Complex disease and pharmacogenetics Flashcards
What is a monogenic genetic condition?
Clear mendelian inheritance pattern, caused by an individual gene with limited environmental influence
What is a complex genetic condition defined as?
There is genetic predisposition but no clear inheritance pattern; phenotype is determined by the interaction of many genes and the environment
What is heritability? How is it measured?
Estimate of the genetic contribution to increased risk of disease
Measured by:
- twin studies
- genome wide association studies
What are twin studies?
Taking both dizygotic twins and monozygotic twins and seeing how different they are despite similar genetic makeup
Dizygotic twins
Dizygotic - Share 50% of their genetic component (variation will be due to genes + environment)
Monozygotic - Share 100% of their genetic component
(variation will be due to environment)
What is GWAS?
What are SNPs?
Genome wide association study - Involves scanning the genomes from many different people and looking for an association between specific genetic variations and particular diseases.
Single Nucleotide Polymorphisms (SNPs):
DNA sequence variations that occur when a single nucleotide is changed.
GWAS look for shared SNPs - to see whether there are susceptibility genes for complex disorders
What is missing heritability and what are the reasons for this?
Gap between what is known about the heritability of the disease and what is found by GWAS
Can be caused by:
- rare variants (SNPs)
- low frequency variants with intermediate effect
- interactions
- miscalculated estimation of heritability
- accuracy and precision of diagnosis
What is meant by a Mendelian trait?
A trait controlled by a single gene
Their inheritance follows Mendel's principle
How are SNPs studied to figure out the susceptibility for a complex disorder?
Single nucleotide polymorphisms
Association study is done
- recruit two groups of individuals, one with disease and one without
- look at variation of SNPs in each group as groups will have specific SNPs
- determine which of those groups the disease has occurred in more frequently in
What is pharmacogenetics?
the study of variability in drug response due to genetic differences.
Variations in enzymes that affect drug metabolism- (CYP450 enzymes: particularly CYP2C9, CYP2C19, and CYP2D6)
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 genes that increase efficacy and decrease the adverse effects
What is meant by personalised medicine?
Tailoring treatment to patients depending on specific characteristics of their disease
