Personalized Medicine And Pharmacogenomics

Question 0

Personalized medicine

Answer 0

In drug therapy, idiopathic disease, cancer, prenatal testing and newborn screening

Question 1

Number of genes present is not directly correlated with complexity of organisms

Answer 1

Humans have 20,500 genes which is only slightly larger than number of genes of zebra fish

DNA sequences of 2 individuals are 99.5% identical

Question 2

Pharmacogenetics

Pharmacogenomics

Answer 2

Pharmacogenetics: this relates heritable variation to inter-individual variation in drug response

Pharmacogenomics: the field of new drug development based on our rapidly increasing knowledge of all genes in the human genome

Drug design influenced by genetics, adverse drug reaction results in FDA rejection of drug

Question 3

Cytochrome P450

Answer 3

Gene family that includes a variety of different enzymes involved in drug metabolism (as well as lipids and hormones)

Mutations in genes result in a change in enzyme’s ability to perform its function

One member of family’s genotype affects ability to metabolize certain drugs: CYP2D6

Question 4

Classes of function

Answer 4

Extensive (normal condition): presence of two functional alleles that work expectedly, most drugs are targeted towards these individuals

Poor metabolizer: nonfunctional allele, difficulty converting drugs to useable forms, accumulation of chemicals in body, toxic, require lower dosage of drug

Ultra metabolizer: duplicate copies of functional alleles, degrades drug rapidly, higher doses or other drugs to be more effective

Intermediate metabolizers: heterozygous with one functional and one mutant allele, can utilize drug but at a slower rate, need lower than normal dose

Question 5

Warfarin

Answer 5

Coumadin is anticoagulant
Synthesis form of drug is warfarin
Useful in rodent poisons, but when used properly can prevent inappropriate thrombosis

React with common medicines, foods with a lot of vit k, excessive alcohol

Vitamin K essential for function of many clotting factors, functional cofactors only work if reduced from of vit K can be converted to oxidized form, oxidized vit K then changed back to reduced form by enzyme vit k reductase (VKOR), warfarin inhibits VKOR which limits cofactors, results in loss of ability to coagulate blood

VKORC1 allele of VKOR gene and CYP2C9 allele of cyt p450 directly affect warfarin metabolism

Question 6

Microarray

Answer 6

Allow genome wide scan of an individual’s genetic complement

Information could be obtained on an individual’s mutational status for selected genes, used to manage patient’s health throughout life

Problem if individual doesn’t want to know this information

Question 7

Regions of homozygosity (ROH)

Answer 7

When Intermediate sized ROH are seen, could be due to identity by descent which occurs in inbred populations, isolated populations or specific ethnic groups

Increases likelihood of expression of recessive disorder

Question 8

Genetic information nondiscrimation act (GINA)

Answer 8

Enacted to prevent genetic discrimination when genetic information is available

Fear that people will lose insurance coverage and job opportunities if companies became aware of genetic diagnosis

Question 9

Personalized medicine in Screening

Answer 9

Prenatal screening

Newborn screening tests newborns for a defined set of genetic diseases

Carrier screening looks at individuals who are phenotypically normal but who may be at risk of having an affected child if their partner is also a mutation carrier for disease