PGX FINAL EXAM QUESTIONS WITH CORRECT ANSWERS
What is a haplotype? - CORRECT ANSWER✅✅-Abstraction of base pair level data (neurotransmitters)
-Need to extract the patterns from that sequence that correspond to a clinical phenotype which
condenses the base pair level data that can guide clinical care
-clusters of alleles inherited together (linkage disequilibrium)
Relate the concept of abstraction to pharmacogenomics haplotypes - CORRECT ANSWER✅✅-
Abstraction is making something simpler
-Can carry the consequence of losing data, but enables results to flow from world to world
-Abstraction is a key part of scientific communication
What is PharmVar? - CORRECT ANSWER✅✅-Originally the "Human Cytochrome P450 (CYP) Allele
Nomenclature Database" -- transitioned in 2017
-*1 is the reference, wild-type gene that functions NORMALLY; baseline allele so it is absent of variants
-Government funded
What is the purpose of PharmVar? - CORRECT ANSWER✅✅serve as a repository for pharmacogene
haplotype definitions, but it DOES NOT contain information for all pharmacogenes
What is HLA Nomenclature? - CORRECT ANSWER✅✅-MHC locus genes are incredibly diverse and
complicated
-Cannot be defined the same as simpler pharmacogene haplotypes
-Requires LONG RANGE SEQUENCING, primer based sequencing, other methods
-Uses a similar star allele nomenclature, but actually much more complicated
-Ex: Stevens johnson syndrome (carbamazepine, allopurinol, abacavir)
What is PharmGKB? - CORRECT ANSWER✅✅-Has haplotype curation, but tightly connected to
PharmVar
-Clinical annotations for genes, haplotypes, and drugs
,What is the main benefit/difference between PharmGKB and PharmVar or HLA Nomenclature
examples? - CORRECT ANSWER✅✅Connections to prescribing information (guidelines)
List the steps for generating and interpreting pharmacogenomics data from genotyping to assignment of
phenotype - CORRECT ANSWER✅✅1. Decide what haplotypes you need to test for.
-Population frequency, phenotype, evidence supporting haplotype, technology availability.
2. Perform genetic testing (or collect existing data if available).
-Methodology agnostic, so long as it is accurate enough to pass clinical muster.
3. Translate!
-Easiest with a 'translation table,' though for 1:1 haplotypes might not be necessary
What is SpartanRX? - CORRECT ANSWER✅✅-A point of care genetic test, doesn't take special training
to do, 4 minutes of hands on time, run time <60 minutes
-Has been proven to work and has been validated.
-It tests for: *1, *2, *3, *17
-Testing these covers the majority of the population, *4 isn't super rare but it isn't popular either.
Probably not practical to test for *4.
What population is Sickle Cell Anemia most prominent in? - CORRECT ANSWER✅✅African Americans
What type of inheritance trait does Sickle Cell Anemia have? - CORRECT ANSWER✅✅Autosomal
recessive
Explain the Sickle Cell Anemia mutant. - CORRECT ANSWER✅✅-A SNP in beta subunit of hemoglobin
leads to sickle shaped red blood cells
-Two copies of the SNP will lead to having the disease
-One Copy will lead to being a carrier
-A -> T substitution (aspartic acid -> valine) = altered protein folding
, What is sickle cell crisis? - CORRECT ANSWER✅✅Accumulation of sickle cells in vessels leads to
vasocclusion resulting in severe pain
What is splenic sequestration crisis? - CORRECT ANSWER✅✅Massive enlargement of spleen, trapping
of sickled RBCs leads to worsened anemia and infections
What is aplastic crisis? - CORRECT ANSWER✅✅Decreased RBC count and severe anemia; often
precipitated by infections
What are chronic sx of Sickle Cell Anemia? - CORRECT ANSWER✅✅-Severe acute or chronic pain
-Recurrent infections
-Enlarged spleen
-Acute chest syndrome
-Pulmonary hypertension
-Stroke
-Multiple organ failure
What is the treatment for Sickle Cell Anemia? - CORRECT ANSWER✅✅-No curative treatment
-Symptomatic pain relief
-Stroke prevention
-Infection prevention
-Chronic transfusions
Explain the concept of gene induction as a treatment option for sickle cell anemia. - CORRECT
ANSWER✅✅-Induction of fetal hemoglobin gene leads to production of γ subunit rather than the
mutant β subunit
-Leads to better oxygenation and lesser symptoms
What is a haplotype? - CORRECT ANSWER✅✅-Abstraction of base pair level data (neurotransmitters)
-Need to extract the patterns from that sequence that correspond to a clinical phenotype which
condenses the base pair level data that can guide clinical care
-clusters of alleles inherited together (linkage disequilibrium)
Relate the concept of abstraction to pharmacogenomics haplotypes - CORRECT ANSWER✅✅-
Abstraction is making something simpler
-Can carry the consequence of losing data, but enables results to flow from world to world
-Abstraction is a key part of scientific communication
What is PharmVar? - CORRECT ANSWER✅✅-Originally the "Human Cytochrome P450 (CYP) Allele
Nomenclature Database" -- transitioned in 2017
-*1 is the reference, wild-type gene that functions NORMALLY; baseline allele so it is absent of variants
-Government funded
What is the purpose of PharmVar? - CORRECT ANSWER✅✅serve as a repository for pharmacogene
haplotype definitions, but it DOES NOT contain information for all pharmacogenes
What is HLA Nomenclature? - CORRECT ANSWER✅✅-MHC locus genes are incredibly diverse and
complicated
-Cannot be defined the same as simpler pharmacogene haplotypes
-Requires LONG RANGE SEQUENCING, primer based sequencing, other methods
-Uses a similar star allele nomenclature, but actually much more complicated
-Ex: Stevens johnson syndrome (carbamazepine, allopurinol, abacavir)
What is PharmGKB? - CORRECT ANSWER✅✅-Has haplotype curation, but tightly connected to
PharmVar
-Clinical annotations for genes, haplotypes, and drugs
,What is the main benefit/difference between PharmGKB and PharmVar or HLA Nomenclature
examples? - CORRECT ANSWER✅✅Connections to prescribing information (guidelines)
List the steps for generating and interpreting pharmacogenomics data from genotyping to assignment of
phenotype - CORRECT ANSWER✅✅1. Decide what haplotypes you need to test for.
-Population frequency, phenotype, evidence supporting haplotype, technology availability.
2. Perform genetic testing (or collect existing data if available).
-Methodology agnostic, so long as it is accurate enough to pass clinical muster.
3. Translate!
-Easiest with a 'translation table,' though for 1:1 haplotypes might not be necessary
What is SpartanRX? - CORRECT ANSWER✅✅-A point of care genetic test, doesn't take special training
to do, 4 minutes of hands on time, run time <60 minutes
-Has been proven to work and has been validated.
-It tests for: *1, *2, *3, *17
-Testing these covers the majority of the population, *4 isn't super rare but it isn't popular either.
Probably not practical to test for *4.
What population is Sickle Cell Anemia most prominent in? - CORRECT ANSWER✅✅African Americans
What type of inheritance trait does Sickle Cell Anemia have? - CORRECT ANSWER✅✅Autosomal
recessive
Explain the Sickle Cell Anemia mutant. - CORRECT ANSWER✅✅-A SNP in beta subunit of hemoglobin
leads to sickle shaped red blood cells
-Two copies of the SNP will lead to having the disease
-One Copy will lead to being a carrier
-A -> T substitution (aspartic acid -> valine) = altered protein folding
, What is sickle cell crisis? - CORRECT ANSWER✅✅Accumulation of sickle cells in vessels leads to
vasocclusion resulting in severe pain
What is splenic sequestration crisis? - CORRECT ANSWER✅✅Massive enlargement of spleen, trapping
of sickled RBCs leads to worsened anemia and infections
What is aplastic crisis? - CORRECT ANSWER✅✅Decreased RBC count and severe anemia; often
precipitated by infections
What are chronic sx of Sickle Cell Anemia? - CORRECT ANSWER✅✅-Severe acute or chronic pain
-Recurrent infections
-Enlarged spleen
-Acute chest syndrome
-Pulmonary hypertension
-Stroke
-Multiple organ failure
What is the treatment for Sickle Cell Anemia? - CORRECT ANSWER✅✅-No curative treatment
-Symptomatic pain relief
-Stroke prevention
-Infection prevention
-Chronic transfusions
Explain the concept of gene induction as a treatment option for sickle cell anemia. - CORRECT
ANSWER✅✅-Induction of fetal hemoglobin gene leads to production of γ subunit rather than the
mutant β subunit
-Leads to better oxygenation and lesser symptoms
