ANEUPLOIDY: CAUSES, TYPES AND EXAMPLES - BIOLOGY - 2025

The aneuploidy is the condition where the cells have one or more chromosomes in excess or missing, differing from the number haploid, diploid or polyploid cells themselves that make up an organism of given species.

In an aneuploid cell, the number of chromosomes does not belong to a perfect multiple of the haploid set, since they have lost or gained chromosomes. Generally the addition or loss of chromosomes corresponds to a single chromosome, or an odd number of them, although sometimes there may be two chromosomes involved.

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Aneuploidies belong to the numerical chromosomal alterations, and are the easiest to identify cytologically. This chromosomal imbalance is poorly supported by animals, being more frequent and less harmful in plant species. Many congenital malformations in humans are caused by aneuploidy.

Causes

The loss or gain of one or more chromosomes in an individual's cells is generally due to loss by translocation or the process of nondisjunction during meiosis or mitosis. As a result, the gene dose of individuals is altered, which in turn causes severe phenotypic defects.

Chromosome number alterations can occur during the first or second division of meiosis, or in both at the same time. They can also arise during mitotic division.

These division failures are carried out in meiosis I or meiosis II, during spermatogenesis and oogenesis, also occurring in mitosis in the early divisions of the zygote.

In aneuploidies, nondisjunction occurs when one of the chromosomes with its homologous pair passes to the same cell pole or is added to the same gamete. This probably occurs due to premature division of the centromere during the first meiotic division in maternal meiosis.

When a gamete with an extra chromosome joins a normal gamete, trisomies (2n + 1) occur. On the other hand, when a gamete with a missing chromosome and a normal chromosome unite, monosomies (2n-1) are produced.

Types

Aneuploidies occur frequently in diploid individuals. These modifications in the number of chromosomes are of great clinical relevance in the human species. They include different types such as nullisomies, monosomies, trisomies, and tetrasomies.

Nullisomy

In cells with nullisomy, both members of a homologous pair of chromosomes are lost, representing them as 2n-2 (n is the haploid number of chromosomes). In humans, for example, with 23 pairs of homologous chromosomes (n = 23), that is, 46 chromosomes, the loss of a homologous pair would result in 44 chromosomes (22 pairs).

A nullisomic individual is also described as one that lacks a pair of homologous chromosomes in its somatic complement.

Monosomy

Monosomy is the deletion of a single chromosome (2n-1) in the homologous pair. In a human being with monosomy, the cell would have only 45 chromosomes (2n = 45). Within the monosomy we find the monoisosomy and monothelosomy.

In monoisosomal cells the chromosome present without its homologous pair is an isochromosome. Monothelosomal or monotelocentric cells possess a telocentric chromosome without its homologous pair.

Trisomy

In trisomies, the appearance or addition of a chromosome in some homologous pair occurs, that is, there are three homologous copies of the same chromosome. It is represented as 2n + 1. In humans with trisomic cells, 47 chromosomes are found.

Some well-studied conditions, such as Down syndrome, occur as a consequence of the trisomy of chromosome 21.

The constitution of the extra chromosome allows trisomy to be classified into:

• Primary trisomic: When the extra chromosome is complete.
• Secondary trisomic: The extra chromosome is an isochromosome.
• Tertiary trisomic: In this case the arms of the remaining chromosome belong to two different chromosomes from the normal complement.

Tetrasomy

Tetrasomy occurs when there is the addition of a complete pair of homologous chromosomes. In man, tetrasomy results in individuals with 48 chromosomes. It is represented as 2n + 2. The pair of additional chromosomes is always a homologous pair, that is, there will be four homologous copies of a given chromosome.

In the same individual, more than one aneuploid mutation can occur, resulting in double trisomic individuals (2n + 1 + 1), double monosomic, nuli tetrasomic, etc. Sixuplo-monosomic organisms have been obtained experimentally, as is the case of white wheat (Triticum aestivum).

Examples

Cell lines formed after a chromosome nondisjunction process are often nonviable. This is because many of these cells are left without genetic information, which prevents them from multiplying and disappearing.

On the other hand, aneuploidy is an important mechanism of intraspecific variation. In the Jimson weed plant (Datura stramonium), a haploid complement of 12 chromosomes is found, so 12 different trisomics are possible. Each trisomic involves a different chromosome, each presenting a unique phenotype.

In some plants of the genus Clarkia, trisomy also acts as an important source of intraspecific variability.

Aneuploidy in humans

In humans, about half of the spontaneous abortions in the first trimester of gestation are caused by a numerical or structural alteration of the chromosomes.

Autosomal monosomies for example are not viable. Many trisomies such as that of chromosome 16 are frequently aborted and in the X chromosome monosomy or Turner syndrome the cells are viable but the X0 zygotes are aborted prematurely.

Aneuploidy of the sex chromosomes

The most common cases of aneuploidies in men are related to the sex chromosomes. Chromosome number alterations are better tolerated than autosomal chromosome alterations.

Aneuploidy affects the copy number of a gene but not its nucleotide sequence. As the dose of some genes is altered, the concentrations of gene products are altered in turn. In the case of sex chromosomes, there is an exception to this relationship between the number of genes and the protein produced.

In some mammals (mice and humans), the inactivation of the X chromosome occurs, which allows the same functional dose of the genes related to said chromosome to exist in females and males.

In this way, the additional X chromosomes are inactivated in these organisms, making it possible for aneuploidy in these chromosomes to be less damaging.

Some diseases such as Turner syndrome and Klinefelter syndrome are caused by aneuploidies in the sex chromosomes.

Klinefelter syndrome

Individuals with this condition are phenotypically male, with some effeminate traits. The presence of an extra X chromosome in male individuals is the cause of this disease, with these individuals presenting 47 chromosomes (XXY).

In severe cases of this condition, men have very high-pitched voices, long legs, little body hair development, and very marked female hips and breasts. Furthermore, they are sterile and may have poor mental development. In milder cases there is a male phenotype and normal cognitive development.

Klinefelter syndrome occurs in approximately one in 800 live male births.

Turner syndrome

Turner syndrome is caused by the partial or total loss of an X chromosome and occurs in women. This chromosomal alteration occurs during gametogenesis by a postzygotic nondisjunction process.

Different karyotype alterations produce different phenotypes in Turner syndrome. When the material of the long arm of one of the X chromosomes (terminal or interstitial) is lost, primary or secondary ovarian failure and small sizes occur in patients with this condition. Lymphedema and gonadal dysgenesis are also common.

Generally, the phenotype of women with this disease is normal, except for short stature. The diagnosis of this syndrome depends, therefore, on the study and the presence of the cytogenetic alteration.

This disease occurs in approximately one out of every 3000 female newborns, with a higher frequency of spontaneous abortions, that is, no more than 5% of the embryos that are formed with this alteration manage to develop fully to term.

Autosomal aneuploidy

Individuals born with autosomal chromosome aneuploidies are rare. In most cases where these types of mutations occur, spontaneous abortions occur, with the exception of aneuploidies of small autosomes such as trisomy of chromosome 21.

It is believed that, since there are no compensation mechanisms for genetic doses in autosomal chromosomes, alterations in their composition are much less tolerated by organisms.

Down's Syndrome

The small size of chromosomes 21 allows the presence of additional copies of genes, being less damaging than in larger chromosomes. These chromosomes have fewer genes than any other autosome.

Down syndrome is the most common autosomal aneuploidy in humans. In the United States, about one in every 700 births has this condition.

It is estimated that 95% of cases are caused by nondisjunction, causing free trisomy 21. The remaining 5% is produced by translocation, frequently between chromosomes 21 and 14. The prevalence of this condition depends largely on the maternal age at conceiving.

It has been determined that between 85 and 90% of cases, the presence of free trisomy 21 is associated with maternal meiotic alterations. Individuals with this condition are characterized by being hypotonic, hyperextensible and hyporeflective.

In addition, they have a moderately small skull, with a flat, branchicephalic occiput, a small nose and ears, and a small, downward-angled mouth with frequent protrusion of the tongue.

References

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