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Gene polymorphism

January 26, 2023

For other concepts, see Polymorphism.

A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population.[1] In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to generally be considered polymorphic.[2]

Genes which control hair colour are polymorphic.

Gene polymorphisms can occur in any region of the genome. The majority of polymorphisms are silent, meaning they do not alter the function or expression of a gene.[3] Some polymorphisms are visible. For example, in dogs the E locus can have any of five different alleles, known as E, Em, Eg, Eh, and e.[4] Varying combinations of these alleles contribute to the pigmentation and patterns seen in dog coats.[5]

A polymorphic variant of a gene can lead to the abnormal expression or to the production of an abnormal form of the protein; this abnormality may cause or be associated with disease. For example, a polymorphic variant of the gene encoding the enzyme CYP4A11, in which thymidine replaces cytosine at the gene's nucleotide 8590 position encodes a CYP4A11 protein that substitutes phenylalanine with serine at the protein's amino acid position 434.[6] This variant protein has reduced enzyme activity in metabolizing arachidonic acid to the blood pressure-regulating eicosanoid, 20-hydroxyeicosatetraenoic acid. A study has shown that humans bearing this variant in one or both of their CYP4A11 genes have an increased incidence of hypertension, ischemic stroke, and coronary artery disease.[6]

Most notably, the genes coding for the major histocompatibility complex (MHC) are in fact the most polymorphic genes known. MHC molecules are involved in the immune system and interact with T-cells. There are more than 32,000 different alleles of human MHC class I and II genes, and it has been estimated that there are 200 variants at the HLA-B HLA-DRB1 loci alone.[7]

Some polymorphism may be maintained by balancing selection.

Differences between gene polymorphism and mutation

A rule of thumb that is sometimes used is to classify genetic variants that occur below 1% allele frequency as mutations rather than polymorphisms.[8] However, since polymorphisms may occur at low allele frequency, this is not a reliable way to tell new mutations from polymorphisms.[9]

Identification

Polymorphisms can be identified in the laboratory using a variety of methods. Many methods employ PCR to amplify the sequence of a gene. Once amplified, polymorphisms and mutations in the sequence can be detected by DNA sequencing, either directly or after screening for variation with a method such as single strand conformation polymorphism analysis.[10]

Types

A polymorphism can be any sequence difference. Examples include:

Clinical significance

Lung cancer

Polymorphisms have been discovered in multiple XPD exons. XPD refers to "xeroderma pigmentosum group D" and is involved in a DNA repair mechanism used during DNA replication. XPD works by cutting and removing segments of DNA that have been damaged due to things such as cigarette smoking and inhalation of other environmental carcinogens.[15] Asp312Asn and Lys751Gln are the two common polymorphisms of XPD that result in a change in a single amino acid.[16] This variation in Asn and Gln alleles has been related to individuals having a reduced DNA repair efficiency.[17] Several studies have been conducted to see if this diminished capacity to repair DNA is related to an increased risk of lung cancer. These studies examined the XPD gene in lung cancer patients of varying age, gender, race, and pack-years. The studies provided mixed results, from concluding individuals who are homozygous for the Asn allele or homozygous for the Gln allele had an increased risk of developing lung cancer,[18] to finding no statistical significance between smokers who have either allele polymorphism and their susceptibility to lung cancer.[19] Research continues to be conducted to determine the relationship between XPD polymorphisms and lung cancer risk.

Asthma

Asthma is an inflammatory disease of the lungs and more than 100 loci have been identified as contributing to the development and severity of the condition.[20] By using the traditional linkage analysis, these asthma correlated genes were able to be identified in small quantities using genome-wide association studies (GWAS). There have been a number of studies looking into various polymorphisms of asthma-associated genes and how those polymorphisms interact with the carrier's environment. One example is the gene CD14, which is known to have a polymorphism that is associated with increased amounts of CD14 protein as well as reduced levels of IgE serum.[21] A study was conducted on 624 children looking at their IgE serum levels as it related to the polymorphism in CD14. The study found that IgE serum levels differed in children with the C allele in the CD14/-260 gene based on the type of allergens they regularly exposed to.[22] Children who were in regular contact with house pets showed higher serum levels of IgE while children who were regularly exposed to stable animals showed lower serum levels of IgE.[22] Continued research into gene-environment interactions may lead to more specialized treatment plans based on an individual's surroundings.

References

  1. ^ "Genetic polymorphism - Biology-Online Dictionary | Biology-Online Dictionary". September 2020.
  2. ^ "Genetic Testing Report-Glossary". National Human Genome Research Institute (NHGRI). Retrieved 2017-11-08.
  3. ^ Chanock, Stephen (2017-05-22). "Technologic Issues in GWAS and Follow-up Studies" (PDF). Genome.gov.
  4. ^ "Dog Coat Colour Genetics".
  5. ^ "E-Locus (Recessive Yellow, Melanistic Mask Allele)". www.animalgenetics.us. Retrieved 2017-11-08.
  6. ^ a b Wu CC, Gupta T, Garcia V, Ding Y, Schwartzman ML (2014). "20-HETE and blood pressure regulation: clinical implications". Cardiology in Review. 22 (1): 1–12. doi:10.1097/CRD.0b013e3182961659. PMC 4292790. PMID 23584425.
  7. ^ Bodmer, J. G.; Marsh, S. G. E.; Albert, E. D.; Bodmer, W. F.; Bontrop, R. E.; Dupont, B.; Erlich, H. A.; Hansen, J. A.; Mach, B. (1999-04-01). "Nomenclature for factors of the HLA system, 1998". European Journal of Immunogenetics. 26 (2–3): 81–116. doi:10.1046/j.1365-2370.1999.00159.x. ISSN 1365-2370. PMID 10331156.
  8. ^ "Genetic Polymorphism and How It Lasts over Generations".
  9. ^ Karki, Roshan; Pandya, Deep; Elston, Robert C.; Ferlini, Cristiano (2015-07-15). "Defining "mutation" and "polymorphism" in the era of personal genomics". BMC Medical Genomics. 8: 37. doi:10.1186/s12920-015-0115-z. ISSN 1755-8794. PMC 4502642. PMID 26173390.
  10. ^ Bull, Laura (2013). Genetics, Mutations, and Polymorphisms. Landes Bioscience.
  11. ^ "What are single nucleotide polymorphisms (SNPs)?".
  12. ^ Mills RE, Pittard WS, Mullaney JM, Farooq U, Creasy TH, Mahurkar AA, Kemeza DM, Strassler DS, Ponting CP, Webber C, Devine SE (2011). "Natural genetic variation caused by small insertions and deletions in the human genome". Genome Research. 21 (6): 830–9. doi:10.1101/gr.115907.110. PMC 3106316. PMID 21460062.
  13. ^ Mullaney JM, Mills RE, Pittard WS, Devine SE (2010). "Small insertions and deletions (INDELs) in human genomes". Human Molecular Genetics. 19 (R2): R131–6. doi:10.1093/hmg/ddq400. PMC 2953750. PMID 20858594.
  14. ^ "Difference Between Minisatellite and Microsatellite".
  15. ^ Hou, S.-M. (2002-04-01). "The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk". Carcinogenesis. 23 (4): 599–603. doi:10.1093/carcin/23.4.599. ISSN 0143-3334. PMID 11960912.
  16. ^ Qin, Qin; Zhang, Chi; Yang, Xi; Zhu, Hongcheng; Yang, Baixia; Cai, Jing; Cheng, Hongyan; Ma, Jianxin; Lu, Jing (2013-11-15). "Polymorphisms in XPD Gene Could Predict Clinical Outcome of Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer Patients: A Meta-Analysis of 24 Studies". PLOS ONE. 8 (11): e79864. Bibcode:2013PLoSO...879864Q. doi:10.1371/journal.pone.0079864. ISSN 1932-6203. PMC 3829883. PMID 24260311.
  17. ^ Benhamou S, Sarasin A (2005). "ERCC2 /XPD gene polymorphisms and lung cancer: a HuGE review". American Journal of Epidemiology. 161 (1): 1–14. doi:10.1093/aje/kwi018. PMID 15615908.
  18. ^ Liang, Gang; Xing, Deyin; Miao, Xiaoping; Tan, Wen; Yu, Chunyuan; Lu, Wenfu; Lin, Dongxin (2003-07-10). "Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population". International Journal of Cancer. 105 (5): 669–673. doi:10.1002/ijc.11136. ISSN 1097-0215. PMID 12740916.
  19. ^ Misra, R Rita; Ratnasinghe, Duminda; Tangrea, Joseph A; Virtamo, Jarmo; Andersen, Mark R; Barrett, Michael; Taylor, Philip R; Albanes, Demetrius (2003). "Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer amongmale smokers in Finland". Cancer Letters. 191 (2): 171–178. doi:10.1016/s0304-3835(02)00638-9. PMID 12618330.
  20. ^ March ME, Sleiman PM, Hakonarson H (2013). "Genetic polymorphisms and associated susceptibility to asthma". International Journal of General Medicine. 6: 253–65. doi:10.2147/IJGM.S28156. PMC 3636804. PMID 23637549.
  21. ^ Baldini, M.; Lohman, I. C.; Halonen, M.; Erickson, R. P.; Holt, P. G.; Martinez, F. D. (May 1999). "A Polymorphism* in the 5' flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E". American Journal of Respiratory Cell and Molecular Biology. 20 (5): 976–983. doi:10.1165/ajrcmb.20.5.3494. ISSN 1044-1549. PMID 10226067.
  22. ^ a b Eder, Waltraud; Klimecki, Walt; Yu, Lizhi; von Mutius, Erika; Riedler, Josef; Braun-Fahrländer, Charlotte; Nowak, Dennis; Martinez, Fernando D.; Allergy And Endotoxin Alex Study Team (September 2005). "Opposite effects of CD 14/-260 on serum IgE levels in children raised in different environments". The Journal of Allergy and Clinical Immunology. 116 (3): 601–607. doi:10.1016/j.jaci.2005.05.003. ISSN 0091-6749. PMID 16159630.

January 26, 2023
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For other concepts see Polymorphism A gene is said to be polymorphic if more than one allele occupies that gene s locus within a population 1 In addition to having more than one allele at a specific locus each allele must also occur in the population at a rate of at least 1 to generally be considered polymorphic 2 Genes which control hair colour are polymorphic Gene polymorphisms can occur in any region of the genome The majority of polymorphisms are silent meaning they do not alter the function or expression of a gene 3 Some polymorphisms are visible For example in dogs the E locus can have any of five different alleles known as E Em Eg Eh and e 4 Varying combinations of these alleles contribute to the pigmentation and patterns seen in dog coats 5 A polymorphic variant of a gene can lead to the abnormal expression or to the production of an abnormal form of the protein this abnormality may cause or be associated with disease For example a polymorphic variant of the gene encoding the enzyme CYP4A11 in which thymidine replaces cytosine at the gene s nucleotide 8590 position encodes a CYP4A11 protein that substitutes phenylalanine with serine at the protein s amino acid position 434 6 This variant protein has reduced enzyme activity in metabolizing arachidonic acid to the blood pressure regulating eicosanoid 20 hydroxyeicosatetraenoic acid A study has shown that humans bearing this variant in one or both of their CYP4A11 genes have an increased incidence of hypertension ischemic stroke and coronary artery disease 6 Most notably the genes coding for the major histocompatibility complex MHC are in fact the most polymorphic genes known MHC molecules are involved in the immune system and interact with T cells There are more than 32 000 different alleles of human MHC class I and II genes and it has been estimated that there are 200 variants at the HLA B HLA DRB1 loci alone 7 Some polymorphism may be maintained by balancing selection Contents 1 Differences between gene polymorphism and mutation 2 Identification 3 Types 4 Clinical significance 4 1 Lung cancer 4 2 Asthma 5 ReferencesDifferences between gene polymorphism and mutation EditA rule of thumb that is sometimes used is to classify genetic variants that occur below 1 allele frequency as mutations rather than polymorphisms 8 However since polymorphisms may occur at low allele frequency this is not a reliable way to tell new mutations from polymorphisms 9 Identification EditPolymorphisms can be identified in the laboratory using a variety of methods Many methods employ PCR to amplify the sequence of a gene Once amplified polymorphisms and mutations in the sequence can be detected by DNA sequencing either directly or after screening for variation with a method such as single strand conformation polymorphism analysis 10 Types EditA polymorphism can be any sequence difference Examples include Single nucleotide polymorphisms SNPs are a single nucleotide changes that happen in the genome in a particular location The single nucleotide polymorphism is the most common form of genetic variation 11 Small scale insertions deletions Indels consist of insertions or deletions of bases in DNA 12 Polymorphic repetitive elements Active transposable elements can also cause polymorphism by inserting themselves in new locations For example repetitive elements of the Alu and LINE1 families cause polymorphisms in human genome 13 Microsatellites are repeats of 1 6 base pairs of DNA sequence Microsatellites are commonly used as a molecular markers especially for identifying the relationship between alleles 14 Clinical significance EditLung cancer Edit Polymorphisms have been discovered in multiple XPD exons XPD refers to xeroderma pigmentosum group D and is involved in a DNA repair mechanism used during DNA replication XPD works by cutting and removing segments of DNA that have been damaged due to things such as cigarette smoking and inhalation of other environmental carcinogens 15 Asp312Asn and Lys751Gln are the two common polymorphisms of XPD that result in a change in a single amino acid 16 This variation in Asn and Gln alleles has been related to individuals having a reduced DNA repair efficiency 17 Several studies have been conducted to see if this diminished capacity to repair DNA is related to an increased risk of lung cancer These studies examined the XPD gene in lung cancer patients of varying age gender race and pack years The studies provided mixed results from concluding individuals who are homozygous for the Asn allele or homozygous for the Gln allele had an increased risk of developing lung cancer 18 to finding no statistical significance between smokers who have either allele polymorphism and their susceptibility to lung cancer 19 Research continues to be conducted to determine the relationship between XPD polymorphisms and lung cancer risk Asthma Edit Asthma is an inflammatory disease of the lungs and more than 100 loci have been identified as contributing to the development and severity of the condition 20 By using the traditional linkage analysis these asthma correlated genes were able to be identified in small quantities using genome wide association studies GWAS There have been a number of studies looking into various polymorphisms of asthma associated genes and how those polymorphisms interact with the carrier s environment One example is the gene CD14 which is known to have a polymorphism that is associated with increased amounts of CD14 protein as well as reduced levels of IgE serum 21 A study was conducted on 624 children looking at their IgE serum levels as it related to the polymorphism in CD14 The study found that IgE serum levels differed in children with the C allele in the CD14 260 gene based on the type of allergens they regularly exposed to 22 Children who were in regular contact with house pets showed higher serum levels of IgE while children who were regularly exposed to stable animals showed lower serum levels of IgE 22 Continued research into gene environment interactions may lead to more specialized treatment plans based on an individual s surroundings References Edit Genetic polymorphism Biology Online Dictionary Biology Online Dictionary September 2020 Genetic Testing Report Glossary National Human Genome Research Institute NHGRI Retrieved 2017 11 08 Chanock Stephen 2017 05 22 Technologic Issues in GWAS and Follow up Studies PDF Genome gov Dog Coat Colour Genetics E Locus Recessive Yellow Melanistic Mask Allele www animalgenetics us Retrieved 2017 11 08 a b Wu CC Gupta T Garcia V Ding Y Schwartzman ML 2014 20 HETE and blood pressure regulation clinical implications Cardiology in Review 22 1 1 12 doi 10 1097 CRD 0b013e3182961659 PMC 4292790 PMID 23584425 Bodmer J G Marsh S G E Albert E D Bodmer W F Bontrop R E Dupont B Erlich H A Hansen J A Mach B 1999 04 01 Nomenclature for factors of the HLA system 1998 European Journal of Immunogenetics 26 2 3 81 116 doi 10 1046 j 1365 2370 1999 00159 x ISSN 1365 2370 PMID 10331156 Genetic Polymorphism and How It Lasts over Generations Karki Roshan Pandya Deep Elston Robert C Ferlini Cristiano 2015 07 15 Defining mutation and polymorphism in the era of personal genomics BMC Medical Genomics 8 37 doi 10 1186 s12920 015 0115 z ISSN 1755 8794 PMC 4502642 PMID 26173390 Bull Laura 2013 Genetics Mutations and Polymorphisms Landes Bioscience What are single nucleotide polymorphisms SNPs Mills RE Pittard WS Mullaney JM Farooq U Creasy TH Mahurkar AA Kemeza DM Strassler DS Ponting CP Webber C Devine SE 2011 Natural genetic variation caused by small insertions and deletions in the human genome Genome Research 21 6 830 9 doi 10 1101 gr 115907 110 PMC 3106316 PMID 21460062 Mullaney JM Mills RE Pittard WS Devine SE 2010 Small insertions and deletions INDELs in human genomes Human Molecular Genetics 19 R2 R131 6 doi 10 1093 hmg ddq400 PMC 2953750 PMID 20858594 Difference Between Minisatellite and Microsatellite Hou S M 2002 04 01 The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk Carcinogenesis 23 4 599 603 doi 10 1093 carcin 23 4 599 ISSN 0143 3334 PMID 11960912 Qin Qin Zhang Chi Yang Xi Zhu Hongcheng Yang Baixia Cai Jing Cheng Hongyan Ma Jianxin Lu Jing 2013 11 15 Polymorphisms in XPD Gene Could Predict Clinical Outcome of Platinum Based Chemotherapy for Non Small Cell Lung Cancer Patients A Meta Analysis of 24 Studies PLOS ONE 8 11 e79864 Bibcode 2013PLoSO 879864Q doi 10 1371 journal pone 0079864 ISSN 1932 6203 PMC 3829883 PMID 24260311 Benhamou S Sarasin A 2005 ERCC2 XPD gene polymorphisms and lung cancer a HuGE review American Journal of Epidemiology 161 1 1 14 doi 10 1093 aje kwi018 PMID 15615908 Liang Gang Xing Deyin Miao Xiaoping Tan Wen Yu Chunyuan Lu Wenfu Lin Dongxin 2003 07 10 Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population International Journal of Cancer 105 5 669 673 doi 10 1002 ijc 11136 ISSN 1097 0215 PMID 12740916 Misra R Rita Ratnasinghe Duminda Tangrea Joseph A Virtamo Jarmo Andersen Mark R Barrett Michael Taylor Philip R Albanes Demetrius 2003 Polymorphisms in the DNA repair genes XPD XRCC1 XRCC3 and APE ref 1 and the risk of lung cancer amongmale smokers in Finland Cancer Letters 191 2 171 178 doi 10 1016 s0304 3835 02 00638 9 PMID 12618330 March ME Sleiman PM Hakonarson H 2013 Genetic polymorphisms and associated susceptibility to asthma International Journal of General Medicine 6 253 65 doi 10 2147 IJGM S28156 PMC 3636804 PMID 23637549 Baldini M Lohman I C Halonen M Erickson R P Holt P G Martinez F D May 1999 A Polymorphism in the 5 flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E American Journal of Respiratory Cell and Molecular Biology 20 5 976 983 doi 10 1165 ajrcmb 20 5 3494 ISSN 1044 1549 PMID 10226067 a b Eder Waltraud Klimecki Walt Yu Lizhi von Mutius Erika Riedler Josef Braun Fahrlander Charlotte Nowak Dennis Martinez Fernando D Allergy And Endotoxin Alex Study Team September 2005 Opposite effects of CD 14 260 on serum IgE levels in children raised in different environments The Journal of Allergy and Clinical Immunology 116 3 601 607 doi 10 1016 j jaci 2005 05 003 ISSN 0091 6749 PMID 16159630 Retrieved from https en wikipedia org w index php title Gene polymorphism amp oldid 1122795245, wikipedia, wiki, book, books, library,

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