Lecture 3 Flashcards
Genotype to Phenotype (variations in CYP2C19)
-ultrarapid metabolizer (UM): alleles w inc activity
-extensive metabolizer (EM): alleles w normal activity
-Intermediate metabolizer (IM): allele w reduced and normal activity
-Poor metabolizer (PM): alleles w reduced activity
how genotype determine phenotype
-variant can change PK or PD
genetic variant effect on PK
-alter enzymatic activity during drug ADME*
-inter-patient difference in concentration, dose, etc
-inter-pt difference in toxicity profiling and efficacy
Genetic variant effect on PD
-alter drug target activity
-create new drug target*
-alter protein structure
-change drug-receptor binding
-inter-pt difference in toxicity and efficacy
CYP2C19?
no star
Minor Allele Frequency (MAF) *
-
Genotype
-combination of alleles read in PGx testing
Genotype Frequency
-2 homologous chromosomes are read at same time
-can only calculate allele freq from population based on number of genotypes observed
Allele freq
-calculated from population based on number of genotypes observed
-for a given population of N individuals, number of homo chromos or alleles is 2N
Allele Frew based on observed genotype data **
-for a population of N individuals w:
-Q number of ppl w T/T
-R # w T/C
-S # w C/C
N = Q+R+S
-number of T allele: 2Q + R
-number of C allele: 2S + R
-divide by 2N for %
Calculate allele Freq practice
-slide 11
How to figure out MAF from known genotype freq *
-allele% = homozygote % + 1/2 heterozygote
-T% = (2Q+R)/2N = (Q/N + R/2N)
-Q/N = freq for T/T
-R/2N = T/C
-S/N = C/C
slide 13 practive ***
slide 13 practice
Common and rare allele *
-allele freq usually stay stable in population
-minor allele freq (MAF)
-Rare allele freq (RAF)
-T>C
-T is common allele, C is rare
Rare allele *
-can be a common allele in another population
Crossover and Recombination
-phenomenon between homologous chromos during meiosis to produce gametes
-important way to exchange genetic info
Recombination
-result of crossover during meiosis that leads to recombinant chromosomes
Haplotype *
-group of genes within organism that were inherited together from a single parent
-refer to inheritance of a cluster of SNPs
The application of haplotype in PGx
-function of gene is combined result of all functional alleles
-C-A-T will have higher enzyme activity (example)
Linkage Disequilibrium (LD) *
-non-random association of alleles at different loci on same chromosome
-no LD when infinite recombination
-complete LD when no recombination
-incomplete LD when recombination occurs in a portion of chromosomes
If the distance between two loci is SHORT enough
-there will be NO recombination in a population
-leads to co-segregation of both loci into next generation = complete linkage
-DNA inherited by segments called haplotype block
If distance between 2 loci is LONG enough
-there will be a large number of recombination in a population
-leads to independent segregation of the two loci into the next generation, a situation same as that 2 loci are located on two different chromosomes
-there is NO linkage between the two loci
-not all loci on the same chromosome are in linkage
-no star
Measures of LD *
-R^2 = how strong the correlation between 2 variables
-R = 0: No LD
-R = 1: complete LD
-R >0.8: strong LD
