The Chromosomal Basis of

Inheritance

•Chromosome structure
•Classification of chromosomes
•Chromosomal aberrations
 chromosomes in prokaryotic and
eukaryotic cell
Chromosomes are structures within the living cells that contain the
genetic material.
In Prokaryotic
 Chromosomes is circular DNA molecules contain the entire set
of genetic instruction essential for life of the cell. (in a region of
the cytoplasm called the nucleoid).
 When circular DNA copied, the genetic information is passed on
to the daughter cells (new cells created by cell division) during
mitosis.

In Eukaryotes
Chromosomes are threadlike strands that are consisting of
chromatin and carrying the genetic information arranged in a
linear sequence.
To pass genetic traits from one generation to the next, the
chromosomes must be copied, and then the copies must be
divided up.
Chromosome Structure
• DNA is long and thin and fragile: needs
to be packaged to avoid breaking.

• First level is the nucleosome, 200 bp of

DNA wrapped twice around a core of 8
histone proteins (small and very
conserved in evolution). A string of
beads.
• The nucleosomes coil up into a 30 nm
chromatin fiber. This level of packaging
exists even during interphase.
• During cell division, chromatin fibers are
attached in loops of variable size to a
protein scaffold. The DNA probably
attaches at specific AT-rich areas called
scaffold attachment regions.
• The loops may be functional units:
active vs. inactive in transcription.
• Further coiling gives the compact
structures we see in metaphase.
•One section of DNA is a gene
 Centromeres
• Sometimes called the “primary
constriction” on a chromosome, based on
microscopic appearance.

• The centromere is the attachment point

for the spindle.

• The centromere is a region of DNA on the

chromosome.

• During cell division, a large protein

structure, the kinetochore, that attaches to
the centromere DNA sequences. The
spindle proteins then get attached to the
kinetochore.

• The centromere is many repeats of about

170 bp element .

• Centromere regions also contain large

amounts of repeated sequence DNA.
 Telomeres
• Telomeres are the DNA sequences at the ends of chromosomes.
Chromosomes that lose their telomeres often fuse with other chromosomes or
become degraded.
• There are telomere-binding proteins that protect the chromosome ends.
Euchromatin and Heterochromatin
• Euchromatin is the location of active genes (although
many genes in euchromatin are not active: depends on
cell type). During interphase euchromatin is extended
and spread out throughout the cell.

• Heterochromatin is darkly staining, condensed, and

late replicating. Genes in heterochromatin are usually
inactive.
– Some heterochromatin is constitutive : always
heterochromatin: especially around centromeres.
Composed mostly of repeat sequence DNA.
– Other heterochromatin is facultative: can be
heterochromatin or euchromatin

7
•CYTOGENETICS

• Microscopic examination of chromosomes

• Karyotype : the chromosome as viewed under the microscope

(nuclear type).

• Cytogenetics : the microscopic study of chromosomes and analysis

of their genetic property it combine genetic and cytology.

• It describes the light microscopic morphology of the component

chromosomes, so that their relative lengths, centromere positions, and
secondary constrictions can be identified.
 Classification of chromosomes
• Main features to identify and classify
chromosomes
– Size
– Location of the centromeres
– Banding patterns
Chromosome size
• Large chromosomes
• Medium chromosomes
• Small chromosomes
• Sex chromosomes
 Chromosome are classified based on
the Locations of their centromeres.

Chromosomes are placed into broad categories depending on the

position of the centromere.
o Metacentric: centromere in the middle, with arms of equal length.
o Sub-metacentric: centromere near the middle, with arms of slightly
different lengths.
o Acrocentric: centromere near one end, with arms of very different
lengths.
o Telocentric: centromere at one end, with only 1 arm.
Counting out chromosome numbers

Normal human karyotype

 Banding patterns
• G-banding: chromosomes are treated with trypsin
enzyme that partially digest chromosomal
proteins when exposed to dye call Giemsa some
chromosomal region bind the dye heavily and
produce dark band (tightly compacted and G
bands contain high proportion of A-T pairs).
• R (reverse Giemsa) bands -are produced by
heat-treating the chromosomes in saline solution
before staining with Giemsa (the R bands rich in
G-C and most active gene are located in this
bands)
• The banding patterns are unique for chromosomes
G-Banded Metaphase Chromosomes
• Cytogenetic maps indicate the positions of
genes with respect to chromosomal features

•Short •Black •Cinnabar •Vestigial •Brown

aristae body eyes wings eyes

•0 •48.5 •57.5 •67.0 •104.5

•Long aristae •Gray •Red •Normal •Red

(appendages body eyes wings eyes
on head)
•Wild-type phenotypes

•Mutant phenotypes
• A linkage map is a genetic map of a chromosome
based on recombination frequencies

•RESULTS
•Recombination
frequencies
•9% •9.5%
•Chromosome
•17%

•b •cn •vg
 Homologous chromosomes

• When chromosomes are divided into pairs,

the individual chromosomes in each pair are
considered homologous, meaning that the
paired chromosomes are identical to one
another in shape and size.

• These homologous chromosomes are

sometimes referred to as homologs for
short.
 Chromosomes carry genes

 Genes are sections of DNA that make up the building plans for
physical traits
 The genes tell the body how, when, and where to make all the
structures that are necessary for the processes of living.
 Each pair of homologous chromosomes carries the same — but
not necessarily identical — genes.
 For example, both chromosomes of a particular homologous
pair might contain the gene for hair color, but one can be a
“brown hair” version of the gene — alternative versions of
genes are called alleles — and the other can be a “blond hair”
allele.
 Chromosomes carry genes
• One chromosome carries the allele A while its homolog
carries the allele a (the relative size of an allele is normally
very small.
• The alleles code for the different physical traits (phenotypes)
you see in animals and plants like hair color or flower shape.
 Chromosomes carry genes
Each point along the chromosome is called a locus
(Latin for “place”). The plural of locus is loci

Most of the phenotypes that you see are produced

by multiple genes (that is, genes occurring at
different loci and often on different chromosomes)
acting together.

For instance, human eye color is determined by at

least three different genes that reside on two
different chromosomes.
 Chromosome numbers haploid and euploid
 Chromosome numbers can get a bit confusing.
 Some organisms (like bees and wasps) have only one set of
chromosomes (cells with one set of chromosomes are
referred to as haploid);
 Humans are diploid, - have two copies of each chromosome.
 Others have three, four, or as many as sixteen copies of each
chromosome!
 The number of chromosome sets held by a particular
organism is called the ploidy.
 The total number of chromosomes doesn’t tell you what the
ploidy of an organism is.
 For that reason, the number of chromosomes of an organism
is often listed as some multiple of n.
 Human sex cells such as egg or sperm are haploid.
Chromosome number and ploidy condition
in commercial important crop species
Common Haploid Chromosome Ploidy
name no. (X)

alfalfa 8 32 4X

Apple 17 34 2X

Oats 13 52 4X

Wheat, durum 7 28 4X

Wheat, bread 7 42 6X

Barley 7 14 2X

Strawberry 7 56 8X

Humans 23 46 2X
 Variation In Chromosome Number
 Euploidy: Loss or gain of a complete set of
haploid chromosomes

 Chromosomes number are multiples of some basic number (n)

 n: number of chromosome in one nuclear genome (haploid)
that is 1xn=n
 2n is called diploid.
 3n (Triploid), 4n (Tetraploid) etc…are called polyploid.

 Aneuploidy: Loss or gain of less than a complete

set of haploid chromosomes

 Variation in the number of particular chromosomes within a set

 Aneuploidies: changes in part of chromosome sets

 A change from euploid number Monosomy, trisomy, tetrasomy

 In Mendel’s Laws of Heredity:
1. Mendel’s “hereditary factors” were genes.
2. Genes are located on chromosomes.

3. Inherited traits are controlled by versions of genes that occur

in pairs.
– The two versions are called alleles.
– E.g., for the pea plant, for the height trait (or gene) there is
a tall allele and a short allele.
4. A diploid organism has 2 alleles for each trait in total.
One allele for each trait is inherited from each parent.

5. One allele always hides or masks the presence of the other.

This is called the principle of dominance. Dominant (R) vs
recessive (r).

6. Alleles are separated during meiosis I. This is called the

‘law of segregation’
 Terminology
• Homozygous ‐ both alleles for a trait are the
same (AA; aa)
• Heterozygous ‐ the alleles for trait are different
(Aa)
• Genotype ‐ the actual genetic makeup for a trait
(AA; aa; Aa)
• Phenotype ‐ the way in which the genotype is
expressed (tall; short)
• Dominant ‐ the allele that masks the presence
of the other (AA; Aa)
• Recessive ‐ the allele that is masked by the
other (aa)
 Alleles, Locus
•Allele for purple flowers

•Pair of
•Locus for flower-color gene homologous
chromosomes

•Allele for white flowers

Homologous chromosomes
 Additional features of eukaryotes that distinguish them
from prokaryotes :-

• Most eukaryotes undergo sexual reproduction

• The genome size of eukaryotes spans a wider range than

that of most prokaryotes

• Eukaryotic genomes have a lower density of genes

• Prokaryotes are haploid; eukaryotes have varying ploidy

• Eukaryotic genomes tend to be organized into linear

chromosomes with a centromere and telomeres.
• The location of a particular
gene can be seen by tagging
isolated chromosomes with a
fluorescent dye that
highlights the gene

Chromosome #15
FISH
Sex Determination and Sex-
Linked Characteristics
 Sex Determination Mechanisms
• There are many ways in which sex differences arise. In
some species, both sexes are present in the same organism,
a condition termed hermaphroditism;

• organisms that bear both male and female reproductive

structures are said to be monoecious

• Species in which the organism has either male or female

reproductive structures are said to be dioecious – Humans
are dioecious.
• Among dioecious species, sex may be determined
 chromosomally,
 genetically, or
 environmentally
A. Chromosomal Sex-Determination Systems:
Sex chromosomes and non-sex chromosomes

XX-XO system:
• XX – female i.e, (22 + XX)
• XO – male i.e. (22 + X)
grasshoppers

XX-XY system:
• XX – female (is the homogametic sex)
• XY – male (is the heterogametic sex)
mammals
 The inheritance of gender

Mother Father
XX XY
Meiosis

Sex cells X X X Y

• X Y
Fertilisation X XX XY Possible
X XX XY children

Chance of a girl 50%

Chance of a boy 50%
Chromosomal Sex-Determination Systems cont.

ZZ-ZW system:
• ZZ – male i.e. Chicken, 76 + ZZ
• ZW – female i.e. Chicken, 76 + ZW

Birds, amphibians, reptiles, butterflies,

moths.
.
Haplodiploidy system: Diploid Haploid

Haploid set – male

Diploid set – female

Bees, wasps, and ants

Bees
Genic balance system

Sex Determination in Drosophila melanogaster

is based on:

Ratio of X : A determines the sex

i.e.,
X - number of ‘X’ chromosomes;
A - number of haploid sets of autosomes
Chromosome compliments and the sexual
phenotypes in Drosophila
 Platypus Ornithorhynchus anatinus
• Is clearly one of life’s It possesses a furry coat and, like
strangest animals found a mammal, is warm blooded and
Australia and New Guinea.
produces milk to nourish its
young, but it lacks teeth, has a bill,
and lays eggs like a bird. The feet
are webbed like those of a duck,
and females have no nipples
(offspring suck milk directly from
the abdominal skin); males have
spurs on their hind legs that
deliver a deadly, snakelike venom.

 The platypus possesses 52 chromosomes

 Possess ten sex chromosomes:
- Female: XXXXXXXXXX (ten X chromosomes),
- Male: XYXYXYXYXY (five X and five Y chromosomes)
 Genic Sex-Determining System

• No sex chromosomes, only the sex-determining

genes at certain loci.
- Plants, fungi, protists

• Genotypes (for example Bb, bb, etc) at one or more areas on

an autosome determine the sex of an individual plant, fungi,
or protozoan.

• Remember:
• Even in chromosomal sex-determining systems, sex is
determined by individual genes found on the sex
chromosomes, the difference is that with chromosomal
determination the chromosomes between males and females
look DIFFERENT
 Non-genetic sex-determination systems
Environmental Sex Determination
• Examples:

1. Temperature - in turtles
Most snakes and lizards have sex chromosomes but
the sexual phenotypes of many turtles, crocodiles and
alligators is affected by tempt during embryonic
development,
 Warm temperature produce females during certain
times of the year.
 Cool temperatures produce males
 2. Position in the stack - Limpet’s

 The marine mollusk, Crepudila fornicata (common slipper limpet) exhibit

sequential hermaphroditism

 Live in stack – each individual can be male or female, the sex depends on
the limpet’s position on the stack.

 The first limpet settles and releases a chemical to attract additional larvae
to settle on top, these larvae develops into males that serves as mates for
the limpet below.

 After a period of time these males develop into females which attract more
larvae that will develop into males for mates
 The Role of Sex Chromosomes

• The X chromosome contains genetic information

essential for both sexes; at least one copy of
an X is required.

• The male-determining gene is located on the Y

chromosome.
• A single Y, even in the presence of several X,
still produces a male phenotype.

• The absence of Y results in a female phenotype.

The male-determining gene in humans

The SRY gene is on

the Y chromosome
and causes the
development of male
characteristics.
 Sex Determination in Humans XX-XY

• SRY gene on the Y chromosome determines

maleness i.e., sex is ultimately determined by
the presence or absence of the SRY gene.

•1/1000

•1/3000

•1/1000
4.2 Sex-Linked Characteristics are Determined
by Genes on the Sex Chromosomes

Z-linked characteristics

Y-linked characteristics
- Hairy ears
 Sex-Linked Characteristics are Determined by Genes on
the Sex Chromosomes
Z-linked characteristics
• The cameo phenotype (plumage) in Indian blue peafowl
(Peacock) is inherited as a Z-linked recessive trait which
produces brown feathers.
• Results from a Z-linked allele that is recessive to the wild-
type blue allele

Y-linked characteristics
Hairy ears -
 Showing variable expressivity and incomplete penetrance
 Could also be autosomal dominant characteristic expressed only in males
 Sex influenced inheritance

 Inheritance can be affected by the sex of an individual,

although the specific gene may not be carried on X
chromosome.

 Eg., the feather phenotype in chicken is controlled by

a pair of alleles on autosomes but the expression of
the alleles is modified by sex Hormones.
baldness in humans is sex influenced inheritance
Pattern baldness is inherited in the following way:
• (B – bald gene) – dominant

Genotype Phenotype
Female Male
- BB (homozygous dominant) Bald Bald
- Bb (heterozygous) Not bald Bald
- bb (homozygous recessive) Not bald Not bald

•Although females may have pattern baldness (BB

genotype), this phenotype is much more prevalent in
males.
Variation in sex chromosome number can
cause sexual abnormality or lethality.

In Drosophila:
•XXX - lethal.
•XXY - female
•XO – male, but sterile.

For drosophila, Y chromosome is not essential

sex characteristic but is important for fertility in
male flies.
 Alterations of chromosome number or
structure cause some genetic disorders

• Large-scale chromosomal alterations in humans and

other mammals often lead to spontaneous abortions
(miscarriages) or cause a variety of developmental
disorders
• Plants tolerate such genetic changes better
than animals do.

• Also, polyploidy is common in plants, but not animals.

• Polyploids are more normal in appearance than aneuploids.
Alterations of chromosome number or structure
cause some genetic disorders cont.

• In non-disjunction,
pairs of homologous chromosomes do not
separate normally during meiosis (Either in
meiosis I or meiosis II).
 non-disjunction:
Meiosis I pairs of
homologous
chromosomes do
not separate
normally during
meiosis
Nondisjunction (Either in meiosis I
or meiosis II).

Meiosis II

Non-
disjunction
Gametes

n1 n1 n1 n1 n1 n1 n n

Number of chromosomes
(a) Nondisjunction of homo- (b) Nondisjunction of sister
logous chromosomes in chromatids in meiosis II
meiosis I
• As a consequence of nondisjunction, some
gametes receive two of the same type of the same
chromosome and another gamete receives no copy :
= Aneuploidy.

– Trisomic cells have three copies of a particular

chromosome type and have 2n + 1 total chromosomes.
– Monosomic cells have only one copy of a particular
chromosome type and have 2n - 1 chromosomes.

• If the organism survives, aneuploidy typically

leads to a distinct phenotype.
 Chromosomal findings in early miscarriages

40% apparently normal, 60% abnormal:

 Trisomy (47 chromosomes – one extra) 30%

 45,X (45 chromosomes – one missing) 10%

 Triploidy (69 chromosomes – three sets) 10%

 Tetraploidy (92 chromosomes – four sets) 5%

 Other chromosome anomalies 5%

(e.g. structural anomalies)
 Turner Syndrome (45, XO)
The individuals have basic female characteristics but
ovaries are underdeveloped – no eggs

1 in 3000 female births

 •Klinefelter Syndrome (47, XXY)
A chromosomal anomaly characterized by the presence of one X-
chromosome and two Y-chromosomes and thought to be associated with
tallness, aggressiveness, and acne - male develop but no sperm.

•2 in 1000 male births

 Klinefelter syndrome cont.:
• 47, XXY
• 48, XXXY,
• 48, XXYY,
• 49 XXXXY, XXXYY:

Phenotypes similar to 47, XXY.

NB: Phenotypical abnormality more pronounced
when there are more numbers of X.

.
 X-Linked Characteristics:
dosage compensation
• The amount of protein produced by X-linked genes
is equal in both sexes regardless to the fact that
females have two copies of those genes

• Solutions vary
– Fruit flies: dosage compensation is achieved by a
doubling of the activity of the genes on the X
chromosome of the male.
– The worm C. elegans: it is achieved by a halving
of the activity of genes on both of the X
chromosomes in the female
– Placental mammals: genes on one of the X
chromosomes in the female are inactivated
creating Barr body
 Inheritance of X-Linked Genes
• X chromosomes have genes for many characters unrelated to
sex, whereas the Y chromosome mainly encodes genes related
to sex determination.
• X-linked genes follow specific patterns of inheritance
• For a recessive X-linked trait to be expressed
– A female needs two copies of the allele (homozygous)
– A male needs only one copy of the allele)**

• X-linked recessive disorders are much more common in

males than in females
• Examples of Some disorders caused by recessive alleles on
the X chromosome in humans
– Color blindness (mostly X-linked)
– Duchenne muscular dystrophy
– Hemophilia
 X Inactivation in Female Mammals
• In mammalian females, one of the two X chromosomes in
each cell is randomly inactivated during embryonic
development. - but NOT PARMANENTLY-

• The inactive X condenses into a Barr body.

[Bar body is the inactivated X chromosome]
- DNA existing in heterochromatic or genetically inert
state.
- Number of bar bodies depends on the number of X in the
cell.

- Mechanism of inactivation – methylation

• Proposed by Mary Lyon and Liane Russell (1961)

A Barr body is an inactivated
X chromosome. (a) Female
cell with a Barr body (indicated
by arrow
 X chromosomes
Allele for
orange fur
Early embryo:
Allele for
black fur

Cell division and

X chromosome
Two cell inactivation
populations
in adult cat: Active X
Inactive X
Active X

Black fur Orange fur

If a female is
heterozygous for a
particular gene
located on the X
chromosome, she
will be a mosaic for X inactivation
that character. and the tortoise
Lyon-Hypothesis: X-inactivation
A precursor cell to all coat color cells

Random inactivation
In humans with more than one X chromosome, the number of
Barr bodies visible at interphase is always one less than the total
number of X chromosomes. For example, men with Klinefelter
syndrome (47,XXY karyotype) have a single Barr body,
whereas women with a 47,XXX karyotype have two Barr bodies

Barr body
 Mosaicism Reveals the Random
Inactivation of one X chromosome

Regions where
sweat glands
are absent.
 Down Syndrome (Trisomy 21)
• Down syndrome is an aneuploid condition
that results from three copies of
chromosome 21.

• It affects about one out of every 700

children born in the United States.

• The frequency of Down syndrome

increases with the age of the mother, a
correlation that has not been explained.
•© 2011 Pearson Education, Inc.
Down Syndrome (Trisomy 21) [47, XX +21 ]
Normal Karyotype
 • Inheritance of X-Linked Genes

• 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 (there are many genes)
•Barr Bodies are Inactivated X
Chromosomes in Females
 What are Chromosomal Mutations?

• Damage to chromosomes due to

physical or chemical disturbances or
errors during meiosis.
• Two Types of Chromosome Mutations:
 Chromosome Structure
 Chromosome Number
 Alterations of Chromosome
Structure
• Breakage of a chromosome can lead to
four types of changes in chromosome
structure
– Translocation moves a segment from one
chromosome to another
– Deletion removes a chromosomal segment
– Duplication repeats a segment
– Inversion reverses orientation of a segment
within a chromosome
•Alterations of Chromosome Structure
Breakage of a chromosome can lead to four types of changes in chromosome structure

(a) Deletion
•A •B •C •D •E •F •G •H

•A deletion removes a chromosomal segment.

•A •B •C •E •F •G •H

(b) Duplication
•A •B •C •D •E •F •G •H

•A duplication repeats a segment.

•A •B •C •B •C •D •E •F •G •H
(c) Inversion
•A •B •C •D •E •F •G •H

•An inversion reverses a segment within a

chromosome.
•A •D •C •B •E •F •G •H

(d) Translocation
•A •B •C •D •E •F •G •H •M •N •O •P •Q •R

•A translocation moves a segment from one

chromosome to a non-homologous chromosome.
•M •N •O •C •D •E •F •G •H •A •B •P •Q •R
 Human Disorders Due to Chromosomal Alterations

• Alterations of chromosome number and structure are

associated with some serious disorders.

• Some types of aneuploidy appear to upset the genetic

balance less than others, resulting in individuals surviving
to birth and beyond.

• These surviving individuals have a set of symptoms, or

syndrome, characteristic of the type of aneuploidy.
The Karyotype: an international description
Total number of chromosomes,

Sex chromosome constitution,

Anomalies/variants.
46,XY
47,XX,+21 Trisomy 21 (Down syndrome)
47,XXX Triple X syndrome
69,XXY Triploidy

45,XX,der(13;14)(p11;q11) Robertsonian translocation

46,XY,t(2;4)(p12;q12) Reciprocal translocation

46,XX,del(5)(p25) Deletion tip of chromosome 5

46,XX,dup(2)(p13p22) Duplication of part of short arm Chr 2
46,XY,inv(11)(p15q14) Pericentric inversion chromosome 11
46,XY,fra(X)(q27.3) Fragile X syndrome
46,XY/47,XXY Mosaicism normal/Klinefelter syndrome
Disorders Caused by Structurally Altered Chromosomes

• The syndrome cri du chat (“cry of the cat”), results

from a specific deletion in chromosome 5
• i.e., (46, XX, 5p-)
– Also known as 5p- (5p minus) syndrome,
– Freq. 1 in 20,000 to 50,000 newborns
• A child born with this syndrome is mentally retarded
and has a cat-like cry; individuals usually die in
infancy or early childhood.
 Certain cancers,
including chronic
myelogenous
•Normal chromosome 9 leukemia (CML)

•Normal chromosome 22

•Reciprocal translocation

•Translocated chromosome 9 • Caused by

translocations of 2
chromosomes. parts of
two chromosomes (9 and
22 switch places)
•Translocated chromosome 22
(Philadelphia chromosome) • diseases of the bone
marrow in which excess
cells are produced