Aneuploidy: Origins, Diagnosis, and Ethical Considerations Essay

This essay provides a comprehensive overview of aneuploidy, a condition characterized by an abnormal number of chromosomes in a cell. It begins by defining aneuploidy and explaining its origins, including nondisjunction during cell division, weak mitotic checkpoints, and merotelic attachment. The essay then explores the molecular techniques used for diagnosis, such as karyotyping, fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH), detailing their methodologies and applications in identifying trisomies and monosomies. Furthermore, the essay addresses the issues related to these diagnostic methods, including technical limitations, the need for fresh samples, and the ethical considerations surrounding genetic testing, such as autonomy, privacy, and the potential for societal harm. The conclusion emphasizes the importance of understanding aneuploidy for genetic counseling and the need for further investigation into the ethical implications of diagnostic procedures.

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Aneuploidy is the existence of an abnormal number of chromosomes in a cell. For
instance, a normal cell has 46 chromosomes that are 23 pair; however, if a cell is comprised
of 45 or 47 chromosomes; the condition is called aneuploidy. This does not involve any
difference in one or more complete sets of chromosomes. A cell that has a complete number
of chromosomes set that is 46 chromosomes is known as euploid cells (1). The absence or
presence of chromosomes is stated to be a common cause of the genetic disorder. There is
some cancer where there is an abnormal number of chromosomes that have an effect on the
genetic makeup; thus, initiating mutation in the body. The mutation causes uncontrolled
growth and cell division are known as apoptosis; thus, exhibiting the signs and symptoms of
cancer. There are about 68% of human tumours that are aneuploidy and the origin of this
aneuploidy occurs during the cell division when the chromosomes are able to separate in a
proper manner between the nondisjunction or two cells thus, resulting in an abnormal
condition (2). The aim of this essay is to gain a vivid knowledge related to aneuploidy. The
essay will be sectioned into three parts that will highlight the origin of aneuploidy, molecular
techniques used for diagnosis of monosomies and trisomies and the issues related to
diagnostic methods.
In one of the study, it was found that in the majority of the aneuploidy case, it
originated from the germline cells that lead to miscarriage (3). The common extra autosomal
chromosomes are found in 13, 18 and 21 in live births. The prevalence of the chromosomal
abnormalities is detected in 1 out of 160 live births in humans. At the time of meiosis, the
germ cells divide gametes (sperm and eggs) and each of the cells has an equal number of
chromosomes. In some cases, the entire pair of chromosomes are transferred into a gamete
and another gamete is devoid of any chromosomes. In most cases, the embryo does not
survive due to the absence or presence of autosomes and abruptly abort. The most common
and frequently occurring aneuploidy among human is trisomy 16. It can be found the survival

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of fetus that have this disorder is nil; however, in case of a mosaic form, the survival rate is
minimum (4).
Figure 1: Incidence of aneuploidy
Another common aneuploidy is trisomy 21 that is known as Down syndrome that has
an occurrence rate of 1 in every 800 births. Trisomy 18 is known as Edward Syndrome affect
1 out of 6000 birth and trisomy 13 affects 1 in 10000 birth; however, only 10% of the infants
with any of these disorders are able to live up to 10 years. The condition of aneuploidy arises
due to the fault in the chromosomal segregation process that may go wrong in a number of
ways. In another study, it was found that nondisjunction occurs due to the weak mitotic
checkpoints (5). The mitotic checkpoints are responsible for restricting or delaying the
process of cell division until all the component required for a cell to go to the next phase are
present. In the case of weak checkpoints, the cells do not notice that a chromosome pair is not
aligned with the mitotic phase and it goes to the next phases. Thus, the separation of
chromosomes either occur normally or fails, thus, generating a daughter cell with an extra
chromosome and another with a lacking of a chromosome. Another reason for aneuploidy is
complete inactive mitotic checkpoints that occur due to nondisjunction in several
chromosomes and in such case, it results in daughter cells having a disjoint set of genetic
material. Merotelic attachment may occur when in kinetochore is associated with both the
mitotic spindle poles (6). The result of such a scenario is one of the daughter cells has a
normal complementary set of chromosome and the second one do not have any. The
multipolar spindles have more than two spindle poles and during the division of mitosis, it

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was observed that one daughter cell has each spindle pole. The other may have an
unpredictable set of chromosomes. The monopolar spindle has one single spindle form and
thus, a daughter cell has double copy number. In the case of the tetraploid intermediate is
similar to monopolar spindle formation and may result in double copy number of a cell and
have double spindle poles. Therefore, it can be stated that there are multiple origins of
aneuploidy that affect the chromosome number in a cell resulting in a defective set of
chromosomes (7).
The abnormalities in the chromosomes need to be detected and identified in order to
treat them. The most widely used molecular techniques that have been employed for the
identification of trisomes and monosomes are karyotyping. As per the opinion of a study,
karyotyping is a technique that involves taking photographs of the chromosomes in an order
that help in the determination of the complementary chromosomes of the individual including
the number of chromosomes and any abnormalities (8). The term is additionally utilised for
the consummate set of chromosomes in a class or a person and it is used for detecting this
complementarity or process in the number. Karyotypes are utilised in describing the
chromosome count of an organism and the look of these chromosomes in term of
homogeneity to under a light microscope. The focus is given on the length, banding pattern,
any distinctions between the sex chromosomes the position of the centromeres and any other
physical characteristics. The preparation and study of karyotypes is a component of
cytogenetic. The use of Giemsa staining for the process of karyotyping (9).

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Figure 1: Different types of Chromosomal banding
Source: (10)
The study of the entire set of chromosome using this process is known as karyolgy.
The chromsomes are observed to be arranged in a typical manner and is kenned and the
photograph that is taken from the microscopic view is known as karyogram or ideogram that
show the chromosomes are arranged in pairs and having defined size and position with
respect to tgew centrosomes (11). The exact or standard number of chromosomes present in a
somatic cel of a particular species or person is known as somatic number and thus designated
as 2n. The germ cell or the sex cell has one pair of chromosomes is stated to be n and in case
of human, the n is 23. Thus, the somatic number in case of human is 2n equal to 46. In the
diploid organism, the autosomal chromosomes are found in two copies and thus, the double
number of chromosomes is usually present in them. The polyploidy cell is comprised of
multiple sets of chromosomes and the haploid contain single copies. With the help of
karyotypes, the chromosomal aberration can be studied, the study of various cellular process,

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linking various taxonomic species, the discovery of drugs and collection of evolutionary
information related past events could be made. The use of fluorescence in situ hybridisation
(FISH) is a type of molecular cytogenetic analysis that helps in identification of trisomes and
monosomes. The process involves fluorescent probes associated with different elements of
the nucleic acid that have similar complementarity. This is used mainly for detection of
presence or absence of DNA sequence on the chromosomes (12). The utilisation of
Fluorescence microscopy has been conducted for ascertaining the attachment of the probes in
the chromosomes and it can be used in genetic counselling, identification of species and
treatment.
Figure 2: Principle of FISH
Source: (13)

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Another molecular cytogenetic technique that is predominantly used in the
identification of chromosomal aberration is Comparative genomic hybridisation (CGH). This
involves the detection of the copy number changes that take place in the chromosomes
without the need for cell culture. The process is a direct method that offers a vivid
understanding of the deletion or addition of the number in the entire genome, especially in the
case of tumour cells. The tumour DNA is tagged with a green fluorochrome that is in turn
mixed with a red tagged DNA and thus, hybridised in a metaphase preparation (14). The
mixed DNA fragment is attached to the locus of the chromosomes and the ratio of the colour
is used for quantification of the chromosomal axis that states the loss or gain of genetic
matter in the cell. The analysis can be done with the help of a computerised system that has
an inbuilt image analysis program.

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Figure 3: The process of CGH
Source: (15)
There are issues related to diagnostic methods used for detection of the abnormalities
in the chromosomes. The issues include the cryptic aberrations due to inhibited resolution by
classic banding techniques, desideratum for fresh sample, in an incremented utilization of
molecular cytogenetic techniques or difficulties in identification of masked have resulted. For
instance in FISH, to identify categorical abnormalities that are utilizable in either the
diagnosis or management of hematologic disorders and are consequential implements for the
identification of the cryptic translocations and sub-telomeric expunctions in dysmorphic or
mentally/developmentally retarded patients (16). The ethical issues are also associated with
the diagnostic methods that cannot be ignored. The issues related to autonomy, privacy
aspect, the best interest of the patient, the role and responsibility related to the genetic health
of the future children that is being posed at risk, gaining maximum benefits from the method
that in many cases have been found to be minimal. The other ethical issues include harm to
the society, the liberty of reproduction, genetic justice, mutual support, and respect for
difference and the aspects of cost effectiveness.
It can be concluded by stating that aneuploidy is chromosomal abnormalities or
aberration that occur due to issue in the cell division. It may have a serious impact on the
individual and in most of the cases, it can be stated that the condition usually is associated to
death and in the majority of case, it can be stated that the person does not live more than 10
years. The cause of aneuploidy is due to a number of factors that have been discussed in a
vivid manner. The diagnostic technique that is commonly used for detection of any fault in
the chromosomal pieces is karyotyping that involves studying the entire set of chromosomes.
This also helps in genetic testing and genetic counselling. Other cytogenetic techniques used

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are FISH and CGH. The technical issues related to these methods are assessed and discussed
that has an implication on the application of these methods by the healthcare professionals.
Moreover, there are ethical issues associated with the testing procedure that requires further
investigation.

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