Gene polymorphism

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, E^m, E^g, E^h, 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

• DRD2
• ANKK1
• COMT
• MAOA
• CYP4A11

Differences between Gene polymorphism and mutation

Mutation results due to DNA sequence changes specifically that happen once an allele is transferred from one generation to another and initiate alterations in the allele status from normal to abnormal. In contrast, gene polymorphism is defined as a variation that occurs in allele in a DNA sequence.^[4]

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 for 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.^[5]

Types of gene polymorphism

There are four types of gene polymorphisms:^[6]

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.^[7]

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.^[8]

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.^[9]

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.^[10]

Clinical significance

Lung Cancer

Polymorphisms have been discovered in multiple XPD exons. XPD refers to ‘’’xeroderma pigmentosum group D’’’ that are 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.^[11]

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.^[12]

References