Download 1 Lecture 20 - Chromosomal abnormalities – structural I. Types of

Lecture 20 - Chromosomal abnormalities – structural
I. Types of abnormalities
A. deletion
B. duplication
C. inversion
1. paracentric
2. pericentric
D. reciprocal translocation
1. Robertsonian translocation – special type of translocation that fuses 2
acrocentric/telocentric chromosomes.
E. position effects
II. Chromosomal deletions
A. effects of deletion
a deletion results in loss of part of chromosome
a+
b+
c+
d+
e+
a+
b+
c+
d+
e+
a+
a+
can test for deletion
by test cross to see
if multiple genes are
missing
aa-
B. How can you tell if deletion present?
1)
e+
e+
X
bb-
cc-
dd-
ee-
a+
b+
c+
d+
e+
a-
b-
c-
d-
e-
these progeny are A B C D E in phenotype
2)
C. deletion mapping
genetic map
polytene
chromosome
a+
e+
a-
b-
c-
d-
e-
these progeny are A b c d E in phenotype
z/del
–
–
+
+
+
+
6 deletions
from region
zeste
in this
region
zw2
in this
region
zw2/del
–
–
–
–
–
+
w/del
+
–
–
–
+
+
white
in this
region
D. Several human genetic diseases result from chromosomal deletions
1. Cri-du-chat – results from deletion of part of chromosome 5
2. Wolf-Hirschorn – results from deletion of part of chromosome 4
1
III. Duplication
A. Duplication repeats part of
chromosome
a duplication repeats part of chromosome
a+ b+ c+ d+ e+
a+ b+ c+ d+ e+
B. Tandem duplications can be further
amplified by unequal crossover
c+
c+
b+
b+
a+
a+
d+
d+
b+
b+
c+
c+
d+
d+
e+
e+
tandem duplications can be further amplified
by unequal crossover
+
a+ b+ c
a+ b+ c+
C. A few points about duplications
1. How can you detect their
presence?
- eg. duplication of fly Bar
gene causes Barred eyes
- can detect cytologically
(chromosome stain)
2. Duplications important in
evolution
d+
b+ c+
d+ e+
d+
b+ c+
d+ e+
+ c+
a+ b
a+ b+ c+
d+ b+
c+
d+ e+
d+ b+
c+
d+ e+
a+ b+ c+
d+
b+ c+
a+ b+ c+
d+ b+
a+ b+ c+
d+ e+
a+ b+ c+
d+
d+ e+
c+
d+ b+
b+ c+
d+ e+
c+
d+ e+
3. Large duplications often
deleterious
IV. Inversion
A. Inversion reverses sequence of part of
chromosome
B. Inversion affects synapsis
c+
+
c +c
c+
b+
b++
b
b+
d+
d+
d+
d+
a+
a+
a+
a+
e+
e+
a+
a+
b+
b+
c+
c+
d+
d+
e+
e+
a+
a+
d+
d+
c+
c+
b+
b+
e+
e+
- inversion causes no problem unless crossover
occurs within inverted sequence
- inversion bearing chromosomes are crossover
“suppressors” because recombinant chromosomes
generally not recovered
e+
e+
C. Two types of inversions
1. paracentric inversion
c+
+
c
c+
c+
b+
b++
b
b+
e+
d+
d+
a+
a+
d+
d+
a+
a+
a+
e+
e+
d+
a+
e+
e+
a+
2
b+
d+
d+
c+
d+
e+
c+
b+
e+
c+
b+
a+
c+
b+
e+
2. pericentric inversion
a+
d+
a+
d+
d+
a+
a+
d+
d+
a+
a+
b+
b++
b
b+
c+
c+
c+
c+
e+
e+
d+
e+
b+
a+
b+
e+
e+
c+
b+
c+
c+
c+
e+
b+
a+
d+
e+
d+
e+
V. Reciprocal translocation
A. reciprocal exchange of DNA between non-homologues
1. heterozygous for translocation
2. homozygous for translocation
a+
a+
a+
a+
u+
u+
u+
u+
b+
b+
b+
b+
d+
d+
d+
d+
c+
c+
c+
c+
v+
v+
w+
w+
w+
w+
v+
v+
e+
e+
y+
y+
z+
z+
x+
x+
e+
e+
x+
x+
y+
y+
b+
b+
b+
b+
a+
a+
a+
a+
u+
u+
u+
u+
z+
z+
v+
v+
v+
v+
d+
d+
d+
d+
c+
c+
c+
c+
w+
w+
w+
w+
y+
y+
y+
y+
x+
x+
x+
x+
z+
z+
z+
z+
e+
e+
e+
e+
B. reciprocal translocation often causes “semi-sterility”
aa++
aa++
bb++
db++
1st segregation in
this orientation
a
+
u
u
v
a
u
c
+
v
b
u
a
c
v
e
d
e
x
e
w
y
x
c
v
x
d
w
b
u
e
w
d
a
+w
+
++ww
w
b
u
v
u
+
u
c
w
v
v
u
+
u
3
d
v
d
w
u
y
z
x
y
z
x
v
a
z
d
e
+
v
+
u
a
w
c
v
b
d
c
b
u
y
x
w
b
u
z
c
b
a
u
x
w
v
a
e
y
x
+u
+
++uu
u
u
e
x
w
e
y
w
+v
+
++vv
v
1st segregation in
this orientation
d
c
b
u
z
c
a
z
z
y
b
a
y
c
b
a
z
y
x
+x
+
++xx
x
dd++
bd++
1st segregation in
this orientation
d
w
b
u
a
c
b
cc++
cc++
e
y
e
x
e
y
x
c
d
z
d
d
w
z
z
e
y
z
C. Roberstonian translocation
- special type of non-reciprocal
translocation in which 2 acrocentric
telocentric chromosomes fuse
or
14
21
rob(14; 21)
in humans, leads to high probability of Down syndrome
if chromosome 21 is involved
metaphase 1
first segregation
in this orientation
first segregation
in this orientation
first segregation
in this orientation
produces trisomy 21
trisomy 14 (lethal)
normal
produces trisomy 21
trisomy 14 (lethal)
normal
aneuploid (lethal)
aneuploid (lethal)
translocation
carrier
aneuploid (lethal)
aneuploid (lethal)
translocation
carrier
VI. Rearrangements may also cause mutations if they break within genes
A. eg. Inversion:
B. Duplication?
a+
a+
a+
a+
gnx
gnx
b+
b+
c+
c+
d+
d+
e+
e+
d+
d+
c+
c+
b+
b+
e+
e+
a+
a+
b+
b+ +
c+
c+
gnx
a+
a+
b+
b+
gnx+
4
c+
c+
d+
d+
b+
b+
gnx–
d+
d+
c+
c+
e+
e+
d+
d+
e+
e+