Clinical Cytogenetics

DR Falih Jabor
Chromosomes are compact of DNA.
Chromosomes are as "DNA packages" that enable all this
DNA to fit in the nucleus of each cell.

Why do scientists look at chromosomes?

Scientists can diagnose or predict genetic disorders by
looking at chromosomes. This kind of analysis is used in
diagnosing certain disorders, such as Down syndrome,
or in diagnosing a specific type of leukemia.
• Our genetic information is stored in 23 pairs of
chromosomes that vary widely in size and shape.

• Chromosome 1 is the largest and is over three times bigger

than chromosome 22. The 23rd pair of chromosomes are
two special chromosomes, X and Y.

• Chromosomes are made of DNA, and genes are special

units of chromosomal DNA.
Chromosome Map
• How Do Scientists Read Chromosomes?

• Size

• Banding pattern.
The size and location of Giemsa bands on
chromosomes.

• Centromere position.
They have a special role in the separation of
chromosomes into daughter cells during cell division.
• Each chromosome has only one centromere.
Centromere position can be described by three ways:
metacentric, submetacentric or acrocentric.

• In metacentric the centromere lies near the center of the

chromosome.

• Submetacentric Chromosomes have a centromere that is

off-center, so that one chromosome arm is longer than the
other.

• In acrocentric The centromere resides very near one end.

• How do chromosomes determine the sex of an individual?
• X + X = FEMALE
• Y + X = MALE
• X + 0 = FEMALE (Turner Syndrome)
• Y + X + X = MALE (Klinefelter Syndrome)
 Structural Changes in Chromosomes

There are 4 common types of structural aberrations;

duplications, deletions , inversions, and translocations.
It is important to understand the consequences of each
type of aberration on fertility, and their potential roles in
evolution.
Deletions :
• A chromosome arises in which a segment is missing.
Deletion are generally harmful to the organism, and the
usual rule is the larger the deletion , the greater the harm.
Very large deletion are usually lethal .
• Deletions; loss of chromosomal material

• Breaks in chromosomes can result from a variety of

factors, including X-rays . While a single break leading to
the loss of the ends of chromosomes should be most
common. Unless telomeres are present to protect and
preserve the ends of the chromosome, exonucleases and
cell division/DNA replication will lead to the loss of broken
chromosomes.

• If the genes of a normal chromosome fall in the order 1-7, a

deletion can be represented as
• The best known examples of deletions affecting humans
are "cri du chat"
• Another rather common example is a deletion on
chromosome 22 that leads to a high rate of leukemia. It is
called the Philadelphia chromosome.

• Deletion of genes involved in regulation of cell division

(tumor suppressor genes) leads to an increased risk for
cancer.
 Cri du chat Syndrome

• Cri du chat is a rare syndrome caused by a deletion

on the short arm of chromosome 5. The name of this
syndrome is French for "cry of the cat,". The cry is
caused by abnormal larynx development, which
becomes normal within a few weeks of birth. Infants
with cri du chat have low birth weight and may have
respiratory problems. Some people with this
disorder have a shortened lifespan, but most have a
normal life expectancy.
• Where does the abnormal chromosome 5 come
from? In 80 percent of the cases, the chromosome
carrying the deletion comes from the father's sperm.
 Williams Syndrome

• Williams Syndrome is caused by a

very small chromosomal deletion on
the long arm of chromosome 7. The
deleted region includes the elastin
gene which encodes a protein that
gives blood vessels the stretchiness
and strength required for lifetime of
use. Because they lack the elastin
protein, people with Williams
Syndrome have disorders of the
circulatory system.
• Duplications; gain of genetic material

• As a result of 'slippage' during DNA replication, extra

copies of genes can rarely occur in chromosomes.
 Down Syndrome

• (Trisomy 21)
• Down Syndrome is a genetic disorder caused by
extra genetic material. The effects of Down
Syndrome vary greatly from person to person but
can include mental retardation, and heart defects.
• People with Down Syndrome have 3 copies of
chromosome 21. For this reason, Down Syndrome is
also called "Trisomy 21".
• Where does the extra chromosome come from? In
90% of Trisomy 21 cases, the additional
chromosome comes from the mother's egg.
 Turner Syndrome

• Turner Syndrome affects girls and

women. Symptoms include short
stature and lack of ovarian
development.
• Women and girls with Turner
Syndrome have only one X
chromosome. This is an example
of monosomy.
• Where does the single X
chromosome come from? In 75 to
80 percent of cases, the single X
chromosome comes from the
mother's egg because the father's
sperm that fertilizes the egg is
missing a sex chromosome.
 Klinefelter Syndrome

• Males are often tall and usually do

not develop secondary sex
characteristics such as facial hair,
or underarm and pubic hair.
• Men and boys with Klinefelter
Syndrome have a Y chromosome
and 2 X chromosomes. This is an
example of trisomy.
• Where does the extra chromosome
come from? In about half of
Kleinfelter cases, the extra X
chromosome is from the mother's
egg, while in the other half of cases
the extra chromosome is from the
father's sperm.
• Inversions; an internal segment of a chromosome is
inverted. If a chromosome is broken in two places, the
sticky ends can heal such that the internal segment is
'flipped-over ' from its normal arrangement.
• Two types of inversions can be distinguished: those where
one break occurs in each arm so the centromere is within
the inverted segment are called pericentric inversions.
• If both breaks occur in the same chromosome arm so the
centromere is not included are called paracentric
inversion.
• Although in the long run the effects of both types of
inversions are similar, there are some important
differences in consequences. Unless one of the breaks
disrupts a functional gene there is not likely to be any
"mutant“ phenotype associated with an inversion.
• An inversion is a chromosome rearrangement in which a
segment of a chromosome is reversed end to end. An
inversion occurs when a single chromosome undergoes
breakage and rearrangement within itself.
• Inversions are of two types: paracentric and pericentric.
Paracentric inversions do not include the centromere and
both breaks occur in one arm of the chromosome.
Pericentric inversions include the centromere and there is
a break point in each arm.
• Inversions usually do not cause any abnormalities in
carriers as long as the rearrangement is balanced with no
extra or missing genetic information. However, there is an
increased chance for the production of unbalanced
chromosome rearrangements in the offspring of carriers.
Families that may be carriers of inversions may be offered
genetic counseling and genetic testing.
• The most common inversion seen in humans is on
chromosome 9. This inversion is generally considered to
have no deleterious or harmful effects, but there is some
evidence it leads to an increased risk for miscarriage for
about 30% of affected couples.
• Reciprocal Translocation: Philadelphia Chromosome
This person has 46 chromosomes with a translocation of material
between chromosome 9 and chromosome 22 (commonly known as the
Philadelphia chromosome). The Philadelphia chromosome show that
most of chromosome 22 has been translocated onto the long arm of
chromosome 9. In addition, the small portion of the short arm of
chromosome 9 is translocated to chromosome 22. This translocation,
which is found only in tumor cells, indicates that a patient has chronic
myelogenous leukemia (CML). In CML, the cells that produce blood
cells for the body grow uncontrollably, leading to cancer.

• The connection between this chromosomal abnormality and CML was

clarified by studying the genes located on the chromosomes at the
sites of the translocation breakpoints. In one of the translocated
chromosomes, part of a gene called abl (pronounced A-ble) is moved
from its normal location on chromosome 9 to a new location on
chromosome 22. This breakage and reattachment leads to an altered
abl gene. The protein produced from the mutant abl gene functions
improperly, leading to CML.