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Chapter 4
Gene Linkage and
Chromosome mapping
© 2006 Jones & Bartlett Publishers
consider the cross
AaBb
gametes?
AB Ab aB ab
1:1:1:1
x
aabb
ab
ratio
Explanation:
A and B are on different chromosomes
and assort independently (law #2)
What if A and B were on the
same chromosome?
homologous pair
of chromosomes
gametes?
AB
ab
AB or ab
1:1 ratio
Explanation:
Genes A and B are linked
ab
ab
ab
Genes are found at particular places on
chromosomes called loci
Genes that have loci on the same
chromosome are inherited together
= linkage
Fig. 4.1. For any pair of alleles, the gametes produced through meiosis
have the alleles in either a parental or in a recombinant configuration.
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bw brown eyes
bw+ wild type (red)
bw
bw+
hv+
hv
hv
X
heavy veins
hv+ wild type (thin veins)
bw
bw
hv
hv
bw
bw
hv
hv
brown eyes
heavy veins
bw
bw
hv+
hv
brown eyes
thin veins
bw+
bw
hv
hv
red eyes
heavy veins
bw +
bw
hv+
hv
red eyes
thin veins
yellow body
wild type (gray) w+
w
white eyes
wild type (red eyes)
y
y+
y
w
w+
X
Y
parental-98.7%
1.3%
y
y
w
w
yellow body
white eyes
y
y+
w
y
y+
w
w+
gray body
red eyes
recombinant
y
y+
w
w
gray body
white eyes
y
y
w
w+
yellow body
red eyes
why did this happen?
crossing-over
during meiosis
(pachytene of prophase I)
crossing over
A
A
a
a
B
B
b
b
fig 3.9b
Fig. 4.1. For any pair of alleles, the gametes produced through meiosis
have the alleles in either a parental or in a recombinant configuration.
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no crossing-over:
w
w
+
m
x
+
m
w = white eyes
Y
+ = wild type (red)
m = miniature wings+ = normal wings
put on board
no crossing-over:
w
w
+
m
x
+
m
w
m
w
m
+
m
w
+
red eyes (wt)
mini wings
Y
white eyes
wt wings
with crossing-over:
w
w
+
m
x
+
m
w
m
Y
w
m
parental
+
m
w
+
w
m
w
m
w
m
+
+
recomb.
Fig. 4.2. Frequency of
recombination between two
mutant alleles is independent of
their presence in the same
chromosome or in the
homologous chromosomes,
Cross 1.
66.5%
33.5%
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Fig. 4.2. Frequency of
recombination between two
mutant alleles is independent of
their presence in the same
chromosome or in the
homologous chromosomes,
Cross 2.
37.7%
62.3%
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Fig. 4.3. The frequency of
recombination between two genes
depends on the genes, Cross 1
98.6%
1.4%
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Fig. 4.3. The frequency of
recombination between two genes
depends on the genes, Cross 2
1.2%
98.8%
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When looking at any two linked genes,
•the recombination rate is consistent,
•varies based on the genes involved
unusual aside:
crossing over does not occur
in male Drosophila
Fig. 4.4. Crossing-over
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When looking at any two linked genes,
if they are close together, crossing-over
between them is less likely
low recombinant % => close together
def:
1 map unit = 1% recombination = 1 cM
parental
recombinant
96.9%
3.1%
Fig. 4.5. The frequency of recombination is used to construct a genetic map.
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one map unit = ?
length of the chromosome in which,
on average, there is one crossing-over
event in every 50 meiotic cells
Fig. 4.6. Diagram of chromosomal configurations in 50 meiotic
cells, in which 1 has a crossover between two genes.
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note:
In order to detect crossing-over, you
must have markers on both sides of
where it occurs
Fig 4.7
Fig. 4.7. Crossing-over outside the region between two genes is
not detectable through recombination
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Two crossing-over events can
“cancel each other out”…
…if they both occur between
your two “markers”
and both include the same
chromatids.
Fig 4.8
Fig. 4.8. Double crossing-over
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mapping
three genes:
cv, rb, y
y and rb
7.5%
cv and rb 6.2%
Fig. 4.9. Three possible genetic maps of Drosophila, depending on
which gene (rb, cv, or y) is in the middle
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mapping
three genes:
cv, rb, y
y and rb
7.5%
cv and rb 6.2%
y and cv
13.3%
polarity ?
Fig. 4.9. Three possible genetic maps of Drosophila, depending on
which gene (rb, cv, or y) is in the middle
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linkage group =
the set of genes present together
on a chromosome
Fig. 4.10. Genetic map
of chromosome 10 of
corn, Zea mays. [Based on
map by E. H. Coe].
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Physical distance is often
but not always
correlated with map distance
crossing over is sometimes differs
in males and females
very little crossing-over occurs in
regions of heterochromatin
Fig. 4.11. Chromosome 2 in Drosophila as it appears in metaphase of mitosis and
in the genetic map
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Double-crossed?
multiple crossing-over events make
life complicated
(and interesting)
we already saw how two crossing-over
events could undo each other if they were
both between the same markers
Fig. 4.12. Types of double crossovers
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Fig. 4.12. Types of double crossovers
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Fig. 4.12. Types of double crossovers
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double crossing is detectable using:
three point crosses
fig 4.13
parental
recombinant
recombinant
parental
Fig. 4.13. Two crossovers that occur between the same chromatids and span the middle
pair of alleles
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*
*
*
*
*
*
*
*
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Analysis of three-point cross:
Two groups with largest numbers represent the
parental (non-recombinant) chromosomes.
(true for any genetic cross)
Two groups with smallest numbers represent the
double recombinant chromosomes.
For the double recombinant chromosomes, the
gene that is “displaced” is in the center.
Fig. 4.14. The order of genes in a three-point testcross may be deduced
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Fig. 4.14. The order of genes in a three-point testcross may be deduced
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Fig. 4.15. Result of single crossovers in a triple heterozygote
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How far apart are the loci?
286 Lz Su Gl
75.4%
272 lz su gl
40
9.9%
33
Lz Su Gl
lz
su
gl
parental
double
Lz Su Gl
Lz Su Gl
lz
lz
su
single
gl
su
single
4
0.8%
2
59
13.9%
gl 44
How many crossing-overs between Lz Su?
286 Lz Su Gl
75.4%
272 lz su gl
lz
9.9%
0.8%
10.7%
parental
40
9.9%
33
Lz Su Gl
su
gl
double
Lz Su Gl
Lz Su Gl
lz
lz
su
single
gl
4
0.8%
2
su
single
59
13.9%
gl 44
How many crossing-overs between Su Gl?
286 Lz Su Gl
75.4%
272 lz su gl
lz
13.9%
0.8%
14.7%
parental
40
9.9%
33
Lz Su Gl
su
gl
double
Lz Su Gl
Lz Su Gl
lz
lz
su
single
gl
4
0.8%
2
su
single
59
13.9%
gl 44
How far apart are the loci?
Lz
10.7 cM
Su
Gl
14.7 cM
Fig. 4.16. Result of double crossovers in a triple heterozygote
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lz-su
0.107 probability of X between Lz and Su
0.147 probability of X between Su and Gl
If crossing over events are independent how
many doubles X’s should there be?
0.107 * 0.147 = 0.0157
0.0157 * 740 = 11.6
actual = 6
predicted number of
double recombinants
Interference
crossing-over in one region reduces the
probability of crossing-over in a nearby
region
C=
observed DCO
expected DCO
=
=
6
11.2
C = coefficient of coincidence
Interference = I = 1-C = 0.48
= 0.52
Fig. 4.17. Mapping function and map distance
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4.4 Polymorphisms
There are slight differences in the DNA
sequence from person to person
~ 1/1000 bp
When there is a variant that is fairly
common is it called a polymorphism
4.4 Polymorphisms
change sequence at restriction site
change fragments that form
RFLPs
restriction fragment length polymorphisms
Fig. 4.18. DNA molecule containing three EcoRI cleavage sites
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Fig. 4.19. Minor difference in the DNA sequence of two molecules can be
detected if the difference eliminates a restriction site
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Fig. 4.20A. DNA sequence polymorphisms. (A) RFLP, in which alleles
differ in the presence or absence of a cleavage site in the DNA
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Another type of polymorphism
SSR’s
simple sequence repeats
Fig. 4.20B. DNA sequence polymorphisms. (B) SSR, in which alleles
differ in the in the number of repeating units present between two
cleavage sites.
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p. 143. Fluorescent dyes are often used to label DNA so that the positions of DAN
fragments in a gel can be identified. [Courtesy of National Cancer Institute]
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Fig. 4.21. Inheritance of sequence polymorphisms
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SNP’s
single nucleotide polymorphisms
most common polymorphisms
End of 4 for now