Nondisjunction is a genetic condition that occurs when chromosomes fail to separate properly during cell division, resulting in daughter cells with abnormal numbers of chromosomes, known as aneuploidy. There are three forms of nondisjunction: failure of a pair of homologous chromosomes to separate in meiosis I, failure of sister chromatids to separate during meiosis II, and failure of sister chromatids to separate during mitosis.
Nondisjunction can occur during anaphase of mitosis, meiosis I, or meiosis II. During anaphase, sister chromatids (or homologous chromosomes for meiosis I), will separate and move to opposite poles of the cell, pulled by microtubules. In nondisjunction, the separation fails to occur causing both sister chromatids or homologous chromosomes to be pulled to one pole of the cell.
Mitotic nondisjunction can occur due to the inactivation of either topoisomerase II, condensin, or separase. This will result in 2 aneuploid daughter cells, one with 47 chromosomes (2n+1) and the other with 45 chromosomes (2n-1) . Nondisjunction in meiosis I occurs when the tetrads fail to separate during anaphase I. At the end of meiosis I, there will be 2 haploid daughter cells, one with n+1 and the other with n-1. Both of these daughter cells will then go on to divide once more in meiosis II, producing 4 daughter cells, 2 with n+1 and 2 with n-1. Nondisjunction in meiosis II results from the failure of the sister chromatids to separate during anaphase II. Since meiosis I proceeded without error, 2 of the 4 daughter cells will have a normal complement of 23 chromosomes. The other 2 daughter cells will be aneuploid, one with n+1 and the other with n-1.
Nondisjunction can be diagnosed by karyotyping, which is the analysis of chromosomes in a sample of cells. Amniocentesis is a procedure that can be carried out to take out amniotic fluid, which is analyzed to diagnose any chromosomal abnormalities in the fetus. Meiotic nondisjunction is of greater clinical significance since most aneuploidies are incompatible with life. However, some will result in viable offspring with a spectrum of developmental disorders.