Complex Disease And Oharmacogenetics Flashcards
What does heritability help us find
How much of our phenotype differences are due to genetics
Monozygotic share 100% genetic component whereas dizygotic share 50%
What does GWAS help with
identification of many genetic loci
What reasons are there for missing heritability when looking at twin studies vs GWAs?
- Rare variants (SNPs)- because we don’t find them statistically significant in GWAs
- Miscalculated estimation of heritability → either with twin studies or GWAs
- Low frequency variants with intermediate effect- same as above- not included in calculation of heritability
- Interactions → i.e. gene-gene and gene-environment interactions not considered in calculation of heritability
- Diagnosis (accuracy and precision) → could be low accuracy/precision
Mendelian traits
- Controlled by a single gene
- Inheritance follows Mendel’s principles
- Examples are earlobe attachment and ABO blood group
Complex traits
- Controlled by multiple genes and the effect of the environment
- Hair, skin, eye colour, height, weight, personality are all complex traits
How do we study Mendelian/monogenic diseases
- They are rare so we can’t easily study them in a population
- Best way to study them is through studying families by producing pedigrees
- Examples are haemophilia, sickle cell anaemia, cystic fibrosis, thalassaemia
How do we study complex disease
- We collect samples of individuals with disease of interest and compare them to healthy individuals
- ## examples: diabetes, cardiovascular disease, cancer, asthma, hypertension, mental health diseases
SNPs
- Single Nucleotide Polymorphisms are DNA sequence variations that occur when a single nucleotide is changed at a specific point in the genome that is present in a sufficiently large fraction of the population (1%)
- E.g. at a specific base position in human genome, the G nucleotide appears in most people but in a minority there is a T there
- Means there’s a SNP at this position with 2 possible nucleotide variants (alleles) → G or T and genotype GT
- SNPs are most common form of variation in human genome
What are genome wide association studies
- Doing association analysis for the whole genome
- Over 10 mil SNPs in genome recognised so far
- This is an agnostic search so there’s a chance for false positiveness → 5% for each SNP but for over 10 mil SNPs the chance increases so we can find associations by chance- called the multiple testing effect
How are Genome wide assocated studies run
- Collect samples from population, genotype each SNP by computers
- We then see each group to see how many diseased people there are
What are pharmacogeomics
The study of variability in drug response due to genetic differences
Its use is for improving drug therapy and prescribing in the future
IF PATIENTS HAVE DIFFERENT RESPONSES TO A DRUG ITS CUZ OF GENETICS PROBABLY
How can genes affect drug interaction
Genes can affect the drug interactions by controlling things like receptors on the surface of the organ cells so could e.g. obstruct the interaction of the drug with the organ
Personalized medicine
Tailoring treatment to patients depending on specific characteristics of their disease
Activation or inactivation
2 fully activated alleles means ultra rapid metabolism
1 fully activated means extensive metaboliser
1 reduced function means intermediate metaboliser
2 non functional means poor metaboliser
Advantages and disadvantages of GWAS
Can identify SNp associations,identifies at risk individuals,discover biological mechanisms,inform drug discovery,identify ethnic differences
Doesn’t identify casual variants,can’t identify all heritability,won’t identify rare variants,environmental influences
