SATHEE: Nondisjunction

Nondisjunction

Nondisjunction is defined as the failure of chromosomes or chromatids to segregate during cell division, resulting in daughter cells with abnormal numbers of chromosomes, known as aneuploidy. This irregular distribution of chromosomes during cell division leads to one cell with an extra chromosome and the other with a less chromosome.

Calvin Bridges and T. H. Morgan discovered nondisjunction in the sex chromosomes of Drosophila melanogaster.

Nondisjunction can be further categorized into mitotic nondisjunction or meiotic nondisjunction.

Mitotic Nondisjunction occurs during Anaphase when Sister Chromatids fail to separate.

Meiotic Nondisjunction is of two types:

Nondisjunction during Meiosis I: In this type, homologous chromosomes fail to segregate at anaphase I, resulting in all the haploid cells having an abnormal number of chromosomes.
Nondisjunction during Meiosis II: In this type, sister chromatids fail to segregate, leading to half of the haploid cells having an abnormal number of chromosomes.

Mitotic nondisjunction can cause somatic mosaicism, as only the daughter cells derived from the affected cell will have an abnormal set of chromosomes. This can lead to certain types of cancer, such as retinoblastoma.

Meiotic nondisjunction can result in chromosomal disorders known as aneuploidy, in which there is a loss or gain of one or more chromosomes. Meiosis I nondisjunction is more common in causing aneuploidy than meiosis II nondisjunction. Aneuploidy can be classified into four categories: monosomy (2n-1), trisomy (2n+1), nullisomy (2n-2), and disomy (n+1).

#Nondisjunction Causes

Nondisjunction is caused by the inactivation of topoisomerase II, separase, or condensin. During anaphase, separase is responsible for breaking the cohesin which binds the sister chromatids together. Condensin and topoisomerase II are involved in removing catenation.

The Spindle Assembly Checkpoint (SAC) regulates the segregation of chromosomes and ensures proper segregation. You may have heard that the chances of having a baby with chromosomal disorders increases with the age of the mother. This is due to the reduced activity of SAC associated with the mother’s age, which leads to inadequate segregation control. The arrest of the division of oocytes at the prophase 1 (diplotene stage) is the main cause of age-related disorders caused by nondisjunction, and also leads to a loss of cohesin.

Nondisjunction is more common in oocytes due to the arrest of the oocyte meiotic division at diplotene of prophase 1, followed by a later arrest at metaphase II which only resumes after fertilization. The majority of aneuploidy in children is derived from the mother.

Nondisjunction Examples

Nondisjunction can lead to aneuploidy, where all cells have an abnormal number of chromosomes, or mosaicism, where only some cells have an abnormal number of chromosomes. Some important examples include:

Down’s Syndrome - Trisomy of autosomes, i.e. chromosome 21, which contains one extra chromosome 21. Rarely, only 1% of cases, Down’s Syndrome with mosaicism is observed, where some of the cells are normal and some are trisomic. This mosaicism is due to nondisjunction during the mitotic division of the zygote.

Edwards Syndrome - Trisomy of the 18th Chromosome.

Patau Syndrome - Trisomy of the 13th Chromosome.

Klinefelter Syndrome - Trisomy of sex chromosomes, where cells have one extra X chromosome (XXY).

Turner Syndrome - Monosomy. One of the X Chromosomes is missing (XO).

Retinoblastoma is caused by a combination of mitotic nondisjunction and mutation of the RB1 gene, which is an example of how nondisjunction can lead to malignancy.

Karyotyping can be used to diagnose Nondisjunction, and Amniocentesis can be carried out to take out amniotic fluid, which can then be analysed to detect any chromosomal abnormalities in the foetus.

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