Lecture #4

Question 1

Ultrarapid metabolizer

Answer 1

normal or increased activity:
an individual carrying two increased activity alleles, or one functional allele plus one increased-activity allele

Question 2

Extensive metabolizer

Answer 2

homozygous wild-type or normal activity: an individual carrying two functional alleles

Question 3

Intermediate metabolizer

Answer 3

heterozygote or intermediate activity: an individual carrying one functional allele plus one loss-of-function allele or one loss-of-function allele plus one increased-activity allele

Question 4

Poor metabolizer

Answer 4

homozygous variant, mutant, low, or deficient activity: an individual carrying two loss-of-function alleles

Question 5

A genetic variant can change PK

Answer 5

alters the enzymatic acitivty during drug ADME; directly leads to inter-pateint difference in drug concentration, duration, dose; as a consequence, leading to inter-patient difference in toxicity profiling and efficacy

Question 6

A genetic variant can change PD

Answer 6

alters the drug target activity/property; creates new drug target; alters the structure of protein; change drug-receptor binding; directly leads to inter-patient difference in drug toxicity and efficacy

Question 7

Minor allele freqeuncy: allele frequency based on observed genotype data

Answer 7

for a population of N individuals with:
Q = # of persons with T/T
R = # of persons with T/C
S = # of persons with C/C
we have:
# of T allele = 2Q+R, then T allele% = (2Q+R)/2N
# of C allele = 2S+R, then C allele% = (2S+R)/2N
N = Q+R+S

Question 8

Allele% =

Answer 8

homozygote% + 1/2heteroxygote%

Question 9

Common and rare allele

Answer 9

allele frequencies usually stay stable in a population: common/major/reference allele - the one with higher frequency > 50%; rare/minor/mutant allele - the one with lower frequency < 50%
terms commonly used: minor allele frequency, rare allele, frequency, a rare allele in one population can be a common allele in another population

Question 10

Haplotype

Answer 10

a haplotype is a group of genes within an organism that were inherited together from a single parent
also refer to the inheritance of a cluster of sinlge nucleotide polymorphisms (SNPs), which are variations at single positions in the DNA sequence among individuals

Question 11

Linkage disequilibrium

Answer 11

LD: non-random association of alleles at different loci on the same chromosome
when there are infinite recombination: no LD
when there is no recombination: complete/perfect LD
when recombination occurs in a portion of chromosomes: incomplete LD

Question 12

Measures of LD

Answer 12

R^2: how strong is the correlation between two variables
R^2 measures the extent of correlation between a pair of variables or the extent of concordance in genotypic associations between loci
varies between 0 and 1; measures the strength of LD

Question 13

R^2 = 0

Answer 13

no LD

Question 14

R^2 = 1

Answer 14

complete LD/perfect LD

Question 15

R^2 >/= 0.8

Answer 15

strong LD