Cytogenetics: Alkitab University - Collage of Medical Techniques Department of Medical Analysis 3 Rd. Stage - A4

Alkitab University – Collage of Medical Techniques
Department of Medical Analysis

3 rd. stage – A4
Cytogenetics
Written by:
Falah Faridoon Ahmed
Muhammed Raheem Hussein
Sandy adel ishaaq
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INTRODUCTION
Cytogenetics is the branch of genetics that studies the structure and
behavior of chromosomes and their relation to human disease and
disease processes. During the past three decades, the importance of
clinical cytogenetics to the practice of obstetrics and gynecology has
dramatically increased because clinical cytogenetics has a direct effect
on the diagnosis, management, and prevention of many disorders
that are caused by chromosome aberrations. For many chromosome
disorders, physicians face medicolegal responsibilities in the areas of
counseling, screening, and diagnosis, and obstetricians and
gynecologists therefore must have knowledge about the human
chromosome constitution and be able to apply basic principles of
chromosome behavior to clinical practice. This chapter reviews
important concepts and developments in cytogenetics and highlights
their applications in the practice of obstetrics and gynecology.
CYTOGENETIC ANALYSIS
A routine cytogenetic analysis involves evaluating 15 to 20 cells to determine
their modal chromosome number and assessing the structural integrity of each
chromosome in the complement. The modal chromosome number can be
determined by counting chromosomes through the microscope. Identification of
an extra or missing chromosome is possible by microscopic examination, and the
finding is confirmed through the preparation of a set of karyotypes. A karyotype
is a photographic or computer-generated representation of the chromosomes in a
cell arranged according to size, centromeric position, and banding pattern.
Assessment of the structural integrity of each chromosome in the complement
can also be made through the microscope, and gross structural chromosome
aberrations can be detected as well. However, a set of two or more karyotypes
always must be prepared. Cells with well-prepared chromosomes that exhibit a
total of 350 to 400 bands in the complement are considered an essential part of
any routine cytogenetic analysis .
A standard chromosome analysis, therefore, requires that the final interpretation

be based on a chromosome count of at least 15 to 20 cells, the preparation and
careful evaluation of two to three karyotypes consisting of well-banded
chromosomes, and the exclusion of any structural chromosome aberrations.
Subtle chromosome aberrations, such as the gain or loss of a single band, usually
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are detected as the result of a detailed analysis of the banding pattern of
chromosomes magnified thousands of times by means of photographic or
computer processing. In this way, homologous chromosomes can be examined
meticulously and compared for small but clinically significant structural
differences. The number of cells analyzed varies according to the reason for
referral, the initial cytogenetic findings, the protocol of each laboratory, and the
quality of the chromosome morphology.
If an abnormal chromosomal complement is present in all of the cells of a

specimen, analysis of a small number of cells 10,11,12 may be sufficient for diagnostic
purposes. The presence of a single cell with a chromosome aberration usually is
attributed to an error in cell division during tissue culture or a technical artifact
arising in the course of harvesting. In most cases, the parents are informed that
such a finding is not associated with anomalous fetal development. Nevertheless,
the presence of an abnormal cell may necessitate analyzing 20 to 50 or more cells
to distinguish between true mosaicism, which could be responsible for fetal
maldevelopment, and pseudomosaicism (false mosaicism) caused by technical
artifact or an in vitro error.
True chromosome mosaicism occurs when there is a mixture of chromosomally

normal and abnormal cells. True mosaicism may be particularly difficult to detect
if present in low frequency. Most cytogenetic analyses are statistically based on
an evaluation of a minimum of 15 to 20 cells to reduce the chance to less than 5%
probability that true mosaicism will not be detected. A counseling dilemma arises
when chromosome mosaicism is observed after chorionic villus sampling or
amniocentesis: does the mosaicism detected in the villi or cultured amniotic fluid
cells represent the chromosome complement of the fetus? Confirmation of
chromosome mosaicism may require additional invasive procedures, such as
percutaneous umbilical blood sampling (PUBS), which would place the patient at
additional obstetric risk. Even attempts at confirmation of chromosome
mosaicism may fail. For example, mosaicism for chromosome 5 present in
cultured amniotic fluid cells, followed by normal chromosome analysis of fetal
blood obtained by PUBS, still resulted in a child with developmental disabilities
because the mosaicism was confined to the skin and was not present in blood
cells.
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TYPES OF CHROMOSOME ABERRATIONS AND THEIR
CLINICAL SIGNIFICANCE
The normal human chromosome complement represents a balanced genetic
constitution: the correct chromosome number and the correct gene content.
Deviations from the normal number of chromosomes (i.e. numeric aberrations)
or the normal morphologic pattern (i.e. structural rearrangements) represent
gains or losses of genetic information from the complement. Genetic imbalances
generally disturb the normal developmental processes of fertilization and
embryogenesis and result in implantation failure, spontaneous abortion,
stillbirth, or a liveborn infant with multiple congenital anomalies. It is possible
for a person to carry a chromosome rearrangement but show no clinical effects
because there is no accompanying genetic imbalance. Such an individual is called
a balanced carrier because the chromosome aberration constitutes a
rearrangement of the genetic material into a new chromosome pattern, with no
gain or loss of genes. Nevertheless, a balanced carrier is at reproductive risk to
transmit the chromosome rearrangement to offspring by gametes that are
balanced or unbalanced. A problem arises when prenatal diagnosis reveals the
presence of a de novo chromosome rearrangement, because it may not be
possible to determine whether or not such a rearrangement is accompanied by a
microscopically undetectable gain or loss of genetic material.
Numeric Aberrations
POLYPLOIDY.
The two common forms of polyploidy in human tissues are triploidy, in which
each haploid set of 23 chromosomes is present three times (3N = 69) (Fig. 6), and
tetraploidy, in which each haploid set is present four times (4N = 92) (Fig. 7). An
increased incidence of triploidy and tetraploidy has been reported when oral
contraceptive use was stopped within 6 months before conception, 18 but this
finding has not been confirmed. One percent of all human conceptions are
estimated to be triploids. In 66% of the cases, triploidy arises from simultaneous
fertilization of an oocyte by two spermatozoa. In the remaining cases, triploidy
arises from unreduced oocytes or spermatozoa (i.e. during gametogenesis, the
chromosome number is not reduced from 46 to 23). 19 Tetraploidy usually arises
as a postzygotic event through the failure of cytokinesis (division of the
cytoplasm) after chromosome duplication and the incorporation ofdaughter
chromosomes into the same cell. Other less likely mechanisms include trispermy
and fertilization of a diploid ovum by two haploid spermatozoa or by a diploid
spermatozoon.X
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Alkitab University – Collage of Medical Techniques

Department of Medical Analysis

A standard chromosome analysis, therefore, requires that the final interpretation

If an abnormal chromosomal complement is present in all of the cells of a

True chromosome mosaicism occurs when there is a mixture of chromosomally

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