SHEK 2105: GENETIK ASAS MANUSIA

Lecture 5: Chromosome and Heredity

Yusrizam Sharifuddin
yusrizam@um.edu.my

Institut Sains Biologi, Universiti Malaya

Institute of Biological Sciences, University of Malaya 1
Mendelian Genetics and Chromosome

Y. Sharifuddin 2
 Chromosome Number

• Each species has a characteristic set of

chromosomes. Humans have 23 pairs (46)

Chromosome vocabulary

Chromatin: -diffuse thread

Euchromatin: -lightly-stained region
Heterochromatin:- darkly-stained region

Haploid (n)
Diploid (2n)
Tetraploid (4n)
Octaploid (8n)

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 Sex Chromosomes

Sex chromosomes in grasshoppers

• Females are XX
• Males are XO

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 Sex Chromosomes

Sex chromosomes in humans

• Sex chromosomes. The terminal regions are

common to both sex chromosomes
• Female gamete is X-bearing; male gamete is Y-
bearing
•Females are XX
•Males are XY • Autosomes (other chromosomes in the
genome)
•During meiosis in males, the X and Y
chromosomes pair

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 Chromosome Theory of Heredity

Studies on the inheritance of a sex-linked trait in Drosophila provided the first

evidence that the meiotic behavior of chromosomes is the basis for
Mendel’s Principles of Segregation and Independent Assortment

• One day in 1910, American geneticist Thomas Hunt Morgan peered through a hand lens
at a male fruit fly, and he noticed it didn't look right. Instead of having the normally
brilliant red eyes of wild-type Drosophila melanogaster, this fly had white eyes.

• Morgan was particularly interested in how traits were inherited and distributed in
developing organisms, and he wondered what caused this fly's eyes to deviate from the
norm. Morgan's fly lab at Columbia University was already in the habit of breeding
Drosophila so that the researchers there could observe the transmission of genetic traits
through successive generations, so Morgan chose to do a simple breeding analysis to find
out more about white eyes.

• Little did Morgan know that, with this white-eyed fly, he was about to confirm the
chromosome theory. Later on, one of Morgan’s students, Calvin B. Bridges obtained
definitive proof for this Chromosome Theory of Heredity

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 Chromosome Theory of Heredity

Morgan’s Experiments
• The wild-type females are assumed to be
homozygous for the w+ allele

• The male fly is assumed to carry the mutant w

allele on its X chromosome and neither of the
alleles on its Y chromosome

• An organism that has only one copy of a gene

is called a hemizygote

• The transmission of the mutant condition in

association with sex suggested that the gene for
eye colour was present on the X chromosome
but not on the Y chromosome

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 Chromosome Theory of Heredity

Morgan’s Experiments

Experimental test to Morgan’s hypothesis that the gene for

eye colour in Drosophila is X-linked. Experiment in which
heterozygous females were crossed to white-eyed males
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 Chromosome Theory of Heredity

Morgan’s Experiments

Experimental test to Morgan’s hypothesis

that the gene for eye colour in Drosophila
is X-linked. Experiment in which
heterozygous females were crossed to
wild-type males

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 Chromosome Theory of Heredity

Genetic Maps

• Morgan and colleagues also identified other X-linked

genes in Drosophila

• But they also identified genes that were not on the X

chromosome. These genes followed the Mendelian
Principle of Segregation but they did not segregate with
sex just like the gene for eye colour did → these genes
were located on the autosomes of the Drosophila
genome

• They concluded that each Drosophila chromosome

contain a different set of genes

• They also studied the locations of different genes on

the chromosomes, assumed to be in a linear array →
produced the world’s first genetic map

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 Chromosome Theory of Heredity

Non-disjunction as Proof of the Chromosme Theory of Heredity

• Non-disjunction: -failure of the
chromosomes to disjoin (separate) during
one of the meiotic divisions

• Could be due to faulty chromosome

movement, imprecise or incomplete pairing,
centromere malfunction or any other factor
affecting the segregation process

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 Chromosome Theory of Heredity

The Principle of Segregation

Mendel’s Principle of Segregation and meiotic chromosome behaviour. The

segregation of alleles corresponds to the disjunction of paired chromosomes in
the anaphase of the first meiotic division

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 Chromosome Theory of Heredity

The Principle of Independent Assortment

Mendel’s Principle of Independent

Assortment and meiotic behaviour

• Alleles on different pairs of

chromosomes assort
independently in the anaphase of
the first meiotic division because
maternally and paternally
inherited chromosomes have
aligned randomly on the
metaphase plate

• But genes on the same pair of

chromosomes do not assort
independently but tend to travel
together during meiosis as they
are physically linked to each other
– violated the Principle
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 Sex-Linked Genes in Human Beings
X- and Y-linked genes have been studied in humans.
An X-Linked Recessive Disorder: Hemophilia

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 Sex-Linked Genes in Human Beings

Genes on Both the X and Y Chromosomes

• The Human Genome Project has identified 307
genes on the human Y chromosome compared to
more than 1000 genes on the X chromosome
• Few genes on the Y chromosome; several of the
genes on the human Y chromosome seem to be
required for male fertility – hence, such mutation
will have small or no chance of being transmitted
to the next generation
• Few Y-linked traits

• Some genes are present on both the X and Y

chromosomes, mostly at the terminal region – do
not follow the distinct sex chromosome linked
pattern of inheritance and mimicks autosomal
segregation
• Pseudoautosomal genes are on both the X and Y
chromosomes

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 Sex Chromosomes and Sex Determination

In some organisms, chromosomes—in particular, the sex chromosomes—determine

male and female phenotypes.
Sex Determination in Human Beings: The Presence the Y Chromosome

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 Sex Chromosomes and Sex Determination

The SRY gene and the Testis-Determining Factor (TDF)

• Evidence localising the gene for the testis-determining factor (TDF) to the short arm
of the Y chromosome in normal males
• The TDF is the product of the SRY gene. In XX males, a small region containing this
gene has been inserted into one of the X chromosomes and in XY females, it has been
deleted from the Y chromosome

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 Sex Chromosomes and Sex Determination

Testicular Feminisation

Testicular feminisation, a condition caused by an X-linked mutation, tfm, that

prevents the production of the testosterone receptor

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 Sex Chromosomes and Sex Determination

Sex Determination in Drosophila:

The Ratio of X Chromosomes to Autosomes

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 Sex Chromosomes and Sex Determination

Other Sex Determination Mechanisms: The ZW System

Homogametic Heterogametic
sex sex

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 Sex Chromosomes and Sex Determination

Other Sex Determination Systems: The Haplo-Diplo System

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 Sex-Linked Genes in Human Beings

• Disorders such as hemophilia and color blindness, which are caused by

recessive X-linked mutations, are more common in males than in females.
• In humans the Y chromosome carries fewer genes than the X chromosome.
• In humans pseudoautosomal genes are located on both the X and Y
chromosomes.

• In humans sex is determined by a dominant effect of the SRY gene on the Y

chromosome; the product of this gene, the testis-determining factor (TDF),
causes a human embryo to develop as a male.
• In Drosophila, sex is determined by the ratio of X chromosomes to sets of
autosomes (X:A); for X:A ≤0.5, the fly develops as a male, for X:A ≥the fly
develops as a female and for 0.5 < X:A < 1.0, it develops as an intersex
• In honeybees, sex is determined by the number of chromosome sets; haploid
embryos develop into males and diploid embryos develop into females.

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 Chromosome Theory of Heredity

Dosage Compensation of X-linked Genes

Biological processes including development of organisms is normally sensitive to any
imbalance in genes number and deviation from this can cause abnormal outcome or
can even be fatal
There are different mechanisms exist for adjusting the unequal dosage of X-linked
genes in male and female animals

Mechanisms of dosage compensation:

• Hyperactivation of X-linked genes in males (Drosophila)

• Inactivation of one copy of X-linked genes in females (mammals)
• Downregulation of X-linked genes in females (Caenorhabditis elegans)

For Drosophila, hyperactivation occur – involves an increase in the activity of genes in

males – achieved by binding of a complex of different proteins binding to various sites on
the X-chromosome → increased gene activity. But in females, no binding → no genes
activity doubling

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 Chromosome Theory of Heredity

X-inactivation

• In placental mammals, dosage compensation is

achieved by the inactivation of one of the female
X-chromosomes

• Inactivated chromosome is randomly chosen but

this inactivation continues throughout the progeny
of that particular cell

• Inactivated chromosomes → Barr body

• Females are genetic mosaics as each maternally

and paternally-inherited X chromosome is
inactivated approximately in half of the cells

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 Chromosome Theory of Heredity

• Colour mosaics due to X chromosome inactivation in female mammals begins with

the formation of clones of cells in a cat embryo that produce different patches of fur
in the adult.
• For tortoiseshell cat, this female is heterozygous for an X-linked coat colour gene.
The orange and black patches are due to inactivation of different alleles in the
pigment-producing cells of the body Y. Sharifuddin 25
 Chromosome Theory of Heredity

• In Drosophila, dosage compensation for X-linked genes is achieved inhyperactivating

the single X chromosome in males

• In mammals, dosage compensation for X-linked genes is achieved by inactivating one

of the two X chromosomes in females

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 Sex-Linked Genes in Human Beings

Calculating the Risk of Inheriting an X-Linked Disorder: Colour-blindness

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