Chromosomal theory of heredity states that chromosomes, not just traits, are inherited. It was developed in 1902 and linked Mendel's work on genes to chromosome behavior. The key points are: chromosomes contain genes and are inherited in pairs from parents; during meiosis homologous chromosomes separate so gametes receive one of each; fertilization restores chromosome pairs. Later, researchers discovered that some genes are linked if on the same chromosome and can be mapped based on recombination rates. Sex chromosomes also carry traits, with mutations on the X chromosome being sex-linked in many species.

1. Chromosomal
theory
of heredity.
Genetics of a sex

2. PLAN
• Chromosome Theory of Inheritance
• Gene Linkage
• Discovery of Crossing-Over and
Recombination
• Sex-Linkage and Sex-determining
Chromosomes

3. Chromosome Theory of Inheritance
Sutton and Boveri in 1902 correlated Mendel's
conclusions about genes (or inherited traits) to the
behavior of chromosomes during mitosis and meiosis.
Sutton is credited with first proposing the chromosome
theory of inheritance:
• Chromosomes are in pairs
• Homologous chromosomes separate during meiosis so
that alleles are segregated
• Meiotic products have one of each homologous
chromosome but not both
• Fertilization restores the pairs of chromosomes
• Genes are located on chromosomes

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6. There are far more genetic traits than
chromosome pairs.
And Mendelian inheritance
patterns require genes to be inherited
independently of each other.
In the early 1900's researchers
raced to find explanations, even as the
explanation was "at hand".

7. The chromosome theory of inheritance is based on a
few fundamental principles
– Chromosomes contain the genetic material
– Chromosomes are replicated and passed allong from
parent to offspring
– The nuclei of most eukaryotic cells contain chromosomes
that are found in homologous pairs. During meiosis, each
homologue segregates into one of the two daughter nuclei
– During the formation of gametes, diferent types of
(nonhomollogous) chromosomes segregate independently
– Each parent contributtes one set of chromosomes to its off
spring. The sets are functionally equivalent
– Each carries a full complement of genes

8. Gene Linkage
In 1908, researchers discovered a dihybrid cross in
sweet peas that did not give the predicted Mendelian
ratio of 9:3:3:1. They could not explain why their
results were closer to 75% and 25% (the 3:1 ratio
expected for a monohybrid cross).
Ultimately it was shown that the flower color and
pollen length (the genesobserved) were on the same
chromosome.
Since we inherit entire chromosomes all genes on
one chromosome are inherited together as a single
unit (called the - linkage group)

9. Discovery of Crossing-Over
and Recombination
Sometimes with a cross involving linked genes, the
researchers would get a few individuals that "mixed" –
or a cross.
Recall that during our discussion of meiosis that
crossing over occurs which results in the exchange
of bits and pieces of DNA between homologous pairs
of hromosomes at the chiasmata during prophase I.
This process of recombination results in gametes
(or meiotic products) that are not identical; some of
the linkage groups have been changed by the
crossing-over.

11. When recombination takes place the expected inheritance
ratio for linked genes is altered slightly by the recombinant
gametes. This frequency of recombination
can be measured (very tediously) for a number of pairs of
genes and used to locate the relative positions of genes on
their respective chromosomes.
This process of pin-pointing specific genes on the
chromosome is called chromosome mapping. Each map
unit, called a centimorgan, is defined as the distance within
which a cross-over is expected in 1% of the gametes

12. Sex-Linkage and Sex-determining
Chromosomes
By the early 1900's it was known that males and
females of most species have one pair of "not-
exactly-matching" homologous chromosomes,
which determine thegender of the individual.
These chromosomes are called the sex
chromosomes.
(The truly matching chromosomes are the
autosomes.)

13. Sex-Linked Genes
Yet no one thought these chromosomes would have genes that
coded for somatic traits until Thomas Hunt Morgan "accidentally"
discovered this. Morgan spent much of his career studying
inheritance patterns of the fruit fly, Drosophila melanogaster.
Fruit flies are good organisms to work with in inheritance studies.
They:
• have a short generation time (important for research spanning a
number of generations)
• are small and easy to keep in a laboratory
• produce reasonably good numbers of offspring
• have a number of easy to see inheritable characteristics
• have a chromosome number of 8 (4 pairs of chromosomes)

14. Morgan was perhaps the first to take full
advantage of the fruit fly in genetics.
One of the things he did was to actively seek
varieties of flies different from the normal, or
"wild" type. While doing so, he happened upon a
"new" trait: white eye.
Morgan made several crosse s using his white-
eyed male, expecting the standard Mendelian
results.
He did not get them. While the ratio of 3:1 was
obtained, all of the white-eyed second generation
offspring were male flies. All females had red
eyes (and 25% of the males also had red eyes).
Morgan concluded that eye color was related to
sex, and proceeded to investigate how.

16. Morgan demonstrated that the sex-determining
chromosomes also carry other genetic information.
The other traits are said to be sex-linked because they
are inherited along with the sex of the individual. Because
the X and Y chromosome are not exactly matching, the X
chromosome can have genes that are not located on
the Y chromosome, and vice-versa. Some of these genes
are unrelated to the sexual characteristics, but are inherited
with the sex-determination.
This is referred to as sex-linkage.

17. Sex-Linked Genes
In humans and other mammals, there are two varieties of sex
chromosomes: a larger X chromosome and a smaller Y
chromosome.
Only the ends of the Y chromosome have regions that are
homologous with corresponding regions of the X chromosome.
The SRY gene on the Y chromosome codes for a protein that
directs the development of male anatomical features.
Females are XX, and males are XY.
Each ovum contains an X chromosome, while a sperm may
contain either an X or a Y chromosome.
Other animals have different methods of sex determination.
A gene that is located on either sex chromosome is called a sex-
linked gene.
Genes on the Y chromosome are called Y-linked genes; there are
few of these.
Genes on the X chromosome are called X-linked genes

18. Humans have 46 chromosomes
– 44 autosomes
– 2 sex chromosomes
• Males contain one X and one Y chromosome
– They are termed heterogametic
• Females have two X chromosomes
– They are termed homogametic
• The Y chromosome determines maleness
In some insects,
– Males are XO and females are XX
• In other insects (fruit fly, for example)
– Males are XY and females are XX
• The Y chromosome does not determines maleness
• Rather, it is the ratio between the X chromosomes
and the number of sets of autosomes (X/A)
– If X/A = 0.5, the fly becomes a male
– If X/A = 1.0, the fly becomes a female

19. The Z–W system in birds and some fish
The sex chromosomes are designated Z and W to distinguish
them from the X and Y chromosomes of mammals
• Males contain two Z chromosomes
– Hence, they are homogametic
• Females have one Z and one W chromosome
– Hence, they are heterogametic
The haplodiploid system in bees.
Males are known as the drones.
– They are haploid
– Produced from unfertilized haploid eggs
• Females include the worker bees and queen bees
– They are diploid
– Produced from fertilized eggs

21. Transmission of Genes Located on Human Sex
Chromosomes
Genes that are found on one of the two types of
sex chromosomes but not on both are termed
sexlinked
– Indeed, sex-linked and X-linked tend to be used
synonymously
– They are said to be hemizygous for their X-linked
genes

22. - Genes that are found on the Y chromosome are
called holandric genes
- The X and Y chromosomes also contain short
regions of homology at one end
– These promote the necesary pairing of the two
chromosomes in meiosis (off spermattogenesis)
The few genes found in this homologous region
follow a pseudoautosomal pattern of inheritance
– Their inheritance patern is the same as that of a
gene found on an autosome

24. Some human sex-linked traits are
• Hemophilia (X)
• Hairy ear rims (Y)
• Red-green color blindness (X)
• Duchenne muscular dystrophy (protein
dystrophin on X)

25. 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

26. Vitamin D-resistant rickets as a dominant X-linked trait:
Hemophila as a recessive X-linked trait:

27. A special feature of the sex chromosomes
The Barr Body
Females have two X-chromosomes. In cells, one of them
is deactivated during embryonic development and forms a
tightly condensed object that lines the nuclear membrane,
the so-call Barr body.
Transcription does not occur on the Barr body except in
certain cells . The choice of which X gets condensed for a
given cell line appears to be random, although there is
evidence that a specific gene coding for a special RNA
molecule is responsible for the X inactivation producing
the Barr body.

28. 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
generation