Module 2 Flashcards
Ways to estimate mutation rate
Disease incidence, molecular clock, de novo mutations in pedigrees, and mutation accumulation experiments
How to solve for disease incidence (Ө)?
Ө = 4 Ne μ (for neutral mutations)
How to solve for neutral mutation rate?
μ
Drift-Barrier Hypothesis
Selection acts to reduce mutation rates. The majority of mutations is fitness-reducing variation rather than neutral or beneficial. Selection acts on the genome-wide mutation rate
What are types of estimators?
Population, pedigree, and gametes
What drives recombination rate variation?
Need one recombination event per chromosome.
Recombination rates are clearly ‘selectable’.
What are the four principles of coalescence?
The rate of coalescence is inversely proportional to Ne.
Neutral mutations do not change tree shape.
A tree always exists, mutations help you see it.
The shape of the tree dictates deserved variation.
What is the purpose of Tajima’s D?
To summarize an SFS when looking at a genetic tree.
What is Tajima’s D for neutral, growing size?
D < 0
What is Tajima’s D for a neutral population structure?
D > 0
What is Tajima’s D for a neutral constant size?
D = 0
In humans, DFE inference strategies are…
Ignore demography, estimate selection
Take a 2-step approach: Estimate demography in neutral, then fix that to estimate selection. Estimate DFE with fixed demography exonic DFE of fixed mutations
Simultaneously estimate demography and DFE (joint estimation)
Treat DFE as a nuisance parameter, and integrate across all possibilities.
