Genetics Of Common Diseases Flashcards
What are monogenic diseases?
- Environment not essential
- Single gene
- Rare (<0.1%)
- Clear inheritance patterns: Mendelian
What are the features of a common genetic disease?
- Environment plays a part (Complex)
- Many genes involved (Polygenic)
- Common
- No clear inheritance pattern
What is a complex genetic disease?
- A disease in which both genetic and environmental factors play a part
- Can be called polygenic or multi factorial diseases
- Complex genetic diseases are much more common than Mendelian monogenic diseases
What are some type of complex diseases?
- Stroke
- Schizophrenia
- Type 2 diabetes
- Hypertension
- Depression
- Asthma
What is not a complex disease?
Purely genetic such as:
Duchenne Mascular Dystrophy, Phenylketonuria, Down’s syndrome
Purely environmental such as:
Poisoning, Mesothelioma, Car accidents
How do we tell if a disease is genetic?
Using twin studies
- Compare the frequency of identical twins having the same disease with that in non identical twins
- Frequency is called the concordance rate
- If higher in identical twins, there is a genetic effect
- If the same, there is an environmental effect
Briefly describe the most expensive twin study
- One twin pair
- One went into space and the other stayed on earth for a year
- Cost $1.5 mil
- Large number of traits analysed and compared
What was the results from The most expensive twin study?
- Differences in a few gene expression levels
- Increased DNA damage
- Increased shorter telomeres
- Some cognitive attenuation in the space twin
What are some problems with twin studies?
- Main criticism is the fundamental assumptions of twin studies are not true
- Twins are not 100% genetically identical
- MZ twins may have more similar environment than DZ
- Twins may not be representative of the population
- Twin registries may have recruitment bias
Describe what genetic association is
- Genetic association is the presence of an allele at a higher frequency in unrelated subjects with a particular disease compared to those that do not have the disease
- Association occurs over much shorter distances compared to linkage, typically <100kb compared to >10 Mb
What is Linkage disequilibrium?
- Underlies Genetic association
- A genetic marker allele that is physically close on the same chromosome to a disease causing allele is more likely to be inherited with it than one that is a long distance away
- Such an allele is genetically associated with the disease
What is Linkage disequilibrium? (PART 2)
- In a population-based study only marker alleles that are very close will be detected as associated
- This is because recombination will occur in lots of different places in all of the different people in the study
What are the requirements for a case control genetic study?
- Large numbers of well defined cases and controls (10,000)
- Equal numbers of matched controls
- Reliable genotyping technology (SNP microarrays/WGS)
- Standard statistical analysis (PLINK)
- Positive associations should be replicated
How should Genome wide association studies be designed?
Recruit large numbers -> Genotype many SNPs -> Plot significance of association against genome location
How should you plot GWAS results?
- GWAS result is a Manhattan plot
- X axis is position of the SNP on the chromosome
- Each chromosome is a different colour to adjacent ones
- Y axis is -log 10 (P value from chi squared test)
- If p=10-9 then –log10(p-value)=9
