Exam 1 Flashcards
Interpreting P Values:
if P > 0.1
no significant association
Interpreting P Values:
if 0.05 < P < 0.1
marginal association
Interpreting P Values:
if P < 0.05
significant association
Interpreting P Values:
if P < 0.01
very significant association
Interpreting Odds Ratio
if OR = 1
no association
Interpreting Odds Ratio
if OR > 1
potential increasing risk
Interpreting Odds Ratio
if OR < 1
potential decreasing risk
Interpreting 95% CI:
if CI is greater than 1
significant risk effect
Interpreting 95% CI:
if CI contains 1
no statistical significance
Interpreting 95% CI:
if CI is less than 1
significant protective effect
what can be used to correct for false positives with SNPs?
Bonferroni Correction
what is the bonferroni correction?
corrected p value = 0.05 / n
n = total number of SNPs
what is IEM
inherited Erythromelalgia – “man on fire” disease
IEM happens because?
Gain of function mutations of Nav1.7
what drug was found to have usefulness for pts with IEM/Nav1.7-V400M mutation
CBZ (carbamazepine)
_________ normalizes activation of Nav1.7-S241T & reverses hyper-excitability
carbamazepine
what is CYP2D6s clinical relevance
many relevant drugs (codeine, carvedilol, tramadol, fluoxetine, metoprolol, tamoxifen, hydrocodone, nortriptyline)
extreme variability in enzyme activity
If a pt is an ultra rapid metabolizer — what is the effect on prodrugs that relate to that gene
actually have increased toxicity risk (because it is being converted so fast to active drug)
clinical relevane of CYP2C9
s-warfarin; phenytoin; glipizide
CYP2C19 clinical relevance **
clopidogrel!!!
PPIs
Antidepressants
clinical relevance of CYP3A5
tancrolimus
need higher doses of it if CYP3A5 is expressed
what is glucuronidation
conjugation of glucose at a functional group
why is UGT1A1 important
bilirubin, sex-steroid hormones,and bile acid
why is it important to replicate GWAS?
one set of a population is not always indicative of the whole population…. need bigger samples…
GWAS can find _______ not _______
find correlation
not cause/effect
what is the null hypothesis
NO ASSOCIATION b/w two things
rejecting null happens when something is statistically significant
For IEM pts, CBZ can cause a ______ shift to the curve
right shift
what is CBZ normally used for?
normally for seizures, it is a non-selective sodium channel blocker
what are MEA’s used for?
MEA = Multi Electrode Array
they are used for extracellular recording of neuronal firing
CBZ tx in pts with the ______ mutation led a switch form chronic pain to acute pain
S241T
how where they able to measure “pain in a dish” for IEM
they took iPSCs (pluripotent stem cells) from IEM pts, treated with CBZ and saw sensory like neurons did not fire like normal (aka without CBZ)
which CYP affects warfarin
CYP2C9
which CYP affects Codeine
CYP2D6
which CYP affects Clopidogrel
CYP2C19
which CYP affects Simvastatin
CYP3A5
which CYP affects Tacrolimus
CYP3A5
which mutation affects Azathioprine/6-mercaptopurine
TPMT mutation
those drugs are substrates to TPMT
which mutation affects Isoniazid (an abx)
NAT (N-acetyltransferase)
which mutation affects Sulfonamides
NAT (N-acetyltransferase)
if pt is a slow acetylator..
which mutation can affect simvastatin
NOT CYP tho
SLCO1B1
which mutation can affect Methotrexate
SLCO1B1
what genes are related to P-GP
MDR1
and
ABCB1
what mutation can affect metformin
OCT1
if an ACE-induced cough occurs what gene/gene product may be altered
Bradykinin B2 receptor
if there is a gene alteration in Estrogen Receptor - alpha what may the effect be
increase in BMD (bone mineral density)
increase in HDL
if there is a gene alteration in Arachidonate 5-lipoxygenase what may the effect be
improvement in FEV1 (the lipoxygenase is related to leukotriene inhibitors - aka monteleukast drug)
what are the most common Adrenergic Beta 1 GPCR variants
Ser49Gly
and
Arg389Gly
what are the most common Adrenergic Beta 2 GPCR variants
Gly16Arg
and
Gln27Glu
the ADRB2 GPCR is located on chromosome _____ and is closely associated with ______
5;
asthma
the ____ allele is associated with a more severe asthma phenotype
Gly16
2 Main VKORC1 variants that matter
1639G>A
and
1173C>T
how many h bonds b/w A and T in DNA
2 bonds
how many h bonds b/w C and G in DNA
3 bonds
how many DNA base pairs are there (in the human genome)
3 billion
about how many genes are there in the human genome
20,000
exons vs introns
which is coding and which is noncoding
coding: exons
non-coding: introns
definition of locus
unique position of a nucleotide in the reference genome
Chromatin vs Chromosome:
unwound DNA - accessible for transcription
chromatin
Humans have _____ chromosomes
or _____ pairs of autosome
46 chromsomes
22 pairs
what is the start codon in mRNA
AUG
how many codons are there
64
how many amino acids are there
20
definition of haplotypes
inheritance of a cluster of single nucleotide polymorphisms (SNPs)
definition of Non-Synonymous SNP
changing the AMINO ACID in the protein
definition of Synonymous SNP
does not change amino acid in protein (prob not changing function of the gene)
what are the types of Non-Synonymous SNPs
missense and nonsense
what is Missense SNP
replacing an amino acid
what is Nonsense SNP
amino acid changes to stop codon
CYP2C19: pt is an ultra rapid metabolizer if their genotype is…?
1/17
or
17/17
CYP2C19: pt is an normal metabolizer if their genotype is…?
1/1
CYP2C19: pt is a poor metabolizer if their genotype is…?
*2/*2 or *2/*3 or *3/*3
what is LD
linkage disequilibrium
NON-random assoc. at different loci on the SAME chromosome
how to measure LD
R^2 – measuring correlation b/w two variables
Measuring LD:
if R^2 = 0 ?
NO LD
Measuring LD:
if R^2 = 1
complete LD/Perfect LD
Measuring LD:
what R^2 values show strong LD?
R^2 > 0.8
Goal of HapMap
to identify sequence variations in various populations
Rank VKORC1: 1639 Genotypes
which one can have a normal/higher dose vs which ones need a lower one
GG - normal/higher
GA - need normal/medium dose
AA - need lower dose
what CYP2C9 frequencies need lower warfarin doses
and which ones can do the normal starting dose
normal: 1/1 or 1/2
more *2 and *3 = need lower doses
which population (race) is more likely to have the VKORC1: 1639G>A variant
Asians
white second
which population (race) is more likely to have the CYP2C9 variations (*2 or *3)
white ppl
