Nondisjunction is defined as the failure of chromosomes or chromatids to segregate during cell division. It leads to daughter cells with abnormal numbers of chromosomes, which is known as aneuploidy. The 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. In the first type, due to nondisjunction during meiosis I, homologous chromosomes fail to segregate at anaphase I and lead to all the haploid cells with an abnormal number of chromosomes. The second type of nondisjunction occurs during meiosis II when sister chromatids fail to segregate. It leads to half of the haploid cells with abnormal chromosomes.
Mitotic nondisjunction leads to somatic mosaicism as only the daughter cells lineage originating from the defective cell contains an abnormal set of chromosomes. It can lead to various forms of cancer such as retinoblastoma.
Meiotic nondisjunction leads to chromosomal disorders known as aneuploidy, where there is loss or gain of one or more chromosomes. Meiosis I nondisjunction is a more common cause of aneuploidy than meiosis II nondisjunction. Aneuploidy can be monosomy (2n-1), trisomy (2n+1), nullisomy (2n-2), disomy (n+1).
Nondisjunction is caused due to inactivation of topoisomerase II, separase or condensin. During anaphase, the cohesin which binds the sister chromatids together is broken by separase. Catenation is removed by condensin and topoisomerase II.
Segregation of chromosomes is regulated by spindle assembly checkpoint or SAC. It ensures proper segregation. You might have heard about the chances of having a baby with chromosomal disorders increases with the age of the mother. It is due to the reduced activity of SAC related to the mother’s age which leads to poor segregation control. The arrest of the division of oocytes at the prophase I (diplotene stage) is the main cause of age-related disorders caused by nondisjunction. It also causes a loss of cohesin.
Nondisjunction is more common in oocytes as the oocyte meiotic division gets arrested first at diplotene of prophase I and then later at metaphase II, which resumes only after fertilization. Most of the aneuploidy in children is derived from the mother.
Nondisjunction causes abnormal number chromosomes in all the cells called aneuploidy or in some cells called mosaicism. Some of the important examples are:
- Down’s syndrome – Trisomy of autosomes, i.e. chromosome 21. It contains one extra chromosome 21. Rarely in only 1% of cases, Down’s syndrome with mosaicism is observed. Here some of the cells are normal and some are trisomic. Mosaicism occurs due to nondisjunction during the mitotic division of the zygote.
- Edwards syndrome – Trisomy of chromosome 18th.
- Patau syndrome – Trisomy of chromosome 13th.
- Klinefelter syndrome – Trisomy of sex chromosomes. Here cells have one extra X chromosome (XXY)
- Turner syndrome – Monosomy. One of the X chromosomes is missing (XO)
- Nondisjunction is also seen to cause malignancy. Retinoblastoma is caused due to mitotic nondisjunction coupled with the mutation of the RB1 gene.
Nondisjunction can be diagnosed by karyotyping. Amniocentesis is carried out to take out amniotic fluid, which is analysed and any chromosomal abnormalities in the foetus can be diagnosed.
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