Nondisjunction

Nondisjunction is an error of chromosome segregation in which homologous chromosomes or sister chromatids fail to separate properly during cell division. As a result, daughter cells receive an abnormal number of chromosomes (aneuploidy). In humans, nondisjunction most often occurs during meiosis I or meiosis II in the germ line, producing gametes with extra or missing chromosomes. It can also occur during mitosis in early embryonic development, leading to mosaicism where some cells have the abnormal chromosome number.

When such a gamete participates in fertilization, the zygote may have trisomy or monosomy for the affected chromosome. Most autosomal monosomies and many autosomal trisomies are lethal or incompatible with life, but a few are viable. The most common viable autosomal trisomies are trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). Sex chromosome aneuploidies include monosomy X (Turner syndrome) and trisomies such as XXX, XXY (Klinefelter syndrome), and XYY. Mosaic forms can show milder or variable features depending on the distribution of abnormal cells.

Detection and study: Nondisjunction can be identified by karyotyping, fluorescence in situ hybridization (FISH), or microarray-based analyses. The risk of nondisjunction increases with maternal age for several autosomal aneuploidies, especially trisomy 21; paternal age effects are less consistent. Nondisjunction is a fundamental mechanism underlying aneuploidy in humans and many other organisms.