Genetics - Complex Diseases and Pharmacogenetics

Question 1

What are Mendelian traits?

Answer 1

traits controlled by a single gene (monogenic), and follow a Mendelian pattern of inheritance.

Question 2

What is an example of a mendelian trait?

Answer 2

ABO blood groups, ear lobe attachment

Question 3

What is the best way to study mendelian traits?

Answer 3

Family studies, using pedigrees and charts.

Question 4

What are complex traits?

Answer 4

Traits controlled by multiple genes and the environment

Question 5

What is an example of complex traits?

Answer 5

Height
Weight
Skin colour

Question 6

What is the best way to study complex traits?

Answer 6

Collect samples of diseases individuals or with a specific phenotype and compressive them with people who don’t express the phenotype.

Question 7

What are SNPs?

Answer 7

Single Nucleotide Polymorphisms - when a single nucleotide is changed in a DNA sequence.

Question 8

What are the most common variations from in the human genome?

Answer 8

SNPs

Question 9

How many base pairs are in the human genome?

Answer 9

3 billion roughly

Question 10

What is an example of a large genome study?

Answer 10

Human Genome Project

Question 11

What are GWAS?

Answer 11

Genome Wide Association Studies - we stratify the population into all of the SNPS

Question 12

How do GWAS occur?

Answer 12

1. We collect samples form the population
2. We then see their genotypes and look at all of the SNPs
3. we do association analysis for all the SNPs across the genome for the trait of interest.
4. This allows us to find the risk allele- the alley that is found most commonly in those expressing the trait of interest.

Question 13

How is a chance of false positiveness introduced in GWAS?

Answer 13

High number of SNPs possible and high number of tests conducted

Question 14

How do we adjust for GWAS false positiveness?

Answer 14

Multiple testing correction

Question 15

How do we gain robust finding for GWAS?

Answer 15

Large number of tests

Question 16

Describe a Manhattan plot.

Answer 16

X axis: genotypes

Y axis: p value

Question 17

What is cardiovascular disease?

Answer 17

Complex trait, includes heart failure, myocardial infarction, stroke, peripheral blood vessel disease.

Question 18

What increases the risk of CVD (modifiable)?

Answer 18

Obesity
T2 diabetes
High cholesterol
High blood pressure

Question 19

What increases the risk of CVD (non-modifiable)?

Answer 19

Age
Sex
Ethnicity
Family history

Question 20

What is heritability?

Answer 20

How much of our phenotype is due to genetics

Question 21

What are monozygotic twins?

Answer 21

Twins who share 100% of their DNA

Question 22

What are dizygotic twins?

Answer 22

Twins who share 50% of their DNA

Question 23

If we were to compare height between MZ and DZ twins, what would we observe?

Answer 23

We would see that the correlation (r) for MZ is twice the value for DZ.

Question 24

What is the calculation for broad sense heritability?

Answer 24

H^2 = 2(rMz - rDz)

Question 25

What can broad sense heritability of 86% for height tell us?

Answer 25

86% of the trait is accounted for by genetics rather than the environment

Question 26

What is missing heritability?

Answer 26

The gap found between heritability form GWAS, and heritability from broad sense heritability

Question 27

What are the reasons for missing heritability?

Answer 27

``` Rare variants (SNPs) Low frequent with intermediate effects Interactions Miscalculation Diagnosis ```

Question 28

How do low frequency variants with intermediate effects, account for missing heritability?

Answer 28

We don't include them in heritability calculations

Question 29

How do interactions account for missing heritability?

Answer 29

We don't consider interaction with environment or other genes.

Question 30

How do miscalculations account for missing heritability?

Answer 30

We may simply miscalculate

Question 31

How does diagnosis account for missing heritability?

Answer 31

Diagnostic procedures from a trait may have low accuracy or precision

Question 32

What is pharmacogenetics?

Answer 32

The study of variability in drug responses due to genetic differences

Question 33

What is the significance of pharmacogenetics?

Answer 33

Important for improving drug therapy and prescribing in the future

Question 34

How may a gene intervention with drug interaction?

Answer 34

May intervene with very first interaction of drug and also when the drug interacts with target organs - the gene may have an effect on target receptors

Question 35

How may genes intervene with drug metabolism?

Answer 35

Gene may increase metabolism (produce no effect as drug cleared quickly) or slow down metabolism (induce large effect of drug as it stay in body for longer).

Question 36

What is personalised medicine?

Answer 36

Tailoring treatment to patients depending on specific characteristics of their disease