Complex Diseases And Pharmacogenetics Flashcards
What is the difference between mendelian and complex diseases?
Mendelian - controlled by a single gene
Complex - multiple genes
What is heritability?
The proportion of variation in the population explained by genetics and inheritance rather than environmental factors
How much of our phenotype is due to genetics?
What are Mendelian traits?
Controlled by a single gene
Inheritance follows mendels principles
Eg. ABO blood group and earlobe attachment
What are complex traits?
Controlled by multiple genes
Eg hair, skin and dye colour. Height and a weight, personality
How are Mendelian diseases studied?
Family studies
Uses pedigrees
Eg haemophilia and sickle cell
How are complex diseases studied?
Samples of individuals with the disease are collected, and compared with healthy individuals
Eg. Diabetes, cardiovascular disease, mental health, asthma
What are SNPs?
Single neucleotode polymorphism
Within an individual, the top strand of the maternal chromosome and the top strand of the paternal chromosome are 99% the same
There is 1% variation. This is an SNPs
They are DNA sequence variations that occur when a single nucleotide is change
What is association analysis?
Within a population, some people will have a disease and some will not.
They are sorted by their genotypes (eg. TT, TG, GG)
Than a statistical test is done to see if the difference in phenotypes is significant
What are genome wide association studies?
Like association analysis but across the whole genome
This includes 10000000 SNPs
Agnostic search (false positives). So needs a largeeeeee sample size
But this gives robust findings
How do genome wide association studies work?
Within a population, healthy and diseased individuals are grouped.
Their whole genotype is found
And association analysis is done for each SNP. Technology allows this to be done in a few mins
Results in an Manhattan plot
What is a risk allele?
An allele that is more frequently observed in individuals with a disease
What is cardiovascular disease?
Leading cause of mortality (17 million deaths annually worldwide)
30% of global mortality and rising
Includes: atherosclerosis, Coronary artery disease, myocardial infarction, heart failure
Risk factors include: obesity, type 2 diabetes, high cholesterol, higher blood pressure
What is a multifactoral diseases?
Some risk factors you can change, some you can’t
Modifiable (eg. Drinking smoking diet)
Non modifiable (eg. Age sex genetics)
How can we investigate heritability?
Compare monozygotic and dizygotic twins?
MZ share 100% of genetic component
DZ share 50%
What it the broad sense heritability equation?
H^2 = 2(rmz - rdz)
Twice the difference in the corellation between mono and di zygotic twins
How can we investigate heritability without twins?
Look at the whole population and their genomes. Then calculate how much of this is determined by genetics and how much is determined by environment
Eg. Height with twins is 80%
Height with population is 77%
What is the gap between investigations of heritability using twins and the population called?
Missing heritability
There is still a gap between what is known about the heritability of the disease and what is found by GWAs
May be caused by: rare variants of SNPs, low frequency variants with intermediate effect, interactions, miscalculated estimation, diagnosis
What is pharmacogenetics?
The study of varaiabilty in drug response due to genetic differences
Improves drug therapy and prescribing in the future
What are the possible outcomes after application of medication?
Recovery
No effect
Side effects
Death
What is personalised medicine?
Tailoring treatment to patients depending on the specific characteristics of their disease
