Canine Genetic Map

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Canine Genetic Map
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Lecture 8
Linkage
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Testing Complex Hypotheses
Mating Inter se mating of dihybrids and
observe 160 progeny.
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Testing Complex Hypotheses
Mating Inter se mating of dihybrids and
observe 160 progeny.
EXPECTATION
Genotype Ratio Expected
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Testing Complex Hypotheses
Mating Inter se mating of dihybrids and
observe 160 progeny.
EXPECTATION
Genotype Ratio Expected A_B_
9 90 A_bb 3 30 aaB_
3 30 aabb 1 10
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Testing Complex Hypotheses
Mating Inter se mating of dihybrids and
observe 160 progeny.
EXPECTATION
Genotype Ratio Expected OBSERVED A_B_
9 90 75 A_bb 3 30 28 aaB_
3 30 42 aabb 1 10 15
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• Have 4 categories
• Calculate ?2 9.93
• d.f. 3
• Test at 5
• C.V. 7.815
• Compare computed ??2 to C.V. and reject
  hypothesis!

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Question What was our hypothesis?
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Question What was our hypothesis? Actually a
composite of 3 separate hypotheses.
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Question What was our hypothesis? Actually a
composite of 3 separate hypotheses.

• 3 to 1 ratio at the A locus

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Question What was our hypothesis? Actually a
composite of 3 separate hypotheses.

• 3 to 1 ratio at the A locus
• 3 to 1 ratio at the B locus

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Question What was our hypothesis? Actually a
composite of 3 separate hypotheses.

• 3 to 1 ratio at the A locus
• 3 to 1 ratio at the B locus
• A and B loci are independent

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Tabular representation of hypotheses
A Locus 3/4 A_ 1/4 aa
9/16 A_B_ 3/16 aaB_ (3/4) x (3/4) (1/4) x
(3/4) 3/16 A_bb 1/16 aabb (3/4) x (1/4)
(1/4) x (1/4)
3/4 B_ 1/4 bb
B Locus
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Testing each part of the complex hypothesis.

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Testing each part of the complex hypothesis.
1) 3 to 1 ratio at the B locus (ignore A)
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Genotype OBSERVED A_B_ 75 A_bb
28 aaB_ 42 aabb 15
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Testing each part of the complex hypothesis.
1) 3 to 1 ratio at the B locus (ignore
A) Expected Observe B_ 120 75 42
117 bb 40 28 15 43 ?21 .225 (fail to
reject)
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Testing each part of the complex hypothesis.
2) 3 to 1 ratio at A locus (ignore B)
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Genotype OBSERVED A_B_ 75 A_bb
28 aaB_ 42 aabb 15
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Testing each part of the complex hypothesis.
2) 3 to 1 ratio at A locus (ignore
B) Expected Observe A_ 120 75 28
103 aa 40 42 15 57 ?21 9.63 (reject 3
to 1 at A locus)
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Although a problem was found at the A locus, we
still need to test for independence.
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FACT ?23 ?21(A locus) ?21(B locus)
?21(independence)

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FACT ?23 ?21(A locus) ?21(B locus)
?21(independence)
HENCE 9.93 9.63 .225 ?21(independence)
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FACT ?23 ?21(A locus) ?21(B locus)
?21(independence)
HENCE 9.93 9.63 .225 ?21(independence) ?21(i
ndependence) .08 (fail to reject)
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Independence
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Independence

• In the context of two loci
• The loci segregate at random with respect to
  each other.

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Independence
Dihybrid (AaBb) Gametes Probability
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Independence
Dihybrid (AaBb) Gametes Probability
AB .25 Ab .25 aB .25
ab .25
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Independence
Dihybrid (AaBb) Gametes Probability
AB .25 Ab .25 aB .25
ab .25
P(AB) P(A) P(B) .5 .5 .25 IF
INDEPENDENT!
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When is this not the case?
Loci are not independent when they are physically
linked.
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NAME (0.2 pts) 1 - Who was chairperson before
Alan Bell? (0.1 pt) 2 Where did I teach before
coming to Cornell? (0.1 pt) 3 Where did I get
my Ph.D? (0.1 pt) 4 I co-teach An Sci 321. Who
is the other instructor? (0.1 pt)
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Linkage Example
R_ rex hair rr normal hair S_ normal
behavior ss shaker
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Parental strains RRss rrSS RRss rex and
shaker rrSS normal hair and normal
behavior
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Parental strains RRss rrSS Dihybrid (F1)
RrSs
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Parental strains RRss rrSS Dihybrid (F1)
RrSs TEST CROSS
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Parental strains RRss rrSS Dihybrid (F1)
RrSs TEST CROSS RrSs rrss observe 400
progeny
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EXPECTATION Genotype Ratio Expected RrSs
1 100 Rrss 1 100 rrSs
1 100 rrss 1 100
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EXPECTATION Genotype Ratio Expected
OBSERVED RrSs 1 100 15 (rex,
normal) Rrss 1 100 185 (rex,
shaker) rrSs 1 100 185 (normal,
normal) rrss 1 100 15 (normal,
shaker)
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• What is observed is certainly not in agreement
  with what is expected.

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• What is observed is certainly not in agreement
  with what is expected.
• The most frequent phenotypes in progeny are the
  same phenotypes associated with the original
  parental strains
• rex/shaker and normal/normal

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Linkage Example Following Chromosomes
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Linkage Example Following Chromosomes
R R s s
r r S S
Parental Strains

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Linkage Example Following Chromosomes
R R s s
r r S S
Parental Strains

R r s S
F1
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Gametes of F1
R r s S
parental-type gametes (same as original parents)
and
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Gametes of F1
R r s S
parental-type gametes (same as original parents)
and
R r S s
recombinant gametes
and
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Recombinant gametes result from a physical
exchange of genetic material between chromosome
pairs -- crossing over.
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Recombinant gametes result from a physical
exchange of genetic material between chromosome
pairs -- crossing over.
F1
R r s S
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Genotype Observed RrSs 15 Rrss
185 rrSs 185 rrss
15
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Genotype Observed RrSs
15 recombinant Rrss 185 parental rrSs
185 parental rrss
15 recombinant
50
crossing over of recombinants type
100 total observed
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crossing over of recombinants type
100 total observed
30 100 400 7.5
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crossing over of recombinants type
100 total observed
30 100 400 7.5
Generally, the further apart two loci are the
greater the chance of a crossover occurring.
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Maximum distance is 50 units! At 50 or more
units apart two loci appear to segregate
independent of each other.
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Joint probability when loci are linked is not
P(R) P(S).
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Joint probability when loci are linked is not
P(R) P(S).
P(Parental gametes) 1/2 1 - recombinant
100
Rs or rS
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Joint probability when loci are linked is not
P(R) P(S).
P(Parental gametes) 1/2 1 - recombinant
100
Rs or rS
P(Recombinant) 1/2
recombination 100
RS or rs
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Parental P(Rs) P(rS) 1/2 (1 - .075)
.4625 Recombinant P(RS) P(rs) 1/2 ( .075 )
.0375
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Parental P(Rs) P(rS) 1/2 (1 - .075)
.4625 Recombinant P(RS) P(rs) 1/2 ( .075 )
.0375
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Three-Loci Example of Linkage
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Three-Loci Example of Linkage
TTBBGG ttbbgg
TtBbGg
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Three-Loci Example of Linkage
TTBBGG ttbbgg
TtBbGg
The trihybrid is test-crossed with a complete
recessive homozygous individual.
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Trihybrid Number gamete Gamete
type observed TBG parental 544 tbg parental
544 tBG recombinant at T 160 Tbg recombin
ant at T 160 TbG recombinant at
B 16 tBg recombinant at B 16 TBg recombinant
at G 80 tbG recombinant at G 80
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Trihybrid Number gamete Gamete
type observed TBG parental 544 tbg parental
544 tBG recombinant at T 160 Tbg recombin
ant at T 160 TbG recombinant at
B 16 tBg recombinant at B 16 TBg recombinant
at G 80 tbG recombinant at G 80
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Trihybrid Number gamete Gamete
type observed TBG parental 544 tbg parental
544 tBG recombinant at T 160 Tbg recombin
ant at T 160 TbG recombinant at
B 16 tBg recombinant at B 16 TBg recombinant
at G 80 tbG recombinant at G 80
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Trihybrid Number gamete Gamete
type observed TBG parental 544 tbg parental
544 tBG recombinant at T 160 Tbg recombin
ant at T 160 TbG recombinant at
B 16 tBg recombinant at B 16 TBg recombinant
at G 80 tbG recombinant at G 80
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Trihybrid Number gamete Gamete
type observed TBG parental 544 tbg parental
544 tBG recombinant at T 160 Tbg recombin
ant at T 160 TbG recombinant at
B 16 tBg recombinant at B 16 TBg recombinant
at G 80 tbG recombinant at G 80
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Parental gametes are most frequent. The least
frequent recombinant involves the B locus. This
places the B locus central to the other two in
ordering these loci.
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Recombination frequencies between the central
locus B and the extreme loci T and G
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Recombination frequencies between the central
locus B and the extreme loci T and G
Between T and B
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Trihybrid Number gamete Gamete
type observed TBG parental 544 tbg parental
544 tBG recombinant at T 160 Tbg recombin
ant at T 160 TbG recombinant at
B 16 tBg recombinant at B 16 TBg recombinant
at G 80 tbG recombinant at G 80
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Recombination frequencies between the central
locus B and the extreme loci T and G
Between T and B
tBG and Tbg TbG and tBg
352 out of 1600 or 22
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Between B and G recombination between B and G
locus
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Trihybrid Number gamete Gamete
type observed TBG parental 544 tbg parental
544 tBG recombinant at T 160 Tbg recombin
ant at T 160 TbG recombinant at
B 16 tBg recombinant at B 16 TBg recombinant
at G 80 tbG recombinant at G 80
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Between B and G recombination between B and G
locus
TBg and tbG TbG and tBg
192 out of 1600 or 12
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Between B and G recombination between B and G
locus
TBg and tbG TbG and tBg
192 out of 1600 or 12
Seems logical that the distance between T and G
is the sum of the distances between T and B and
between B and G
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Between B and G recombination between B and G
locus
TBg and tbG TbG and tBg
192 out of 1600 or 12
Seems logical that the distance between T and G
is the sum of the distances between T and B and
between B and G
22 12 34
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This distance (34) between T and G is larger
than that observed from actual recombination
involving T and G.
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Trihybrid Number gamete Gamete
type observed TBG parental 544 tbg parental
544 tBG recombinant at T 160 Tbg recombin
ant at T 160 TbG recombinant at
B 16 tBg recombinant at B 16 TBg recombinant
at G 80 tbG recombinant at G 80
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This distance (34) between T and G is larger
than that observed from actual recombination
involving T and G. In these data, calculating
the recombination frequency for T and G yields
30 instead of 34.
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TG 30 TB 22 BG 12
34

recombination
based on sum
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TG 30 TB 22 BG 12
34

recombination
based on sum
T B G
t b g
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TG 30 TB 22 BG 12
34

recombination
based on sum
T B G
t b g
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TG 30 TB 22 BG 12
34

recombination
based on sum
Recombination doesnt detect a TG crossover
T b G
T B G
t B g
t b g
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Recombinant Map
Map based on experimental recombination
frequencies. Distance referred to as centiMorgans
(cM) one cM 1 crossing over one cM
1,000,000 base pairs
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Physical Map
Map based on information such as sequencing
data. Physical and recombination maps are
consistent in ordering genes but may not be in
distance measures. Some regions more prone to
crossing over (exaggerates cM distance) while
others are less prone.