Genetics - Complex Diseases and Pharmacogenetics Flashcards
What are Mendelian traits?
traits controlled by a single gene (monogenic), and follow a Mendelian pattern of inheritance.
What is an example of a mendelian trait?
ABO blood groups, ear lobe attachment
What is the best way to study mendelian traits?
Family studies, using pedigrees and charts.
What are complex traits?
Traits controlled by multiple genes and the environment
What is an example of complex traits?
Height
Weight
Skin colour
What is the best way to study complex traits?
Collect samples of diseases individuals or with a specific phenotype and compressive them with people who don’t express the phenotype.
What are SNPs?
Single Nucleotide Polymorphisms - when a single nucleotide is changed in a DNA sequence.
What are the most common variations from in the human genome?
SNPs
How many base pairs are in the human genome?
3 billion roughly
What is an example of a large genome study?
Human Genome Project
What are GWAS?
Genome Wide Association Studies - we stratify the population into all of the SNPS
How do GWAS occur?
- We collect samples form the population
- We then see their genotypes and look at all of the SNPs
- we do association analysis for all the SNPs across the genome for the trait of interest.
- This allows us to find the risk allele- the alley that is found most commonly in those expressing the trait of interest.
How is a chance of false positiveness introduced in GWAS?
High number of SNPs possible and high number of tests conducted
How do we adjust for GWAS false positiveness?
Multiple testing correction
How do we gain robust finding for GWAS?
Large number of tests
Describe a Manhattan plot.
X axis: genotypes
Y axis: p value
What is cardiovascular disease?
Complex trait, includes heart failure, myocardial infarction, stroke, peripheral blood vessel disease.
What increases the risk of CVD (modifiable)?
Obesity
T2 diabetes
High cholesterol
High blood pressure
What increases the risk of CVD (non-modifiable)?
Age
Sex
Ethnicity
Family history
What is heritability?
How much of our phenotype is due to genetics
What are monozygotic twins?
Twins who share 100% of their DNA
What are dizygotic twins?
Twins who share 50% of their DNA
If we were to compare height between MZ and DZ twins, what would we observe?
We would see that the correlation (r) for MZ is twice the value for DZ.
What is the calculation for broad sense heritability?
H^2 = 2(rMz - rDz)
What can broad sense heritability of 86% for height tell us?
86% of the trait is accounted for by genetics rather than the environment
What is missing heritability?
The gap found between heritability form GWAS, and heritability from broad sense heritability
What are the reasons for missing heritability?
Rare variants (SNPs) Low frequent with intermediate effects Interactions Miscalculation Diagnosis
How do low frequency variants with intermediate effects, account for missing heritability?
We don’t include them in heritability calculations
How do interactions account for missing heritability?
We don’t consider interaction with environment or other genes.
How do miscalculations account for missing heritability?
We may simply miscalculate
How does diagnosis account for missing heritability?
Diagnostic procedures from a trait may have low accuracy or precision
What is pharmacogenetics?
The study of variability in drug responses due to genetic differences
What is the significance of pharmacogenetics?
Important for improving drug therapy and prescribing in the future
How may a gene intervention with drug interaction?
May intervene with very first interaction of drug and also when the drug interacts with target organs - the gene may have an effect on target receptors
How may genes intervene with drug metabolism?
Gene may increase metabolism (produce no effect as drug cleared quickly) or slow down metabolism (induce large effect of drug as it stay in body for longer).
What is personalised medicine?
Tailoring treatment to patients depending on specific characteristics of their disease
