Download Prof. Kamakaka`s Lecture 5 Notes

LECTURE 5: LINKAGE
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Linked genes, recombination, and chromosomal mapping
Mendel's Law of Independent Assortment is a consequence of the
fact that chromosomes segregate independently in meiosis
Take two individuals
One heterozygous and one homozygous
AaBb
x
aabb
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Chromosome alignment in MeiosisI
These results are readily explained by the two alternative
ways the chromosomes can line up on the metaphase plate
during meiosis I:
A
a
A
a
OR
B
AB
b
b
ab
Ab
B
aB
Because the A and B genes assort independently, AaBb
dihybrids constructed from different parental genotypes will
behave the same.
AABBxaabb
AAbbxaaBB
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AABB
x
AAbb
aabb
x
aaBB
B
a
b
a
AaBb
AaBb
x
aabb
AaBb
b
A
B
A
OR
x
aabb
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Why 50:50
Why not 25:25:25:25
A dihybrid cross involving the genes A and C produced the
following results:
·
A= Tall
a= short
·
C= Cream
c = white
Cross I:
Cross II:
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In these crosses, independent assortment is not occurring.
For example in the first cross, the alleles Tall and Cream
behave as if they are linked to one another. Similarly in the
second cross the alleles Tall and white appear as if they are
linked to one another.
These results are readily explained if the genes A and C lie
next to one another on a chromosome:
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Cross I:
A-C
a-c
A-C
a-c
A-C
a-c
a-c
a-c
A= Tall
a= short
C= Cream
c = white7
Cross II:
A-c
a-C
A-c
a-C
A-c
a-c
a-C
a-c
A= Tall
a= short
C= Cream
c = white8
Purple vestigial
Morgans experiment in Drosophila to determine if the genes pr
and vg were linked.
PR+ = normal red eyes
pr = purple eyes
VG+ = normal wings
vg = vestigial wings
P
F1
If they are on different
chromosomes they should
assort independently
If they are next to one another
on the same chromosomes they
should not assort independently
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When Morgan performed this cross, he obtained the following
result:
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The chromosomes that have gone through this crossover are
known as crossover products or recombinants. The original
chromosomes and those that have not undergone a crossover
are known as parental.
Evidence for the model that chromosomes physically exchange
during meiosis is found in meiotic structures known as
chiasmata.
During meiosisI when homologs pair, non-sister chromatids
appear to cross with each other. The resulting cross-shaped
structure is known as a chiasmata.
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Crossing-over through the microscope
Duplicated homologous chromosomes
Synapsis
Crossing over between
Non-sister chromatids
AnaphaseI
Segregation of homologous
chromosomes
Haploid gametes
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Answer:
How does one determine whether two genes reside on
different chromosomes or reside on the same chromosome as
linked genes?
To explain this we need to define the terms parental and
recombinant:
Parents:
Gametes:
F1:
Meiosis produces the following gametes:
Recombinant gametes are those with different allelic
combinations than those gametes of the previous generation.
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Coupling/repulsion
Genes located on the same pair of homologous chromosomes are
called LINKED GENES
Therefore when the A and C alleles are introduced from one
parent they are physically located on the same chromosome and
they do not assort independently. We say that they are linked.
In the above cross we say that the A and C genes are linked.
Therefore when we write the genotype of a dihybrid for two
linked genes, there are two possible conformations:
AaCc
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If genes A and B are on different chromosomes:
F1 diploid
Test cross
progeny
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Genes A and B are linked on the same chromosome
F1 diploid
Test cross
progeny
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Recombination frequency
A
B
A
B
parental
A
a
B
b
A
b
recombinant
a
b
a
B
recombinant
a
b
parental
If a crossover occurred between linked genes each time
homologs paired, the recombinant frequency would be 50%
This is because crossing-over involves only two of the four
chromatids on the metaphase pair (each of the paired
homologs consists of two sister chromatids).
For example, the frequency of recombinant gametes between
linked genes A and B is 50% if crossing-over occurred each
time the homologs paired.
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A
B
A
a
B
b
a
b
A
B
A
a
B
b
a
b
A
B
A
b
a
B
a
b
A
B
A
B
a
b
a
b
A B
A
B
A B
a b
A
B
a
b
a
b
a
b
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However there are many instances in which the homologs pair and
crossing over does not occur between genes A and B.
It occurs somewhere else
Consequently the overall frequency of recombinants is significantly
reduced from 50%
A
B
A
B
A
a
B
b
A
B
a
b
a
b
a
b
parental
parental
parental
parental
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Distance
The larger the distance between two genes residing on the
same chromosome, the higher the probability there is that a
crossover event will occur between them.
That is for any chromosome, there is a fixed probability per a
given distance on the chromosome that a crossover event will
event.
Sturtevant realized that this property could be used to map
genes with respect to one another. For each pair of genes on a
chromosome a recombination frequency can be determined.
By determining the recombination frequency between many
pairs of genes on a chromosome, the relative distance between
genes and the order of the genes on the chromosome can be
determined.
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For example Sturtevant identified three recessive mutations
that reside on the X chromosome of Drosophila
By calculating recombination frequencies between each pair of
genes we can begin to establish where these three genes reside
on the X chromosome with respect to one another
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To determine the distance between the w gene and the sn gene
P
w sn/w sn
x
W+ SN+/Y
F1
w sn/W+ SN+
x
w sn/Y
F2
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Fill out the phenotypes- recombinants can be determined by phenotype analysis
Recombination frequency equals the number of recombinants over
total number of progeny
# recombinant progeny =
# total progeny
1 map unit (m.u.) = 1% recombination frequency
Therefore _________________separate the w and sn genes.
This is a relative distance- depends upon recombination between
two genes. Not an absolute distance like bp
In the above cross, we could have determined recombination
frequency by counting only males (or only females)
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The next issue is where does cv map with respect to w and sn:
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