Complex disease and Pharmogenetics

Question 1

what is the mendelian trait?

Answer 1

• Controlled by single gene
• Inheritance follows Mendel’s principles
• E.G. earlobe attachment and ABO blood group

Question 2

What is a complex trait?

Answer 2

• Controlled by multiple gene + the effect of environment
• Hair, skin, eye colour
• Height, weight
• Personality

Question 3

What is an examples of a mendelian/monogenic disease?

Answer 3

E.G of mendelian/monogenic disease 
Haemophilia
Sickle cell anaemia 
Cystic Fibrosis
Thalassaemia

Question 4

What is an example complex disease?

Answer 4

Diabetes, Cardiovascular Disease, Cancer, Asthma, Hypertension, Mental Health Diseases, etc

Question 5

What are SNPs?

Answer 5

-Single nucleotide polymorphisms
-SNPs – DNA sequence variations that occur when a single nucleotide is changed
Alleles at this SNP are “G” and “T”
-SNPs are the most common form of variation in the human genome

Question 6

What are genome-wide associate studies?

Answer 6

• Agnostic search (False Positiveness)
• Concept of multiple testing
• Needs large sample size
• Robust findings
• Over 10,000,000 SNPs in the genome recognised so far

Question 7

What is the human genome?

Answer 7

Human genome: 3 billion base pairs (nucleotides)

Question 8

What are the statistics of cardiovascular disease (CVD)?

Answer 8

• Leading cause of mortality
• 17 million annual deaths worldwide
• 30% of global mortality
• Estimated to keep rising

Question 9

What is CVD?

Answer 9

• Stenosis and blockage of blood vessels (Atherosclerosis)
• Coronary artery disease
• Myocardial infarction
• Heart failure
• Stroke
• Diseases of peripheral vessels

Question 10

What are high risk conditions?

Answer 10

Obesity
Type 2 Diabetes
High cholesterol
High blood pressure

Question 11

What is CVD?

Answer 11

Multifactorial

Question 12

How can you help CVD?

Answer 12

1. Understand biology of CVD
2. Ability to predict CVD
3. Identify high risk groups
4. Intensify preventive strategies in high risk groups

Question 13

What is heritability?

Answer 13

How much of our phenotypic differences is due to genetics

Question 14

What is the case with monozygotic twins?

Answer 14

100% shared genetic components

Question 15

What is the case with Dizygotic twins?

Answer 15

50% shared genetic component

Question 16

What are GWAs?

Answer 16

1. GWAs help identification of many genetic loci
2. There is still a huge gap between what is known about the heritability of the disease and what is found by GWAs.
3. e.g. if a phenotype has a known heritability of 40%, the GWAs loci for that phenotype may be less than 5-10%.
4. This is a so-called missing heritability

Question 17

What are reasons suggested for missing heritability?

Answer 17

• Rare variants
• Low frequency variants with intermediate effect
• Interactions
• Miscalculated estimation of heritability
• Diagnosis (accuracy and precision)

Question 18

What is missing heritability?

Answer 18

Difference between heritability (reins) and heritability from GWAs

Question 19

What are pharmacogenetics?

Answer 19

• The study of variability in drug response due to genetic differences
• Improve drug therapy and prescribing in the future
• Balance out high effect and low side effect

Question 20

What is personalised medicine?

Answer 20

Tailoring treatment to patients depending on specific characteristics of their disease