The Genetics of Common Disease Flashcards
What does genetic variation cause?
It leads to phenotypic differences
What are mendelian diseases?
Diseases caused by a mutation in one gene
Give an example of a mendelian disease
Cystic fibrosis - a three base deletion removing the phenylalanine codon
What is the genetic cause of most common traits/diseases?
Most are multi-factorial so many genes may affect the disease/trait.
Examples of multifactorial diseases
Type 2 diabetes
Hypertension
Alzheimers disease
What is heritability?
It is a measure of how well differences in people’s genes account for differences in their traits.
How is heritability calculated?
Using twin studies
If heritability is close to one what does this indicate?
It indicates that almost all of the variability in a trait comes from genetic differences, with very little contribution from environmental factors.
If a trait is has a higher concordance in monozygotic twins, what does this mean?
It means the more of a trait is determined by a genetic contribution rather than environmental like in dizygotic twins
How is heritability of ECG indices estimated?
By looking at the difference in the correlation of monozygotic (MZ) and dizygotic (DZ) twin pairs.
What does a high heritability score mean?
There is a stronger resemblance
What is a SNP?
A single change in a base pair. The most common variation in the human genome .
What are SNPs used to identify and how?
Using GWAS, they are used to identify genes involved in complex diseases.
What is the purpose of a typical GWAS?
- A typical GWAS collects data to find out the common variants in a number of individuals, bot with and without a common trait (e.g. a disease), across the genome, using genome wide SNP arrays.
Simply describe how a SNP microarray works
- Amplify and fragment the target gene
- Hybridise by capturing and labelling when it binds to the array
- Labelled probes bind to sample, differentiating between the two alleles
- Make it bright enough then measure intensity of the array to confirm how many SNPs are present
Why is SNP-SNP association or linkage disequilibrium important?
It is fundamental to our ability to sample the whole genome with relatively few SNPs
Define linkage disequilibrium (LD)
The difference between the observed frequency of the particular combination of alleles at two loci and the frequency expected for random association
What decreases between two SNPs if there is distance?
LD decreases as it is more likely to have a recombination event between them.
Where does the LD vary?
The extent the LD varies depends on the region of the genome
When can strong LDs be beneficial?
It is beneficial as there is fewer SNPs needed to capture variation in a region so cheaper and quicker to analyse
What is the causal variant?
The variant responsible for the association signal at a locus
How is the causal variant identified?
Often the causal variant is not included on the SNP chips so further work is required to narrow down the region of association and identify the causal variant.
When are variants found at a higher frequency?
They are found at a higher frequency in disease/trait cases than in controls.
Why is statistical analysis carried out in GWAS?
To indicate how likely a variant is to be associated with a trait
