1. CHROMOSOMAL
AND
GENE ABERRATION
(Duplication, Deletion, Inversion, Translocation)
ENDAYA, DANICA FAYE M.
MANGOSING VIDA FAYE S.

2. Introduction
Congenital abnormalities can be caused by an
anomaly in the number or structure of the
chromosomes. Disorders in the
gametogenesis, that is, in the first and second
meiotic divisions in the formation of oocytes
and sperm cells, lead to such defects.

3. Staining method
Chromosomal mutations can be
made visible with staining methods
(banding techniques). Following
the staining the chromosomes are
analyzed using a 1000x
enlargement. With this one can
recognize the chromosomes as
striped cords and display them in a
karyogram, after they have been
ordered according to their size and
the positions of the centromeres.
Various groups of similar
chromosomes are created in this

4. Today, small aberrations are examined using a
molecular cytogenetic (FISH) approach.
Among other things, the FISH (fluorescence-in-
situ-hybridizing) method makes possible the
targeted identification of partial aneuploidies
such as deletions, duplications and unbalanced
translocations (see below) that cannot be
resolved with a light microscope.
A comprehensive array of DNA probes and
techniques are today available from which one
can choose for utilization, depending on the
diagnostic problem being worked on. With the
FISH method chromosomal alterations can be
analyzed down to a size of ca. 5 million
nucleotides

5. Origin of the
deviating
chromosome
structure

6. Structural aberrations are the result of
chromosomal breaks that occur during
meiosis.
 deletion,
 duplication
 isochromosome formation lead to an abnormal phenotype.
while;
 insertion
 inversion
 translocation can be balanced.
This means that the carrier of this structural chromosome
aberration can escape notice phenotypically, because the
entire genetic material is present.

7. Deletion
A deletion can happen in every chromosome
and exhibit every size. The consequences of a
deletion depends on the size of the missing
segment and which genes are found on it.

8. Cri du Chat syndrome
 A partial deletion on the short
arm (p) of chromosome 5 is
responsible for the
“cri du chat" syndrome
 The "cri du chat" syndrome
manifests itself through cat-like
crying of the newborn. This
disorder is accompanied by
microcephaly, severe
psychosomatic and mental
retardation and cardiac defects.

9. Duplication
 A chromosome duplication is the
doubling of a chromosome piece.
 A duplication is sometimes termed a
"partial trisomy".
 If, therefore, a duplication is
present, the person is equipped with
3 copies of the genes in the
associated chromosome segment.
This means that extra directions
(genes) are present, leading to
congenital abnormalities or
developmental problems.

10. Fragile X syndrome
 The fragile X syndrome results
from multiple duplications of a
CGG segment (trinucleotide) in
the 5' untranslated region of the
FMR1 gene on the X chromosome
(Xq27).
 Since it is an X linked mutation
men are more affected than
women. The fragile X syndrome
leads to one of the most frequent
forms of inherited mental
retardation. In addition, the
syndrome causes a
prognathism, the face is long and
small and the patient has large

11. Inversion
 If chromosome pieces that have been broken
out become inserted again, but reversed, an
inversion has occurred.
 The phenotype of this disorder is usually
unobtrusive, since the entire chromosomal
information is still present.

12.  When the interchanged region includes the
centromere, one refers to it as a pericentric
inversion,

13.  otherwise to a paracentric inversion

14. Insertion
 If chromosome pieces are reinserted
somewhere else, this is referred to as an
insertion. Carriers of such insertions can be
phenotypically inconspicuous because no
information has been lost.

15. Isochromosomiebildung
 Isochromosome formation is a relatively frequent
chromosomal aberration, mainly in X
chromosomes. Here the chromosomes are not
divided along their length (see the normal division
of the chromosomes figure) but transversely.
 The resulting isochromosomes (karyogram) either
have two short or two long arms. Persons with this
X chromosome anomaly have the same
phenotype as patients suffering from Turner's
syndrome (45, X0). This is explained by the fact
that a X chromosome arm is missing.

16. Normal division
Isochromosome formation
of the
chromosome

17. Reciprocal translocation
 In a reciprocal translocation two broken
off chromosome pieces of non-
homologous chromosomes are
exchanged. This is a relatively frequent
anomaly. One finds it with an incidence
of 1:500 newborns.

18.  Reciprocal translocations are frequently
balanced because the entire genetic material
is present. Problems occur, though, in gamete
formation.

19. Cancer and Tumors
Today it is known that balanced
translocations can also lead to
pathogenic disorders in that proto-
oncogenes, which as normal
genes in their customary
environment are frequently
responsible for the controlling cell
proliferation, can be transformed
into oncogenes through
translocation events. They are
the cause for the origin of many
tumors and types of cancer
because in other environments they
achieve totally different effects.

20. Robertsonian translocation
 Another frequently observed
anomaly (1:1'000 newborns) is
the robertsonian
translocation, which occurs
between two acrocentric
chromosomes of groups G
and D. It is also referred to as
the centric fusion of two
acrocentric chromosomes.

21.  Carriers of such robertsonian translocations
are phenotypically inconspicuous. Also
here, though, problems arise when it comes to
gamete formation because, normally, the
diploid chromosome set is halved thereby.

22. END
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