CHROMOSOMAL DISORDERS
LEARNING OBJECTIVES
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Describe the normal karyotype
Define various types of structural abnormalities of chromosmes including:
Deletion,Ring chromosome,Inversion,
isochromosome and translocations
Discuss the cytogenetic disorders involving autosomes Trisomy 21(Down
syndrome)
Discuss the cytogenetic disorder involving sex chromosomes(Klinefelter
syndrome,Turner syndrome)
CTOGENETICS
It refers to the study of the chromosomes, their structure and the
abnormalities.
DNA and histone proteins are packaged into structures called chromosomes.
Understanding basic terms
 Diploid human genome
6-7 b bps of DNA orgnized into 23 pairs of chromosomes
 Each chromosome is single continous strand o f DNA complexed with
histone and other proteins
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Karyotyping
Karyotype is a test to identify and evaluate the size, shape, and number of
chromosomes in a sample of body cells.
Basic tool of Cytogeneticist
Helps to study the human genes for several genetic diseases
They are stained with Giemsa dye which highlights A-T base pairs creating
“G Bands” (areas on the chromosome that are rich in A-T pairs).
 It is performed on rapidly dividing cells as WBC’s
 a sample of blood,
 bone marrow,
 the amniotic fluid or
 the tissue from the placenta
 skin
What does a Karyotype Show?
 Check if the 46 chromosomes are present
 Check the presence of the two identical chromosomes and 2 sex
chromosomes
 Check if there are any missing or rearranged chromosomes
What a Karyotype does not show?
 Presence and location of small mutations.
 So if diseases are caused by small mutations they cannot be predicted
 Individual DNA strands or genes
 The number of genes in any given area of a chromosome.
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Karyotype analysis
The traditional process for karyotyping involves adding a dye to
metaphasic chromosomes
Different dyes that affect different areas of the chomosomes are
used for a range of identification purposes
One common dye used is Giemsa; That process is known as Gbanding
Each chromosome can then be identified by its banding pattern
Karyotype analysis
 In the normal situation one chromosome from each pair is
inherited from the mother and the other from the father.
 However, abnormalities can occur in which a whole chromosome
or a portion of a chromosome can be added or deleted.
 This occurrence results in addition or subtraction of genes, which
can cause significant problems with growth and development.
RING CHROMOSOME
 It is a chromosome whose arms have fused together to form a ring
 Ring chromosomes may form in cells following genetic damage by
mutagens like radiation, they may also arise spontaneously during
development.
 Normally, the ends of a chromosome are lost, enabling the arms to
fuse together.
 However, ring formation can also occur with only one end being
lost.
 In rare cases, the telomeres at the ends of a chromosome fuse without any
disappearing of material.
INVERSION
 when a chromosome breaks in two places and the resulting piece
of DNA is reversed and re-inserted into the chromosome.
 Inversions that involve the centromere are called pericentric
inversions; those that do not involve the centromere are called
paracentric inversions.
ISOCHROMOSOME,
 An isochromosome is an abnormal chromosome with two identical arms,
either two short (p) arms or two long (q) arms.
 The chromosome arm is already copied during S phase of the cell cycle.
 During mitosis (or meiosis I or II), the sister chromatid sets line up along the
midline in metaphase.
The affected chromosome simply lines up at a right angle to its normal position,
and as anaphase begins, the centromere is divided in the opposite plane from all
the other chromosomes.
This leaves the two long arms together and the two short arms together.
TRANSLOCATION
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In a balanced translocation, pieces of chromosomes are
rearranged but no genetic material is gained or lost in the
cell.
TRANSLOCATION
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An unbalanced translocation occurs when a child inherits a
chromosome with extra or missing genetic material from a parent
with a balanced translocation.
Down’s syndrome
 A well-known example of a chromosome trisomy is Down syndrome.
 Down syndrome, also called trisomy 21, occurs when a person has 3 copies
of chromosome 21 instead of the usual 2 copies.
Cytogenetic disorders involving autosomes
Trisomy 21 (down syndrome)
• Down syndrome is the most common chromosomal condition affecting newborn
babies
• Characteristics may include intellectual delay, distinct facial features,
problems with the heart and digestive tract
Down syndrome is due to one of the following:
– An additional copy of chromosome 21 (trisomy 21) in all of the cells of the body
(about 95% of cases)
– An additional copy of chromosome 21 in some of the cells of the body (mosaic
trisomy 21- about 1% of cases)
– A chromosomal translocation involving chromosome 21 (about 4% of cases)
The chance for having a child with Down syndrome due to trisomy 21 increases
with the mother’s age
– If a woman has had a child with trisomy 21 there may be a small additional
increase in risk over her age risk for having
another child with the condition
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MONOSOMY
An example of a monosomy for a single chromosome is Turner syndrome
where there is only a single X chromosome present instead of the normal
two X chromosomes.
A karyotype with Turner syndrome (monosomy X)
The absence of a short arm of chromosome 4 may be called monosomy 4p,
or a 4p deletion.
The presence of an additional long arm of chromosome 3 may be called
trisomy 3q or a 3q duplication.
Turner’s syndrome
 1:5000 live female births
 Short stature,edma hands and feet, webbed neck congenital heart diease,
lack of secondary sex charchterics.
 50% are due to paternal nondisjunction
 30-40% are mosaic for 45,X cell line/46, XX Cell line
 There is incresed risk of gonadoblastoma in these patients
KLINEFELTER’S SYNDROME
Males with KF syndrome have additional chromosome
47,XXY
1:1000 live male births
Tall stature femle body gynecomastia
No mental retardation
Extra X CHROMOSOME MATERNAL IN ORIGIN
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