Download Lecture 3: Chromosomes and sex determination

Lecture 3: Chromosomes and sex determination
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Sex chromosomes
Sex linkage
Chromosome nondisjunction
Sex determination
Sex-linked traits in humans
Red-eyed and white-eyed Drosophila
The parallel behavior of Mendel’s factors
(=genes) and chromosomes in meiosis
Sutton and Bovery in 1902 were the first to come up
with this idea. It laid the foundation for the
chromosome theory of heredity.
¾ existence alleles in pairs (A, a) is due
diploidy (2n)
¾ equal segregation is due to disjoining of
homologs in Anaphase I
¾ independent assortment is due to alternative
methaphase alignments of two pairs of
homolologs
¾ constant number of chromosomes in
individuals
¾ different species have different but constant
numbers
¼ AB
¾ phenotypic difference between sexes
correlate with inheritance of certain
chromosomes (sex chromosomes)
¼ ab
Fruit fly Drosophila
Thomas Hunt Morgan
1866-1945
Columbia Univ. 1910-1927
Nobel Prize in 1933
Caltech 1927-1942
II, III, IV: autosomes
I: sex chromosomes
Human sex chromosomes
Inheritance pattern of sex chromosomes (X and Y)
Females:
homogametic
sex (only X)
Males:
heterogametic sex
(½ X and ½ Y)
Notice: equal ratio
between the
sexes is a
consequence of
the Law of Equal
Segregation
Inheritance pattern of sex chromosomes (X and Y)
X-chromosomes:
from mothers to
sons and
daughters;
from fathers to
daughters
Inheritance pattern of sex chromosomes (X and Y)
from father
X-chromosomes:
from mothers go
to sons and
daughters;
from fathers to
daughters
Strictly
paternal
mode of
inheritance
of Y
chromosome
to son
Inheritance of X-linked traits (eye color)
F1
Thomas Morgan around 1909
all red-eyed
Inheritance of X-linked traits (eye color)
F2
F1
all red-eyed
3 red (2 ♀:1♂) : 1 white
♂
Inheritance of X-linked traits (eye color)
Let’s call the mutant allele of the gene for eye color w (for
white mutation). Then the wild type allele is w+
Morgan hypothesized the following:
1.The gene for eye color resides on X chromosome.
2.Females with red eyes are homozygous w+ / w+.
3.Males with white eyes are hemizygous w / Y, because Y
chromosome does not carry anyF2
allele of this gene.
F1
4.Wild type allele w+ is dominant, mutant allele w is
recessive, then heterozygous females w+ / w have red
eyes.
all red-eyed
Then he could explain the results of the cross
3 red (2 ♀:1♂) : 1 white
♂
Inheritance of X-linked traits (eye color)
F2
3 red (2 ♀:1♂) : 1 white
♂
Inheritance of X-linked traits (eye color)
F2
3 red (2 ♀:1♂) : 1 white
♂
Inheritance of X-linked traits (eye color)
Inheritance of X-linked traits (eye color) – a reciprocal cross
Reciprocal cross produced a different result!
In general, such results indicate sex linkage for a
gene in question
™ Morgan’s work indicated that the inheritance of a
particular gene (w, eye color) correlates with the
inheritance of a particular chromosome (X
chromosome).
™ This suggests that the w gene resides on the X
chromosome.
™ This correlation was a strong evidence (but yet
the final proof) in support of the chromosome theory
of heredity.
"Non-disjunction as proof of the chromosome theory of heredity"
Calvin Bridges
1889-1938
"Non-disjunction as proof of the chromosome theory of heredity"
The same cross as Morgan’s reciprocal cross:
Most of the progeny were as expected.
But rarely (1 case out of 2,000) the cross
produced “exceptional” progeny:
white-eyed females and red-eyed males
expecting the same results:
Meiotic non-disjunction of the X-chromosome
"Non-disjunction as proof of the chromosome theory of heredity"
The same cross as Morgan’s reciprocal cross:
Most of the progeny were as expected.
But rarely (1 case out of 2,000) the cross
produced “exceptional” progeny:
white-eyed females and red-eyed males
Explanation of the “exceptional” progeny:
♀
expecting the same results:
♂
Humans:
♀XX: No Y chromosomes
♂XY: One Y chromosome
X0 - females (sterile)
XXY - males
Different types of chromosomal
sex determination
¾ In humans, Y chromosome actively
(dominantly) defines maleness (SRY region)
¾ In Drosophila, Y chromosome does not
define maleness, but is required for male
fertility
♀XX: Two X chromosomes per 3 pairs of autosomes
♂XY: One X chromosome per 3 pairs of autosomes
X0 - males (sterile), XXY – females
"Non-disjunction as proof of the chromosome theory of heredity"
Explanation of the “exceptional” progeny:
♀
♂
Aberrant number of chromosomes in
‘exceptional’ progeny was verified by direct
microscopic examination
Inheritance of X-linked recessive traits
in humans: hemophilia in European royalty
Queen Victoria was heterozygous for the X-linked recessive hemophilia allele.
The trait may have arisen as a mutation in one of her parents’ germ cells or in
her own germ line
Inheritance of X-linked recessive traits in humans
Examples:
¾ hemophilia - inability of blood to clot, caused by defective Factor VIII, there are also other types;
¾ Duchenne’s muscular dystrophy - fatal, death by early adulthood;
¾ red-green color blindness;
¾ testicular feminization syndrome (androgen insensitivity) – the individuals are XY but phenotypically
develop as females (although sterile)
¾ 1,500 genes total
Inheritance of
autosomal
recessive traits
in humans
Both sexes are affected
The trait may not be seen
for many generations
(heterozygotes)
Inbreeding is often
involved in revealing the
trait (to produce
homozygotes)
Inheritance of
autosomal dominant
traits in humans
Both sexes are affected with equal ratio
Both sexes transmit the trait
The trait is seen in every generation
Inheritance of X-linked dominant traits
in humans: faulty tooth enamel and hypertrichosis
Both sexes are affected
May look similar to autosomal dominant but:
Males pass the trait only to daughters
Females pass the traits to daughters and to sons
Inheritance of Y-linked traits in humans
= SRY (Sexdetermining
Region of Y)