Class 3 1. Construction of genetic maps 2. Single marker QTL analysis 3. QTL cartographer.
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Transcript of Class 3 1. Construction of genetic maps 2. Single marker QTL analysis 3. QTL cartographer.
Class 3
• 1. Construction of genetic maps
• 2. Single marker QTL analysis
• 3. QTL cartographer
Genetic maps 1
• Under the assumption of no interference the number of crossovers in disjoint intervals are independent.
• Consider one linkeage group in the backcross population.
• Let r1, …, rm denote the recombination fractions for consecutive intervals.
• Let n1, …, nm denote the observed number of recombinations in consecutive intervals
Genetic maps 2
• The corresponding likelihood function
• Maximum likelihood estimates of r1, …, rm
m
i
nni
nim
ii rrrrL1
1 )1(),,(
n
nr ii ˆ
Building linkage groups
• Testing for H0: ri=1/2
• Be aware of the multiple testing problem
• Usually stringent test criteria are used
• e.g. in (Doerge 1996) the critical
p-value=2*10-4
Deciding on the order of markers
• Maximizing the likelihood function over all possible marker orders.
• Minimizing the total length of the map.
• Computationally involved
• Alternative – rapid chain delineation (Doerge, 1996)
Rapid chain delineation
• 1. Choose the pair of markers with the smallest distance estimate
• 2. Add the next marker, closest to ones already in the chain.
• 3. Repeat step 2 as long as there any markers left.
• 4. Check if changing the order of any two neigboring markers improves the objective function.
• 5. Check if changing the order within any triplet of neigboring markers improves the objective function.
Example 1
B C D E
A 0.09 0.56 0.50 0.55
B 0.50 0.51 0.50
C 0.17 0.30
D 0.16
Example 2
B C D
A 0.09 0.19 0.17
B 0.26 0.22
C 0.32
Xia- genotype of i-th individual at locus a
Xia = 1/2 - individual is heterozygous at locus a
Xia = -1/2 - individual is homozygous at locus a Data for QTL mapping
Y1,...,Yn - vector of trait values for n backcross individuals
X=[Xij], 1 ≤ i ≤ n, 1 ≤ j ≤ m - genotypes of m markers
Single marker QTL analysis
Single marker analysis
• Student test.
• Regression approach
• F2 population (possibility of detecting dominance) – ANOVA or regression.
QTL Cartographer
• Your data• Backcross population• Marker genotypes• 22 markers spaced every 10 cM on two
chromosomes (11 markers on each).• 500 individuals• Rows correspond to markers.• Coding : 0 – homozygote, 1 -heterozygote
• Trait data for 500 individuals
• Before entering the data to QTL Cartographer
• Change the coding for marker genotypes from 1.00000+e01 to 1 (the same with 0)
• In the file with trait values change a dot for a comma
• Add a trait name at the top of a file
QTL Cartographer
• To create a new data set
• Click New and follow the instructions
• While entering a map information it is better to copy it from the previously prepared text file than to use a Cartographer editor.
• When entering a marker data click on the icon ``arranged in marker order’’