Complex Disease And Pharmacogenetics Flashcards
(23 cards)
What is meant by a Mendelian trait?
A trait controlled by a single gene
Inheritance follows Mendel’s principles
Phenotype will follow dominant allele
What is meant by a complex trait?
Controlled by multiple genes
Effect of environment also involved in the presentation of complex traits
E.g. hair, skin, eye colour, personality
Is the ABO blood group a Mendelian or Complex trait?
Mendelian
What is the best way to study Mendelian disease?
Family studies - Pedigrees
How can you study Complex diseases?
Collect data from people suffering from the complex disease of interest
Compare their DNA to that of the healthy individuals
What is a Single Nucleotide Polymorphism (SNP)?
DNA sequence variations that occur when a single nucleotide is changed
How do you carry out an association analysis (e.g - for SNP prevalence)?
Stratify population according to genotype and specific SNP (TT, TG, GG)
Look at the number of disease cases in each group
Assess significance using a set p value
Why might there be false positives when looking at over 10,000,000 SNPs?
Larger sample, more of a likelihood that diseases occur purely by chance
How is the issue of false positives accounted for?
- Multiple testing
To correct the effect of false positives, the new P value for a genome wide association study is ~ 5x10^-8
This means that a much larger sample size is required than normal
This allows robust findings
What is meant by a risk allele?
An allele that is more frequently observed in individuals who are suffering from disease
What is the graph used to plot significance of the differences between SNPs called in GWAS?
Manhattan plot
Give some examples of the modifiable factors affecting CVD
Drinking habits Eating habits Smoking High blood pressure Sedentary lifestyle
Give some examples of the non-modifiable factors affecting CVD
Sex
Age
Genetic factors
Why is it important to investigate the genetic factors of complex disease (e.g CVD)
- Understand biology of condition
- Ability to predict condition
- Can identify high risk groups
- Intensify preventative strategies in high risk groups
What is the use of genetic risk scores?
Depending on how many SNPs an individual has, you can determine what percentage each one of those will contribute to that individual having a condition and also the severity (level) of the condition.
What do we mean by the term heritability?
How much of our phenotype differences is due to genetics
Give one way we can compare heritability and describe why this can be done
MZ twins share 100% of DNA
DZ twins share 50% of DNA
Role of genetics can be compared
What is missing heritability?
The gap between the known heritability of a gene and the GWAs loci for that phenotype
Give suggested reasons for missing heritability
Rare variants (SNPs)
Low frequency variants with intermediate effect
Interactions
Miscalculated estimation of heritability
Diagnosis (accuracy and precision)
What is meant by pharmacogenetics and what is its purpose?
Study of variability in drug response due to genetic differences
To improve drug therapy and prescribing in future
How does metabolism affect the effect of a drug?
Increased metabolism = Less effect of drug as it is quickly removed
Reduced metabolism = More effect of drug as it may cause overdose
What is the ideal scenario for a drug to be in and how could studies of genetics help this?
Increased efficacy
Decreased adverse effects
Find susceptibility genes that mean increased efficacy and decreased adverse effects of drugs, meaning that drugs are more tailored to individuals
What is meant by personalised medicine?
Tailoring treatment to patients depending on specific characteristics of their disease
