Polymorphism

DNA is coded in triplets of bases called codons. A duplication or multiple repeat of nucleotide sequences results in polymorphism, the existence of two or more alleles in a population resulting in frequency of greater than 0.01 frequency of a specific phenotype. Polymorphisms occur in approximately one in 500 nucleotides and must have at least two phenotypes, of which neither is rare. The most common form of polymorphism is ABO blood grouping. Both A type and B type are dominant, and only need to have the alleles from one parent for the type to be expresse. O is recessive, and needs to inherit the O type from both parents. Polymorphisms have been noted in people with sickle-cell anemia and their lowered susceptibility to malaria.

Genetic typing can be done with the products of polymerase chain reactions (PCR). A heat stable DNA polymerase replicates a specific portion of the DNA at or around the site known to contain the polymorphism. The closer the nucleotides are to the mutation, the more accurate the test. When the quantity is large enough the sample can be run through gel electrophoresis to determine migration and distinguish markers along the DNA. The association of a specific polymorphism with a specific gene is seen in affected members of a population or family, and a lack of association of these specific sequencing is noted in those who are unaffected.

Polymorphism may result in diseases, as with trinucleotide sequences that increase in number, as in the case of the repeat of CGG on the X chromosome. This can cause a form of mental disability called Fragile X, and an unstable trinucleotide CAG repeat on chromosome 4, the dominant inherited gene, causes Hun-tington's Chorea. These genetic diseases have no cure, treatment can only treat the manifested symptoms.

Other polymorphisms affect the plasma proteins a1-antitrypsin, haptoglobin, transferrin, ceruloplasmin and immunglobulins. These phenotypic variations [Page 1401]due to multiple forms of alleles in the genome, are dependant on the location of the base pairs and can affect how the body metabolizes medications and fights infection. Xenobiotics (compounds foreign to the body) are converted to create polar compounds, increasing their water solubility and making them easier for the body to excrete. Approximately 50 percent of drugs ingested are metabolized by a class of enzymes called Cytochrome P450s (CP450s), in a wide range of reactions first through hydroxylation, and then by conjugation or methylation. With polymorphisms, less of the enzyme needed may be available, resulting in an accumulation of the medication in the blood and a variation in drug response.

From a global health perspective, research continues on genetic disorders, including polymorphisms and their impact on health disorders and the potential for correction.