13-14

Question 1

what are quantitative or complex traits defined by

Answer 1

Interplay with the envrionment and many genes (polygneic)

Question 2

what is a quantitative trait locus?

Answer 2

a genomic region that contains one or more genes affecting the phenotypic variation in a quantitative trait

Question 3

how is an unknown QTL identified and localised?

Answer 3

by its linkage to one or more polymorphic genetic markers

Question 4

what is QTL mapping?

Answer 4

form of linkage mapping based on recombination frequencies of the known marker loci

Question 5

How do you begin QTL mapping

Answer 5

make two inbred lines which are homozygous for marker and trait.
F1 will be heterozygous.
by back crossing F1 with parentals and F2 sib mating get recombinant inbred lines (RIL)

Question 6

what is an ideal makrer used in QTL mapping

Answer 6

• linked to controlling trait
• polymorphic so can see differences between individuals or species
• can be SNPs, microsatellites, strs etc.
• inherited in a mendelian fashion.
• neutral - not subject to selection.

Question 7

How can you determine marker and QTL are linked

Answer 7

score the phenotype and marker genotype for all offspring.
if seemes to be an association
eg. M1M1 = heavier and M2M2 = lighter, can assume to be linked.
if not linked there would be no difference between marker genotype and mass.

Question 8

how do you analyse offspring and marker relationsgip

Answer 8

offspring grouped according to marker genotype and phenotypes averaged for each marker genotype.
if group means vary significantly than a QTL resides in the vicinity of the marker. - same linkage block.

Question 9

how can you verify that QTL resides in vicinity of marker?

Answer 9

repeated detection and QTL controlling trait under more than one set of environmental conditions. - must be stable across all environmetns and over years.

Question 10

what frequencies are coupling and recombination expected to be at

Answer 10

coupling = highest freq
recombinant + coupling = second higher
recombinant/ recombinant = lowest.

Question 11

how do you calculate marker means?

Answer 11

group into classes for each marker type

eg. marker homozygous 1, marker homozygous 2 and marker heterozygous.

Question 12

if there is tight linkage what would you expect a high amount of?

Answer 12

coupling/coupling

Question 13

what are the marker means a function of?

Answer 13

additive and or dominance effects.

Question 14

what happens if group means vary significantly?

Answer 14

then a qtl resides in the vicinity of the makrer and the linkage block

Question 15

what can you do if marker means differ

Answer 15

work out estimated values of a and d using genotypic scale of measurement for quantitative traits

Question 16

why will estimated values be different to true values of a and d

Answer 16

due to recombination between QTL and marker

Question 17

what will the frequency of gametes be if you cross two homozygotes of M1M1Q1Q1 and M2M2Q2Q2

Answer 17

frequency M1Q1 or M2Q2 = 1-r/2
frequency of M1Q2 or M2Q1 = r/2
r= recombination distance

Question 18

how do you calculate the midpoint and what does it tell us

Answer 18

marker mean of heterozygote - marker means of biggest homo + smallest homo/2
if = 0 shows that heterozygote is equal to mid point and so no dominance - any other number shows dominance

Question 19

what is the degree of dominance?

Answer 19

d^/a^

Question 20

what is the QTL effect size

Answer 20

difference between homozygote marker means over different between largest and smallest range
accounts for percentage of phenotypic difference that between largest and smallest.

Question 21

what are the advantages of single marker mapping?

Answer 21

simplicity
genetic map not needed
can do anaylses using standard packages like anovva and t test

Question 22

what are the disadvantages of single marker mapping

Answer 22

must exclude individuals lacking genotype info

need high density of markeers, markers throughout or might miss QTL

Question 23

what is interval mapping with multiple markers?

Answer 23

where two marker loci are considered at the same time, to see if there is a QTL between them
uses mapped locations of pairs of adjacent or flanking markers to predict location of QTL
predictions are done in small intervals essentially creating a sliding window moving along chromosome from one end to another

Question 24

what statistical analysis do we need to do to decide whether two homozygous marker means are different enough to indicate a QTL

Answer 24

threshold level of significance is determined by the LOD score or a permutation test.

Question 25

how do you work out the ODDs?

Answer 25

probability of (data|QTL)/ probability of (data| no QTL)
log(ODDs)

Question 26

what is taken into account when setting the threshold of significance for lods?

Answer 26

number of statistical comparisons to take into account false positives

Question 27

what does threshold for significance vary with for lods?

Answer 27

permutation tests of the phenotypic data for individuals in presence or absence of QTL.

Question 28

describe interval mapping

Answer 28

phenotypic data are evaluated directly without adjusting for possible genetic influences from outside the interval - probability of QTL lying between each marker
doesnt take into account anything outside of this interval - any epistasis, might over estimate effect.

Question 29

describe composite interval mapping

Answer 29

intervals outside the interval of interest are considered as well, take into account regions either side

Question 30

what are the draw backs of QTL mapping

Answer 30

cant identify causal gene of QTL as could be many
mapping studies localise QTL’s to about 0-20cM which could contain 100’s of genes
although higher marker density of linkage map gives more precise location the denser the map more likely false positives will be detected.