. This can additionally be applied to increase the accuracy of facial reconstructions by providing information that may otherwise be unknown, and this information can be used to help identify suspects even without a STR DNA profile match. Some cons to using SNPs versus STRs is that SNPs yield less information than STRs, and therefore more SNPs are needed for analysis before

513-3287: A group of programs for the prediction of SNP effect was developed: Prothrombin 1A2C , 1A3B , 1A3E , 1ABI , 1ABJ , 1AD8 , 1AE8 , 1AI8 , 1AIX , 1AWF , 1AWH , 1AY6 , 1B5G , 1B7X , 1BA8 , 1BB0 , 1BCU , 1BHX , 1BMM , 1BMN , 1BTH , 1C1U , 1C1V , 1C1W , 1C4U , 1C4V , 1C4Y , 1C5L , 1C5N , 1C5O , 1CA8 , 1D3D , 1D3P , 1D3Q , 1D3T , 1D4P , 1D6W , 1D9I , 1DE7 , 1DIT , 1DM4 , 1DOJ , 1DWB , 1DWC , 1DWD , 1DX5 , 1E0F , 1EB1 , 1EOJ , 1EOL , 1FPC , 1G30 , 1G32 , 1G37 , 1GHV , 1GHW , 1GHX , 1GHY , 1GJ4 , 1GJ5 , 1H8D , 1H8I , 1HAI , 1HAO , 1HAP , 1HBT , 1HLT , 1HUT , 1HXE , 1HXF , 1IHS , 1JMO , 1JOU , 1JWT , 1K21 , 1K22 , 1KTS , 1KTT , 1LHC , 1LHD , 1LHE , 1LHF , 1LHG , 1MH0 , 1MU6 , 1MU8 , 1MUE , 1NM6 , 1NRN , 1NRO , 1NRP , 1NRQ , 1NRR , 1NRS , 1NT1 , 1NU7 , 1NU9 , 1NY2 , 1NZQ , 1O0D , 1O2G , 1O5G , 1OOK , 1OYT , 1P8V , 1PPB , 1QBV , 1QHR , 1QJ1 , 1QJ6 , 1QJ7 , 1QUR , 1RD3 , 1RIW , 1SB1 , 1SFQ , 1SG8 , 1SGI , 1SHH , 1SL3 , 1SR5 , 1T4U , 1T4V , 1TA2 , 1TA6 , 1TB6 , 1THP , 1THR , 1THS , 1TMB , 1TMU , 1TOM , 1TQ0 , 1TQ7 , 1TWX , 1UVS , 1VR1 , 1VZQ , 1W7G , 1WAY , 1WBG , 1XM1 , 1XMN , 1YPE , 1YPG , 1YPJ , 1YPK , 1YPL , 1YPM , 1Z71 , 1Z8I , 1Z8J , 1ZGI , 1ZGV , 1ZRB , 2A0Q , 2A2X , 2A45 , 2AFQ , 2ANK , 2ANM , 2B5T , 2BDY , 2BVR , 2BVS , 2BVX , 2BXT , 2BXU , 2C8Y , 2FEQ , 2FES , 2GDE , 2GP9 , 2H9T , 2HGT , 2HNT , 2HPP , 2HPQ , 2HWL , 2JH0 , 2JH6 , 2OD3 , 2PGB , 2PGQ , 2PW8 , 2R2M , 2THF , 2ZFQ , 2ZFR , 2ZG0 , 2ZHE , 2ZHF , 2ZHW , 2ZI2 , 2ZIQ , 2ZNK , 2ZO3 , 3B23 , 3B9F , 3BEF , 3BEI , 3BF6 , 3BIU , 3BIV , 3BV9 , 3C1K , 3C27 , 3D49 , 3DA9 , 3DD2 , 3DT0 , 3DUX , 3E6P , 3EE0 , 3EQ0 , 3F68 , 3GIC , 3GIS , 3HAT , 3HKJ , 3HTC , 3JZ2 , 3LDX , 3LU9 , 3NXP , 3P17 , 3P6Z , 3P70 , 3PO1 , 3QGN , 3QLP , 3QTO , 3QTV , 3QWC , 3QX5 , 3R3G , 3RLW , 3RLY , 3RM0 , 3RM2 , 3RML , 3RMM , 3RMN , 3RMO , 3S7H , 3S7K , 3SHA , 3SHC , 3SI3 , 3SI4 , 3SQE , 3SQH , 3SV2 , 3T5F , 3TU7 , 3U69 , 3U8O , 3U8R , 3U8T , 3U98 , 3U9A , 3UTU , 3UWJ , 3VXE , 3VXF , 4BAH , 4BAK , 4BAM , 4BAN , 4BAO , 4BAQ , 4BOH , 4DIH , 4DII , 4DT7 , 4DY7 , 4E05 , 4E06 , 4E7R , 4H6S , 4H6T , 4HFP , 4HTC , 4THN , 5GDS , 7KME , 8KME , 1A46 , 1A4W , 1A5G , 1A61 , 1AFE , 1AHT , 1DWE , 1FPH , 1HAG , 1HAH , 1HDT , 1HGT , 1IHT , 1NO9 , 1TBZ , 1TMT , 1UMA , 2C8W , 2C8X , 2C8Z , 2C90 , 2C93 , 2CF8 , 2CF9 , 2CN0 , 2JH5 , 2PKS , 2UUF , 2UUJ , 2UUK , 2V3H , 2V3O , 2ZC9 , 2ZDA , 2ZDV , 2ZF0 , 2ZFF , 2ZFP , 2ZGB , 2ZGX , 2ZHQ , 3DHK , 3EGK , 3JZ1 , 3K65 , 3PMH , 3QDZ , 4AX9 , 4AYV , 4AYY , 4AZ2 , 4CH2 , 4CH8 , 4HZH , 4I7Y , 4LOY , 4LXB , 4LZ1 , 4LZ4 , 4MLF , 4N3L , 4NZE , 4NZQ , 4O03 , 4RKJ , 4RKO , 4RN6 , 4YES , 4UD9 , 4UDW , 4UE7 , 4UEH , 5AF9 , 5AFY , 5AFZ , 5AHG , 5CMX , 4UFD , 5EDM , 5E8E , 5EDK , 4UFE , 4UFG , 4UFF , 5A2M , 5JDU 2147 14061 ENSG00000180210 ENSMUSG00000027249 P00734 P19221 NM_000506 NM_001311257 NM_010168 NP_000497 NP_034298 Prothrombin ( coagulation factor II )

570-416: A level of around 0.9 units/mL after 6 months of life. In the blood coagulation pathway, thrombin acts to convert factor XI to XIa, VIII to VIIIa, V to Va, fibrinogen to fibrin , and XIII to XIIIa. In the conversion of fibrinogen into fibrin, thrombin catalyzes the cleavage of fibrinopeptides A and B from the respective Aα and Bβ chains of fibrinogen to form fibrin monomers. Factor XIIIa

627-404: A new N-terminal Ile-NH3. The historic model of activation of serine proteases involves insertion of this newly formed N-terminus of the heavy chain into the β-barrel promoting the correct conformation of the catalytic residues. Contrary to crystal structures of active thrombin, hydrogen-deuterium exchange mass spectrometry studies indicate that this N-terminal Ile-NH3 does not become inserted into

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684-523: A powerful tool to map genomic regions or genes that are involved in disease pathogenesis. Recently, preliminary results reported SNPs as important components of the epigenetic program in organisms. Moreover, cosmopolitan studies in European and South Asiatic populations have revealed the influence of SNPs in the methylation of specific CpG sites. In addition, meQTL enrichment analysis using GWAS database, demonstrated that those associations are important toward

741-751: A profile of a suspect is able to be created. Additionally, SNPs heavily rely on the presence of a database for comparative analysis of samples. However, in instances with degraded or small volume samples, SNP techniques are an excellent alternative to STR methods. SNPs (as opposed to STRs) have an abundance of potential markers, can be fully automated, and a possible reduction of required fragment length to less than 100bp.[26] Pharmacogenetics focuses on identifying genetic variations including SNPs associated with differential responses to treatment. Many drug metabolizing enzymes, drug targets, or target pathways can be influenced by SNPs. The SNPs involved in drug metabolizing enzyme activities can change drug pharmacokinetics, while

798-596: A single base change (point mutation) that can be detected by genetic testing, which is unaffected by intercurrent illness or anticoagulant use. Measurement of an elevated plasma prothrombin level cannot be used to screen for the prothrombin G20210A mutation, because there is too great of an overlap between the upper limit of normal and levels in affected patients. Patients with the prothrombin mutation are treated similarly to those with other types of thrombophilia, with anticoagulation for at least three to six months. Continuing anticoagulation beyond three to six months depends on

855-585: A wide range of diseases across a population. For example, a common SNP in the CFH gene is associated with increased risk of age-related macular degeneration. Differences in the severity of an illness or response to treatments may also be manifestations of genetic variations caused by SNPs. For example, two common SNPs in the APOE gene, rs429358 and rs7412, lead to three major APO-E alleles with different associated risks for development of Alzheimer's disease and age at onset of

912-415: Is a transglutaminase that catalyzes the formation of covalent bonds between lysine and glutamine residues in fibrin. The covalent bonds increase the stability of the fibrin clot. Thrombin interacts with thrombomodulin . As part of its activity in the coagulation cascade, thrombin also promotes platelet activation and aggregation via activation of protease-activated receptors on the cell membrane of

969-426: Is a hypothesis driven approach. Since only a limited number of SNPs are tested, a relatively small sample size is sufficient to detect the association. Candidate gene association approach is also commonly used to confirm findings from GWAS in independent samples. Genome-wide SNP data can be used for homozygosity mapping. Homozygosity mapping is a method used to identify homozygous autosomal recessive loci, which can be

1026-622: Is a possibility in combining the advantages of SNPs with micro satellite markers. However, there are information lost in the process such as linkage disequilibrium and zygosity information. Variations in the DNA sequences of humans can affect how humans develop diseases and respond to pathogens , chemicals , drugs , vaccines , and other agents. SNPs are also critical for personalized medicine . Examples include biomedical research, forensics, pharmacogenetics, and disease causation, as outlined below. One of main contributions of SNPs in clinical research

1083-424: Is also called the factor II mutation. Prothrombin G20210A is congenital. Prothrombin G20210A is not usually accompanied by other factor mutations (i.e., the most common is factor V Leiden). The gene may be inherited heterozygous (1 pair), or much more rarely, homozygous (2 pairs), and is not related to gender or blood type. Homozygous mutations increase the risk of thrombosis more than heterozygous mutations, but

1140-444: Is also inactivated by antithrombin , a serine protease inhibitor . The molecular weight of prothrombin is approximately 72,000 Da . The catalytic domain is released from prothrombin fragment 1.2 to create the active enzyme thrombin, which has a molecular weight of 36,000 Da. Structurally, it is a member of the large PA clan of proteases. Prothrombin is composed of four domains; an N-terminal Gla domain , two kringle domains and

1197-550: Is available as a powder for reconstitution into aqueous solution . It can be applied topically during surgery, as an aid to hemostasis . It can be useful for controlling minor bleeding from capillaries and small venules, but ineffective and not indicated for massive or brisk arterial bleeding. Thrombin, combined with fibrinogen , is sold under the brand name Fibrimex for use as a binding agent for meat. Both proteins in Fibrimex derives from porcine or bovine blood. According to

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1254-416: Is central to the mode of action of most anticoagulants . Warfarin and related drugs inhibit vitamin K -dependent carboxylation of several coagulation factors, including prothrombin. Heparin increases the affinity of antithrombin to thrombin (as well as factor Xa ). The direct thrombin inhibitors , a newer class of medication, directly inhibit thrombin by binding to its active site. Recombinant thrombin

1311-563: Is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin ( Factor IIa ) ( EC 3.4.21.5 , fibrose, thrombase, thrombofort, topical, thrombin-C, tropostasin, activated blood-coagulation factor II, E thrombin, beta-thrombin, gamma-thrombin) is a serine protease , that converts fibrinogen into strands of insoluble fibrin , as well as catalyzing many other coagulation-related reactions. After

1368-523: Is genome-wide association study (GWAS). Genome-wide genetic data can be generated by multiple technologies, including SNP array and whole genome sequencing. GWAS has been commonly used in identifying SNPs associated with diseases or clinical phenotypes or traits. Since GWAS is a genome-wide assessment, a large sample site is required to obtain sufficient statistical power to detect all possible associations. Some SNPs have relatively small effect on diseases or clinical phenotypes or traits. To estimate study power,

1425-679: Is not homogenous; SNPs occur in non-coding regions more frequently than in coding regions or, in general, where natural selection is acting and "fixing" the allele (eliminating other variants) of the SNP that constitutes the most favorable genetic adaptation. Other factors, like genetic recombination and mutation rate, can also determine SNP density. SNP density can be predicted by the presence of microsatellites : AT microsatellites in particular are potent predictors of SNP density, with long (AT)(n) repeat tracts tending to be found in regions of significantly reduced SNP density and low GC content . There are variations between human populations, so

1482-499: Is one of the most common genetic risk factors for venous thromboembolism. Increased production of prothrombin heightens the risk of blood clotting. Moreover, individuals who carry the mutation can pass it on to their offspring. The mutation increases the risk of developing deep vein thrombosis , which can cause pain and swelling, and sometimes post-thrombotic syndrome , ulcers , or pulmonary embolism. Most individuals do not require treatment but do need to be cautious during periods when

1539-476: Is the precursor to thrombin , which plays a key role in causing blood to clot ( blood coagulation ). G20210A can thus contribute to a state of hypercoagulability , but not particularly with arterial thrombosis . A 2006 meta-analysis showed only a 1.3-fold increased risk for coronary disease . Deficiencies in the anticoagulants Protein C and Protein S further increase the risk five- to tenfold. Behind non-O blood type and factor V Leiden , prothrombin G20210A

1596-559: The intergenic regions (regions between 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 coding region are of two types: synonymous SNPs and nonsynonymous SNPs. Synonymous SNPs do not affect the protein sequence, while nonsynonymous SNPs change the amino acid sequence of protein. SNPs that are not in protein-coding regions may still affect gene splicing , transcription factor binding, messenger RNA degradation, or

1653-399: The prothrombinase complex. Prothrombin is produced in the liver and is co-translationally modified in a vitamin K -dependent reaction that converts 10-12 glutamic acids in the N terminus of the molecule to gamma-carboxyglutamic acid (Gla). In the presence of calcium, the Gla residues promote the binding of prothrombin to phospholipid bilayers. Deficiency of vitamin K or administration of

1710-498: The SNPs involved in drug target or its pathway can change drug pharmacodynamics. Therefore, SNPs are potential genetic markers that can be used to predict drug exposure or effectiveness of the treatment. Genome-wide pharmacogenetic study is called pharmacogenomics . Pharmacogenetics and pharmacogenomics are important in the development of precision medicine, especially for life-threatening diseases such as cancers. Only small amount of SNPs in

1767-468: The SNPs with relatively small effect on diseases. For common and complex diseases, such as type-2 diabetes, rheumatoid arthritis, and Alzheimer's disease, multiple genetic factors are involved in disease etiology. In addition, gene-gene interaction and gene-environment interaction also play an important role in disease initiation and progression. As there are for genes, bioinformatics databases exist for SNPs. The International SNP Map working group mapped

Prothrombin G20210A - Misplaced Pages Continue

1824-429: The accompanying G20210A location specifier (unhelpfully, since prothrombin mutations other than G20210A are known). Single-nucleotide polymorphism In genetics and bioinformatics , a single-nucleotide polymorphism ( SNP / s n ɪ p / ; plural SNPs / s n ɪ p s / ) is a germline substitution of a single nucleotide at a specific position in the genome . Although certain definitions require

1881-402: The anticoagulant warfarin inhibits the production of gamma-carboxyglutamic acid residues, slowing the activation of the coagulation cascade. In human adults, the normal blood level of antithrombin activity has been measured to be around 1.1 units/mL. Newborn levels of thrombin steadily increase after birth to reach normal adult levels, from a level of around 0.5 units/mL 1 day after birth, to

1938-469: The blood vessel, potentially resulting in cerebral ischemia and infarction ( stroke ). Beyond its key role in the dynamic process of thrombus formation, thrombin has a pronounced pro-inflammatory character, which may influence the onset and progression of atherosclerosis. Acting via its specific cell membrane receptors (protease activated receptors: PAR-1, PAR-3 and PAR-4), which are abundantly expressed in all arterial vessel wall constituents, thrombin has

1995-423: The circumstances surrounding thrombosis, for example, if the patient experiences a thromboembolic event that was unprovoked, continuing anticoagulation would be recommended. The choice of anticoagulant (warfarin versus a direct oral anticoagulant) is based on a number of different factors (the severity of thrombosis, patient preference, adherence to therapy, and potential drug and dietary interactions). Patients with

2052-428: The combination of genetic predisposition (high baseline prothrombin levels) and the additional pro-coagulant influence of oral contraceptives alters the hemostatic balance of fibrinolysis to trigger thrombosis. Because prothrombin is also known as factor II , the mutation is also sometimes referred to as the factor II mutation or simply the prothrombin mutation ; in either case, the names may appear with or without

2109-410: The cost of the analysis is significantly lowered. These techniques are based on sequencing a population in a pooled sample instead of sequencing every individual within the population by itself. With new bioinformatics tools there is a possibility of investigating population structure, gene flow and gene migration by observing the allele frequencies within the entire population. With these protocols there

2166-407: The description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872. Prothrombin was discovered by Pekelharing in 1894. Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly enhanced by binding to activated Factor V (Va), termed

2223-581: The disease. Single nucleotide substitutions with an allele frequency of less than 1% are sometimes called single-nucleotide variants (SNVs) . "Variant" may also be used as a general term for any single nucleotide change in a DNA sequence, encompassing both common SNPs and rare mutations , whether germline or somatic . The term SNV has therefore been used to refer to point mutations found in cancer cells. DNA variants must also commonly be taken into consideration in molecular diagnostics applications such as designing PCR primers to detect viruses, in which

2280-528: The fusion protein, thrombin can be used to selectively cleave between the arginine and glycine residues of the cleavage site, effectively removing the purification tag from the protein of interest with a high degree of specificity. Prothrombin complex concentrate and fresh frozen plasma are prothrombin-rich coagulation factor preparations that can be used to correct deficiencies (usually due to medication) of prothrombin. Indications include intractable bleeding due to warfarin . Manipulation of prothrombin

2337-483: The genetic model for disease needs to be considered, such as dominant, recessive, or additive effects. Due to genetic heterogeneity, GWAS analysis must be adjusted for race. Candidate gene association study is commonly used in genetic study before the invention of high throughput genotyping or sequencing technologies. Candidate gene association study is to investigate limited number of pre-specified SNPs for association with diseases or clinical phenotypes or traits. So this

Prothrombin G20210A - Misplaced Pages Continue

2394-529: The human genome may have impact on human diseases. Large scale GWAS has been done for the most important human diseases, including heart diseases, metabolic diseases, autoimmune diseases, and neurodegenerative and psychiatric disorders. Most of the SNPs with relatively large effects on these diseases have been identified. These findings have significantly improved understanding of disease pathogenesis and molecular pathways, and facilitated development of better treatment. Further GWAS with larger samples size will reveal

2451-401: The manufacturer it can be used to produce new kinds of mixed meats (for example combining beef and fish seamlessly). The manufacturer also states that it can be used to combine whole muscle meat, form and portion these, thus cutting down on production costs without a loss in quality. General secretary Jan Bertoft of Swedish Consumers' Association has stated that "there is danger of misleading

2508-433: The platelet. Thrombin bound to thrombomodulin activates protein C , an inhibitor of the coagulation cascade. The activation of protein C is greatly enhanced following the binding of thrombin to thrombomodulin , an integral membrane protein expressed by endothelial cells. Activated protein C inactivates factors Va and VIIIa. Binding of activated protein C to protein S leads to a modest increase in its activity. Thrombin

2565-550: The possibility of blood clotting are increased; for example, during pregnancy, after surgery, or during long flights. Occasionally, blood-thinning medication may be indicated to reduce the risk of clotting. A 2005 article concluded that heterozygous carriers who take combined birth control pills are at a 15-fold increased risk of venous thromboembolism, while carriers also heterozygous with factor V Leiden have an approximate 20-fold higher risk.A more recent and larger study in 2023, however, concluded that heterozygous carriers had

2622-407: The potential to exert pro-atherogenic actions such as inflammation, leukocyte recruitment into the atherosclerotic plaque, enhanced oxidative stress, migration and proliferation of vascular smooth muscle cells, apoptosis and angiogenesis. Thrombin is implicated in the physiology of blood clots . Its presence indicates the existence of a clot. In 2013 a system for detecting the presence of thrombin

2679-411: The prediction of biological traits.   SNPs have historically been used to match a forensic DNA sample to a suspect but has been made obsolete due to advancing STR -based DNA fingerprinting techniques. However, the development of next-generation-sequencing (NGS) technology may allow for more opportunities for the use of SNPs in phenotypic clues such as ethnicity, hair color, and eye color with

2736-405: The prothrombin G20210A mutation who have not had a thromboembolic event are generally not treated with routine anticoagulation. However, counseling the patient is recommended in situations with increased thrombotic risk is recommended (pregnancy, surgery, and acute illness). Oral contraceptives should generally be avoided in women with the mutation as they increase the thrombotic risk. This is because

2793-588: The relative increased risk is not well documented. Other potential risks for thrombosis , such as oral contraceptives may be additive. The previously reported relationship of inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis ) and prothrombin G20210A or factor V Leiden mutation have been contradicted by research. Activation of prothrombin is crucial in physiological and pathological coagulation. Various rare diseases involving prothrombin have been described (e.g., hypoprothrombinemia ). Anti-prothrombin antibodies in autoimmune disease may be

2850-567: The sequence flanking each SNP by alignment to the genomic sequence of large-insert clones in Genebank. These alignments were converted to chromosomal coordinates that is shown in Table 1. This list has greatly increased since, with, for instance, the Kaviar database now listing 162 million single nucleotide variants (SNVs). The nomenclature for SNPs include several variations for an individual SNP, while lacking

2907-455: The sequence of noncoding RNA. Gene expression affected by this type of SNP is referred to as an eSNP (expression SNP) and may be upstream or downstream from the gene. More than 600 million SNPs have been identified across the human genome in the world's population. A typical genome differs from the reference human genome at 4 to 5 million sites, most of which (more than 99.9%) consist of SNPs and short indels . The genomic distribution of SNPs

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2964-448: The substitution to be present in a sufficiently large fraction of the population (e.g. 1% or more), many publications do not apply such a frequency threshold. For example, a G nucleotide present at a specific location in a reference genome may be replaced by an A in a minority of individuals. The two possible nucleotide variations of this SNP – G or A – are called alleles . SNPs can help explain differences in susceptibility to

3021-1089: The two alleles: homozygous A, homozygous B and heterozygous AB, leading to many possible techniques for analysis. Some include: DNA sequencing ; capillary electrophoresis ; mass spectrometry ; single-strand conformation polymorphism (SSCP); single base extension ; electrochemical analysis; denaturating HPLC and gel electrophoresis ; restriction fragment length polymorphism ; and hybridization analysis. An important group of SNPs are those that corresponds to missense mutations causing amino acid change on protein level. Point mutation of particular residue can have different effect on protein function (from no effect to complete disruption its function). Usually, change in amino acids with similar size and physico-chemical properties (e.g. substitution from leucine to valine) has mild effect, and opposite. Similarly, if SNP disrupts secondary structure elements (e.g. substitution to proline in alpha helix region) such mutation usually may affect whole protein structure and function. Using those simple and many other machine learning derived rules

3078-417: The variant can be detected) rarely play a role in the length of treatment. The polymorphism is located in a noncoding region of the prothrombin gene ( 3' untranslated region nucleotide 20210), replacing guanine with adenine . The position is at or near where the pre-mRNA will have the poly-A tail attached. Diagnosis of the prothrombin G20210A mutation is straightforward because the mutation involves

3135-491: The viral RNA or DNA sample may contain SNVs. However, this nomenclature uses arbitrary distinctions (such as an allele frequency of 1%) and is not used consistently across all fields; the resulting disagreement has prompted calls for a more consistent framework for naming differences in DNA sequences between two samples. Single-nucleotide polymorphisms may fall within coding sequences of genes , non-coding regions of genes , or in

3192-409: The β-barrel in the apo form of thrombin. However, binding of the active fragment of thrombomodulin appears to allosterically promote the active conformation of thrombin by inserting this N-terminal region. There are an estimated 30 people in the world that have been diagnosed with the congenital form of Factor II deficiency, which should not be confused with the prothrombin G20210A mutation, which

3249-502: Was developed in mice. It combines peptide-coated iron oxide attached to "reporter chemicals". When a peptide binds to a thrombin molecule, the report is released and appears in the urine where it can be detected. Human testing has not been conducted. Due to its high proteolytic specificity, thrombin is a valuable biochemical tool. The thrombin cleavage site (Leu-Val-Pro-Arg-Gly-Ser) is commonly included in linker regions of recombinant fusion protein constructs. Following purification of

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