Aneuploidy is a chromosomal abnormality involving an abnormal number of chromosomes, which can lead to genetic disorders like Turner's syndrome and Down's syndrome. It can be classified into types such as hypoploidy (e.g., monosomy) and hyperploidy (e.g., trisomy), with various implications for human health and development. While it can provide insights into tumor treatments, aneuploidy is often associated with detrimental effects like sterility and severe phenotypic abnormalities.

1. ANEUPLOIDY
(Introduction, classification,
merits and demerits)
Bushra Hafeez

2. ANEUPLOIDY:
Aneuploidy is a type of chromosomal abnormality in which numbers of
chromosomes are abnormal.Generally, the aneuploid chromosome set differs from
wild type by only one or a small number of chromosomes. It is a genetic disorder
causes birth defects. It is the second major category of chromosome mutations in
which chromosome number is abnormal.
Aneuploid nomenclature is based on the number of copies of the specific
chromosomein the aneuploid state. Forexample, the aneuploid condition 2n − 1
is called monosomic (meaning “one chromosome”) because only one copy of some
specific chromosome is present instead of the usual two found in its diploid
progenitor. The aneuploid 2n + 1 is called trisomic,2n − 2 is nullisomic, and
n + 1 is disomic.
How it occurs?
Aneuploidy occurs during cell division due to nondisjunction of chromosomes
which leads to unequal distribution of chromosomes to the daughter cells. Weak
mitotic checkpoint leads to nondisjunction. In Aneuploidy, there is either reduction
or partial increase of the chromosome number. Reduction is said to be hypoploidy,
while increase is said to be hyperploidy. Hypoploidy is due to loss of one or two
chromosomes.
Aneuploidy occurs during cell division when the chromosomes do not separate
properly between the two cells. Chromosome abnormalities occur in 1 of 160 live
births. This generally happens when cytokinesis starts occurring while karyokinesis
is still under the process. Most cases of aneuploidy result in termination of the
developing fetus, but there can be cases of live birth; the most common extra
chromosomes among live births are 21, 18 and 13
CLASSIFICATION OF ANEUPLOIDY
There are different types of Aneuploidy:-
 Hypoploidy
Describes a cell or organism which has less than the normal total number of
chromosomes. i.e.
 Monosomy (2n-1).
 Nullisomy (2n-2).

3.  Hyperploidy
Describes a cell or organism which has more than the normal total number of
chromosomes. i.e.
 Trisomy (2n+1)
 Tetrasomy (2n +2).
Monosomy:
In monosomic diploid individuals, (in the genome) one of the pairs of homologues
would undergo a loss ofone chromosomeand it becomes aunivalent while all others
are bivalents. The diploids cannot generally withstand such a loss, while polyploids
can withstand it. This is due to the fact that polypliods (see later in the same chapter)
have more than two homologues for every pair.
Theoretically the number ofmonosomies possiblein an individual equals its haploid
number. In common wheat where there are 21 pairs of chromosomes; there are 21
possibilities for monosomies.
E.R. Sears has artificially induced these 21 monosomies in a wheat variety called
Chinese spring. Monosomies have been induced in cotton (Endrizzi et al) and
tobacco (Clausen and Cameron).
While diploids with monosomies do not survive, there are instances as in tomato,
where monosomies could be produced. Here the chromosome number is 2n=24.
Double monosomies (2n-1 -1) have two homologues lost from two different
bivalents.
During meiotic prophase together with the normal bivalents there will be two
separate univalents indicating that both these have lost their partners. Similarly in
triple monosomyone homologue each is lost from three different bivalents and three
univalents appear at the meiotic prophase.
Aneuploidy has been noticed in human beings also. A classical instance is the
Turner's syndrome named after the discoverer H.H. Turner (1938). It occurs in .23
infants for every 1000 births.
Nullisomy:
In this, an entire pair of homologous chromosomes will be missing (2n-2). This
should not be mistaken with double monosomywhere 2 chromosomes are lost from
two different pairs. In nullisomics, the metaphase plate at meiosis I will apparently
show no abnormality and only a comparison with the normal can detect the loss of
one whole pair of chromosomes. Nullisomics have been identified in wheat and
other plants.

4. Trisomy
A trisomy is a type of polysomy in which there are three instances of a particular
chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an
abnormal number of chromosomes).
The number of chromosomes in the cell where trisomy occurs is represented as, for
example, 2n+1 if one chromosomeshows trisomy, 2n+1+1 if two showtrisomy, etc.
 Full trisomy, also called primary trisomy, means that an entire extra
chromosome has been copied.
 Partial trisomy means that there is an extra copy of part of a chromosome.
 Secondary trisomy - the extra chromosome a duplicated arms (the arms are
identical, it is an isochromosome).
 Tertiary trisomy - the extra chromosomeis made up of copies of arms from
two other chromosomes.
Trisomies are sometimes characterised as autosomal trisomies (trisomies of the
non-sex chromosomes) and sex-chromosome trisomies.
Tetrasomy
A tetrasomy is a form of aneuploidy with the presence of four copies, instead of the
normal two, of a particular chromosome.
Full tetrasomy of an individual occurs due to non-disjunction when the cells are
dividing (meiosis I or II) to form egg and sperm cells (gametogenesis). This can
result in extra chromosomes in a sperm or egg cell. After fertilization, the resulting
fetus has 48 chromosomes instead of the typical 46.
Tetrasomy is a developmental disorder that affects many parts of the body. This
condition usually causes feeding difficulties in infancy, delayed development,
intellectual disability, changes in muscle tone, distinctive facial features, and other
birth defects. However, the signs and symptoms vary among affected individuals.
Disomics (n + 1)
A disomic is an aberration of a haploid organism. In fungi, they can result from
meiotic nondisjunction. In the fungus Neurospora (a haploid), an n − 1 meiotic
productaborts and does not darken like a normal ascospore;so we may detect MI
and MII nondisjunctions by observing asci with 4:4 and 6:2 ratios of normal to
aborted spores, respectively, as shown here.

5. In these organisms, the disomic (n + 1) meiotic productbecomes a disomic
strain directly. The abortion patterns themselves are diagnostic for the presence of
disomics in the asci. Another way of detecting disomics in fungi is to cross two
strains with homologous chromosomes bearing multiple auxotrophic mutations; for
example:
From such a cross, large populations of ascospores are plated onto minimal
medium. Only ascosporesof genotype + + + + + + can grow and form colonies. Most
of these colonies are found to be disomics and not multiple crossovertypes.
Somatic aneuploids
Aneuploid cells can arise spontaneously in somatic tissue or in cell culture. In such
cases, the initial result is a genetic mosaic of cell types.
Human sexual mosaics—individuals whose bodies are a mixture of male and
female tissue—are good examples. One type of sexual mosaic, (XO)(XYY), can be
explained by postulating an XY zygote in which the Y chromatids fail to disjoin at
an early mitotic division, so both go to one pole:

6. The phenotypic sex of such individuals depends on where the male and female
sectors end up in the body. In the type of nondisjunction being considered,
nondisjunction at a later mitotic division would producea three-way mosaic
(XY)(XO)(XYY), which contains a clone of normal male cells. Other sexual
mosaics have different explanations; as examples, XO/XY is probably due to early
X-chromosome loss in a male zygote and (XX)(XY) is probably the result of a
double fertilization (fused twins). In general, sexual mosaics are called
gynandromorphs.
Origin of a human sexual mosaic (XY)(XO) by Y chromosome loss at the first mitotic division of the
zygote. (a) Fertilization. (b) Chromosome loss. (c) Resulting male and female cells. (d) Mosaic blastocyst.

7. MERITS OF ANEUPLOID
 Genetic alterations that exhibit synthetic lethality with the aneuploid state
either by exaggerating the adverse effects of aneuploidy and/or by interfering
with pathways essential for the survival of aneuploid cells could provide the
basis for the discovery of new tumor treatments
 Studies in yeast have begun to identify second-site suppressors of the
proliferation defect of aneuploid yeast cells. This approach identified many
genetic alterations, prominent among them mutations in the proteasomal
degradation system. These results not only increase our understanding of the
defects underlying the aneuploid condition but also may shed light on the
evolution of tumors
 Recent studies raised doubts overwhether aneuploidy affects gene expression
at the proteome level or whether it can bring phenotypic variation and
improved fitness over euploid counterparts. A profiling study of a large set of
aneuploid yeast strains grown under a variety of conditions demonstrates that
aneuploidy can affect both the transcriptome and the proteome, and generate
significant phenotypic variation that can lead to fitness gains.
DEMERITS OF ANEUPLOID
 Aneuploidy causes sterility in crosses.
 Aneuploidy effected organism cannot be further used as parent in
hybridization programmes.
 Imbalances in gene expression lead to the profound phenotypes associated
with aneuploid conditions, such as Down’s syndrome, with the ultimate goal
of developing therapeutic interventions.
 Other common human aneuploidy is the condition known as Klinefelter's
syndrome (Jacobs & Strong, 1959). Klinefelter's males have a total
chromosome number of 47, which includes two X chromosomes and one Y
chromosome.
 Monosomies are the opposite of trisomies, in that affected individuals are
missing one chromosome, reducing their total chromosome number to 45
leading to Turner’s syndrome.