Transcript PowerPoint Presentation - Mammalian X

As you all know genes reside on chromosomes. This basic fact
is called the chromosome theory of inheritance. However
earlier in this century, the issue of where the units of
heredity resided was fiercely debated.
The notion the genes were located on the chromosomes came
from the recognition that the behavior of Mendel's particles
during meiosis parallels the behavior of chromosomes at
meiosis.
Mendel’s Laws of independent assortment imply that genes on
the same chromosome are inherited together and genes on
different chromosomes are inherited independently.
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Sex-linked
Although these were convincing correlations, actual proof of the
chromosome theory required the discovery of sex linkage.
Remember, Mendel had found that reciprocal crosses produce
equal results with respect to the progeny. In general geneticists
confirmed his results.
However exceptions did arise. The most famous exception was
that discovered by Tomas Hunt Morgan in the fruit fly Drosophila
melanogaster. Drosophila eyes are normally bright red.
Morgan discovered an exceptional white-eyed male.
He performed the following crosses:
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Morgans crosses
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X and Y chromosomes
Somehow eye color was linked to sex
The key to understanding this pattern of inheritance arose
from work demonstrating that males and females of a given
species often differ in the chromosome constitution.
For example, they found that male and female Drosophila both
have four chromosome pairs. However in males one of the pairs
the members differed in size:
Female Drosophila:
Male Drosophila:
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Sex chromosomes
Morgan realized that difference in chromosome constitution was
the basis of sex determination in Drosophila:
Females produce only X-bearing gametes, while males produce X
and Y-bearing gametes.
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If the gene for eye color resides on a X chromosome
There is no counterpart for this gene on the Y chromosome5
Formal explanation
Females have 2 copies of the eye color gene
males have one copy
W (red) is dominant over w (white)
Red
XWXW
white
XwY
F1
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Formal explanation
Females have 2 copies of the eye color gene and males have one copy
W (red) is dominant over w (white)
Red
XWXw
Red
XWY
F2
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Formal explanation
The reciprocal cross
White
XwXw
Red
XWY
F1
In the F1 all the females are red and all the males are white
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Formal explanation
Red
XWXw
White
XwY
F2
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This explanation also accounts for the fact that equal numbers of
male and female progeny are produced.
With this explanation of sex determination, Morgan realized that he
could explain the inheritance patterns of eye color by assuming:
1.
The gene determining eye color resides on the X chromosome
(red and white eyes represent normal and mutant alleles of this gene)
2. There is no counterpart for this gene on the Y chromosome
Thus females carry two copies of the gene, while males carry
only a single copy.
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Red-green color blindness
Red-green color blindness means that a person cannot distinguish
shades of red and green. Males are affected 16 times more often
than females, because the gene is located on the X chromosome.
In color-blind men, the green or red cones worked improperly.
The genes for the red and green receptors were altered in these
men
X-linked red-color blindness is a recessive trait. Females
heterozygous for this trait have normal vision. The color perception
defect manifests itself in females only when it is inherited from
both parents.
By contrast, males inherit their single X-chromosome from their
mothers and become red green color blind if this X-chromosome
has the color perception defect.
The dominant (normal) X chromosome is represented as XCB.
The recessive (mutant) chromosome is represented as Xcb.
Since males have only one X-chromosome, if this chromosome has
the red-green color blind allele, the males will have the color
perception defect.
Females have 2 X-chromosomes. Both X-chromosomes must carry
the mutant allele for the females to be color blind. Red-green color
blind females are homozygous for the recessive allele.
Females with one mutant allele and one normal allele are
heterozygous "carriers". They are not color blind, but they can pass
the color blindness to their children.
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Sex determination
Bridges a student of Morgan set up the cross outlined above in
large numbers
P cross:
white females
XwXw
x
x
red males
XWY
As expected, he obtained red-eyed females (XwXW) and whiteeyed males (XwY)
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Primary exception
About 1 in every 2000 progeny he obtained a white-eyed
fertile female or a red-eyed sterile male.
These were called primary exceptional progeny
How can these exceptional progeny be explained?
Bridges suggested that occasionally during meiosis the X
chromosomes fail to separate during meiotic division.
Normal separation of the X chromosomes
ｷ
produces Xw gametes
Failure of X chromosome separation
ｷ
(non disjunction) XwXw and nullo gametes
autosome
X
autosome
X
disjunction
Non-disjunction
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Bridges and non-dysjunction
white
XwXw
red
XWY
F1
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Bridges assumed that XXX and Y0 progeny die and the only
two viable progeny types were XXY and X0
In this model sex is determined by the number of X
chromosomes rather than the presence or absence of the Y
chromosome
This model makes a strong prediction that is genes reside on
chromosome the exceptional red-eyed males should be X0 and
the exceptional white eyed females should be XXY.
THAT IS WHAT BRIDGES FOUND
(something to think about: What classes of progeny would be
expected from the cross XwXwY x XWY ?)
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Sex chromosomes and sex
In Drosophila, it is the number of X's that determine sex.
In mammals it is the presence or absence of a Y chromosome
that determines sex.
Species
XX
XY
XXY
XO
Drosophila
female
male
female
male
Humans
female
male
male
female
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Bridges and Triploids
White
XwXwY
Y
XwXw
Xw
XwY
red
XWY
XW
Y
XWY
YY
Red male
XW XwXw
lethal
Y XwXw
lethal
white female
XW Xw
Y Xw
Red female
White male
XW XwY
Y XwY
Red female
White male
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Triploidy
Species that are triploid, reproduce asexually (plant species)
What are the consequences of triploidy during mitosis and
meiosis?
Haploid
Diploid
Triploid
Mitosis
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Triploidy
Species that are triploid, reproduce asexually (plant species)
What are the consequences of triploidy during mitosis and
meiosis?
Haploid
Diploid
Triploid
Mitosis
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Meiosis and triploids
MeiosisI
This is for one chromosome. If there are n chromosomes in
20an
organism, then balanced gametes (equal copies of all
chromosomes) are very rare.
Meiosis and triploids
MeiosisI
4N
3N
3N
Triploids produce
unbalanced gametes
2N
This is for one chromosome. If there are n chromosomes in
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organism, then balanced gametes (equal copies of all
chromosomes) is very rare.
Seedless watermelons
Triploidy is useful in agriculture.
Biological control:
Cross a tetraploid watermelon with a diploid watermelon
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And triploid toads
Triploid toads
Nature Genetics 30, 325 - 328 (2002)
Tetraploid green toads reproduce through diploid eggs and sperm
cells.
A new taxon was discovered at an isolated site in the Karakoram
mountain range.
Every wild toad caught from eight localities was triploid
Did not find a single diploid or tetraploid Batura toad. Both males
and females were found
3N female
3N male
N
elimination
N
elimination
2N
2N
2N
N
N
3N
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Sex in organisms
Sex chromosomes and sex linkage:
In Drosophila, it is the number of X's that determine sex while
in mammals it is the presence or absence of a Y chromosome
that determines sex.
Homogametic sex- Producing gametes that contain one type of
chromosome (females in mammals and insects, males in birds
and reptiles)
Heterogametic sex- Producing gametes that contain two types
of chromosomes (males in mammals and insects, females in birds
and reptiles)
Species
XX
XY
XXY
XO
Drosophila
female
male
female
Male (sterile)
Humans
female
male
male
female
Bridges could tell genotype by where the sex chromosome went
and therefore established that chromosomes carried genes
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Non-sex chromosomes are called autosomes
Humans have 22 autosomes, Drosophila has 3
Homogametic sex-
XX-
females in humans
males in birds
Heterogametic sex-
XY-
males in humans
Hemizygous
gene present in one copy in a diploid
organism
Human males are hemizygous for
genes on the X-chromosome
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Sex linked
Described below is an actual case history of the use of pedigree
analysis:
After the death of a wealthy individual (II:3), a man claiming to
be his son (III:3) filed a paternity suit and claimed the
inheritance.
The deceased had only two living nephews (III:1 and III:2 who
were sons of his brothers (II:1 and II:2). In determining
whether the man was actually the son and had the rights to the
inheritance which of the following markers would be most useful
Autosomal
X-linked
Y-linked
$$$
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Surname project
Y
Y
Y
Y
All males in this pedigree will have the SAME Y-chromosome!!!
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Mendelian genetics in Humans: Autosomal and Sexlinked patterns of inheritance
Obviously examining inheritance patterns in humans is much more
difficult than in Drosophila because defined crosses cannot be
constructed. In addition humans produce at most a few offspring
rather than the hundreds produced in experimental genetic
organisms such as Drosophila
It is important to study mendellian inheritance in humans because
of the practical relevance and availability of sophisticated
phenotypic analyses.
Therefore the basic methods of human genetics are observational
rather than experimental and require the analysis of matings that
have already taken place rather than the design and execution of
crosses to directly test a hypothesis
To understand inheritance patterns in human genetics you often
follow a trait for several generations to infer its mode of
inheritance. For this purpose the geneticist constructs family trees
or pedigrees. Pedigrees trace the inheritance pattern of a
particular trait through many generations. Pedigrees enable
geneticists to determine whether a familial trait is genetically
determined and its mode of inheritance (dominant/recessive,
autosomal/sex-linked)
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Pedigree symbols:
Male
Female
Sex Unknown
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Affected individual
Spontaneous
abortion
Number of individuals
Deceased
Termination
of pregnancy
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Pedigree symbols:
relationship line
Sibship line
line of descent
individual’s lines
consanguinity
Monozygotic
Dizygotic
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Characteristics of an autosomal recesssive trait:
Patterns in pedigrees of Autosomal recessive traits:
There are several features in a pedigree that suggest a recessive
pattern of inheritance:
1.
Rare traits, the pedigree usually involves mating between two
unaffected heterozygotes with the production of one or more
homozygous offspring.
2. The probability of an affected child from a mating of two
heterozygotes is 25%
3. Two affected individuals usually produce offspring all of whom
are affected
4. Males and females are at equal risk, since the trait is autosomal
5. In pedigrees involving rare traits, consanguinity is often involved.
In the pedigree shown below, an autosomal recessive inheritance
pattern is observed:
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Characteristics of an autosomal dominant trait:
1. Every affected individual should have at least one affected parent.
2. An affected individual has a 50% chance of transmitting the trait
3. Males and females should be affected with equal frequency
4. Two affected individuals may have unaffected children
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The following pedigree outlines the typical inheritance pattern
found in red-green color-blindness.
Does this fit an autosomal recessive or autosomal dominant
pattern of inheritance?
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Characteristics of a sexlinked trait:
Hemizygous males and homozygous females are affected
Phenotypic expression is much more common in males than in
females, and in the case of rare alleles, males are almost
exclusively affected
Affected males transmit the gene to all daughters but not to any
sons
Daughters of affected males will usually be heterozygous and
therefore unaffected.
Sons of heterozygous females have a 50% chance of receiving the
recessive gene.
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