Complex Traits Flashcards
(38 cards)
What are complex traits?
Coupling genetic factors along with environmental influences
What do association studies include?
transmission disequilibrium testing
case-control association studies
Characteristics of complex diseases
incomplete penetrance
phenocopies
high frequency of disease-causing allele
Relative risk calculation
λ= frequency in relative of affected person/ population frequency
What does a higher λ mean?
The higher the contribution of the genetic component in determining the disease risk
What does an λ of 15 mean?
If you have a sibling that is affected, your risk of being affected is 15x higher
What happens when there is a genetic component involved in disease manifestation?
The liability distribution among siblings of affected individuals shift to the right, signifying an elevated risk for them to develop the disease
Affected sib-pairs method
If the marker locus is linked to trait locus, an excess of shared alleles among affected sib-pairs will be expected
State what affected sib-pair might share and the probabilities
may share 0,1,2 alleles identical by descent with probabilities 0.25, 0.5, 0.25 respectively
What happens if we perform this test for many markers in the genome?
We can identify those that present a distortion in the expected ratio. If the distortion favours the 1 and 2 shared alleles while lowering the % of 0 shared alleles then there might be a linkage between the marker and risk factor
Advantages of affected sib-pairs method
- non parametric analysis eliminates the need for specifying allele frequencies or inheritance patterns
- provides a precise location of the disease gene
- initial insight into the localisation of risk factors on the chromosome
Disadvantages of affected sib-pairs method
- limited power compared to parametric methods
Linkage disequilibrium
The non-random association in a population of alleles at closely linked loci: tendency of alleles that are close on the same chromosome to be co-inherited throughout generations
Why do markers near a risk factor tend to be inherited together?
Because the same chromosome block is maintained across generations due to limited recombination in chromosomal regions
Where does recombination frequency take place?
At specific positions
How is the genome organised?
In specific haplotype blocks conserved throughout generations
What do the red squares show in a linkage disequilibrium map of a chromosome?
1:1 relationship in terms of linkage disequilibrium
The redder the squares the higher the LOD score
What does maximum linkage disequilibrium mean?
2 loci are always segregating
What does it mean when we see a triangle in a linkage disequilibrium map of a chromosome?
All the loci that are underneath are in linkage disequilibrium
What does the transition from one triangle to the next in a linkage disequilibrium map of a chromosome mean?
A hotspot for crossing over event
How many SNPs are required for genome wide association studies?
500,000 non-African SNPs
1,000,000 African SNPs
Why are more African SNPs required?
The African genome is heterogenous: it is more ancient and therefore there was more time to create new recombinations and new haplotype blocks
What is the difference between linkage and association?
Association is a relation between alleles while linkage is a relation between loci.
What is case-control study?
2 populations: one is the case, individuals affected by a specific disease and the other one is control, healthy individuals
