Download Sutton-Boveri theory: The chromosome theory of inheritance

Sutton-Boveri theory: The chromosome theory of inheritance
• postulated independently in 1902 that genetic information is carried by chromosomes
• based on studies on chromosome behavior during the formation of germ cells
Sex chromosome systems
no sex chromosomes: e. g. in mosquitos
XX in
XY in
XX in
XO in
ZW in
Mammals (humans); flies (Drosophila)
true bugs (hemiptera);
Caenorhabditis elegans (xx hermaphrodites)
Birds; Amphibians (Xenopus!); butterflies
ZZ in
ZO in
ZZ in
certain Reptiles, e. g. hawksbill sea turtle
X:A
Drosophila
X:A
1
1
3A XX
0.666
3A XXY
0.666
intersex
intersex
0.5
0.5
0.5
-
• whenever Y is present, human is a male, while Y does not determine sex in flies
X:A = X to autosome ratio; e. g. 1X + 2 sets of homologous A
X:A=0.5
Klinefelter Syndrome (47, XXY)
male but sterile (no sperm);
some female characteristics
1 in 500 male births
Turner Syndrome (45, X)
Female development
but sterile (no eggs)
1 in 3000 female births
Dosage compensation
Problem: males and females have different dosages of X-chromosomal genes,
but must produce same amounts of X-chromosomal gene products
GENES:
PRODUCTS:
A
B
C
D
A
B
C
D
A
B
C
D
A
B
C
D
B
C
B
C
WITHOUT
dosage compensation!
A
B
C
D
A
B
C
D
B
C
B
B
Solution:
B
Drosophila: single X chromosome in males is hyperactivated; produces about
twice as much gene product as one X in females
Humans: all but one X chromosome are inactivated by heterochromatization;
only one X chromosome is genetically active
Barr body
Barr bodies + 1 = total number of X
Lyon hypothesis,1961: either paternal or maternal X is the target of random
inactivation during early embryogenesis and the inactivated state is then
maintained over consecutive cell generations
Xm Xp
Xm Xp
Xm Xp
Xm Xp
Xm Xp
Xm Xp
Anhidrotic Ectodermal Displasia
hemizygous men: no sweat glands, no teeth, sparse hair growth
(hemizygous: only one allele of a gene present;
males are hemizygous for all X-chromosomal genes)
heterozygous women: mosaic expression of the disease
Thomas Hunt Morgan, 1910
reciprocal cross
Cross B
Cross A
x
P1
Gametes
F1
Gametes
F2
Xw+
Xw+
x
Xw
all
w
Xw+ X
all
Y
Xw
all
Xw+
Y
Xw
Xw+
all
Xw
Xw+
Y
all
Xw
1/2
1/2
1/2
1/2
1/2
1/2
Y
Calvin Bridges, 1914:
Meiotic Non-Disjunction proves chromosome theory of inheritance
reciprocal cross
Cross B
x
P1
Gametes
Nondisjunction
Xw
Xw
Xw+
Xw+
F1
Xw Xw
Xw Xw Xw+
Y
Y
Xw Xw Y
die
O
Xw+ O
sterile
YO
die
X-linked human genetic disorders
• about 100 known X-linked recessive human diseases
• examples:
• red-green colorblindness:
• 8% of males (Western European)
• 0.4% of females (Western European)
• hemophilia (“bleeder’s disease”):
• caused by lack of different proteins (“factors”)
required for blood clotting
• 2 main forms:
• hemophilia A; 75% of the cases; more severe form;
factor VIII is missing
• hemophilia B; 25% of the cases; less severe form
factor IX is missing
• therapy: administration of missing factor isolated from blood
or produced from the cloned gene
Hemophila as a recessive X-linked trait:
Inheritance of X-linked recessive disorders
almost exclusively males affected:
• one copy of the mutant allele is sufficient,
because men are hemizygous for all X-chromosomal genes
women are rarely affected:
• two copies of the mutant allele are required, one from hemizygous (sick)
father + one from heterozygous mother (carrier)
female carriers:
• sons have 50% chance to be hemizygous for mutant allele and sick
• daughters all healthy but 50% carriers
hemizygous, sick fathers:
• cannot pass on the disease to their sons
• daughters all healthy but all carriers (given that mother is no carrier)
disease usually skips a generation:
father passes disease through daughter to grandson
Hemophila as a recessive X-linked trait:
Vitamin D-resistant rickets as a dominant X-linked trait: