Class 36

# Class 36 - Gene mapping in humans: Intro to Cancer How many...

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Gene mapping in humans: Intro to Cancer

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How many hours did you spend studying for exam 3? A. Less than 2 hours B. 3-4 hours
I thought exam 3 was: A. Easy B. Medium C. Difficult D. I would prefer not to say

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Probability calculation LOD or z = 0.577 R = 1 NR = 5 denom = 0.156 numerator = 0.059 So log of odds or LOD (z) = = By convention, an odds ratio of 1000/1 is accepted as “proof” that the rate of recombination guessed at is true. So how to get higher LOD scores if you only have six kids? It can be shown mathematically that one can combine LOD scores across families by simple addition. So one must accumulate additional families in which recombination/linkage with the markers tested is occuring
Process of linkage determination in humans Collect as many 3 generation pedigrees with trait as possible For every marker available, determine phase and recombinant fraction in each family Calculate as we have, the LOD score for all values of θ from 0-0.5 Sum over all families and determine what value of θ has max. LOD or z max 5

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Sample plots of LOD vs θ LOD is a function of the recombinant fraction and θ LOD=( θ ) R ( θ ) NR / (0.5) R+NR Curve shows LOD vs. θ LOD max at θ =0.25 - means marker is most likely 25 map units from trait LOD depends on: Observed recombinant fraction in each family DETERMINABLE θ the recomb rate or distance which may vary between 0 - 0.5
Things to know for the test about linkage mapping in humans Low numbers of recombinants per family LOD is log of the odds ratio Odds ratio is a ratio of the probability of observing a particular outcome (i.e. 1 recombinant per 6 kids) given some recombination rate ( θ ) that varies between 0 and 0.5 LOD score is expressed as a function of θ so expressed as LOD 4.0 (or Z max ) at θ =.25 θ is the recombination distance between markers A LOD of >3.0 means linkage at that value of θ - any lower value is not conclusive

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