PED 3005

Question 1

what is pharmacogenetics

Answer 1

study of unusual responses to drugs and other foreign compounds that have a hereditary basis

Question 2

what is pharmacogenomics

Answer 2

individualisation of drug therapy using information from the human genome project
relies on using information from gene sequencing

Question 3

what is genetic polymorphisms

Answer 3

a mutation that occurs at a population frequency of at least 1 in 100
can be base substitution, insertion or deletion

Question 4

what is a functional polymorphism

Answer 4

effect on biological activity due to:
- amino acid substitution
- an effect on transcription factor binding
- an altered splice site (e.g. exon skipping, or a new splice site created)
- whole gene sequences deleted or duplicated

Question 5

what is a synonymous mutation

Answer 5

involved a single nucleotide change in the coding region that does not alter the amino acid sequence of the translated protein

Question 6

what is a non-synonymous mutation

Answer 6

involve a change to the to the nucleotide sequence in the coding region that will result in an altered amino acid sequence, which may alter protein structural and will have a functional consequence

Question 7

what are the consequences of pharmacogenetics polymorphisms

Answer 7

toxicity
- exaggerate response or effect on inappropriate target
- depends on therapeutic window
lack of response
- target does not respond or drug metabolised or excrete too rapidly
- prodrug not activated

Question 8

what are the phenotypic approaches to the identification of pharmacogenetics polymorphisms

Answer 8

can get information about a physical characteristic
enzyme activity
pattern of drug metabolism

Question 9

what are the genotypic approaches to the identification of pharmacogenetics polymorphisms

Answer 9

study gene of pharmacological relevance for the presence of genetic polymorphisms
- examine phenotypic effect of these polymorphisms using in vitro or in vivo approaches

Question 10

what are the limitations of phenotypic approaches

Answer 10

enzyme activity measurements problematic - tissue needs to be accessible
studies on patterns of drug metabolites often difficult - need a suitable probe drug or chemical and good analytical chemical techniques
particularly difficult in studies of drug receptors

Question 11

what are the advantages of genotypic approaches

Answer 11

looking directly at gene of interest
can use blood sample, buccal cells or saliva as source of DNA (white blood cells give better quality DNA)

Question 12

what are the disadvantages of genotypic approaches

Answer 12

may need to relate polymorphisms to functions which can be technically complex
there are techniques and algorithms available which can predict functional effects on protein structure and activity

Question 13

how can we genotype for known polymorphisms

Answer 13

PCR followed by restriction digest which recognises one allele but not the other
allele specific PCR
primer extension methods e.g. sequenom
t

Question 14

what does RFLP stand for

Answer 14

restriction fragment length polymorphism

Question 15

what is the NAT2 gene

Answer 15

gene involved in metabolism of chemotherapeutic drug Isoniazid