CYTOGENETICS

BY
AHMED BAHIELDIN
HUSSEIN SABIT
Chromosome Deletions
 Backgroun
d
Four different classes of structural
chromosome changes are:
deletions,
duplications,
inversions, and
translocations
• In deletions and inversions the
chromosome breaks are confined to
one pair of chromosomes only,
whereas in duplications and
translocations more than one
chromosome pair can be involved
Deletion is the loss of genetic material. Any number of nucleotides can
be deleted, from a single base to an entire piece of chromosome.
Deletions can be caused by errors in chromosomal crossover during
meiosis. This causes several serious genetic diseases.
• Loss of segment of DNA
• Intragenic deletion: small deletion within
gene – inactivates gene; non-revertible
mutation
• Multigene deletion
– many genes deleted
– often severe consequences
• gene imbalance
• expression of deleterious recessive mutation
(pseudodominance)
• Visible as deletion loop
Deletions on one chromosome can unmask
recessive alleles on the other chromosome
called pseudodominance

Deletion loop
 Causes

• Losses from translocation

• Chromosomal crossovers within a
chromosomal inversion
• Unequal crossing over
• Breaking without rejoining
 Types

• Types of deletion include the following:

• Terminal Deletion - a deletion that occurs
towards the end of a chromosome.
• Intercalary Deletion - a deletion that
occurs from the interior of a chromosome.
 Effects
• Small deletions are less likely to be fatal; large
deletions are usually fatal - there are always
variations based on which genes are lost. Some
medium-sized deletions lead to recognizable
human disorders.
• Deletion of a number of base pairs that is not
evenly divisible by three will lead to a frameshift
mutation, causing all of the codons occurring
after the deletion to be read incorrectly during
translation, producing a severely altered and
potentially nonfunctional protein.
 .cont
• Deletions are responsible for an array of genetic
disorders, including some cases of male
infertility and two thirds of cases of Duchenne
muscular dystrophy. Deletion of part of the short
arm of chromosome 5 results in a syndrome
called Cri du chat. French for "cry of the cat"
syndrome. It is found in approximately 1 in
50,000 live births. The surviving infants have a
distinctive cry, severe mental retardation, and
shortened life span.
 Examples
• Chromosome 1, 1p36 deletion syndrome is a
medical condition caused by a rare
chromosomal disorder where deletion of a
portion of chromosome 1 causes various
abnormalities such as
• heart defects, mental retardation,
developmental delay, and short stature
• The symptoms are variable depending on the
exact location of chromosomal deletion
Chromosome 1
 ?What is 22q11.2 deletion syndrome
• 22q11.2 deletion syndrome is a disorder caused
by the deletion of a small piece of chromosome
22. The deletion occurs near the middle of the
chromosome at a location designated q11.2.
• The features of this syndrome vary widely, even
among affected members of the same family,
and involve many parts of the body.
• Characteristic signs and symptoms include heart
defects that are often present from birth, an
opening in the roof of the mouth (a cleft palate)
or other palate defects, and mild differences in
facial features.
 .Cont
• People with 22q11.2 deletion syndrome often experience
recurrent infections caused by problems with the
immune system, and some develop autoimmune
disorders such as rheumatoid arthritis and Graves'
disease. Affected individuals may also have kidney
abnormalities, low levels of calcium in the blood (which
can result in seizures), a decrease in blood platelets
(thrombocytopenia), significant feeding difficulties, and
hearing loss. Skeletal differences are possible, including
mild short stature and, less frequently, abnormalities of
the spinal bones.
 Chromosome 6p deletion
syndrome
• A rare chromosomal disorder where part
or all of the short arm (p) of chromosome
6 is deleted resulting in various
abnormalities which are determined by the
size of the deleted portion.
 Symptoms of Chromosome 6p deletion syndrome
• Low -set ears
• Malformed ears
• Widely spaced eyes
• Dental caries
• Cleft lip
• Short neck
• Umbilical hernia
• Short phalanges
• Single palmar creases
• Eczema
• Growth retardation
• Motor retardation
• Speech retardation
• Mental retardation
• Deafness
Breakage-Reunion and Exchange
Hypotheses
• Structural chromosome changes depend
on breakage of chromosomes and on
reunion of chromosome segments
• Chromosome breakage results in sticky
ends with the tendency for reunion with
other such injured ends
• According to this hypothesis, breaks occur
spontaneously or as a result of mutagens
and usually rejoin in the original order by
repair process "restitution"
Breakage-Reunion and Exchange
Hypotheses
• If restitution to the original structure does not take place, the
chromosomes may undergo structural changes through the
phenomenon of reunion, i.e., new arrangement
• An alternative to the breakage-reunion hypothesis, is the
newer exchange hypothesis
• According to this hypothesis, the primary event that leads to
chromosome aberrations is not breakage but the formation of
so-called primary lesions
• Such lesions are regions of instability in the chromosomes or
chromatids
• The visible evidence of such lesions are the gaps
 Spontaneous and Induced Chromosome
and Chromatid Aberrations

• The timing of irradiation determines whether the

aberration involves a chromatid or a chromosome
• After the S period, only one chromatid will be
involved in the lesion
• Before the S period, both sister chromalids are
affected
• Spontaneous aberrations are the result of naturally
occurring radiations, i.e., chromosomal anomalies
can also be produced by viral infections !!!
• i.e., measles, chicken pox and Simian tumor virus
SV40, the sites of the chromosome breakage appear
to be nonrandom
Spontaneous and Induced Chromosome
and Chromatid Aberrations

• Inducing chromosome aberrations include the

application of various agents such as radiation,
chemicals, viruses, temperature changes or drugs
(caffeine, and 8-ethoxycaffeine)
• Sister chromatid exchange (SCE): there is a close
linkage between chromosome aberrations and sister
chromatid exchanges
• Powerful mutagens such as ionizing radiation (alpha,
beta, gamma rays from radioactive sources, x-rays,
protons, neutrons) cause only slight increases in
SCE frequency
 Spontaneous and Induced Chromosome
and Chromatid Aberrations

• A small but significant rise in the number of SCE's was

observed after the exposure of fresh human lymphocytes to 30
minute treatments with diagnostic ultrasound
• Chromatid-type damage, like triradial chromosomes and
chromosome-type damage, like dicentrics, were observed in
Louis-Bar syndrome lymphocytes, a defect of DNA repair in
these patients- lack the full complement of functional
polynucleotide ligases that are able to join breaks in one strand
of a DNA double helix
• Postreplication repair is considered to be error-prone
Terminal Deficiencies
• A deficiency is a structural change of a chromosome resulting in the
loss of a terminal acentric chromosome, chromatid, or subchromatid
segment and in the loss of the genetic information which this
chromatin segment contains followed by a healing of its broken end
• In contrast, a deletion involves an intercalary chromosome segment
and requires two chromosome breaks. However, in practice, the term
"deletion" frequently is used for both of these types of structural
chromosome changes
• Generally, in both instances, a centric and an acentric chromosome
segment are produced
• The centric segment will persist during cell division, while the
acentric fragment will be lost
 Terminal Deficiencies

• Large deficiencies will lead to the death of the cell

involved or will, at least, prohibit sexual
reproduction
• In plants, the treatment seems to make a difference
• If maize was treated with ultraviolet radiation,
terminal deficiencies mainly resulted. If x-rays were
applied, only interstitial deletions were observed !!!
• If the break occurs in the heterochromatic portion of
the chromosome, it is more likely to heal than if it
happens in the euchromatin, the frequency of
recovered x-ray-induced breaks is highest in
heterochromatin and lowest in euchromatin
 Terminal Deficiencies

• In Drosophila X chromosome, up to 11 bands

are involved in terminal deficiency
• If only 8 bands in this region are lost, this
deficiency is lethal to the whole organism in
the homozygous condition. A loss of 4 bands
is viable in the homozygous.
• On the other hand, loss of heterochromatic
segments can occur almost unnoticed. Large
pieces of the Y chromosome of Drosophila
may be deficient without any lethal effect
Interstitial Deletions

The loss of an intercalary or interstitial chromosome

segment
vary from the absence of a single nucleotide to large
chromosome segments
The genetic proof for a deletion is its failure to back-
mutate to the original form
Bm1 gene in the short arm of chromosome 5 close to the
centromere:
• The recessive allele bm1 expresses brown midrib,
producing a brown color in lignified cell walls. The
absence of Bm1, as well as bm1, (interstitial deletion)
also produces brown midrib
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