Structural abnormalities of

chromosomes
Chromosomes

p
Centromere

Chromosome 5
 Classification of structural chromosomal
anomalies
Structural (may be due to de novo error in meiosis or
inherited)

Translocations - reciprocal
- Robertsonian (centric fusion)
Deletions
Duplications
Inversions
 Structural Abnormalities
1.Deletions:
1.A portion of the chromosome is missing or deleted.

2.The implications of this deletion depends on how

big the deletion is, and what genes are now missing
due to the deletion.
Deletions
 Deletions

• Loss of chromosomal material

• Large-scale deletions are lethal
• Example: Cri du chat Syndrome
– Deletion of short arm of chromosome 5
– Affects motor and mental function
– Infant cry resembles a meowing cat
– Specific chromosomal break points are
associated with specific phenotypic changes
 Cri du chat
Syndrome
Variation in phenotype
associated with region
deleted has been observed

Researchers have identified

regions with genes involved
in larynx and nervous
system development
Fig. 6.26
 Cri-du chat syndrome
Deletion in Chromosome 5
 Structural Abnormalities
2. Duplications:
• A portion of the chromosome is duplicated, resulting in
extra genetic material.
• The person with the duplication actually has 3 copies of a
particular piece of DNA, rather than the normal 2.
• Sometimes the extra piece of genetic material is on the
chromosome on which it's normally found, and other
times it's on a different chromosome.
• In general, duplications are less harmful than deletions;
however, the extra genetic material can cause birth
defects and health problems.
 Structural Abnormalities
3. Translocations:
1. When a portion of one chromosome is
transferred to another chromosome.
2. There are two main types of translocations. In
a reciprocal translocation, segments from two
different chromosomes have been exchanged.
In a Robertsonian translocation, an entire
chromosome has attached to another at the
centromere.
 Types of Translocations
• An example of reciprocal translocation.
Breaks occur first in both chromosome 4
and chromosome 20. Then one fragment
of chromosome 4 attaches to a fragment
of chromosome 20 and another fragment
of chromosome 4 attaches to another
fragment of chromosome 20
Types of Translocations
 Types of Translocations
• The Philadelphia chromosome results when a piece of chromosome #9
switches places with a piece of chromosome #22.
• The translocation forms an extra-long chromosome #9 and an extra-short
chromosome #22, which is the Philadelphia chromosome that contains the
abnormal, fused BCR-ABL gene.
• Chronic myelogenous leukemia (also known as chronic myeloid leukemia)
or CML is a slowly progressing cancer of the blood and bone marrow.
• It is characterized by an overproduction of white blood cells which do not
mature, ultimately cannot carry out their intended function and crowd out the
healthy cells.
• CML is distinguished from the other types of leukemia by a genetic
abnormality in the white blood cells called the Philadelphia chromosome
which promotes the growth of leukemia cells and seems to be present in
nearly 90% of CML cases.
• Named for the city where it was discovered, the Philadelphia chromosome
is thought to be acquired after birth and is formed when two chromosomes
(9 and 22) switch some of their gene material forming a new chromosome.
Burkitt’s lymphoma

Ig- myc
Robertsonian translocation
 Structural Abnormalities
4. Inversions:
1. A portion of the chromosome has broken off,
turned upside down and reattached, therefore the
genetic material is inverted.
 Chromosomal abnormality resulting from
two breaks in a single chromosome.
• Two breaks in a single
chromosome can cause 
inversion, deletion or ring
structure.
• Inversion: The segment
between two breakpoints is
inverted before resealing the
breaks.
• Deletion: The breaks reseal
without including the segment
between breakpoints.
• Ring chromosome: Two ends
of the segment between
breakpoints are joined to form
a circular structure.
 Structural Abnormalities
• Ring chromosomes typically result in mental and/or
physical abnormalities. This is most likely due to the loss
of genetic material in the ends of the chromosome when
a ring forms. Some examples of disorders caused by
ring chromosomes include:
1. ring chromosome 20 syndrome - associated with epilepsy
2. ring chromosome 14 syndrome - associated with mental
retardation, skin pigment abnormalities, seizures and abnormal
facial features
3. ring chromosome 13 syndrome - associated with mental retardation
and abnormal facial features
4. ring chromosome 15 syndrome - associated with mental
retardation, dwarfism and small head size (called microcephaly)
Structural Abnormalities
 Structural Abnormalities
1. A marker chromosome is
a very small, unidentified
chromosome that can be
seen on a karyotype.
Individuals with marker
chromosomes usually
have this marker
chromosome in addition
to the normal 46
chromosomes.
 Other Chromosomal
Abnormalities
• Uniparental disomy • How does UPD happen? Three
possible mechanisms have been
– Both copies of a proposed for the origin of UPD:
chromosome are • the loss of a chromosome from a
inherited from a single trisomic zygote, "trisomic rescue"
parent • the duplication of a chromosome
– Due to error in cell from a monosomic zygote,
"monosomic rescue"
division • the fertilization of a gamete with
– Examples two copies of a chromosome by
• Females affected with a gamete with no copies of the
rare X-linked disorders same chromosome, called
• Prader-Willi and gamete complementation.
Angelman syndromes • All of these mechanisms require
two consecutive "mistakes".
 Fragile Sites
on the Human X Chromosome
• Fragile sites occur on various
autosomal and sex chromosomes.
• One, on the tip of the X
chromosome, results in fragile X
syndrome.
• Fragile X results in apparently
normal neurological development,
with the effects of mental retardation
becoming apparent during early
learning (age 3-5).
• This disease is one of several CAG
expansion diseases. In the general
population we all carry a limited copy
of this nuceotide sequence, it is only
when the copy number increases
that the encoded protein (FRP,
Fragile X Protein) is decreased in Fig. 6.30
neuronal expression.
 The Karyotype: an international description
Total number of chromosomes,

Sex chromosome constitution,

Anormalies/variants.

46,XY
47,XX,+21
47,XXX
69,XXY
45,XX,der(13;14)(q10;q10)
46,XY,t(2;4)(p12;q12)
46,XX,del(5)(p25)
46,XX,dup(2)(p13p22)
46,XY,inv(11)(p15q14)
46,XY,fra(X)(q27.3)
46,XY/47,XXY
The Karyotype: an international description
Total number of chromosomes,

Sex chromosome constitution,

Anomalies/variants.
46,XY
47,XX,+21 Trisomy 21 (Down syndrome)
47,XXX Triple X syndrome
69,XXY Triploidy

45,XX,der(13;14)(p11;q11) Robertsonian translocation

46,XY,t(2;4)(p12;q12) Reciprocal translocation

46,XX,del(5)(p25) Deletion tip of chromosome 5

46,XX,dup(2)(p13p22) Duplication of part of short arm Chr 2
46,XY,inv(11)(p15q14) Pericentric inversion chromosome 11
46,XY,fra(X)(q27.3) Fragile X syndrome
46,XY/47,XXY Mosaicism normal/Klinefelter syndrome