Lecture 7: Linkage analysis

Question 1

What does linkage analysis depend on?

Answer 1

1) The relation between markers and DSL (theta)
2) Penetrance functions
3) Modes of inheritance
4) Inheritance pattern

Question 2

What is the genetic phase?

Answer 2

The haplotype information of the alleles - so which chromosome of the parents a specific allele belongs to.

Question 3

What is a diplotype?

Answer 3

Pair of haplotypes - e.g. Ab | Ab.

Question 4

What is a haplotype?

Answer 4

The collection of alleles on one gamete.

Question 5

What is a doubly heterozygote?

Answer 5

When the person is heterozygote on two sites, e.g. AB/ab or Ab/aB.

Question 6

How can we get haplotype information?

Answer 6

If we have heterozygotes on markers, we can sometimes infer the haplotype information of parents from their children.

Question 7

What is the purpose of the direct counting method?

Answer 7

The direct counting method wishes to find information on theta of two markers based on doubly heterozygotic pairings.

Question 8

The steps in the direct counting method:

Answer 8

1) Identify doubly heterozygous matings.
2) Count recombinant and non-recombinant allele transmissions
3) Test H0 = theta = 0.5

Question 9

What test is used for step 3 in direct counting?

Answer 9

Mcnemars test - chi(df1)^2 = (r-s)^2/n

r = number of recombinants

s = number of non-recombinants

Question 10

What is the definition of a LOD score?

Answer 10

log10 of the odds. Usually for the theta.

Question 11

Formula LOD-score:

Answer 11

LOD = -log10(LR(theta))

LR is the likelihood ratio of theta.