Complex disease and Pharmogenetics Flashcards
what is the mendelian trait?
- Controlled by single gene
- Inheritance follows Mendel’s principles
- E.G. earlobe attachment and ABO blood group
What is a complex trait?
- Controlled by multiple gene + the effect of environment
- Hair, skin, eye colour
- Height, weight
- Personality
What is an examples of a mendelian/monogenic disease?
E.G of mendelian/monogenic disease Haemophilia Sickle cell anaemia Cystic Fibrosis Thalassaemia
What is an example complex disease?
Diabetes, Cardiovascular Disease, Cancer, Asthma, Hypertension, Mental Health Diseases, etc
What are SNPs?
-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
What are genome-wide associate studies?
- 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
What is the human genome?
Human genome: 3 billion base pairs (nucleotides)
What are the statistics of cardiovascular disease (CVD)?
- Leading cause of mortality
- 17 million annual deaths worldwide
- 30% of global mortality
- Estimated to keep rising
What is CVD?
- Stenosis and blockage of blood vessels (Atherosclerosis)
- Coronary artery disease
- Myocardial infarction
- Heart failure
- Stroke
- Diseases of peripheral vessels
What are high risk conditions?
Obesity
Type 2 Diabetes
High cholesterol
High blood pressure
What is CVD?
Multifactorial
How can you help CVD?
- Understand biology of CVD
- Ability to predict CVD
- Identify high risk groups
- Intensify preventive strategies in high risk groups
What is heritability?
How much of our phenotypic differences is due to genetics
What is the case with monozygotic twins?
100% shared genetic components
What is the case with Dizygotic twins?
50% shared genetic component
What are GWAs?
- GWAs help identification of many genetic loci
- There is still a huge gap between what is known about the heritability of the disease and what is found by GWAs.
- e.g. if a phenotype has a known heritability of 40%, the GWAs loci for that phenotype may be less than 5-10%.
- This is a so-called missing heritability
What are reasons suggested for missing heritability?
- Rare variants
- Low frequency variants with intermediate effect
- Interactions
- Miscalculated estimation of heritability
- Diagnosis (accuracy and precision)
What is missing heritability?
Difference between heritability (reins) and heritability from GWAs
What are pharmacogenetics?
- 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
What is personalised medicine?
Tailoring treatment to patients depending on specific characteristics of their disease
