Medical Genetics
Structural Chromosomal
Aberration
Structural Chromosomal
Aberrationin which there
Structural abnormalities: is
abnormalities in the structure of chromosome
i.e.
–Changing the structure of a chromosome
–loss or gain
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There are Six main types of structural
Deletion aberrations:
•Ring chromosome
•Inversion
–paracentric & pericentric
•Duplication
•Isochromosome
•Translocation
–Robertsonian & reciprocal
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Chromosome Structural Changes
Deletion
Due to breakage
•A pieceof a chromosome is lost or removed
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Deletion
Involves loss of part of a chromosome
•Results in monosomy of that chromosomal segment
•Clinical effects due to
–Insufficient gene products
–Unmasking of mutant alleles on normal chromosome
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Wolf-Hirschhorn syndrome
•deletion of distal arm of chromosome 4p
•growth and mental retardation
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• Breaks occur Ring chromosome
in both arms of a chromosome. The two
broken ends anneal; the two acentric fragments are lost.
Results in double deletion (in p and in q).
• Epilepsy, mental retardation and craniofacial
abnormalities
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Inversion
Chromosome segment breaks off
•Segment flips around backwards
•Segment reattaches
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Inversion
Two breaks in one chromosome
The fragment generated rotates 180 c and reinserts
into the chromosome
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• Inversion may be classified into two types:
– Pericentric - (involve p & q) include the
centromere
– Paracentric - (involves only one arm) do not include
the centromere
Duplication
Occurs when a gene sequence is repeated
Four types of duplication:
1. Tandem duplication
2. Reverse tandem duplication
3. Displaced duplication
4. Translocation duplication
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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.
Duplication
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Isochromosome
• Mirror image chromosome
• Loss of one arm with duplication of other
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Translocation
Involves two chromosomes that aren’t homologous
•Part of one chromosome is transferred to another
chromosomes
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Translocation
Translocation -exchange of chromosomal material
between two or more chromosomes
•Reciprocal
•Robertsonian
•If no essential chromosome material lost or genes
damaged then the individual is clinically normal
•However, there is an increased chance of
chromosomally unbalanced offspring
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Reciprocal Translocation
Involves two chromosomes
•One break in each chromosome
•The two chromosomes exchange broken segments
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Robertsonian translocation
Named after W. R. B. Robertson who first
identified them in grasshoppers in 1916
•Most common structural chromosome abnormality
in humans
–Frequency =1/1000 live births
•Involves two acrocentric chromosomes
•Two types
–Homologous acrocentrics involved
–Non-Homologous acrocentrics involved
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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.
● Robertsonian translocation
● This translocation occurs as such
● Breaks occur at the extreme ends of the short arms of
two non-homologous acrocentric chromosomes
● The small acentric fragments are lost
● The larger fragments fuse at their centromeic regions to
form a single chromosome
● This type of translocation is the most common type
of chromosomal rearrangement in humans
● As, Robertsonian Translocation 13-14
Several types, with varying results.
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Wolf Hirshhorn Syndrome
4p-
Very rare. Affected children are small, with
microcephaly and abnormal facies. There are
cardiac, renal, and genital abnormalities. Most are
stillborn or die in infancy.
Cri-du-chat (Cat cry syndrome)
The name of the syndrome came from a catlike
mewing cry from small weak infants with the
disorder.
The chromosome deficiency is in the short arm of
chromosome 5 .
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Cri-du-chat Syndrome
-5p
- Microcephaly (small head)
- Broad face (Moon-shaped face)
- Saddle nose
-Heart disease
-Mentally retarded
-Malformed larynx
-Normal lifespan
Cri-du-Chat is Caused by the Loss of the Short Arm of One Copy of
Chromosome 5
Aniridia-Wilms Tumor Syndrome
-1 in 50,000,000 births
-46 chromosomes
XY or XX
-#11 Deletion of upper arm
Aniridia-Wilms Tumor Syndrome
-Mentally retarded
-Growth retarded
-Blindness
-Tumors on kidneys
-Short lifespan
Thirteen Q Deletion Syndrome
1 in 500,000 births
46 chromosomes
XY or XX
#13 Deletion of lower arm
Thirteen Q Deletion Syndrome
-Mentally retarded -Deformed face
-No thumbs -Heart disease
-Short lifespan
Prader-Willi Syndrome
1 in 5,000,000 births
46 chromosomes
XY=97%
XX=3%
#15 Deletion of lower arm
Prader-Willi Syndrome
-Small bird-like head
-Mentally retarded
-Respiratory problems
-Obesity
-Short lifespan
Eighteen Q Deletion Syndrome
1 in 10,000,000 births
46 chromosomes
XY or XX
#18 Deletion of lower arm
Eighteen Q Deletion Syndrome
-Mentally retarded
-Heart disease
-Abnormal hands and feet
-Large eyes
-Large ears
-Normal lifespan
Cat-Eye Syndrome
1 in 1,000,000 births
46 chromosomes
XY or XX
#22 Deletion of bottom
arm
Cat-Eye Syndrome
-Fused fingers and toes
-Mentally retarded
-Small jaw
-Heart problems
-Normal lifespan
