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Nondisjunction during meiosis I occurs when homologous chromosome pairs fail to separate properly during anaphase I. Mutations affecting the synaptonemal complex, which initially joins homologous chromosomes, can disrupt this process. Defects in the spindle apparatus, which normally drags separated chromosomes to opposite poles, also contribute to this error.

Nondisjunction during meiosis II occurs when sister chromatids fail to separate during anaphase II, often due to spindle problems or cohesion defects at the centromere. This produces two normal haploid cells, one cell with an extra chromosome, and one with a missing chromosome, resulting in aneuploid gametes.

When an abnormal gamete produced by nondisjunction fuses with a normal gamete during fertilization, the resulting zygote has an abnormal chromosome number and becomes aneuploid. Monosomy occurs with one too few chromosomes (45; 2n-1), while trisomy has one too many (47; 2n+1). Down Syndrome exemplifies trisomy, where individuals possess three copies of chromosome 21.

Nondisjunction appears more frequent when homologous chromosomes fail to recombine. X and Y chromosomes undergo less crossing over and the synaptonemal complex compared to autosomes, which may explain the higher frequency of sex chromosome nondisjunction. Proper chromosome recombination is essential for normal meiosis.

Nondisjunction can produce individuals with various sex chromosome combinations, including one or more additional sex chromosomes such as XXY, XXX, or XYY, or a single sex chromosome denoted X0. These individuals typically have normal lifespans but may experience significant physiological and reproductive consequences.

Nondisjunction occurs more frequently during oogenesis than spermatogenesis in humans. Additionally, postzygotic nondisjunction, a failure of mitotic chromatid separation in early zygotes, produces similar consequences to meiotic nondisjunction and accounts for approximately 2% of Down Syndrome cases. This demonstrates sex-specific variation in meiotic error rates.

Aneuploid zygotes, which result from nondisjunction errors during meiosis, account for approximately 70% of spontaneous abortions during gestation. This high percentage demonstrates the significant impact of chromosome number abnormalities on early human development and fetal viability. Nondisjunction is therefore a major contributor to pregnancy loss.