Complex Disease and Pharmocogenetics

Question 1

What are Mendelian Triat

Answer 1

Controlled by single gene

Inheritance follows Mendel’s principles

Question 2

What is a complex triat

Answer 2

Controlled by multiple gene + the effect of environment

Question 3

What is an example of a mendelian triat

Answer 3

Earlobe attachment

ABO blood group

Question 4

What is an example of a complex trait

Answer 4

Height, skin, eye colour, personality

Question 5

What are mendelian disease

Answer 5

Haemophilia

Sickle cell anaemia

Cystic Fibrosis

Thalassaemia

Question 6

What are examples of complex diseases

Answer 6

Diabetes

Cardiovascular disease

Cancer

Asthma

Hypertension

Mental Health Disease

Compare them with healthy individuals

Question 7

What is the variation in chromosome base sequence between paternal and maternal

Answer 7

1% variation

Called single nucleotide polymorphisms

Question 8

What is single nucleotide polymorphism

Answer 8

Where DNA sequence variations occur when a single nucleotide is changed

Question 9

In 2001 how many base paris were published in the human genome

Answer 9

3 billion base pairs

Question 10

What are genome wide association studies

Answer 10

Stratifying the sample population into different genotype group

10,000,000 SNPs in the genome

Question 11

What are the genome-wide association studies disadvantages

Answer 11

False positive (concept of multiple testing)

Need large sample size

Robust findings

Question 12

How do we perfomr genome wide association studies

Answer 12

Get disease and healthy cases

Perform gene analysis

One by one SNPs - using computer is faster

Question 13

What is a risk allele

Answer 13

Alelle that can put you at risk of a disease

Question 14

Facts about CVD

Answer 14

Leading cause of mortality

17 million annual deaths worldwide

30% of global mortality

Question 15

CVD examples

Answer 15

Myocardial infarction

Heart Failure

Stroke

Disease of the peripheral vessel

Stenosis and blockage of blood vessels (atherosclerosis)

Question 16

High risk conditions that increase risk of CVD

Answer 16

Modifiable - drinking, smoking, high blood pressure, diet, Obesity

Non modifiable - sex, age, genetics Type 2 Diabetes

Question 17

Does high blood pressure relate to genes

Answer 17

Yes

Higher blood pressure leads to CVD, stroke, hypertension

Question 18

How can we understand our phenotype diffferences

Answer 18

Compare MZ and DZ twins

Question 19

What is broad sense heritability

Answer 19

Heritability based on gene studies

Question 20

Formula for heritability estimate

Answer 20

2 (Monozygotic twins - dizygotic twins)

Question 21

What is the case of missing heritability

Answer 21

GWAs help identify many genetic loci

Gap between herabiltiy of disease and GWAs

Question 22

Reasons for msising heritability

Answer 22

Rare variants of SNPs but ignored

Low frequency variants

Interaction of genes and enviornment

Diagnosis (accuracy and precision)

Question 23

What is heritability

Answer 23

Proportion of variation in the population explained by genetics and inheritance rather that environmental factors

Question 24

What is pharmacogenetics

Answer 24

Study of variability in drug repsonse due to genetic differences

Question 25

Genes that affect drug metabolism

Answer 25

CYP2D19

CYP2D6

ABCB1

Question 26

Ways in which gene can affect response of body to drugs

Answer 26

Tissues may have different receptors - obstruction

Genes can exert metabolism of drug

Question 27

What is personalised medicine

Answer 27

Tailoring treatment to patients depending on specific characteristics of their disease