Classical and Non Classical Pharmacogenomics Flashcards
What is DNA?
how is it packed?
polymer of nucleotides containing sugar, phosphate, one of 4 nitrogenous bases ATCG
double helix
long molecule packed into thread-like structures called chromosomes located in nucleus of cell
How many pairs of chromosomes in humans?
23 pairs
22 pairs are autosomes
1 pair is sex chromosome (XX, XY)
what is the gene function?
- exact function of most DNA unknown in human genome
- central dogma is info that we want to transmit from generation to generation is encoded in DNA
non-coding vs coding DNA
98-99% non coding: regulated process where genes are translated into proteins
1-2% coding: blueprint that encodes protein (enzymes structural elements, signaling molecules)
Explain the process of splicing
- Exons are coding portions
- Introns have functions unknown but likely to regulate
- Identify promotor, unwinds helix into single helix
- Splicing process - introns are removed
- Coding parts come together
- mRNA is translated into protein when it is moved to cytoplasm and attached to ribosomes
- If promoter is moved, there will be different splicing, mRNA is changed due to unwinding at a different position
- splicing can result in diff mRNA sequences, 1 gene can encode multiple proteins even with diff functions
Explain translation
tRNA has 2 sides: anticodon and one side that pulls the correct amino acids forming a peptide chain
Continues until it reaches the stop codon UAG UAA, UGA
Name 4 types of genetic variants/polymorphisms
- SNPs
- Indels
- VNTR (variable number tandem repeats)
- CNV (copy number variants)
- haplotypes (combo of alleles or set of SNPs found on same chromosome)
Define indels
- insertion or deletion of DNA into an organism’s genome
- small insertions and deletions ranging from 1-10 000 bp in length
Define CNV
- structural variation where you have a stretch of DNA which is duplicated in some people and sometimes tripled or quadruplicated
- relationship to human disease not known yet
- some cancers are associated with elevated copy numbers of particular genes
Define Haplotypes
- combo of alleles or a set of single SNPs found on same chromosome (clusters of SNPs)
How prevalent is an SNV?
where are they found?
- exists in 1-2% of poulation
- SNP can be found in coding or non coding regions resulting in no alterations, when a diff codon results in same aa
- or diff proteins that could be functional or nonfunctional
- SNP would be important in both coding and non-coding regions and can affect regulation and splicing of the protein
What is an SNP with no functional consequence in the non-coding region?
silent mutation
What is affected if an SNP with a functional consequence in the non-coding region?
splicing or transcription
What is an SNP with a functional consequence in the coding region?
non-synonymous
What nonsynonymous mutation leads to a change in the aa?
missense
What nonsynonymous mutation leads to an early stop codon?
nonsense
What is an SNP with no functional consequence in the coding region?
synonymous
what is a poor metabolizer (PM)?
what are the implications
slow metabolism of a drug results in increased levels of parent drug in bloodstream
- side effects and toxicity
- responds poorly or not at all to drug
what is a intermediate metabolizer (IM)?
what are the implications
metabolism of drug occurs slower than normal
- side effects, mild toxicity
- limited benefit of drug
what is a extensive metabolizer (EM)/normal metabolizer (NM)?
what are the implications
- average expected range of metabolism
- few side effects
- gain benefit of drug
what is a ultrarapid metabolizer (UM)/rapid metabolizer (RM)?
what are the implications
metabolize drugs too quickly for therapeutic effect
- increased risk of adverse drug reactions
- no benefit from drug
