Week 3 : Genetics and Population Health

Question 1

What is deoxyribonucleic acid (DNA) made up of?

Answer 1

• A deoxyribose sugar
• A base

Question 2

List the 4 possible bases.

Answer 2

Adenine - A
Thymine - T
Cytosine - C
Guanine - G

Question 3

What is Mendelian Inheritance?

Answer 3

Refers to certain patterns of how traits are passed from parents to offspring (one gene + environment)

Question 4

What is Complex Inheritance?

Answer 4

Traits that have a genetic component that does not follow strict Mendelian inheritance and may involve the interaction of two or more genes or gene-environment interactions.

Question 5

What is a genetic predisposition?

Answer 5

An increased likelihood of developing a particular
disease based on a person’s genetic makeup.

Question 6

List 2 ways we can detect genetic variants.

Answer 6

• DNA Microarray
• Genetic Sequencing

Question 7

How does DNA Microarraying work?

Answer 7

Sample DNA from blood or saliva is extracted, cut into fragments and analysed on a DNA-microarray chip.

Question 8

What is read depth?

Answer 8

The number of times the genome is read during sequencing.

Question 9

Why are candidate-gene studies not usually successful?

Answer 9

• Small sample sizes
• Inadequate or loose statistical thresholds
• Inefficient number of genetic markers tested

Question 10

What does GWAS mean?

Answer 10

Genome-wide association studies

Question 11

What is the GWAS pipeline?

Answer 11

Large patient sample > Simultaneous genotyping > Statistical analysis

Question 12

How many SNPs are tested during GWAS?

Answer 12

All SNPs

Question 13

What is the issue with GWAS?

Answer 13

Restricting to Europeans limits the generalisability of
findings and may miss genes poorly captured by
European genetic variation.

Question 14

How can genetic data be used in criminal investigations?

Answer 14

• Racial profiling
• Matching DNA from the crime scene

Question 15

What is a polygenic risk score (PRS)?

Answer 15

It’s a score used to estimate an individuals genetic risk/liability for a certain disease or trait.

Question 16

How is PRS calculated?

Answer 16

Based on GWAS results.

Question 17

What is PRS used for?

Answer 17

• Identify shared etiology between phenotypes
• Evaluate clinical utility of genetic data for complex disease
• Stratification of samples.
• Comparing outcome between patients with low/high risk
• Utilise powerful summary statistics from large studies to inform genetic risk profiles in small
  samples

Question 18

Why is knowing underlying genetic risks important?

Answer 18

• Prediction of health
• Personalised treatment
• Improve diagnosis, select optimal treatment, preventative medicine.
• Another piece of the info to add to other data to help decision making in healthcare

Question 19

What does having a polygenic score in the 95th percentile mean?

Answer 19

You do not have a 95% risk of developing the disease, but out of 100 people your
background risk is higher than 95 others.