Lecture 6: Linkage and association analysis

Question 1

What is a genetic map?

Answer 1

A group of markers with known genetic position.

Question 2

What is genetic distance?

Answer 2

two things:

1) Physical distance - base pairs
2) Genetic distance - based on recombination fraction.

Question 3

What is the genetic distance measured in?

Answer 3

Expected number of crossovers per gamete between two loci.

Measured in Morgans. called L.

L = E[# crossovers] / 2

Question 4

What is an epsilon function?

Answer 4

A function that goes to zero when its variable goes to zero.

Question 5

*Why is haldanes metric a distance?

Answer 5

It satisfies:

1) theta = 0, haldane = 0
2) d(A,B) = d(B,A)
3) d(A,C) <= d(A,B) + d(B,C)

Question 6

What is haldanes distance?

Answer 6

dH(A,B) = -log(1-2*theta(AB))/2

Question 7

Rule of thumb bp to cm:

Answer 7

1 cm = 10^6 bp

Question 8

What is the point of multi point linkage analysis?

Answer 8

When the distance on a chromosome are too small to have them at LD, information on other nearby markers can be used.

Question 9

What hypothesis is used when testing for linkage?

Answer 9

H0: theta = 0.5

H: theta 0-0.5

If the chromosome small, we use markers and their mutual information:

H: dH(Xi, DSL) = dH(xi, x)

H0: dH(xi, DSL) = 1.5

Question 10

What is the basis for association analysis?

Answer 10

After linkage analysis the region is covered in SNPs and the outcome is modelled. Can be done in a a number of ways.

Question 11

Formal definition of LD:

Answer 11

allele freq = pA, pa, pB, pb

Haplotype freq = pAB, paB, pAb, pab

LE means that allele freq and haplotypes are related in concordance to table (can be multiplied.)

Question 12

What is the LD coefficient?

Answer 12

D = pAB - pA*pB

Explains how far away two loci is from LD.