User:Eemartin2/sandbox

Adding to the Gene Polymorphism page:

-elaborate on each type of SNP

-Include synonymous vs. non synonymous SNPs and the implications and selection of each

-coding vs. non-coding regions

-how to use polymorphisms to measure mean heterozygosity and percent polymorphic in a given population

-how specific polymorphisms are found and their applications in human health

-Genome.gov has good basic information that can be used and further supported with secondary academic literature

- https://www.genome.gov/pages/about/od/opg/multi-ic_symposia/may2007/techissues.pdf

- https://ghr.nlm.nih.gov/primer/genomicresearch/snp

- http://learn.genetics.utah.edu/content/precision/snips/

Article Outline:

Lead section:

-Elaborate on the implications of polymorphism at a locus (the phenotypic/genetic changes that occur because of the polymorphism). Follow up with the dog coat color already present but elaborate on each of the different alleles mentioned.

-The variation at loci are maintained through natural selection (hyperlink for natural selection)

-Find source for MHC gene sentence in the third paragraph. Elaborate on what processes these genes are involved in.

Differences Between Gene Polymorphism and Mutation section:

-Specify that gene polymorphisms are present in >1% of population and mutations are present in <1% of the population.

-Polymorphisms cannot be maintained solely by mutation or immigration. They are selected for.

-Polymorphisms are continuous throughout all cells in a person's body while some mutations are only present in a subset of somatic cells (i.e. cancer)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4502642/

Research Example 1 and 2:

1: Drug-metabolizing gene family CYP2C19. Specific variants are considered poor metabolizers and can affect proton pump inhibitors, antidepressants, malaria medication, etc. Toxicity is an issue in poor metabolizers and knowing which can affect several health issues.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2014584/

2: Insulin pathway SNP polymorphisms in insulin-like growth factor-I and phosphoinositide 3-kinase affect plasma levels which affect life longevity. Specific polymorphisms showed higher plasma levels than others, leading to a potential advantage in the form of longevity.

https://link.springer.com/content/pdf/10.1007%2Fs11515-009-0033-6.pdf

Article Draft (new text added in bold):

A gene is said to be polymorphic if more than one allele occupies that gene’s locus within a population. 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. '''Gene polymorphisms can occur in the coding or non-coding region of the genome. The majority of polymorphisms are silent, meaning that they occur in the non-coding region and therefore do not alter the function or expression of a gene. If a gene polymorphism is located in the coding region of the genome, it can alter the expression of the gene and create variation within a given population. This variation is maintained by balancing selection. For example, in dogs the E locus, can have any of five different alleles, known as E, Em, Eg, Eh, and e. Varying combinations of these alleles contribute to the pigmentation and patterns seen in dog coats .'''

A polymorphic variant of a gene may 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 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. 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.

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 800 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. '''

Mutation results from DNA sequence changes that specifically 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. Gene polymorphisms generally occur in populations at a frequency of 1% or more while mutations usually occur at a frequency of less than 1%. '''Additionally, gene polymorphisms are present in all cells of an individual's body while mutations have the ability to be present in a specific subset of somatic cells. An example of this phenomenon is the mutation of somatic cells leading to cancer in a specific area of an organism's body.'''

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'''. Asp312Asn and Lys751Gln are the two common polymorphisms of XPD that result in a change in a single amino acid. This variation in Asn and Gln alleles is has been related to individuals having a reduced DNA repair efficiency. '''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, to finding no statistical significance between smokers who have either allele polymorphism and their susceptibility to lung cancer'''. 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. 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. 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. 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. Continued research into gene-environment interactions may lead to more specialized treatment plans based on an individual's surroundings.'''

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’s coding sequence, then different phenotypes may appear as a result of protein variation that is caused by sequence changes. '''Polymorphisms can be identified in the laboratory using a variety of methods. The first step is amplifying the coding sequence of the gene using PCR. Once amplified, a number of methods can be used to identify a mutation or polymorphism including DNA sequencing and single strand conformation polymorphism analysis (SSCP).'''

New Sources: citations 2, 3, 5, 7, 9, 10, 11, 13, 14, 16, 17, 19

Hyperlinks: balancing selection, Major Histocompatibility Complex, T-cells, pack-years, genome-wide association study, PCR, DNA sequencing