# Determining linkage Flashcards

What are CEPH families?

Uncharacteristically large human families used in several studies to map polymorphisms in the human genome

What are the 4 criteria that had to be met for a family to be a CEPH family?

- 3 generations
- Both sets of grandparents had to be alive
- Both parents had to be alive
- Mean sibship of 8.3

How do we determine linkage in humans?

Count number of recombinants in offspring from parents with informative meiosis

Why is determining linkage so hard in humans?

Can’t control crosses and families are so small, so resolution is low. Need to run statistics to determine if the number of parental and recombinant offspring is different from the expected 50:50 ratio if the loci were unlinked

What do we calculate to determine if two loci are linked or not in humans?

Lod scores

What do Lod scores calculate?

Theta - the recombination frequency

What Lod score is statistically significant and indicates linkage?

3

What is the formula for Lod scores when we know phase? What does each symbol mean?

Lod theta = log of (1-theta)^P x (theta)^R/(0.5)^R+P

Theta = probability of a gamete being recombinant 1-theta = probability of a gamete being parental P = number of parental offspring R = number of recombinant offspring

Do we usually calculate Lod scores for a single value of theta?

No, will calculate for multiple values. Computer programs will run hundreds

What would the Lod score for unlinked loci be?

-2 or less

What is the maximum likelihood score?

The value of theta with the highest LOD score. The most likely value for RF

What do we do when we have multiple LOD scores >3?

The highest one is considered the true theta. Any others less than 1 away from the highest are support intervals

Even though we can calculate the LOD scores when we don’t know phase, why is it less powerful?

Have to account for both possible phases, so we’re less certain of the theta values

What does a LOD score of negative infinity mean?

Excludes that possibility of theta entirely

What do we do with maximum likelihood scores that are less than 3?

Not complete garbage. Since each meiosis event in a family and between families is independent, we can add LOD scores from different kindreds together to increase confidence