Structural
Chromosomal
Anomalies
Genetics – Module 3
Dr Ramakrishnan, Anatomy @
PKDIMS
STRUCTURAL CHROMOSOMAL
ABNORMALITIES
➢A heritable alteration/change in the
genetic material - Mutation
➢ Mutations drive evolution – but also can
be pathogenic
Dr Ramakrishnan, Anatomy @
PKDIMS
BALANCED REARRANGENT
The chromosomal complement is
complete with no loss or gain of genetic
material per cell.
Generally harmless, except if one of the
breakpoints damages an important
functional gene.
Dr Ramakrishnan, Anatomy @
PKDIMS
UNBALANCED REARRANGEMENT
The chromosomal complement contains an
incorrect amount of genetic material.
Clinical effects are usually severe.
Dr Ramakrishnan, Anatomy @
PKDIMS
CAUSES OF MUTATION
Vast majority occur spontaneously through
errors in DNA replication & repair
Some can arise through exposure to
mutagenic agents
Ionizing Radiation
Chemicals
Viral infections
Dr Ramakrishnan, Anatomy @
PKDIMS
Mutation - Results
Different types of change in DNA
sequence can occur due to mutation
No effect
Improper functioning of gene
Alteration of gene product
Dr Ramakrishnan, Anatomy @
PKDIMS
CELLS INVOLVED IN MUTATION
Somatic cells - which will not affect the
progeny.
Gonadal cells – may be passed on to the
progeny producing abnormality in all
the cells.
Such an individual becomes a
carrier of the anomaly.
Dr Ramakrishnan, Anatomy @
PKDIMS
Mutation - types
Point mutation
Frameshift mutation
Dr Ramakrishnan, Anatomy @
PKDIMS
Point mutation
Replacement of a
single nucleotide
with another
nucleotide
Single base
substitution
Results in altered
sequence of amino
acid
Dr Ramakrishnan, Anatomy @
PKDIMS
Point mutation –
structural types
Transition
⚫ Purine=Purine
⚫ Pyrimidine=Pyrimidine
Transversion
⚫ Purine=Pyrimidine
Dr Ramakrishnan, Anatomy @
PKDIMS
Point mutation –
functional types
Nonsense mutation
Missense mutation
Silent mutation
Conservative mutation
Non-conservative mutation
Dr Ramakrishnan, Anatomy @
PKDIMS
Frameshift mutation
Mutation caused by
insertion/deletion of
a base
Changes the
reading frame
Results in a
completely different
translation
Dr Ramakrishnan, Anatomy @
PKDIMS
STRUCTURAL CHROMOSOMAL
ABNORMALITIES
1. Translocation (t) – Reciprocal
Robertsonian
2. Deletion (del)
3. Duplication (dup) / Insertion (ins)
4. Inversion (inv) – Pericentric
Paracentric
5. Ring Chromosome (r)
6. Isochromosome (i)
Dr Ramakrishnan, Anatomy @
PKDIMS
TRANSLOCATIONS
Exchange of segments between
non - homologous chromosomes.
Two types : Reciprocal
Robertsonian
Dr Ramakrishnan, Anatomy @
PKDIMS
Reciprocal translocation :
Break occurs in 2 chromosomes
with exchange of segments –
2 new derivative chromosomes
Dr Ramakrishnan, Anatomy @
PKDIMS
46,XY, t (2;4) (q12;q35)
Dr Ramakrishnan, Anatomy @
PKDIMS
2. Robertsonian translocation :
Breakpoints are located at or close to
the centromeres of 2 acrocentric
chromosomes (centric fusion).
+
p arms
are lost
Dr Ramakrishnan, Anatomy @
PKDIMS
DELETIONS
Loss of a segment of a chromosome
Interstitial deletion : 2 breaks in
one arm followed by reunion.
Dr Ramakrishnan, Anatomy @
PKDIMS
Terminal deletion:
Due to a break in the
terminal part of an arm.
• Deletions more than 2% of
the total haploid genome is
lethal.
Dr Ramakrishnan, Anatomy @
PKDIMS
Microscopic deletions – can be
visualized under a microscope.
Ex Cri-du-chat Syndrome – deletion of
short arm of chromosome 5
Low birth weight
Mental retardation
Cat like cry
Microcephaly
Hypotonia
Round face
Dr Ramakrishnan, Anatomy @
PKDIMS
46,XX, del (6) (q 22 q ter)
Dr Ramakrishnan, Anatomy @
PKDIMS
MICRODELETIONS
Loss of a submicroscopic segment of
chromosome, which can be detected
only by high resolution banding
Eg.
Prader-Willi syndrome (15 q)
DiGeorge syndrome (2 q)
Dr Ramakrishnan, Anatomy @
PKDIMS
INSERTION
A segment of one chromosome is
inserted to another chromosome.
Dr Ramakrishnan, Anatomy @
PKDIMS
DUPLICATION
Duplication of a
segment due to
unequal crossing
over / inversion -
during
gametogenesis.
Dr Ramakrishnan, Anatomy @
PKDIMS
INVERSION
A part of the chromosome is
detached and later unites
with the same chromosome
in inverted position.
➢ The genes are placed in
altered loci.
➢ Inversions are balanced
rearrangements
Dr Ramakrishnan, Anatomy @
PKDIMS
1. Pericentric Inversion : Inversion
segment involves the centromere.
Dr Ramakrishnan, Anatomy @
PKDIMS
2. Paracentric Inversion : Inversion
segment involves only one arm.
Dr Ramakrishnan, Anatomy @
PKDIMS
RING CHROMOSOME
The chromosome is deleted at both
ends and the deleted sticky ends join
to form a ring.
Dr Ramakrishnan, Anatomy @
PKDIMS
ISOCHROMOSOME
Loss of one arm with duplication of the
other.
Centromere splits transversely.
Forms 2 metacentric chromosomes of
unequal length with duplication of
genes.
Dr Ramakrishnan, Anatomy @
PKDIMS
HEREDITARY FRAGILE SITES
Gaps/breaks in the chromosome
On Xq distal end – Fragile-X
Syndrome.
Dr Ramakrishnan, Anatomy @
PKDIMS
CHROMOSOMAL FRAGILE SITES-
FRAGILE X SYNDROME.
Dr Ramakrishnan, Anatomy @
PKDIMS
FRAGILE X SYNDROME
CLINICAL FEATURES :
TRIANGULAR FACE,
PROMINENT MANDIBLE,
LARGE EARS,
MACRO ORCHIDISM,
MENTAL RETARDATION.
Dr Ramakrishnan, Anatomy @
PKDIMS
