Lecture 10 Flashcards
What is the problem with single markers and QTL detection?
It can only be used for simple detection of QTL linked to a marker, rather than estimation of QTL position and effect
Why can a single marker only detect the QTL and not infer anything about its position and effect?
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.
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?
Because the markers don’t fully represent the QTL anymore.
What basic genetics concept is “the size of QTL effect” referring to?
The allele substitution effect.
Instead of using a single marker, what is the “next-step” way to detect QTLs? Briefly, how do they work?
with flanking markers which use information from two or more markers simultaneously.
What is the first step in flanking markers for QTL detection?
Calculation of the probability of inheriting QTL alleles given marker haplotypes
What does P(Q/Haplotype) depend on?
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)
What is alpha? Give a brief definition.
The (gene) allele substitution effect
- The effect of moving from inheriting q from SIRE to inheriting Q
Given alpha, what is the theoretical mean of progeny inheriting q, and Q, respectively?
- The mean of progeny inheriting q is µ.
- the mean of progeny inheriting Q is µ + alpha.
Is alpha the same between q and Q?
No, it is different.
For calculating the expected mean of marker groups, why must we use a weighted mean?
Because only marker genotypes are observed
If there are 4 unknown parameters and 4 haplotype groups, are the parameters estimable?
Yes: can estimate independently
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?
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.
With two unknown parameters alpha and µ and four means (4 groups of progeny) are the parameters estimable?
Yes
What is interval mapping?
stepping along the chromosome
Briefly Explain Interval Mapping.
Step along the chromosome, calculate alpha, µ and some test statistic.
From an interval test, at what point is the QTL most likely positioned? at what point are the estimates considered the best estimates?
The point of the maximum test statistic is the most likely position of the QTL and alpha and µ are best estimators.
What strong assumption does interval mapping make?
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.
Can interval mapping integrate adjacent marker intervals?
Yes. Adjacent marker intervals can be analyzed separately and the results joined. An example is a Log of Odds (LOD) profile
What is an advantage to interval mapping?
The entire genome can be scanned for QTL
What are two statistical methodologies commonly used for interval mapping?
- Maximum likelihood
- linear regression