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Transcript
Variation in submergence
tolerance
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http://www.a2mediagroup.com/data/images/news/categories/riceplant.jpg
Linkage mapping (quantitative)
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intolerant
tolerant
Fine-mapping
Finding the causative variant
http://www.plantsci.cam.ac.uk/Haseloff/SITEGRAPHICS/Agrotrans.GIF
Transgenic test
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Transgenic test
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http://homepages.strath.ac.uk/~dfs99109/BB310/CFTRgene.jpg
Coding variants
Fig. 2B
Single-locus:
AA x BB
AB
(F1)
AB x AB
AA
AB
BA
BB
(F2)
1 locus, incomplete dominance
AB
BA
AA
BB
“Effect of having a
B”
25%
50%
25%
AA
AB
BA
BB
Two loci
long chrom
short chrom
locus 2
locus 1
Two loci
long chrom
short chrom
Parent A
A A
A A
locus 2
locus 1
Two loci
long chrom
long chrom
short chrom
Parent A
short chrom
Parent B
A A
A A
B B
locus 2
locus 1
B B
locus 2
locus 1
Two loci
long chrom
long chrom
short chrom
Parent A
short chrom
AA/AA x BB/BB
A A
Parent B
A A
B B
locus 2
locus 1
B B
locus 2
locus 1
Two loci
long chrom
long chrom
short chrom
Parent A
short chrom
AA/AA x BB/BB
A A
Parent B
A A
B B
locus 2
locus 1
B B
locus 2
AB/AB
(F1)
locus 1
Two loci
long chrom
long chrom
short chrom
Parent A
short chrom
AA/AA x BB/BB
A A
Parent B
A A
B B
locus 2
locus 1
B B
locus 2
AB/AB
Locus1/Locus 2
(F1)
locus 1
Two loci
long chrom
long chrom
short chrom
Parent A
short chrom
AA/AA x BB/BB
A A
Parent B
A A
B B
locus 2
locus 1
B B
locus 2
AB/AB
(F1)
Locus1/Locus 2
AB/AB x AB/AB
16 possibilities
(F2)
locus 1
Two loci, incomplete dominance
Two loci, incomplete dominance
or BA
Two loci, incomplete dominance
or BA
or BA
Two loci, incomplete dominance
How many squares of the Punnett square are represented here?
or BA
or BA
Two loci, incomplete dominance
Effect
of B at
locus 2
Two loci, incomplete dominance
Effect
of B at
locus 2
Two loci, incomplete dominance
0
0.5
1.0
Phenotype
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1.5
Two loci, incomplete dominance
*
0
What is the genotype?
A. AA/AA
B. AB/AA
C. BB/AA
D. AA/AB
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0.5
1.0
Phenotype
1.5
Two loci, incomplete dominance
*
0
What is the genotype?
A. AA/AB
B. BB/AB
C. AB/AB
D. AA/BB
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0.5
1.0
Phenotype
1.5
Two loci, incomplete dominance
*
0
How many F2’s have this genotype?
A. 1/16
B. 2/16
C. 3/16
D. 4/16
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0.5
1.0
Phenotype
1.5
Two loci, incomplete dominance
Notation is
different, trait is
qualitative; math
is the same.
Fig. 3.17
2-locus interaction
Leghorn
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http://www.projects.roslin.ac.uk/chickmap/organism.html
Junglefowl
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Two loci
long chrom
long chrom
short chrom
Parent J
J
J
short chrom
JJ/JJ x LL/LL
J
Parent L
J
L
locus 2
locus 1
L
L
L
locus 2
JL/JL
(F1)
Locus1/Locus 2
JL/JL x JL/JL
16 possibilities
(F2)
locus 1
2-locus interaction
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2-locus interaction
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Effect
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of J at
locus 2
2-locus interaction
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Effect
of J at
locus 2
2-locus interaction
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Effect
of J at
locus 2
Effect of variation at locus 2 depends on genotype at
locus 1: non-additive
2-locus interaction
For example: locus 1 is polymorphism in a transcription factor gene that affects protein binding affinity, locus 2 is in a
binding site
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Effect
of J at
locus 2
Effect of variation at locus 2 depends on genotype at
locus 1: non-additive
2-locus interaction
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Effect
of J at
locus 2
Locus 2 is epistatic to locus 1: effects of locus 1 are
masked in individuals with JJ or JL,LJ at locus 2
Locus 2 follows a dominance model: JJ and JL,LJ have
the same phenotype, LL differs
“The dominant allele of locus 2 does the masking”
Other foibles in QTL mapping
Pathogenic yeast
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Pathogenic yeast
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How did YJM145 gain the ability to grow at body temperature?
A model quantitative trait
A model quantitative trait
Lab parent
A model quantitative trait
Lab parent
Pathogenic parent
A model quantitative trait
100 progeny ≥ pathogenic parent
Lab parent
Pathogenic parent
NO progeny as extreme as diploid hybrid
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NO progeny as extreme as diploid hybrid
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NO progeny as extreme as diploid hybrid
Lab parent
Pathogenic parent
Diploid hybrid
Did the mapping…
Significant linkage to yeast chrom XIV and chrom XVI.
Did the fine-mapping…
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Did the fine-mapping…
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Which gene is causative?
Lab
Pathogenic
Lab
Pathogenic
Tested in hybrid diploids
Lab
Pathogenic
Lab
Pathogenic
Tested in hybrid diploids
Lab
Pathogenic
Lab
Pathogenic
Tested in hybrid diploids
Lab
Pathogenic
Different
in
sequence
Lab
Pathogenic
Tested in hybrid diploids
One mutant gene…
From pathogenic strain
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One mutant gene…
From pathogenic strain
From lab strain QuickTime™ and a
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One mutant gene…
From pathogenic strain
So diploid with this gene
from the pathogenic
strain grows BETTER at
From lab strain QuickTime™ and a
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Two mutant genes…
From pathogenic strain
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a lab strain
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Two mutant genes…
From pathogenic strain
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Again, diploid with this
gene from the
pathogenic strain grows
BETTER at high T.
Three mutant genes
From lab strain
From pathogenic strain
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Diploid with this gene
from the pathogenic
strain grows WORSE
at high T!
Three mutant genes
From pathogenic strain
From pathogenic strain
From pathogenic strain
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Three mutant genes
From pathogenic strain
From pathogenic strain
From pathogenic strain
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Three mutant genes
From pathogenic strain
From pathogenic strain
From pathogenic strain
Alleles from the
same strain at
different genes/loci
can have different
effects.
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No common coding alleles across
strains
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No common coding alleles across
strains
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And no expression differences of >3-fold…
Three mutant genes in same “locus”
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Three mutant genes in same “locus”
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Three mutant genes
So why did 0/900 haploid progeny have
a phenotype as extreme as the diploid
hybrid?
NO progeny as extreme as diploid hybrid
Lab parent
Pathogenic parent
Diploid hybrid
NO progeny as extreme as diploid hybrid
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Lab parent
Pathogenic parent
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Diploid hybrid
Linked mutations of opposite effect
Path
Linked mutations of opposite effect
Path
Lab
Linked mutations of opposite effect
Path
Lab
Very unlikely
“Multiple linked loci”