Complex Diseases and Pharmacology Flashcards
How can an AC genotype be formed at a locus?
If we have an A allele at the bottom of the maternal chromosome and C allele at the top of the paternal chromosome, this forms an AC genotype at this locus
What are Mendelian traits?
Controlled by a single gene
Inheritance follows Mendel’s principles
What are complex traits?
Controlled by multiple genes and effect of environment
E.g. hair, skin, eye colour
How do we study mendelian/ monogenic diseases?
Very rare diseases so can’t be easily studied
Best way is to look at families
E.g. CF, Haemophilia
We collect samples from different families and study that
How do we study complex diseases?
Controlled by many genes
We collect samples of individuals with disease in population and compare them to healthy individuals
E.g. Diabetes, CVD, Cancer
How can we find variations in the genome?
Single nucleotide polymorphisms (SNPs) are a DNA sequence variation that occur when a single nucleotide is changed
SNPs are the most common variation in the human genome
Population is stratified according to genotypes and a specific SNP
We than carry out statistical analysis to see if there’s differences in diseases cases in one group compared to another- associated analysis
What are genome wide associated studies?
An association analysis for the whole genome
Needs large sample size
How is a genome wide association study carried out?
Collect samples from population
Each persons genome is surveyed and association analysis is carried out to see if genetic variations are more frequent in those with a disease compared to those without a disease
If there are then there are variant alleles associated with the variant
What is the risk allele?
When we stratify groups based on genotype we have a disease group and a healthy group
Risk allele is an allele that is more frequently observed in individuals suffering from the disease
What is an example of a complex trait?
Cardiovascular disease
High risk conditions increase risk of CVD. includes:
Obesity
T2D
High cholesterol
Some risk factors of CVD are modifiable and some are non-modifiable
For genetic factors we can identify high risk groups
What is heritability?
Study of how much of our phenotype differences are due to genetics
What percentage of genetic components do twins share?
Monozygotic twin share 100% genetic components
Dizygotic twins share 50% genetic components
How do we calculate broad sense heritability?
H^2 = 2 (rMZ - rDZ)
What is missing heritability?
A smaller value for heritability is calculated than expected
GWAs can identify many genetic loci however there still may be a gap between heritability of a disease and what GWAs finds- this is missing heritability
What are reasons for missing heritability?
Rare variants (SNPs)
Low frequency variant with intermediate effect
Interactions (gene-gene and gene-environment)
Miscalculated estimation of heritability
Diagnosis (low accuracy and precision)
