3: Complex disease and pharmacogenetics

Question 1

Mendelian traits

Answer 1

controlled by single gene
phenotype easily identified
disease either present or not - genotype dictates phenotype

Question 2

Complex traits

Answer 2

controlled by multiple genes (polygenetic) + env affects
quantitative traits - weight, height, intelligence, BP
E.G - CVD

Question 3

Heritability is

Answer 3

proportion of variation inn population explained by genetics and inheritance rather than environmental factors

Question 4

Causes of phenotypic differences (3)

Answer 4

genetic differences
shared environment
unique environment

Question 5

What studies are used to investigate heritability

Answer 5

Twin studies -
effect of genetics and environment in relation to conditions
- used to guide treatment

Question 6

Monozygotic twins

Answer 6

100% shared DNA
Identical - same genome, trait represented equally in both twins

Question 7

Dizygotic twins

Answer 7

50% shared DNA
non- identical : share 50% genome

Question 8

Missing heritability hypothesis

Answer 8

not known half of genetic cause of disease

Question 9

Reasons for missing heritability hypothesis

Answer 9

-Rare variants: SNPs such low frequency only small effect
-Low frequency variants with intermediate effect
-Interactions (may need 2+ susceptibility genes to interact)
Miscalculated estimation of heritability
Diagnosis - accuracy and precission

Question 10

SNP is

Answer 10

Single nucleotide polymorphisms

Question 11

What are SNPs

Answer 11

DNA sequence variations that occur when a single nucleotide is changed
Most common variation in the human genome - accounts for majority of polymorphism responsible for human disease

Question 12

GWAS

Answer 12

genome wide association studies

Question 13

How can we use SNPs

Answer 13

Association study used to identify susceptibility genes
looks at prevalence of SNP in two groups with and without disease
human genome - inexpensive and powerful, whole genome encoding

Question 14

Limitations of GWAS

Answer 14

Doesn’t identify casual variants - further testing required
Cant identify all heritability
Thresholds - wont identify rare variants
Environmental influence - epigenetics

Question 15

Benefits of GWAS

Answer 15

identify SNP-variant associations
Identify individuals at risk
discovery of novel biological mechanisms
Inform drug discovery or repurposing
identify ethnic difference

Question 16

Whole genome sequencing

Answer 16

every SNP identified
Clear identification of disease (+risk)
Very long, expensive, time consuming
need to know gene susceptibility - relies on GWAS to determine risk

Question 17

Pharmacogenomics

Answer 17

study of variability in drug response due to genetic differences

Question 18

Use of pharmacogenomics

Answer 18

improve drug therapy and prescribing in future
if genes and their response to treatment known - allows for personalised medicine

Question 19

journey of drug through body

Answer 19

absorption > activation > target (effect) >inactivation >excretion

Question 20

Pharmacokinetics

Answer 20

what the body does to the drug

Question 21

Drug absorption

Answer 21

Majority of drugs administered orally
absorbed in small intestine
by use of specific transporter proteins
(either increase absorption or enhance removal)

Question 22

Drug metabolism

Answer 22

many SNPs identified in drug metabolising enzymes
Some drugs require metabolism to become activated - prodrugs

Question 23

4 drug targets

Answer 23

receptors
enzymes
ion channels
transport proteins