Molecular genetics polymorphism

Essential to the definition of Pharmacogenetics is the term genetic polymorphism. It is extrapolated that there are at least three million genetic polymorphisms in the human genome. Historically, a genetic polymorphism was defined as a genetic variation with a population frequency of 1% and above, but the larger inter-ethnic variation of population frequencies makes a strict definition based on such frequencies impractical. The most common molecular type of polymorphism is the... 

Meyer, U.A. (1994a). The molecular basis of genetic polymorphisms of drug metabolism. /. Pharm. Pharmacol, 46(1), 409-15. 

Meyer UA, Zanger UM. Molecular mechanisms of genetic polymorphisms of drug metabolism. Annu Rev Pharmacol Toxicol 1997 37 269-296. 

There must be ample information on the molecular genetic nature of the disorder (mode of inheritance, gene frequency, polymorphic nature of the locus, genetic heterogeneity of the disorder). 

These data emphasize the complex nature of the molecular mechanisms controlling polymorphic DPD activity in vivo. The clinical utility for genetic polymorphism testing to date is not optimal because of its low sensitivity and unknown specificity (28). Overall, it can be remarked that the splice site mutation IVS14+1G>A causes severe, even lethal, 5-FU-related toxicity. Unfortunately, the roles of other polymorphisms in the DPYD gene in the severe 5-FU-related toxicity are not clarified. 

It is a truism that gene frequencies vary by ethnicity. Polymorphisms are not meaningful unless they can be studied in the context of the ethnic group that harbors them. In the case of risk reduction statistics, for example, it is well known that Jewish Ashkenazim are at 1/27 risk of carrying Tay-Sachs disease. But what is often not understood by the naive observer is that their risk can be reduced to 1/1250 through the prudent application of molecular genetic testing. On the other... 

Maestrini, E., Lai, C., Marlow, A., Matthews, N., Wallace, S., Bailey, A., Cook, E., Weeks, D., Monaco, A., and International Molecular Genetics of Autism Consortium. (1999) Serotonin transporter (S-HTT) and gamma-aminobuyric acid receptor subunit beta-3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. Am J Med Genet (Neuropsychiatr Genet), 88 492-496. 

Milk XO has a molecular weight of c. 300 kDa and consists of two subunits. The pH optimum is about 8.5 and the enzyme requires flavin adenine dinucleotide (FAD), Fe, Mo and an acid-labile compound as co-factors cows deficient in Mo have low XO activity. The amino acid composition of XO has been determined by a number of workers at least five genetic polymorphic forms have been reported. 

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