Pharmacogenomics

Pharmacogenomics refers to the entire spectrum of genes that determine drug behavior and sensitivity.  It assesses the genetic basis of drug response and toxicity in target patient populations. Pharmacogenetics focuses on drug response as a function of genetic differences among individuals.

It is already known that genetic polymorphisms in drug-metabolizing enzymes can have a profound effect on toxicity and efficacy of medications used to treat patients.  Knowledge of the genetic basis for drug disposition and response should make it possible to select many medications and their dosages on the basis of each patient's inherited ability to metabolize, eliminate, and respond to specified drugs.

Most drugs interact with specific target proteins to exert their pharmacological effect, such as receptors, enzymes, or proteins involved in signal transduction, cell cycle control, or many other cellular events. Cell membrane receptors, largely heterotrimeric GTP-binding protein (G protein) coupled receptors constitute the largest subgroup of drug targets underlying current drug therapy with enzymes as the next largest subgroup.

On average, two unrelated persons have over 99.9% of DNA sequence similarity. So what makes people different? Well despite this huge similarity, it still leaves about 3 million bases where two unrelated persons can be heterozygous. Genetic components that can make two people different include:

• SNP's or single nucleotide polymorphisms are points in the genome at which one base can differ between individuals. If a particular SNP is inherited with a disease, it is also a strong indication that a gene that confers susceptibility lies somewhere nearby. There are thought to be some ten million common SNPs scattered trhoughout the human genome.

Perlegen   

• epigenetic modifications; alterations in gene expression patterns, without changes in DNA sequences are referred to as epigenetic mechanisms. These modifications consist of methyl groups attached to C-G dinucleotides in the DNA. They can also be due to histone proteins which undergo chemical modifications such as methylation, phosphorylation, acetylation and ubiquitination.

see the Human EPIgenome consortium    Epigenetic modifications are very important in embryogenesis. All of our genomes contain distinct maternal and paternal imprints that are inherited after fertilization by embryos and endure into adulthood. These modifications which are recognized as differential methylation of specific DNA sequences in sperm and oocytes, regulate expression of imprinted genes, which confer functional differences between parental genomes during development.

• ethnic variations; ethnicity is a term used for categorizing the highly diverse human population into more homogenous distinct ethnic groups based on their common ancestry and cultural characteristics. Certain diseases have a higher incidence depending on one's ethnicity. For example, diabetes and hypertension is higher among blacks then white.     Ancestry by DNA   

Genetic Testing;  A genetic test analyzes DNA, RNA, chromosomes (cytogenetic tests) , proteins and certain metabolites in order to detect heritable disease related genotypes, mutations, phentoypes for clinical purposes.

DNA sequencing technology/VisiGen Biotechnologies    GeneTests   

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