Linkage with heterozygotes

1
Linkage with heterozygotes

• Two possible configurations
• cis AB // ab
• trans Ab // aB

A a B b
A a b B
2
Linkage

• If two genes are close enough together, they will
  not assort independently

AB//ab ---
Crossing over
3
Crossing Over

• Occurs during prophase I, after synapsis
• Exchange between chromatids of homologous pairs
• Results in recombination of linked alleles

4
Crossing over results in 2 parental gametes and 2
recombinant gametes
Cis
A B A b a B a b
parental
A B a b
x
recombinant
recombinant
parental
5
Trans
A b A B a b a B
A b a B
x
6
Crossing over and mapping

• Crossing over occurs every time homologues
  synapse
• Random location
• Chance it occurs between 2 loci is dependent on
  distance

7
Crossing over and mapping

• Closer together less crossing over less
  recombination
• Farther apart more crossing over more
  recombination
• recombination used as measure of distance
• 1 recomb. 1 map unit

8
Crossing over and mapping

• Test cross used to map loci
• heterozygote x homozygous recessive
• Why a heterozygote?

A b a B
A B a b
x
9
Crossing over and mapping

• Homozygous recessive parent used to pass on
  invisible chromosomes
• Offsprings phenotype direct reflection of
  alleles from heterozygous parent

a b
10
Crossing over and mapping

• Homozygous recessive parent used to pass on
  invisible chromosomes
• Offsprings phenotype direct reflection of
  alleles from heterozygous parent

a b
a B
11
Crossing over and mapping

• Homozygous recessive parent used to pass on
  invisible chromosomes
• Offsprings phenotype direct reflection of
  alleles from heterozygous parent

a b
a b
12
Crossing over and mapping
NOTE Since crossing over occurs during prophase
I, there are ALWAYS two parental
(non-recombinant) types produced!
A B A b a B a b
A B
x
a b
There can never be more recombinant types than
parental types! At most 1111
13
Results of Test Cross w/Linkage
Drosophila P Long wings, gray body x
vestigial, black F1
long, gray
Test cross F1 x vestigial,
black
14
Results of Test Cross w/Linkage
F1 x vestigial black produces
415 long, gray 92 vestigial, gray 88 long,
black 405 vestigial black
Independent assortment would give these 4
phenotypes in 1111 ratio.
P R R P
v b v b
1000
recombination (92 88)/1000 0.18
18 18 map units
15
Practice Two-pt. cross in Dahlias
Heterozygous, red, single-flowered x white,
double
16 red, single 112 red, double 98 white,
single 14 white, double 240
16
Working Backwards . . .

• If know distance, can make predictions
• C and D are 10 m.u. apart
• should see 10 recombination

17
Working Backwards . . .
B and J are 14 map units apart. Cross B
j // b J x b j // b j If 300 offspring
are produced, how many are expected to be B J?
Expect 14 recombinant types (0.14)(300)
42
21 B J 21 b j
129 B j 129 b J
18
Linkage and pedigrees
A woman who is known to be a carrier of
hemophilia and whose father was colorblind
marries a colorblind man. Colorblindness and
hemophilia are 10 map units apart. They have two
daughters. One is colorblind and one is not.
Which daughter is more likely to be a carrier of
hemophilia?
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Three-Point Mapping Cross

• Mapping 3 loci at once
• Same principle as 2 loci
• 1 complication double crossovers

20
A B
C
X X
a b
c
21
Three-Point Mapping Cross

• The chance of having a cross over between all 3
  loci is small
• the double cross over class will be the two
  smallest
• sometimes, one or both may not occur at all
• just 6 or 7 phenotypes appear

22
Three-Point Mapping Cross
Drosophila
P scute, echinous, crossveinless x wild
type F1 wild test
cross wild F1 x sc, ec, cv
23
Three-Point Mapping Cross . . .
wild F1 x sc, ec, cv
sc ec cv 1158 1455 sc
163 ec cv 130 sc ec 192
cv 148 sc cv 1 ec
1 3248
P P R R R R DCO DCO
Compare 1 DCO w/ 1 P to see which locus
switched-
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Three-Point Mapping Cross . . .
P DCO ec
25
Three-Point Mapping Cross . . .
We now know the gene order
sc ec cv
cv ec sc
Now we can map each end locus to the center.
Always map the smallest distances!
26
sc ec cv 1158 P
1455 P sc 163 R
ec cv 130 R sc ec 192
R cv 148 R sc
cv 1 DCO ec 1
DCO 3248
sc to ec distance
27
sc ec 1158 P 1455
P sc 163 R ec
130 R sc ec 192 R
148 R sc 1
DCO ec 1 DCO 3248
sc to ec distance

Parentals sc ec


Recombinants sc ec

(163 130 1 1) / 3248 295/3248
0.0908 9.08 9.08 m.u.
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sc ec cv 1158 NR
1455 NR sc 163 R
ec cv 130 R sc ec
192 R cv 148 R sc
cv 1 DCO ec
1 DCO 3248
ec to cv distance
29
ec cv 1158 P
1455 P 163 R
ec cv 130 R ec
192 R cv 148 R
cv 1 DCO ec
1 DCO 3248
ec to cv distance
Parentals ec cv



Recombinants ec cv

(192 148 1 1) / 3248 342 / 3248
0.1053 10.53 10.53 m.u.
30
sc ec cv
-- 9.1 --
-- 10.5 --
31
Mapping Restrictions

• Cant directly map loci 49 m.u. apart
• 50 recombination independent assortment
• see 1111 ratio

32
3-pt. Review

• I.D. non-recombinants double cross overs
• compare P and DCO to establish order
• Choose one pair (end to middle)
• find recombination freqs. for pair
• Map second pair
• find recomb. freqs.
• Add distances to find distance between 2 end loci

33
3-pt. Practice
het., wild-type female x ebony, scarlet,
spineless male
wild 67 ebony 8 ebony, scarlet
68 ebony, spineless 347 ebony, scarlet,
spineless 78 scarlet 368 scarlet,
spineless 10 spineless 54
34
e p s e e
s e p e p s
s p s p
wild 67 ebony 8 ebony, scarlet
68 ebony, spineless 347 ebony, scarlet,
spineless 78 scarlet 368 scarlet,
spineless 10 spineless 54
R R R R
DCO DCO
P P
35
A heterozygous wild-type schmoo is crossed to
a freckled, dimpled, giggling schmoo with the
following results
wild freckled, dimpled, giggling freckled,
dimpled freckled, giggling dimpled,
giggling freckled dimpled giggling
9 10 54 17 113 132 23 42
36
Coefficient of Coincidence and Interference

• Generally see fewer DCOs than expected
• In eukaryotes, presence of one cross over
  inhibits a second one close by
• Interference
• Difference in expected vs. observed measured by
  coefficient of coincidence

37
Coefficient of Coincidence and Interference
sc ec cv
sc ec cv 1158 1455 sc
163 ec cv 130 sc ec 192
cv 142 sc cv 1 ec
1 3248
9.1
10.5
observed DCO freq 2/3248 0.0006 expected
DCO freq .091 x .105 .0096
coefficient of coincidence c obs. DCO/ exp.
DCO .0006/.0096 0.06
38
Coefficient of Coincidence and Interference

• c ranges from 0 to 1
• low c high interference
• see much fewer DCOs than expected
• high c low interference
• see close to as many DCOs as expected