CYTOGENETICS: PRE-FINAL

have one X and one Y chromosome. In females,

one of the X chromosomes in each cell is
inactivated and known as a Barr body. This
ensures that females, like males, have only one
functioning copy of the X chromosome in each
cell.

Types of Chromosomes:

Telocentric

A chromosome whose centromere is located at

one end. The centromere is located very close to
the end of the chromosome that the p arms
would not, or barely, be visible.

Centromere found at end of chromosome,

meaning no p arm exists (chromosome not
found in humans).

Acrocentric
Human Chromosomes. A chromosome where the centromere is not
Humans have 23 pairs of chromosomes. Pairs 1- central and is instead located near the end of the
22 are autosomes. Females have two X chromosome. Humans usually have five pairs of
chromosomes, and males have an X and a Y acrocentric autosomes (chromosomes 13, 14,
chromosome. 15, 21, 22). The Y chromosome is also
acrocentric.
Of the 23 pairs of human chromosomes, 22 pairs
are autosomes (numbers 1–22 in Figure Centromere severely off-set from centre, leading
above). Autosomes are chromosomes that to much shorter p arm (e.g. chromosomes 13 -
contain genes for characteristics that are 15, 21, 22, Y).
unrelated to sex. These chromosomes are the Submetacentric
same in males and females. The great majority of
human genes are located on autosomes. A submetacentric chromosome is a chromosome
whose centromere is located near the middle. As
The remaining pair of human chromosomes a result, the chromosomal arms (i.e. p and q
consists of the sex chromosomes, X and Y.
Females have two X chromosomes, and males
 CYTOGENETICS: PRE-FINAL

arms) are slightly unequal in length and may also pregnancy that can diagnose it before birth,
form an L-shape. however more often it’s diagnosed later in life. If
not found before birth, it can sometimes be
Centromere off-centre, leading to shorter p arm
diagnosed because the baby has a smaller penis
relative to q arm (e.g., chromosomes 2, 4 - 12,
than expected, or later in the teenage years if
17, 18, X).
puberty doesn’t start or progress as expected.
Metacentric
Edward Syndrome
A chromosome whose centromere is centrally
Edwards syndrome, also called trisomy 18
located. As a result, the chromosomal arms (i.e.,
syndrome, is an autosomal chromosomal
p and q arms) are almost equal in length. A
disorder due to an extra copy of chromosome 18.
metacentric chromosome would have the X
Edwards syndrome is one of the autosomal
shape.
trisomy syndrome, second in frequency only to
Centromere is in middle, meaning p and q arms trisomy 21. It is a very severe genetic condition
are of comparable length (e.g. chromosomes 1, that affects how your child’s body develops and
3, 16, 19, 20). grows. Children diagnosed with trisomy 18 have
a low birth weight, multiple birth defects and
GENETIC DISORDERS: defining physical characteristics.
Down Syndrome Turner Syndrome
Down syndrome is a genetic condition where Turner syndrome, a condition that affects only
people are born with an extra chromosome. females, results when one of the X
Most people have 23 pairs of chromosomes chromosomes (sex chromosomes) is missing or
within each cell in their body, for a total of 46. A partially missing. Turner syndrome can cause a
person diagnosed with Down syndrome has an variety of medical and developmental problems,
extra copy of chromosome 21, which means including short height, failure of the ovaries to
their cells contain 47 total chromosomes instead develop and heart defects.
of 46. This changes the way their brain and body
develop. Cloning of Genes

Klinefelter Syndrome • Gene cloning is the process in which

a gene of interest is located and copied
Klinefelter syndrome (KS) is a genetic condition (cloned) out of all the DNA extracted
where there’s an extra X chromosome present in from an organism.
a male’s genetic code. Instead of having a total • Gene cloning involves separation of
of 46 chromosomes, they have 47 — with two specific gene or DNA fragments from a
copies of the X chromosome and one copy of the donor cell, attaching it to small carrier
Y chromosome (47,XXY). There are some forms molecule called vector and then
(called mosaic) where only some (not all) of the replicating this recombinant vector into
person’s cells have this change (other cells can a host cell.
either have the typical 46 XY, or can have
another abnormality).

Klinefelter syndrome is a congenital condition,

which means it’s present from the time of birth.
There are certain tests that can be done during
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Steps of Cloning: • Therapeutic cloning produces

embryonic stem cells for experiments
1. Isolation of target DNA fragments (often
aimed at creating tissues to replace
referred to as inserts).
injured or diseased tissues.
2. Ligation of inserts into an appropriate cloning
Artificial cloning occurs when the creation of the
vector, creating recombinant molecules (e.g.,
clone is due to human intervention, rather than
plasmids).
via natural occurrence. Artificial cloning is
3. Transformation of recombinant plasmids into carried out for many purposes, using a variety of
bacteria or other suitable host for propagation. techniques. It also may be carried out on several
individual structural levels, including genes,
4. Screening/selection of hosts containing the individual cells, tissues and whole organisms.
intended recombinant plasmid.
Mutation
Natural Method
• A mutation is a change in the DNA
Natural cloning is the production of clones (an
sequence of an organism. Mutations can
exact copy of an organism) without the
result from errors in DNA replication
involvement of genetic engineering techniques.
during cell division, exposure to
Budding, fragmentation, and
mutagens or a viral infection.
parthenogenesis are some examples of natural
• Is an alteration in the nucleic acid
cloning processes. Natural cloning is also
sequence of the genome of an organism,
observed in humans and mammals. This happens
virus, or extrachromosomal DNA.
when the fertilized egg splits into two embryos
• Mutations are errors in codons caused
that carry the same DNA. Identical twins have
by changes in nucleotide bases. Some
the same genetic construction but are different
mutations may not have much effect.
from the parent. It may occur accidentally in the
For example, if the codon GAA becomes
case of identical twins, alongside an organism's
the codon GAG, because the genetic
main mode of reproduction or be the organism's
code is degenerate, the codon will still
main mode of reproduction such as in bacteria.
code for the amino acid glutamate. Such
The reproductive process that results in the
ineffectual mutations are called silent
natural creation of clones is called asexual
mutations. Some mutations, however,
reproduction and while it occurs mainly in single-
can have a huge affect on coding for
celled organisms, some simpler multicellular
amino acids, which can in turn affect
organisms like plants can also do it!
what proteins are produced, which can
Artificial Method have a profound effect on cellular and
organismal function.
There are three different types of artificial
• The most common mutations occur in
cloning: gene cloning, reproductive cloning and
two ways: 1) a base substitution, in
therapeutic cloning.
which one base is substituted for
• Gene cloning produces copies of genes another; 2) an insertion or deletion, in
or segments of DNA. which a base is either incorrectly
• Reproductive cloning produces copies of inserted or deleted from a codon.
whole animals.
 CYTOGENETICS: PRE-FINAL

Base Substitutions Mutations • S phase. DNA synthesis replicates the

genetic material. Each chromosome now
Base substitutions can have a variety of effects. consists of two sister chromatids.
The silent mutation cited above is an example of
a base substitution, where the change in • G2 phase. Metabolic changes assemble
nucleotide base has no outward effect. A the cytoplasmic materials necessary for
missense mutation refers to a base substitution mitosis and cytokinesis.
when the change in nucleotide changes the
amino acid coded for by the affected codon. A • M phase. A nuclear division (mitosis)
nonsense mutation refers to a base substitution followed by a cell division (cytokinesis).
in which the changed nucleotide transforms the
codon into a stop codon. Such a change leads to Mitosis
a premature termination of translation, which
can badly affect the formation of proteins. Mitosis is a form of eukaryotic cell
division that produces two daughter cells
Insertion/Deletion Mutations with the same genetic component as the
When a nucleotide is wrongly inserted or deleted parent cell. Chromosomes replicated
from a codon, the affects can be drastic. Called a during the S phase are divided in such a
frameshift mutation, an insertion or deletion can way as to ensure that each daughter cell
affect every codon in a particular genetic receives a copy of every chromosome. In
sequence by throwing the entire three by three actively dividing animal cells, the whole
codon structure out of whack. For example, process takes about one hour.
given the code: Prophase

GAU GAC UCC GCU AGG, which codes for the • Prophase occupies over half of
amino acids aspartate, aspartate, serine, alanine, mitosis. The nuclear membrane
breaks down to form a number of
arginine.
small vesicles and the nucleolus
disintegrates. A structure known
If the A in the GAU were to be deleted, the code
as the centrosome duplicates
would become: GUG ACU CCG UAG G
itself to form two daughter
centrosomes that migrate to
In other words, every single codon would code opposite ends of the cell. The
for a new amino acid, resulting in completely centrosomes organize the
different proteins coded for during translation. production of microtubules that
The physical results of such mutations are, form the spindle fibers that
understandably, usually catastrophic. constitute the mitotic spindle.
The chromosomes condense into
compact structures. Each
• G1 phase. Metabolic changes prepare replicated chromosome can now
the cell for division. At a certain point - be seen to consist of two identical
the restriction point - the cell is chromatids (or sister chromatids)
committed to division and moves into held together by a structure
the S phase. known as the centromere.
• First part of cell division.
 CYTOGENETICS: PRE-FINAL

• Centromeres migrate to the • The cell begins to elongate.

poles.
Telophase
Prometaphase
• The final stage of mitosis, and a reversal
• The chromosomes, led by their of many of the processes observed
centromeres, migrate to the during prophase. The nuclear membrane
equatorial plane in the mid-line of reforms around the chromosomes
the cell - at right-angles to the grouped at either pole of the cell, the
axis formed by the centrosomes. chromosomes uncoil and become
This region of the mitotic spindle diffuse, and the spindle fibers disappear.
is known as the metaphase plate. • Daughter nuclei begin forming.
The spindle fibers bind to a • A cleavage furrow (for cell division)
structure associated with the begins to form.
centromere of each chromosome Cytokinesis
called a kinetochore. Individual
spindle fibers bind to a • The final cellular division to form two new
kinetochore structure on each cells. In plants a c ell plate forms along
side of the centromere. The the line of the metaphase plate; in
chromosomes continue to animals there is a constriction of the
condense. cytoplasm. The cell then enters
interphase - the interval between
Metaphase mitotic divisions.
• The chromosomes align themselves
along the metaphase plate of the spindle
apparatus.
• Spindle from centromeres are attached
to chromosomes that are aligned in the
center of the cell
Anaphase

• The shortest stage of mitosis. The

centromeres divide, and the sister
chromatids of each chromosome are
pulled apart - or 'disjoin' - and move to
the opposite ends of the cell, pulled by
spindle fibers attached to the
kinetochore regions. The separated
sister chromatids are now referred to as
daughter chromosomes. (It is the
alignment and separation in metaphase
and anaphase that is important in
ensuring that each daughter cell receives
a copy of every chromosome.
• Daughter chromosomes are pulled
toward the poles.