Genetics of complex disorders Flashcards
What are Mendelian traits?
Controlled by a single gene
e.g. earlobe attachment, ABO blood group
What are complex traits?
Controlled by multiple gene + environment
e.g. hair, skin, height, weight
Give some examples of Mendelian diseases
Haemophilia
Sickle Cell Anaemia
Cystic Fibrosis
Thalassaemia
Give some example of complex diseases
Diabetes
Cancer
Asthma
Mental Health Disease
What are Single Nucleotide Polymorphisms?
DNA sequence variations that occur when a single nucleotide is changed
Most common form of variation in the human genome
What are genome-wide association studies?
Agnostic search Concept of multiple testing Needs large sample size Robust findings Aims to recognise SNPs
What is the additive model?
Adding a risk allele results in a trend
Increases or decreases risk of disease
What are the main features of CVD?
Stenosis Atherosclerosis Coronary artery disease Myocardial infarction Heart failure Stroke Diseases of peripheral vessels
What are risk factors of CVD?
Obesity
Type 2 diabetes
High cholesterol
High blood pressure
How can genetics be used in the treatment of complex diseases e.g. CVD?
Understand biology
Ability to predict
Identify high risk groups
Identify preventative strategies in high risk groups
What is GRS?
Genetic Risk Score
What is missing heritability?
Huge gap between what is know about the heritability of the disease and what is found by GWAs
What are some reasons for missing heritability?
Rare variants we cannot find in GWAs due to limits of sample size
Low frequency variants with immediate effects
Interactions
Miscalculated estimation of heritability
What is pharmacogenetics?
The study of variability in drug response due genetic differences
What are the benefits of pharmacogenetics?
Improve drug therapy and prescribing in the future
