What is Nondisjunction and What are its Effects?

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Calvin Bridges and Thomas Hunt Morgan discovered the process of nondisjunction in dividing cells in the year 1910. This is one of the most common forms of chromosomal aberration that occurs in humans. This article explains what is nondisjunction, how does it occur, and some of the causes and effects of this condition.
Meaning of nondisjunction
Did You Know
Most human aneuploidy syndromes seem to be of maternal origin. Female meiosis is more prone to error because these cells are arrested in their diplotene phase and have relatively fewer crossovers as compared to that of the male gametes.
Almost all cells in the bodies of higher eukaryotic animals contain two sets of chromosomes―one that is inherited by the mother, and the other is of paternal origin. Such cells are termed as diploid cells (denoted as 2n).
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The sex cells, or gametes, are usually haploid in nature. They arise when the diploid cells of the germinal epithelium undergo reduction division, i.e., meiosis. The male haploid gamete fertilizes the female haploid gamete to give rise to a diploid zygote. This zygote may undergo several rounds of mitotic divisions to give rise to a new individual.

Cells usually double their number of chromosomes in the S phase―before undergoing a round of cell division (either meiosis or mitosis). During cell division, there is either separation of the homologous chromosomes (pair of chromosomes derived from each parent) or the sister chromatids (identical copy of the chromosomes generated in the S phase) into newly formed daughter cells and is known as disjunction of chromosomes.

Nondisjunction can be defined as a state in which the chromosomes fail to separate from each other during cell division. This gives rise to cells with abnormal number of chromosomes, and this condition of the cells is known as aneuploidy.

Types of Nondisjunction
Depending on the stage in which nondisjunction has occurred, it can be classified into three types.

In Meiosis I

nondisjunction in meiosis I


In this process, the separation of homologous chromosomes in anaphase I of meiosis doesn't take place. This results in two daughter cells carrying an extra chromosome (n + 1), and two daughter cells with one less chromosome (n - 1). The effects of nondisjunction in meiosis I are more far-reaching than that in meiosis II. This is because all four gametes that arise have altered number of chromosomes.


In Meiosis II

nondisjunction in meiosis II


In this process, separation of sister chromatids in anaphase II fails, resulting in an uneven distribution of the chromatids into the newly formed daughter cells. If this type of nondisjunction takes place, two cells have normal number of chromosomes (n), whereas in two cells, the number of chromosome has increased by one (n + 1). There is a good chance that this aneuploidy might go unnoticed in females as only one of the newly formed daughter cells develops into an ovum.

In Mitosis

nondisjunction in mitosis


In mitosis, there is a separation of sister chromatids into newly formed daughter cells. When nondisjunction occurs, the sister chromatids fail to separate from each other in the anaphase and results in aneuploidy of cells―(2n + 1) in some and (2n - 1) in others. This is also known as the chromatin or the anaphase bridge. This may lead to mosaicism (a condition some cells are normal while other show aneuploidy) of somatic cells in an individual.


Effects of Nondisjunction

Nondisjunction can lead to the loss of a chromosome and give rise to a condition known as monosomy, denoted as (n - 1) or (2n - 1). It can also lead to the addition of a chromosome and is known as trisomy, denoted as (n + 1) or (2n + 1). These abnormalities can give rise to a number of conditions. Here are a few of them.

Turner Syndrome: In this condition, there is monosomy of the sex linked chromosome, the resulting zygote has only one X chromosome (X + 0). As only X chromosome is present the resulting zygote, it develops into a female. These females are usually sterile with underdeveloped sexual characters. Their stature is usually short, have a webbed neck and low-set ears. They have been observed to suffer from heart defects, diabetes, and hypothyroidism. Intelligence is normal in these females.

Down Syndrome: This results from the trisomy of the autosomal chromosome 21. The frequency of this condition is one in every thousand births. Nondisjunction is mostly of maternal origin. Individuals with this syndrome usually have a lower intelligence and poor immunity. These individuals usually have slanting eyes and experience a stunted growth. The mouth is usually small, and the tongue may be protruding. These individuals usually suffer from heart defects and thyroid abnormalities.

Klinefelter Syndrome: It occurs due to trisomy of sex-linked chromosomes, due to the nondisjunction of paternal sex chromosomes in meiosis I. The individuals suffering from this syndrome exhibit the development of breasts as well as underdeveloped male sex characteristics. These males are more susceptible to autoimmune disorders, breast cancer, and osteoporosis―conditions that usually affect females.
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Retinoblastoma: Nondisjunction in mitosis can lead to abnormalities like cancer. Retinoblastoma protein is a tumor suppressor protein located on chromosome 13. Mutations in the gene encoding for this protein, RB1 gene on one chromosome could cause a loss of the wild type gene from the other chromosome in subsequent rounds of replication. This loss of the functional suppressor prompts cells to divide unchecked. Retinoblastoma is a rare cancer that develops in immature cells of the retina. It is usually found to affect young children and results in the loss of vision in the affected eye.
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