Pharmacogenomics Flashcards Preview

PBS 601 Cellbio/biochem > Pharmacogenomics > Flashcards

Flashcards in Pharmacogenomics Deck (19):
1

pharmacogenomics

‘the study of a combination of genes that affects response to a drug’

2

The following regions of a gene are also non‐coding : 

promoter, 5’‐UTR, introns, 3’‐UTR

3

single nucleotide polymorphism (SNP)

change in a single base within the DNA sequence

4

An allele

the variable form of a specific gene

5

wildtype

if it has the sequence that is considered ‘normal’ for a population, i.e. occurs with the highest frequency

6

allelic variant

can be used to describe differences in DNA sequence that exist between the alleles on the maternal and paternal chromosomes

7

haplotype

combination of alleles that are located within a chromosome, or more typically for pharmacogenomics, is defined as the combination of SNPs (allelic variants) that are located within a particular gene

8

Tag SNPs

  • Some SNPs are inherited together, i.e. they ‘travel’ together – if we know the inheritance of certain SNPs is linked, we only need to assess the presence of 1 of the SNPs within the group to know that the others are present.
  • Tag SNPs can be used to establish haplotypes for patients/determine what haplotype a patient belongs to.

9

PM

  • Poor metabolizers 
  • two non‐functional (null) alleles

10

IM 

  • Intermediate Metabolizer 
  • Two reduced function alleles OR one null allele and the other with reduced function

11

EM

  • Extensive metabolizer 
  • At least one or two functional alleles (i.e. normal)

12

UM

  • Ultra Rapid metabolizer 
  • More than 2 functional alleles

13

The most common reasons for mismatch between genotype and phenotype are : 

  1. Dominant negative behavior of the mutant/non‐functional protein (it can inhibit the function of the wildtype protein)
  2. Haploinsufficiency (only half the amount of protein that is needed is synthesized because the mutant mRNA isn’t translated).

14

Translocations can result in : 

  1. A gene moving from a region of euchromatin to a region of heterochromatin (or vice versa),
  2. A gene moving to a region next to a ‘strong’ promoter (or ‘weak’ promoter).

Both result in an alteration in gene expression levels

15

What could result in an alteration in protein expression levels ? 

  1. Promoter methylation : decrease transcription ---> decrease mRNA --> decrease protein expression

    E.g. methylation of cytosines in the promoter region inhibits transcription through preventing formation of transcription initiation complex = no/reduced transcription = no/reduced translation of the protein that gene codes for. Methylation of the promoter of a gene that codes for a protein involved indrug metabolism can therefore affect drug metabolism/patient response to a drug

  2. Gene deletion : will decrease expression of proteins
  3. Mutation in an intron : will affect the expression if they occur in an enhancer or silencer element
     

16

Truncated (nonsense) or abnormal (frameshift) proteins

often recognized as defective by cell and degraded in the lysosome

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Amplification

increased expression

18

Deletion

decreased expression

19

Genotype

A set of alleles that determines the expression of a particular characteristic (can also be used to predict phenotype/disease)