Chromosomal Aberrations

Lecture Outline
• Numerical Aberrations
• Aneuploidy
• Polyploidy

• Structural Aberrations
• Deletion
• Translocation
• Inversion
• Isochromosome
• Duplication
Lecture Objectives

• Define numerical and structural chromosomal

aberrations.
• Discuss different types of numerical and structural
chromosomal aberrations.
• Give examples of genetic disorders caused by
chromosomal aberrations.
 Terminologies
• Ploidy Is the number of
sets of chromosomes in a
biological cell.
• Haploid = n (in normal
gametes)
• Diploid=2n (in Normal
somatic cell)
• Euploidy = to have
multiple sets of
chromosomes
e.g. (3n,4n etc)
Chromosomal Aberrations
• Any aberrations in the shape, size, structure or
number of a chromosome.

• Can occur during meiotic or mitotic divisions.

• Two types:
1. Numerical aberrations
2. Structural aberrations
1. Numerical Aberrations

• Are defined as a gain or loss of one or more whole

chromosome(s) or a whole set of chromosomes
(whether an autosome or a sex chromosome)

• Represent a significant proportion of chromosomal

changes found in humans.
• Constitutive (present in all cells) due to meiosis
• Mosaic (present in some cells) due to mitosis

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1. Numerical Aberrations
• They represent a significant cause of pregnancy loss
as well as abnormalities found in live births.

• Can result in either

• Aneuploidy or
• Polyploidy

Aneuploidy = abnormal number of individual chromosomes

Polyploidy = abnormal number of chromosome sets. Usually
more than 2 in diploid organisms e.g. 3n, 4n etc
Aneuploidy
• Is a chromosome
number that is not an
exact multiple of 23 (i.e.
the normal haploid
number).

• Most common are

trisomy (2n + 1) &
monosomy (2n – 1).

• e.g. Down syndrome

(Trisomy 21), Turner
syndrome (45,X)
Aneuploidy..,
• Caused most often by an addition or loss of 1 or 2
chromosomes.
• This change may result from anaphase lag or
nondisjunction.

❖Anaphase lag
• During meiosis or mitosis, one chromosome lags behind
& is left out of the cell nucleus.
• This results in one normal cell & one cell with
monosomy.

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❖Nondisjunction
• Is the failure of chromosomes to separate during
meiosis or mitosis.
• Mitotic nondisjunction is the failure of sister chromatids
to segregate at anaphase.
• If mitotic nondisjunction occurs at an early stage of
embryonic development, then clinically significant
mosaicism may result.

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Friday, November 20, 2020 11
Types of Aneuploidy

• Monosomy: loss of a single chromosome. 2n − 1

• Trisomy: gain of a single chromosome. 2n + 1

• Nullisomy: loss of both members of a homologous
pair of chromosomes. 2n − 2
• Disomy: Gain of both members of a homologous pair
Down Syndrome (Trisomy 21)
⚫ Is a developmental
disorder caused by an
extra copy of
chromosome 21.

⚫ The extra chromosome

causes mental and
physical developmental
delays.
Down Syndrome (Trisomy 21)
⚫ Incidence ≈ 1 in 800 live births.
Down Syndrome (Trisomy 21)
 Klinefelter syndrome (47, XXY)

⚫ A genetic condition
caused when
someone has two X
chromosomes and
one Y chromosome.

⚫ ≈ 1 in 500 males
affected
Klinefelter syndrome (47, XXY)
⚫ Often symptoms may be subtle and many people do
not realize they are affected.

⚫ XXY is usually caused by nondisjunction.

⚫ Affects primarily sexual development.

Klinefelter syndrome (47, XXY)
⚫ Typically, testes don't fully develop, and the levels of
the hormone testosterone are lower than average.

⚫ Changes that appear at puberty are

− Low growth of facial and body hair
− Development of breast tissue and small testes
Klinefelter syndrome (47, XXY)
 Turner Syndrome
⚫ Caused by a
missing or
incomplete X
chromosome
(typically due to
nondisjunction).

⚫ A genetic
condition that
only affects
females
Turner Syndrome
Turner Syndrome

⚫ Incidence ≈1 in 2000 live births.

⚫ The genes affected are involved in growth and sexual

development → shorter than normal & abnormal
sexual characteristics.
Turner Syndrome
Edwards Syndrome (Trisomy 18)
⚫ Second most
common autosomal
trisomy
⚫ ≈ 1 per 6000
newborn babies
⚫ Death usually 3-4
months
⚫ Due to
nondisjunction
Edwards Syndrome (Trisomy 18)
⚫ Congenital heart
defects

⚫ Facial clefts

⚫ Spina bifida

⚫ Severe
developmental
delay

⚫ Dysmorphic
features (diagram)
 Patau Syndrome (Trisomy 13)
⚫ ≈1 in every 5000 births

⚫ Male or female

⚫ 90% of infants die

before 1 yr of age.

⚫ Due to nondisjunction
 Patau Syndrome (Trisomy 13)

Brain malformation
(Holoprocenphaly)
Polyploidy Triploidy

• A gain of one or more

set of chromosomes is
known as polyploidy.
• E.g. triploidy when
cells have (3n) or
tetraploidy when the
cells have (4n) etc.
Polyploidy
• Polyploidy generally results in spontaneous
abortions.

• It results from a pathological condition known as

endoreduplication.
• Failure of cytoplasmic division that should follow the
nuclear division and therefore the original duplicated
two sets will remain in one cell.

• Other causes: formation of diploid sperm,

fertilisation by two sperms (Dispermy) etc.
Polyploidy and Aneuploidy
• Poly – many, polyploidy = more than one set of
chromosomes
• Aneu – one, aneuploidy = one chromosome is
represented three times instead of the usual two
(one from each parent).
Aneuploidy Polyploidy
Abnormal number of individual Abnormal number of chromosome sets.
chromosomes. Can be fewer or extra Usually more than 2 in diploid
organisms. So can 3n, 4n etc
More common in humans Rare in humans with the exception of
endopolyploidy
Causes chromosomal disorders, some of Triploid and tetraploid types can also be
them are lethal lethal
Various types include disomy, Various types include the triploid,
monosomy, trisomy, nullisomy octaploid, hexaploidy, tetraploid etc.
 Structural Chromosomal Anomalies
• Rearrangement because of chromosome breakage
and subsequent reunion in a different configuration.

• May be either genetically balanced or unbalanced.

• In balanced structural anomalies, there is no change in the
amount of essential genetic material.
• In unbalanced structural anomalies, there is a gain or loss
of essential chromosome segments.

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Structural Chromosomal Anomalies
• The total number of chromosomes is usually
normal (46 per cell) but they are morphologically or
structurally abnormal.
Structural Chromosomal Anomalies..,
• The following types exist:
• Deletion
• Isochromosome
• Inversion
• Translocations
• Duplication

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 Structural Abnormalities
Translocation
⚫ Transfer of a segment of one chromosome to
another non-homologous chromosome.

⚫ In humans there are two major types of

translocation:
⚫ Reciprocal translocation (Balanced translocation)
⚫ Robertsonian translocation
Reciprocal Translocation
• When two fragments of chromosomes exchange
material without any loss of genetic material
Reciprocal Translocation
• Since no genetic material is lost, balanced
translocation is often clinically silent.

• But it can also cause disease as in the t(9,22) which

causes chronic myelogenous leukaemia.
Robertsonian translocation

• When two acrocentric

chromosome lose their
short arm and fuse at
the centromere.

• Eventually the cell is

left with 45
chromosomes.
Inversions

⚫ Chromosome rearrangement in which a segment of

a chromosome is reversed end to end.

⚫ Are formed by two breaks in the same chromosome

with exchange of the two ends.

⚫ Types:
⚫ Pericentric Inversions
⚫ Paracentric Inversions
Paracentric Inversion
• Paracentric chromosome is formed when both
breaks occur in the same arm.
• Centromere is not included in the inverted segment
Pericentric Inversion

• Pericentric chromosome in which one break occurs

in each arm of the chromosome.
• The centromere is included in the inverted
segment.
Deletions

– Portions of the chromosome are lost (genetic

material is missing)

– Has the following subtypes:-

• Terminal deletions
• Interstitial deletions
• Ring chromosomes
Terminal Deletions
• Arise from a single break.

• The acentric fragments

that are formed are lost at
the next cell division.

• E.g. Cri-du chat syndrome

(5p minus syndrome)
Interstitial Deletions

• Arise from 2 breaks.

• Loss of the interstitial

acentric segment &
reunion of the two
remaining segments.

• E.g. Prader willi

syndrome
• (Micro deletion of
chromosome 15)
Ring chromosome

⚫ When a break occurs

on each arm of
chromosomes followed
by fusion of the
exposed ends to create
a circular structure.

⚫ Distal fragments lost

because they lack the
centromere
• May be denoted as for example 46,XX, r(15).
 Isochromosomes

⚫ Results from aberrant

division of the
centromere during
separation of the two
sister chromatids.

⚫ This aberrant division

takes place in a horizontal
way rather than the
perpendicular natural
way.
Isochromosomes
• Either two identical
short arms or two
identical long arms.

• The most common

isochromosome is an
isochromosome of the
long arm of the X
chromosome, i(Xq), in
some individuals with
Turner syndrome.
Duplication
⚫ Part of the chromosome is
repeated, resulting in extra
genetic material.

⚫ Due to errors in DNA

replication.
References & Credits
• Adem MA (2006); Students Lecture Note Series Molecular
Biology and Applied Genetics For Medical Laboratory Technician
Jimma University, Ethiopia.
• Gunder LM and Martin SA (2011). Essentials of Medical Genetics
for Health Professionals. by Jones & Bartlett Learning, LLC,
Sudbury, MA, USA
• Moore CM, and Best RG, Chromosomal Genetic Disease:
Structural Aberrations: Encyclopedia Of Life Sciences / & 2001
Nature Publishing Group / www.els.net 1
• Robbins SL and Kumar V (2007). Basic Pathology (8th Edition). WB
Saunders Co. London.

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