L25 QTL mapping in inbred populations

Question 1

Quantitative Trait Loci mapping consists of…

Answer 1

identifying the genetic position of loci involved in quantitative trait variation and estimate their effects

1. position
2. magnitude of effect

QTL mapping allowed the fusion of molecular are quantitative genetics

Question 2

Two main sets of resources were developed to identify the molecular basis of quantitative trait variation

Answer 2

1. inbred lines (cross) through linkage mapping (tracking along family pedigree)
2. outbred lines through Association mapping (using natural population)

Question 3

Linkage mapping with a single marker

Answer 3

see onenote

Construct a genetic map:

1. calculate linkage between markers
2. assembling markers into linkage groups

the limiting factor is more the number of genotypes generated int he cross rather than the number of markers

Question 4

Step-wise test of the marker effect

Answer 4

see onenote

Question 5

Testing each marker independently

Answer 5

see onenote

Question 6

Neutral marker

Answer 6

see onenote

a marker is by definition neutral

not the gene/allele responsible for the genetic effect

a marker potentially co-segregates with the gene (s) underlying the QTL

QTL mapping determines the position(s) on the genetic map where the markers show the strongest linkage with the phenotype

Question 7

Interval mapping between markers

Answer 7

see onenote

no exam questions for slide 15 to 19

find the probability/frequency of each gamete type

Recombination between the two markers = r

Recombination between between marker and QTL = rA and rB

Interval mapping leads to joint estimates of:

1. genetic effect
2. position of QTL (+ confidence interval)

Question 8

Rise and fall of QTL in inbred lines

Answer 8

see onenote slides

In ideal world = QTL interval encompasses obvious candidate genes

QTL mapping very successful at identifying major genes but could have been identified using mendelian genetics

Question 9

Statistical power

Answer 9

probability of detecting a statistical effect based on a given environmental design

Question 10

The power to detect QTL depends on:

Answer 10

• sample size to gain precise estimate of variance components
• size of effect/penetrance of genetic effect; the bigger, the easier to detect

Question 11

small sample size

Answer 11

leads to overestimation of small effect of QTL = Beavis effect

not enough observation of residual variance and overestimation of genetic covariance between individuals i.e. the genetic variance

Small QTL can be missed and if they are not, they will be overestimated

Question 12

Precision problem

Answer 12

see onenote

Question 13

How can resolution be increased?

Answer 13

• can increase marker but only until map is saturated

Increase overall number of recombination in progeny by:

• increase population size
• advance number of generations

Question 14

Recombinant inbred lines

Answer 14

see onenote

• straightforward strategy to achieve higher resolution in QTL mapping

relies on additional generation(s) of selfing or backcrossing to increase:

1. number of recombination
2. derive fully isogenic inbred lines

multiple generations of backcrossing increase positional resolution

interval mapping becoming less relevant due to increase in sequencing throughput but crosses (inbred designs) remain very powerful

Question 15

Isogenic

Answer 15

having the same or closely similar genotypes.