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A [[gene]] is said to be '''polymorphic''' if more than one [[allele]] occupies that gene’s [[Locus (genetics)|locus]] within a population.<ref>http://www.biology-online.org/dictionary/Genetic_polymorphism</ref> For example in dogs the E locus, which controls coat pattern, can have any of five different alleles, known as E, E<sup>m</sup>, E<sup>g</sup>, E<sup>h</sup>, and e.<ref>http://www.doggenetics.co.uk/masks.html</ref>
A [[gene]] is said to be '''polymorphic''' if more than one [[allele]] occupies that gene’s [[Locus (genetics)|locus]] within a population.<ref>http://www.biology-online.org/dictionary/Genetic_polymorphism</ref> For example in dogs the E locus, which controls coat pattern, can have any of five different alleles, known as E, E<sup>m</sup>, E<sup>g</sup>, E<sup>h</sup>, and e.<ref>http://www.doggenetics.co.uk/masks.html</ref>


A polymorphic variant of a gene may lead to the abnormal expression or to the production of an abnormal form of the gene; this may cause or be associated with disease. For example, a polymorphic variant of 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. This variant protein has reduced enzyme activity in metabolizing [[arachidonic acid]] to the blood pressure-regulating [[eicosanoid]], [[20-Hydroxyeicosatetraenoic acid]]; humans bearing this variant in one or both of their CYP4A11 genes have an increased incidence of [[hypertension]], ischemic [[stroke]], and [[coronary artery disease]].<ref>Cardiol Rev. 2014 Jan-Feb;22(1):1-12. doi: 10.1097/CRD.0b013e3182961659. Review</ref>
A polymorphic variant of a gene may lead to the abnormal expression or to the production of an abnormal form of the gene; this may cause or be associated with disease. For example, a polymorphic variant of 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. This variant protein has reduced enzyme activity in metabolizing [[arachidonic acid]] to the blood pressure-regulating [[eicosanoid]], [[20-Hydroxyeicosatetraenoic acid]]; humans bearing this variant in one or both of their CYP4A11 genes have an increased incidence of [[hypertension]], ischemic [[stroke]], and [[coronary artery disease]].<ref name="pmid23584425">{{cite journal | vauthors = Wu CC, Gupta T, Garcia V, Ding Y, Schwartzman ML | title = 20-HETE and blood pressure regulation: clinical implications | journal = Cardiology in Review | volume = 22 | issue = 1 | pages = 1–12 | year = 2014 | pmid = 23584425 | pmc = 4292790 | doi = 10.1097/CRD.0b013e3182961659 }}</ref>


Most notably, the genes coding for the Major Histocompatibility Complex ([[Major histocompatibility complex|MHC]]) are in fact the most polymorphic genes known. In fact there are more than 800 different [[alleles]] of human [[Major histocompatibility complex|MHC]] class I and II genes.
Most notably, the genes coding for the Major Histocompatibility Complex ([[Major histocompatibility complex|MHC]]) are in fact the most polymorphic genes known. In fact there are more than 800 different [[alleles]] of human [[Major histocompatibility complex|MHC]] class I and II genes.
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'''1- Single Nucleotide Polymorphisms (SNPs):''' SNPs are a single nucleotide changes that happen in the genome in a particular location . The Single Nucleotide Polymorphism is known to be the most common form of genetic variation. A major and the cause of this SNPs is the replacement of the nucleotide '''Cytosine (C)''' with''' Thymine (T)''' in a part of the DNA. SNPs may cause a disease through the affection in a specific gene or regulatory region near this gene resulting in disturbance in the gene's function <ref>https://ghr.nlm.nih.gov/primer/genomicresearch/snp</ref>.
'''1- Single Nucleotide Polymorphisms (SNPs):''' SNPs are a single nucleotide changes that happen in the genome in a particular location . The Single Nucleotide Polymorphism is known to be the most common form of genetic variation. A major and the cause of this SNPs is the replacement of the nucleotide '''Cytosine (C)''' with''' Thymine (T)''' in a part of the DNA. SNPs may cause a disease through the affection in a specific gene or regulatory region near this gene resulting in disturbance in the gene's function <ref>https://ghr.nlm.nih.gov/primer/genomicresearch/snp</ref>.
'''2- Small-scale insertions/deletions:''' Small insertions and deletion are called ( [https://en.wikipedia.org/wiki/Indel INDELs]) and this type of gene polymorphism is dependent on insertion or deletion of DNA bases in an organism. Nowadays, two million INDELs have been discovered in approximately seventy-nine various humans genomes. Furthermore, small insertions/ deletions are existed on genes coding exons and this may consider a fundamental factor that leads to diseases inheritance in humans <ref>Mills, R. E., Pittard, W. S., Mullaney, J. M., Farooq, U., Creasy, T. H., Mahurkar, A. A., ... & Devine, S. E. (2011). Natural genetic variation caused by small insertions and deletions in the human genome. Genome research, gr-115907.</ref>.
'''2- Small-scale insertions/deletions:''' Small insertions and deletion are called ( [https://en.wikipedia.org/wiki/Indel INDELs]) and this type of gene polymorphism is dependent on insertion or deletion of DNA bases in an organism. Nowadays, two million INDELs have been discovered in approximately seventy-nine various humans genomes. Furthermore, small insertions/ deletions are existed on genes coding exons and this may consider a fundamental factor that leads to diseases inheritance in humans.<ref name="pmid21460062">{{cite journal | vauthors = Mills RE, Pittard WS, Mullaney JM, Farooq U, Creasy TH, Mahurkar AA, Kemeza DM, Strassler DS, Ponting CP, Webber C, Devine SE | title = Natural genetic variation caused by small insertions and deletions in the human genome | journal = Genome Research | volume = 21 | issue = 6 | pages = 830–9 | year = 2011 | pmid = 21460062 | pmc = 3106316 | doi = 10.1101/gr.115907.110 }}</ref>


'''3- Polymorphic Repetitive Elements:'''
'''3- Polymorphic Repetitive Elements:'''
Alu which is a repetitive element from [https://en.wikipedia.org/wiki/Alu_element Alu] family , can trigger a polymorphism in human genome. Alu element is defined as a small area of DNA sequence with 300 base pairs. Alu element also has a role in RNA polymerase III for its compression of a RNA promoter. It has been found that Alu is repeated in more than 10% of human genome. Insertion and repetitive of Alu element in human genome can cause mutations and disorders that are related to carcinogenesis <ref>Mullaney, J. M., Mills, R. E., Pittard, W. S., & Devine, S. E. (2010). Small insertions and deletions (INDELs) in human genomes. Human molecular genetics, 19(R2), R131-R136. #Khitrinskaya, I. Y., Stepanov, V. A., & Puzyrev, V. P. (2003). Alu repeats in the human genome. Molecular Biology, 37(3), 325-333</ref>.
Alu which is a repetitive element from [https://en.wikipedia.org/wiki/Alu_element Alu] family , can trigger a polymorphism in human genome. Alu element is defined as a small area of DNA sequence with 300 base pairs. Alu element also has a role in RNA polymerase III for its compression of a RNA promoter. It has been found that Alu is repeated in more than 10% of human genome. Insertion and repetitive of Alu element in human genome can cause mutations and disorders that are related to carcinogenesis.<ref name="pmid20858594">{{cite journal | vauthors = Mullaney JM, Mills RE, Pittard WS, Devine SE | title = Small insertions and deletions (INDELs) in human genomes | journal = Human Molecular Genetics | volume = 19 | issue = R2 | pages = R131–6 | year = 2010 | pmid = 20858594 | pmc = 2953750 | doi = 10.1093/hmg/ddq400 }}</ref>


'''4- Microsatellite variation:''' Microsatellites are characterized for the repetition for 1-6 base pairs of DNA sequence. In Genetics, microsatellites are commonly used as a molecular markers especially for identifying the relationship between alleles. Diseases that are correlated with microsatellites are Fragile X Syndrome, Myotonic dystrophy, Friedreich ataxia, Kennedy disease, Huntington disease, Haw river syndrome, and Spinocerebellar ataxia. <ref>http://www.majordifferences.com/2013/11/difference-minisatellite-and.html#.WMDEohiZMb0</ref>.
'''4- Microsatellite variation:''' Microsatellites are characterized for the repetition for 1-6 base pairs of DNA sequence. In Genetics, microsatellites are commonly used as a molecular markers especially for identifying the relationship between alleles. Diseases that are correlated with microsatellites are Fragile X Syndrome, Myotonic dystrophy, Friedreich ataxia, Kennedy disease, Huntington disease, Haw river syndrome, and Spinocerebellar ataxia.<ref>http://www.majordifferences.com/2013/11/difference-minisatellite-and.html#.WMDEohiZMb0</ref>.


== Clinical signficance ==
== Clinical signficance ==
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=== Lung Cancer ===
=== Lung Cancer ===


Polymorphisms have been discovered in multiple XPD exons. XPD refers to ‘’’xeroderma pigmentosum group D’’’ that is needed for excision repairs of bulky cuts in the DNA, which are mostly produced by smoking. Asp312Asn and Lys751Gln are the two polymorphisms that are consequence in conversions in an amino acid. Alternation in Asn and Gln alleles is stated to having a role in reducing the repair efficiency in humans that leads to a risk of lung cancer <ref>Simone Benhamou, Alain Sarasin; ERCC2 /XPD Gene Polymorphisms and Lung Cancer: A HuGE Review. Am J Epidemiol 2005; 161 (1): 1-14. doi: 10.1093/aje/kwi018</ref>.
Polymorphisms have been discovered in multiple XPD exons. XPD refers to ‘’’xeroderma pigmentosum group D’’’ that is needed for excision repairs of bulky cuts in the DNA, which are mostly produced by smoking. Asp312Asn and Lys751Gln are the two polymorphisms that are consequence in conversions in an amino acid. Alternation in Asn and Gln alleles is stated to having a role in reducing the repair efficiency in humans that leads to a risk of lung cancer.<ref name="pmid15615908">{{cite journal | vauthors = Benhamou S, Sarasin A | title = ERCC2 /XPD gene polymorphisms and lung cancer: a HuGE review | journal = American Journal of Epidemiology | volume = 161 | issue = 1 | pages = 1–14 | year = 2005 | pmid = 15615908 | doi = 10.1093/aje/kwi018 }}</ref>


=== Asthma ===
=== Asthma ===


By using the traditional linkage analysis, asthma correlated genes have been identified in small quantities. Genome-wide association (GWA) study was used to determine and investigate the genes that are involved in asthma followed by a confirmation of asthma candidate genes. The genes were identified but unfortunately not characterized <ref>March, M. E., Sleiman, P. M., & Hakonarson, H. (2013). Genetic polymorphisms and associated susceptibility to asthma. Int J Gen Med, 6(253-265), 6.</ref>.
By using the traditional linkage analysis, asthma correlated genes have been identified in small quantities. Genome-wide association (GWA) study was used to determine and investigate the genes that are involved in asthma followed by a confirmation of asthma candidate genes. The genes were identified but unfortunately not characterized.<ref name="pmid23637549">{{cite journal | vauthors = March ME, Sleiman PM, Hakonarson H | title = Genetic polymorphisms and associated susceptibility to asthma | journal = International Journal of General Medicine | volume = 6 | issue = | pages = 253–65 | year = 2013 | pmid = 23637549 | pmc = 3636804 | doi = 10.2147/IJGM.S28156 }}</ref>


== References ==
== References ==

Revision as of 17:18, 24 March 2017

Genes which control hair colour are polymorphic.

A gene is said to be polymorphic if more than one allele occupies that gene’s locus within a population.[1] For example in dogs the E locus, which controls coat pattern, can have any of five different alleles, known as E, Em, Eg, Eh, and e.[2]

A polymorphic variant of a gene may lead to the abnormal expression or to the production of an abnormal form of the gene; this may cause or be associated with disease. For example, a polymorphic variant of 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. This variant protein has reduced enzyme activity in metabolizing arachidonic acid to the blood pressure-regulating eicosanoid, 20-Hydroxyeicosatetraenoic acid; humans bearing this variant in one or both of their CYP4A11 genes have an increased incidence of hypertension, ischemic stroke, and coronary artery disease.[3]

Most notably, the genes coding for the Major Histocompatibility Complex (MHC) are in fact the most polymorphic genes known. In fact there are more than 800 different alleles of human MHC class I and II genes.

Examples

Causes

Gene polymorphisms are caused by duplications, deletions, and a mutation of triplication of high quantity of DNA base pairs sequences. In addition, Polymorphisms may occur due to changes inside introns or changes in regions that one or multiple DNA bases that are between genes. If the changes occur in a gene’ coding sequence, then different phenotypes may appear as a result of protein variation that is caused by sequence changes. These changes are located exactly in genes’ coding sequence.[4].

Types

There are four types of gene polymorphisms: [5]

1- Single Nucleotide Polymorphisms (SNPs): SNPs are a single nucleotide changes that happen in the genome in a particular location . The Single Nucleotide Polymorphism is known to be the most common form of genetic variation. A major and the cause of this SNPs is the replacement of the nucleotide Cytosine (C) with Thymine (T) in a part of the DNA. SNPs may cause a disease through the affection in a specific gene or regulatory region near this gene resulting in disturbance in the gene's function [6].

2- Small-scale insertions/deletions: Small insertions and deletion are called ( INDELs) and this type of gene polymorphism is dependent on insertion or deletion of DNA bases in an organism. Nowadays, two million INDELs have been discovered in approximately seventy-nine various humans genomes. Furthermore, small insertions/ deletions are existed on genes coding exons and this may consider a fundamental factor that leads to diseases inheritance in humans.[7]

3- Polymorphic Repetitive Elements: Alu which is a repetitive element from Alu family , can trigger a polymorphism in human genome. Alu element is defined as a small area of DNA sequence with 300 base pairs. Alu element also has a role in RNA polymerase III for its compression of a RNA promoter. It has been found that Alu is repeated in more than 10% of human genome. Insertion and repetitive of Alu element in human genome can cause mutations and disorders that are related to carcinogenesis.[8]

4- Microsatellite variation: Microsatellites are characterized for the repetition for 1-6 base pairs of DNA sequence. In Genetics, microsatellites are commonly used as a molecular markers especially for identifying the relationship between alleles. Diseases that are correlated with microsatellites are Fragile X Syndrome, Myotonic dystrophy, Friedreich ataxia, Kennedy disease, Huntington disease, Haw river syndrome, and Spinocerebellar ataxia.[9].

Clinical signficance

Lung Cancer

Polymorphisms have been discovered in multiple XPD exons. XPD refers to ‘’’xeroderma pigmentosum group D’’’ that is needed for excision repairs of bulky cuts in the DNA, which are mostly produced by smoking. Asp312Asn and Lys751Gln are the two polymorphisms that are consequence in conversions in an amino acid. Alternation in Asn and Gln alleles is stated to having a role in reducing the repair efficiency in humans that leads to a risk of lung cancer.[10]

Asthma

By using the traditional linkage analysis, asthma correlated genes have been identified in small quantities. Genome-wide association (GWA) study was used to determine and investigate the genes that are involved in asthma followed by a confirmation of asthma candidate genes. The genes were identified but unfortunately not characterized.[11]

References

  1. ^ http://www.biology-online.org/dictionary/Genetic_polymorphism
  2. ^ http://www.doggenetics.co.uk/masks.html
  3. ^ 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.
  4. ^ http://www.wikilectures.eu/index.php/Genetic_Polymorphisms
  5. ^ https://www.ncbi.nlm.nih.gov/Class/MLACourse/Modules/MolBioReview/variation.html
  6. ^ https://ghr.nlm.nih.gov/primer/genomicresearch/snp
  7. ^ 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.
  8. ^ 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.
  9. ^ http://www.majordifferences.com/2013/11/difference-minisatellite-and.html#.WMDEohiZMb0
  10. ^ 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.
  11. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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