Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate correctly and move to the opposite poles of the cells. This produces daughter cells with abnormal chromosome numbers. Nondisjunction is common during anaphase I or anaphase II of meiosis. Mutations in synaptonemal complex proteins that attach homologous chromosomes increase the chances of nondisjunction in anaphase I of meiosis I. In contrast, mutations in topoisomerases and condensins that hold sister chromatids together promote nondisjunction during anaphase II of meiosis II.

Nondisjunction of chromosomes in germ cells results in gametes possessing additional or fewer chromosomes than normal. Nondisjunction is more frequent during oogenesis than during spermatogenesis. When a gamete with abnormal chromosomes fertilizes a gamete with a normal chromosome number, the resulting zygote has an abnormal number of chromosomes or aneuploidy. Such aneuploid zygotes can have fewer chromosomes than normal, leading to monosomy (45; 2n-1), or more chromosomes than normal, leading to trisomy (47; 2n+1). Some females lack one of the X chromosomes, a typical case of monosomy (45, X), and develop Turner Syndrome. In other instances, individuals who develop Down Syndrome have trisomy with three copies of chromosome 21.