Lecture 10

Question 1

What is the problem with single markers and QTL detection?

Answer 1

It can only be used for simple detection of QTL linked to a marker, rather than estimation of QTL position and effect

Question 2

Why can a single marker only detect the QTL and not infer anything about its position and effect?

Answer 2

The further the QTL is from the marker, the smaller the contrast between the groups receiving alternate alleles due to more recombination (r). Therefore, the size of the QTL estimated (alpha) is not independent of its position.

Question 3

The further the QTL is from the marker, the smaller the contrast between the groups receiving alternate alleles due to more recombination (r) and therefore, the size of the QTL estimated (alpha) is not independent of its position. Why is this?

Answer 3

Because the markers don’t fully represent the QTL anymore.

Question 4

What basic genetics concept is “the size of QTL effect” referring to?

Answer 4

The allele substitution effect.

Question 5

Instead of using a single marker, what is the “next-step” way to detect QTLs? Briefly, how do they work?

Answer 5

with flanking markers which use information from two or more markers simultaneously.

Question 6

What is the first step in flanking markers for QTL detection?

Answer 6

Calculation of the probability of inheriting QTL alleles given marker haplotypes

Question 7

What does P(Q/Haplotype) depend on?

Answer 7

The probability of Q per haplotype depends on
- the distance between markers
- and the position of the QTL
(these are both related to recombination rates)

Question 8

What is alpha? Give a brief definition.

Answer 8

The (gene) allele substitution effect

- The effect of moving from inheriting q from SIRE to inheriting Q

Question 9

Given alpha, what is the theoretical mean of progeny inheriting q, and Q, respectively?

Answer 9

• The mean of progeny inheriting q is µ.

- the mean of progeny inheriting Q is µ + alpha.

Question 10

Is alpha the same between q and Q?

Answer 10

No, it is different.

Question 11

For calculating the expected mean of marker groups, why must we use a weighted mean?

Answer 11

Because only marker genotypes are observed

Question 12

If there are 4 unknown parameters and 4 haplotype groups, are the parameters estimable?

Answer 12

Yes: can estimate independently

Question 13

In detecting a QTL with flanking markers, how is it possible to determine r1, r2, r12? What assumptions are needed for this? And what does it lead to?

Answer 13

It is possible to determine them using a mapping function. Assuming a putative QTL position and knowing the distance between A and B from the linkage map. Leads to interval mapping.

Question 14

With two unknown parameters alpha and µ and four means (4 groups of progeny) are the parameters estimable?

Answer 14

Yes

Question 15

What is interval mapping?

Answer 15

stepping along the chromosome

Question 16

Briefly Explain Interval Mapping.

Answer 16

Step along the chromosome, calculate alpha, µ and some test statistic.

Question 17

From an interval test, at what point is the QTL most likely positioned? at what point are the estimates considered the best estimates?

Answer 17

The point of the maximum test statistic is the most likely position of the QTL and alpha and µ are best estimators.

Question 18

What strong assumption does interval mapping make?

Answer 18

Information on the markers outside the two markers flanking the QTL position, does not increase the ability to find a QTL inside the interval. This is a STRONG assumption.

Question 19

Can interval mapping integrate adjacent marker intervals?

Answer 19

Yes. Adjacent marker intervals can be analyzed separately and the results joined. An example is a Log of Odds (LOD) profile

Question 20

What is an advantage to interval mapping?

Answer 20

The entire genome can be scanned for QTL

Question 21

What are two statistical methodologies commonly used for interval mapping?

Answer 21

• Maximum likelihood

- linear regression