2. INTRODUCTION
Chromosomal mutations are abnormal structural and numerical changes of
chromosomes, thus called as chromosomal aberrations. There are two types of
chromosomal aberrations, they are;
• Structural Aberrations –
Gross structural changes of chromosomes
• Numerical aberrations –
Ploidy or numerical changes of chromosomes
3. STRUCTURAL ABERRATION
• Structural changes of chromosomes involves the gain, loss, or relocation of
chromosome segments and genes. In effect, they bring about changes in the
number and arrangement of genetic loci, with marked genetic effects.
• Structural aberrations are of four basic types, namely,
1. DELETION
2. DUPLICATION
3. INVERSION
4. TRANSLOCATION
4. DELETION
• Deletion is the loss of a chromosome segment,
together with the genes contained in it. It is also
known as deficiency.
Loss of terminal segment with a single break in
the chromosome is called terminal deletion.
Loss of an intercalary segment with two break in
the chromosome is called intercalary deletion.
• In any case the lost segment would be acentric,
that is, without centromere.
• Deletion often results in abnormal phenotype or
lethality.
5. A B C D E F G
Break
A B C D E F G
Deficiency with single break is known as terminal
deletion which involves loss of terminal segment.
TERMINAL DELETION
INTERCALARY DELETION
Break
B C A D E F G
Deficiency with double break is known as
intercalary deletion which involves loss of
intercalary segment.
6. TYPES OF DELETION
1. Homozygous deletion- A segment is lost from both the chromosomes of a
homologous pair. It is most usually lethal.
2. Heterozygous deletion- A segment is lost from one of the two homologues. It
mainly causes abnormal phenotype.
Meiotic pairing of homologous with heterozygous
deletion involves the formation of an unpaired loop
or bulge in the normal chromosome. The loop is
formed in the region which corresponds to the lost
part of the deficient chromosome.
7. GENETIC EFFECTS OF DELETION
Deletions involve loss of genes. The intensity of their effects depends on number
and quantity of lost genes. Heterozygosity for small deletions are usually viable,
but abnormal. However, homozygosity for small deletions may have lethal
effects.
• Pseudodominance – Some heterozygous deletions involve the loss of
dominant alleles, without effecting their counterparts in other homologue. This
often results in the expression of persisting recessive alleles. The expression of
recessive alleles due to deletion of the dominant allele is called
pseudodominance.
Example – Waltzing mouse – It is the mouse which moves about erratically until
it gets exhausted, is a result of pseudodominance.
8. In human genome, deletion mutation results in drastic phenotypic changes.
• Granulocyte leukemia- It is caused due to the deletion in the long arm of
chromosome 21. This is non-heritable somatic mutation, occurs when there
are too many granulocytes in the blood. It’s a condition that’s closely related to
chronic myelogenous leukemia (CML) and other bone marrow disorders.
Granulocytes are white blood cells that have small granules or particles.
• Cri-du-chat syndrome- It is a well known case of deletion mutation in man.
Also called Cat- cry syndrome. Caused by the heterozygous deletion in the
short arm of Chromosome 5. The effected children are mentally retarded and
they cry just like a cat mews. The disorder is characterized by intellectual
disability and delayed development, small head size ,low birth weight, and
weak muscle tone (hypotonia) in infancy. Also have distinctive facial features,
including widely set eyes (hypertelorism), low-set ears, a small jaw, and a
rounded face. Some children with cri-du-chat syndrome are born with a heart
defect.
9. DUPLICATION
• Duplication is the doubling or repetition of a
chromosome segment during chromosome
duplication. So, in this case a set of gene exist
more than once, and this extra set is generally
called repeat.
• The duplicate segment may be incorporated
either with the parent chromosome or with
another chromosome or it may exist as a
separate piece.
• Duplications are believed to be an important
raw material for organic evolution.
10. TYPES OF DUPLICATION
• Tandem duplication - The extra segment and the parent segment are next to
each other and both of them have the same polarity or order of genes.
• Reverse tandem duplication -The extra segment lies next to the parent
segment with reversed polarity or reverse gene sequence.
• Displaced duplication - The duplicate segment lies some distance away
from the parent segment or it gets translocated to a non-homologous
chromosome.
Duplication can be two kinds, namely,
• Homozygous duplication - both the homologous of a a pair of chromosome
will have homologous duplicate sequence.
• Heterozygous duplication -only one of the pairs of chromosomes will have
a duplicate sequence.
11. A B
B B
A A C D E F
A B B A C D E F
A B C D A B E F
H I J K A B L
TANDEM DUPLICATION
REVERSE TANDEM DUPLICATION
DISPLACED DUPLICATION IN SAME CHROMOSOME
DISPLACED DUPLICATION IN DIFFERENT CHROMOSOME
DUPLICATE SEGMENT EXIST AS A NEW CHROMOSOME
12. GENETIC EFFECTS OF DUPLICATION
• A classical example of tandem duplication is the
‘bar eye’ of drosophila. The normal eye of female
drosophila is oval, whereas, its bar eye is like an
oblong narrow bar.
• Bar eye is shown due to duplication at a specific
site in the X chromosome called ,Bar Locus 16A .
This locus contains the dominant allele for normal
eye. The narrowness of the eye is directly
proportional to the number of duplications of the
bar locus.
In duplication heterozygous- the eye becomes smaller and narrower than normal
eye; that is the bar eye.
In duplication homozygous- the eye become extremely small and narrow; that is
the double bar eye.
• Any further duplication of bar locus would make the eye still narrower.
13. INVERSION
• Inversion is the reversal of the linear orientation
of a chromosome segment and the order of its
gene sequence.
• Inversion is exclusively found in the intercalary
segments.
• It involves breakage of a chromosomal segment
and its subsequent re-insertion into the same
location in a reversed orientation.
• Normally, two breaks occur in the chromosome
and are called inversion points.
14. TYPES OF BREAKS
• Paracentric breaks- The break exclude the centromere, and both the
breaks occur on one side of the centromere in the same arm.
• The break separates an acentric arm.
• Rotation and re-insertion of an acentric segment is called paracentric
inversion.
• Pericentric breaks- The break include the centromere, and they occur one
on either side of the centromere, so one in each arm.
• The break separates a centric arm.
• Rotation and re-insertion of a centric segment is called pericentric
inversion.
15. E F
E F
A B C D E F
A C B D
A B C D
A B E D C F
Break
Rotation at 180
PARACENTRIC INVERSION
Break
Rotation at 180
PERICENTRIC INVERSION
16. GENETIC EFFECTS OF INVERSION
The effects of inversion are not so drastic as those of deletion and duplication.
• One of the best-characterized recurrent inversions giving rise to disease causes
hemophilia A, an X-linked disorder caused by mutations in the factor VIII gene. A
recurrent inversion has been found in approximately 43% of patients.
• Produces phenotypic changes due to change in location of genes.
• Inversion serves as a crossing over suppressor and reduces crossing over
frequency.
17. TRANSLOCATION
• Translocation is the chromosomal aberration
which involves the re-organization of
chromosomes through the transfer or change
in position of chromosome segment without
gain or loss of genes.
• It involves transfer of a segment from one
location to another in the same chromosome
or from one chromosome to a non-
homologous one.
18. TYPES OF TRANSLOCATION
• Intrachromosomal translocation- It is a three break aberration resulting in
change of position of a segment within a chromosome, either from one arm to
other or from one location to another in same arm. It is also know as internal
translocation or chromosomal shift.
• Interchromosomal translocation- It is the transfer of a segment from one
chromosome to another.
• It is of two types;
1. Transpositional / Interstitial translocation– Non-reciprocal one way
transfer of chromosome segment from one chromosome to another.
2. Reciprocal / Mutual / Inter-change translocation– Mutual exchange of
segments between two chromosomes, either homologous or non-
homologous.
19. A B C D E F A D E B C F
Break
INTRACHROMOSOMAL TRANSLOCATION
INTERCHROMOSOMAL TRANSLOCATION
A B C D E F M N O P
A D E F M B C N O P
A B C D E F M N O P Q R
A N O D E F M B C P Q R
TRANSPOSITIONAL
TRANSLOCATION
RECIPROCAL
TRANSLOCATION
20. GENETIC EFFECTS OF TRANSLOCATION
• Causes change in chromosomes and gene combinations, alters linkage
relationship of genes etc.
• Translocation mainly leads to infertility, miscarriages, or children with
abnormalities.
• Several forms of cancer are caused due to the translocation of chromosome
segments, mainly leukemia.
21. NUMERICAL ABERRATION
• Numerical aberration is also known as ploidy changes.
• They involve gain or loss of either individual chromosomes or monoploid set
of chromosome.
• The major cause of ploidy changes is non- disjunction.
• Numerical aberration are two basic types;
1. EUPLOIDY
2. ANEUPLOIDY
22. EUPLOIDY
• Euploidy changes involves the duplication or loss of one or more monoploid
sets.
• Euploidy includes
1. Monoploidy – The somatic cells contain only one basic set of chromosomes.
2. Diploidy – The somatic cells contain two basic set of chromosomes.
3. Polyploidy – The somatic cell contains more than two basic genome set. It
is of two types;
• Autopolyploidy- Condition in which the multiple genomes are identical and
derived from the same species.
• Allopolyploidy- Condition in which the multiple genomes are distinctly
different and derived from different species through hybridization.
23. SIGNIFICANCE OF POLYPLOIDY
• Polyploidy serves as a mechanism of speciation and evolution.
• Autopolyploidy is found in many plants, allopolyploids are mainly hybrids
such as mule.
• They are significant in agriculture and horticulture.
24. ANEUPLOIDY
• Aneuploidy is the condition in which individual chromosomes or chromosome
pairs are added to or lost from the somatic chromosome compliment.
• It usually results from mitotic or meiotic non-disjunction.
• Aneuploidy is of two kinds;
1. HYPOPLOIDY – It is the aneuploidy due to chromosome loss.
• Monosomy- One chromosome is lost from diploid set, (2n-1).
Example – Turner’s syndrome (XO)
• Nullisomy – Loss of a homologous pair of chromosome from a somatic set, (2n-2).
They often don’t survive.
25. 2. HYPERPLOIDY – It is the aneuploidy due to chromosome gain. Also known
as polysomy.
• Trisomy – Addition of an extra chromosome to a diploid set. (2n+1)
Example:
a. Down’s syndrome – Trisomy 21
b. Edward’s syndrome – Trisomy 18
c. Patau’s syndrome – Trisomy 13
d. Klinefelter’s syndrome – (XXY)
• Tetrasomy – Addition of a homologous pair of chromosome to diploid set.
(2n+2)
Example:
a. Pallister-Killian syndrome – Tetrasomy 12p
b. Cat-Eye syndrome – Tetrasomy 22
26. REFERENCES
• Cell and molecular biology – Karp
• Molecular Cell Biology – Lodish
• Cell Biology, Classical Genetics, Human Genetics, Molecular
Biology- K.K Bhaskaran
• NORD – National Organization for Rare Disorders
• www.ncbi.nlm.nih.gov
• www.sciencedirect.com
• Genomemedicine.biomedcentral.com
