1 - Intro Flashcards
(43 cards)
Define pharmacogenomics
General study of all of the different genes that determine drug response
How can genetic variations affect PK?
- Drug uptake channels
- Transporters
- Drug metabolizing enzymes (CYP), etc.
How can genetic variations affect PD?
- Drug receptors
- Receptor gated channels
- Enzyme targets
- Second messengers
Define allele
2 copies of a gene, one from each parent
Define locus
Region on a chromosome
Define genotype
- Entire genetic makeup of the cell/ organism
- 2 alleles for a specific gene or group of genes
Define haplotype
- Group of alleles (or polymorphisms) on the same chromosome that are inherited together
- Can refer to a combination of alleles or to a set of SNPs found on the same chromosome
Define wild type
- Normal sequence of the gene in the population
- Gene that is most often expressed in the population
Define polymorphism
Variation in DNA sequence present in 1% or more of the population
What are the types of polymorphisms?
- Single nucleotide polymorphism (SNP)
- Variable number tandem repeats (VNTR) – more than 1 nucleotide change (in tandem repeats)
- Gene insertion or deletion
- Multiple copies of a gene
Types of single nucleotide polymorphisms (SNP)
- Nonsense mutation -> premature stop codon SNP
- Silent mutation -> synonymous SNP (nucleotide change that still results in the same AA)
- Missense mutation -> non-synonymous SNP
What is the difference between SNP deletions and insertions?
- Deletion SNP will cause frame shift; almost certainly results in premature stop codon
- Insertion SNP will cause frame shift; typically results in premature stop codon
What can VNTR’s cause?
- No effect on activity
- Result in frame shift (causing no activity)
- No frame shift but no activity
- Loss of some activity
What is a gene deletion and what does it cause?
- Deletion of thousands of base pairs
- Results in loss of gene (no activity)
What is a gene duplication and what does it cause?
- Duplication of the sequence of a gene
- Results in more activity, but the increase in activity isn’t always linear w/ increasing copies of said gene
Define intron
Removed from gene and doesn’t appear in final mRNA
Define exon
Sequence that makes up the final mRNA
What can polymorphisms w/in introns cause?
- May not change gene activity but could change gene expression
- In the intron-exon boundary, may result in splice variant
What can polymorphisms w/in exons cause?
Likely affect gene activity (unless a synonymous SNP)
What can be caused by improper splicing?
- Mutation could result in the forced formation of a splice variant (splice variant may still have activity)
- Mutation could also truncate the protein (almost certainly will result in an inactive protein)
Define promoter
DNA sequence where transcription factors bind to initiate transcription (+1 is the position of first base of the primary RNA transcript)
Define enhancer
- DNA sequence that binds proteins that increase the rate of transcription
- Usually located far upstream or downstream of the gene
- Can be more than 1 for a given gene
- Can also be found w/in introns
What can polymorphisms in the promoter cause?
- Can alter transcription of the gene
- Could reduce transcription but also possible that the gene won’t express at all (may occur by reducing binding of transcription factors)
- However, depending on the polymorphism, transcription may also increase
What can polymorphisms in the enhancer regions cause?
- Can affect transcription of the gene
- Enhancers are sometimes found w/in introns (another reason why polymorphisms w/in introns can affect transcription of genes)
- The polymorphism can disrupt the enhancer
