Chromosomes

DNA
DNA is a polymer made from many thousands of nucleotides strung together

Nucleotide is made of a
• Deoxyribose (5 carbon Sugar)
• Phosphate group
• Base (A,C,G,T)

DNA and its Building Nucleotides:

Guanine (G), Adenine (A),
Cytosine (C), Thymine (T).

The amount of (G) equals the amount of

(C);
and the amount of (A) equals the amount
of (T)

A-T two hydrogen bonds

G-C three hydrogen bonds
What is a chromosome?
Chromosome are given the name (Chromo = color; Soma = body) due to their
marked affinity for basic dyes.

Metaphase: Chromosomes are

the most easily observed and
studied during metaphase when
they are very thick, quite short and
well spread in the cell.

A chromosome is an organized structure of DNA and protein found in cells.

Chromosomes contain DNA-bound proteins, which serve to package the DNA

and control its functions.

Chromosomal DNA encodes most or all of an organism's genetic information;

some species also contain plasmids or other extra-chromosomal genetic
elements.
Cell Division
Prokaryotic chromosome
Prokaryotic cells (bacteria) contain their chromosome as circular DNA. Usually
the entire genome is a single circle, but often there are extra circles
called plasmids.

The bundled DNA is called the nucleoid. It concentrates the DNA in part of the
cell, but it is not separated by a nuclear membrane as in eukaryotes.

The DNA is accessible to enzymes that

make RNA and protein.

In the bacterial cell, the DNA gets

transcribed to RNA, and the RNA gets
translated to protein before it is even
completed.
Plasmid
A plasmid is a small ring of DNA that carries accessory genes. Usually these
genes are for antibiotic resistance!

Plasmids usually occur naturally in bacteria, but are sometimes found

in eukaryotic organisms

Plasmids used in genetic engineering are called vectors.

Plasmids serve as important tools in genetics and biotechnology labs, where

they are commonly used to multiply (make many copies of) or express particular
genes

Another major use of plasmids is to make large amounts of proteins. In this case,
researchers grow bacteria containing a plasmid harboring the gene of interest.
Chromosomes in eukaryotes
Eukaryotic cells contain their DNA within the nuclear membrane.
The DNA double helix is bound to proteins called histones. The histones
have positively charged (basic) amino acids to bind the negatively charged
(acidic) DNA.
The DNA is wrapped around the histone core of eight protein subunits, forming
the nucleosome. The nucleosome is clamped by histone H1 (About 200 base
pairs (bp) of DNA coil around one histone).

There are 5 major types of histones:

H1, H2A, H2B, H3, and H4 – which
are very similar among different
species of eukaryotes.
Chromatin
Chromatin is the complex of DNA and protein found in the eukaryotic nucleus,
which packages chromosomes.

The structure of chromatin varies significantly between different stages of

the cell cycle, according to the requirements of the DNA.
Interphase chromatin

During interphase (the period of the cell cycle where the cell is not dividing),
two types of chromatin can be distinguished:
1-Euchromatin, which consists of DNA that is active, e.g., being expressed as
protein.
2-Heterochromatin, which consists of mostly inactive DNA. It seems to serve
structural purposes during the chromosomal stages.

Heterochromatin can be further distinguished into two types:

A-Constitutive heterochromatin, which is never expressed. It is located
around the centromere.
B-Facultative heterochromatin, which is sometimes expressed.
Human chromosomes
Chromosomes in humans can be divided into two types: autosomes and sex
chromosomes.

Certain genetic traits are linked to a person's sex and are passed on through
the sex chromosomes.

The autosomes contain the rest of the genetic hereditary information. All act
in the same way during cell division.

Human cells have 23 pairs of chromosomes (22 pairs of autosomes and one
pair of sex chromosomes), giving a total of 46 per cell.
 Prokaryote vs Eukaryote Genetics
PROKARYOTES EUKARYOTES
single chromosome plus plasmids many chromosomes
circular chromosome linear chromosomes
made only of DNA made of chromatin, a nucleoprotein
(DNA coiled around histone proteins)

found in cytoplasm found in a nucleus

copies its chromosome and divides copies chromosomes, then the cell
immediately afterwards grows, then goes through mitosis to
organise chromosomes in two equal
groups

In eukaryotes, transcription of genes in RNA occurs in the nucleus, and

translation of that RNA into protein occurs in the cytoplasm. The two processes
are separated from each other.

In prokaryotes, translation is coupled to transcription: translation of the new

RNA molecule starts before transcription is finished.
 Centromeres and Telomeres

Centromeres and telomeres are two

essential features of all eukaryotic
chromosomes.

Each provide a unique function i.e.,

absolutely necessary for the stability of the
chromosome.

Centromeres are required for the

segregation of the chromosomes during
meiosis and mitosis.

Telomeres provide terminal stability to the

chromosome and ensure its survival
 Centromere
The region where two sister chromatids of a chromosome appear to be joined or
“held together” during metaphase is called Centromere

When chromosomes are stained they typically show a dark-stained region that is
the centromere.

During mitosis, the centromere that is shared by the sister chromatids must divide
so that the chromatids can migrate to opposite poles of the cell.

On the other hand, during the first meiotic division the centromere of sister
chromatids must remain intact

whereas during meiosis II they must act as they do during mitosis.

As a result, centromeres are the first parts of chromosomes to be seen moving

towards the opposite poles during anaphase.
Kinetochore
The actual location where the attachment of spindle fibers to centromere
occurs is called the kinetochore and is composed of both DNA and protein.

DNA sequence within these regions is called CEN DNA.

Typically CEN DNA is about 120 base pairs long and

consists of several sub-domains, CDE-I, CDE-II and
CDE-III.

Mutations in the first two sub-domains have no effect

upon segregation, but a point mutation in the CDE-III
sub-domain completely eliminates the ability of the
centromere to function during chromosome
segregation.

Therefore CDE-III must be actively involved in the binding of the spindle fibers to
the centromere.
Telomere
The two ends of a chromosome are known as telomeres and they are required
for the replication and stability of the chromosome.
The centromere divides each chromosome into two regions: the small one,
which is the p region, and the big one (q region)
As a convection, the p region is represented in the upper part of the image ,
while the q region is the bottom part
When telomeres are damaged or removed due to chromosome breakage, the
damaged chromosome ends can readily fuse or unite with broken ends of
other chromosome.
Thus the ends of broken chromosomes are sticky, whereas the normal end is
not sticky, suggesting the ends of chromosomes have unique features.

Species Repeat Sequence

Telomere Arabidopsis TTTAGGG
Human TTAGGG
Repeat Oxytricha TTTTGGGG
Sequences Slime Mold TAGGG
Tetrahymena TTGGGG
Trypanosome TAGGG
Numbers of chromosomes
Constant for each cell in the body (except sex cells which only have half sets).
Constant throughout the life of an individual (you don’t lose or gain chromosomes)
Constant for all members of a species

Normally, all the individuals of a species have the same number of

chromosomes.

Presence of a whole sets of chromosomes is called euploidy.

It includes haploids, diploids, triploids, tetraploids etc.

Gametes normally contain only one set of chromosome – this number is called
Haploid (1n)
Somatic cells usually contain two sets of chromosome and is called Diploid (2n)

When a change in the chromosome number does not involve entire sets of
chromosomes, but only a few of the chromosomes - is Aneuploidy.
Monosomics (2n-1) Trisomics (2n+1)
Nullisomics (2n-2) Tetrasomics (2n+2)
karyotypes
A karyotype is the number and appearance of chromosomes in the nucleus of
a eukaryotic cell.

The term is also used for the complete set of chromosomes in a species, or an
individual organism

Karyotypes can be used for many purposes; such as, to study chromosomal
aberrations, cellular function, and to gather information about
past evolutionary events

The basic number of chromosomes in the somatic cells of an individual or a

species is called the somatic number and is designated 2n.

Thus, in humans 2n = 46, while in the sex cells the chromosome number
is n (humans: n = 23).

So, in normal diploid organisms, autosomal chromosomes are present in two

copies.
Identifying chromosomes
In a karyotype, chromosomes are arranged and numbered by size, from
largest to smallest.

This arrangement helps scientists quickly to identify chromosomal alterations

that may result in a genetic disorder

To make a karyotype, scientists take a picture of someone's chromosomes, cut

them out and match them up using size, banding pattern and centromere
position as guides

Making a Karyotype
1-First the chromosomes
are stained

2-Then they are

organized by height and
centromere location
The chromosomes of a human

Female Male
Karyotypes Nomenclature
Total number of chromosomes, then the makeup of the sex chromosomes and
any extra chromosomes
Example
46, XX
46, XY
47, XY, +21
Chromosomal Aberrations
The somatic (2n) and gametic (n) chromosome numbers of a species ordinarily
remain constant.

Somatic cells of a diploid species contain two copies of each chromosome, which
are called homologous chromosome.

Each chromosome of a genome contains a definite numbers and kinds of genes,

which are arranged in a definite sequence.

Sometime due to mutation or spontaneous (without any known causal

factors), variation in chromosomal number or structure do arise in nature.

Chromosomal aberration may be grouped into two broad classes:

1. Structural 2. Numerical
Structural Chromosomal Aberrations

Chromosome structure variations result from chromosome breakage.

Broken chromosomes tend to re-join; if there is more than one break, rejoining
occurs at random and not necessarily with the correct ends.

The result is structural changes in the chromosomes.

Chromosome breakage is caused by X-rays, various chemicals, and can also

occur spontaneously.

There are four common type of structural aberrations:

1. Deletion or Deficiency
2. Duplication or Repeat
3. Inversion
4. Translocation.
Consider a normal chromosome with
genes in alphabetical order: a b c d e f

1. Deletion: part of the chromosome has been

removed:
abcef

2. Dupliction: part of the chromosome is

duplicated:
abcddef

3. Inversion: part of the chromosome has been re-

inserted in reverse order: a b c e d f

4. translocation: parts of two non-homologous

chromosomes are joined:
If one normal chromosome is a b c d e f and the
other chromosome is u v w x y z
then a translocation between them would be
a b c d y z and u v w x e f
Deletion or deficiency
Loss of a chromosome segment is known as deletion or deficiency , It can be
terminal deletion or intercalary deletion

A single break near the end of the chromosome would be expected to result
in terminal deficiency.

If two breaks occur, a section may be deleted and an intercalary deficiency

created.

Terminal deficiencies might seem

less complicated. But majority of
deficiencies detected are intercalary
type within the chromosome.
Cri-du-chat (Cat cry syndrome):
The name of the syndrome came from a cat-like mewing cry from small weak
infants with the disorder.

Other characteristics are microcephaly (small head), broad face and saddle
nose, physical and mental retardation.

Cri-du-chat patients die in infancy or early childhood.

The chromosome deficiency is in the short arm of chromosome 5 .

A Boy with Cri-du-Chat Syndrome –

Duplication
The presence of an additional chromosome segment, as compared to that normally
present in a nucleus is known as Duplication.
In a diploid organism, presence of a chromosome segment in more than two copies
per nucleus is called duplication.
Four types of duplication:
1. Tandem duplication
2. Reverse tandem duplication
3. Displaced duplication
4. Translocation duplication

The extra chromosome segment may be located immediately after the normal
segment in precisely the same orientation forms the tandem

When the gene sequence in the extra segment of a tandem in the reverse order i.e,
inverted , it is known as reverse tandem duplication

In some cases, the extra segment may be located in the same chromosome but away
from the normal segment – termed as displaced duplication

The additional chromosome segment is located in a non-homologous chromosome is

translocation duplication.
Inversion
When a segment of chromosome is oriented in the reverse direction, such
segment said to be inverted and the phenomenon is termed as inversion.

Inversion occur when parts of chromosomes become detached , turn through

180 degree and are reinserted in such a way that the genes are in reversed
order.

For example, a certain segment may be broken in two places, and the breaks
may be in close proximity because of chance loop in the chromosome.
When they rejoin, the wrong ends may become connected.

The part on one side of the loop connects with broken end different from the
one with which it was formerly connected.

This leaves the other two broken ends to become attached.

The part within the loop thus becomes turned around or inverted.
Inversion may be classified into two types:
Pericentric - include the centromere
Paracentric - do not include the centromere

In natural populations, pericentric inversions are much less frequent than

paracentric inversions.

In many species, however, pericentric inversions are relatively common

Translocation
Integration of a chromosome segment into a nonhomologous chromosome is
known as translocation.

Three types:
1. simple translocation
2. shift
3. reciprocal translocation.
Variation in chromosomes number
Organism with one complete set of chromosomes is said to be euploid (applies to
haploid and diploid organisms).

Aneuploidy - variation in the number of individual chromosomes

The discovery of aneuploidy dates back to 1916 when Bridges discovered XO male
and XXY female Drosophila, which had 7 and 9 chromosomes respectively, instead
of normal 8.

Nullisomy - loss of one homologous chromosome pair.

Monosomy – loss of a single chromosome.
Trisomy - one extra chromosome.
Tetrasomy - one extra chromosome pair.
More about Aneuploidy
Non-Disjunction
Generally during gametogenesis the homologous chromosomes of each pair
separate out (disjunction) and are equally distributed in the daughter cells.
But sometime there is an unequal distribution of chromosomes in the daughter
cells.
The failure of separation of homologous chromosome is called non disjunction.
Trisomy in Humans
Down Syndrome
The best known and most common chromosome related syndrome.
Formerly known as “Mongolism”
Down's syndrome, also known as trisomy 21, is a chromosomal
condition caused by the presence of all or part of a third copy of chromosome
21.
Patients having Down syndrome will be
Short in stature (four feet tall), broad
short skulls, wild nostrils, large tongue,
stubby hands

Some babies may have short necks,

small hands, and short fingers.

They are characterized as low in

mentality.
Patau syndrome
Patau syndrome is a syndrome caused by a chromosomal abnormality, in
which some or all of the cells of the body contain extra genetic material
from chromosome 13.

Chromosome Nomenclature: 47, +13

Chromosome formula: 2n+1
Clinical Syndrome: Trisomy-13

Estimated Frequency Birth: 1/20,000

Main Phenotypic Characteristics:

Mental deficiency and deafness, cleft lip, cardiac anomalies
Edwards syndrome
Edwards syndrome (also known
as Trisomy 18 (T18)) is a genetic
disorder caused by the presence of all or
part of an extra 18th chromosome.

This genetic condition almost always

results from non-
disjunction during meiosis.
Chromosome Nomenclature: 47, +18
Chromosome formula: 2n+1
Clinical Syndrome: Trisomy-18
Estimated Frequency Birth: 1/8,000
Main Phenotypic Characteristics:
Multiple congenital malformation of many organs, malformed ears, small
mouth and nose with general elfin appearance.

90% die in the first 6 months.

Amniocentesis for Detecting Aneuploidy
Chromosomal abnormalities are sufficiently well understood to permit genetic
counseling.

A fetus may be checked in early stages of development by karyotyping the

cultured cells obtained by a process called amniocentesis.

A sample of fluid will taken from mother and fetal cells are cultured and after a
period of two to three weeks, chromosomes in dividing cells can be stained and
observed.

If three No.21 chromosomes are present, Down syndrome confirmed.

The risk for mothers less than 25 years of age to have the trisomy is about 1 in 1500
births.
At 40 years of age, 1 in 100 births
At 45 years 1 in 40 births.
Turner syndrome
It is a chromosomal abnormality in which
all or part of one of the sex
chromosomes is absent (unaffected
humans have 46 chromosomes, of which
two are sex chromosomes).

Chromosome Nomenclature: 45, X

Chromosome formula: 2n - 1
Clinical Syndrome: Turner
Estimated Frequency Birth: 1/2,500 female

Main Phenotypic Characteristics:

Female with retarded sexual development, short stature, webbing of skin
in neck region, cardiovascular abnormalities, hearing impairment.
Klinefelter Syndromes
Klinefelter's syndrome,
also 47,XXY or XXY syndrome, is
a genetic disorder in which there is
at least one extra X chromosome to a
standard human male karyotype, for
a total of 47 chromosomes rather
than the 46 found in genetically
normal humans.

Chromosome Nomenclature: 47, XXY

Chromosome formula: 2n+1
Clinical Syndrome: Klinefelter
Estimated Frequency Birth: 1/500 male

Main Phenotypic Characteristics:

Pitched voice, subfertile with small testes, developed breasts, long limbs.