The cause of Down syndrome is a failure of chromosome 21 to separate during meiosis, usually oogenesis, which results in a gamete with two copies; this is called a nondisjunction. Nondisjunction can happen in anaphase I (a failure of homologous chromosomes to separate), this causes two gametes to have extra copies of chromosome 21.  It can also occur during anaphase II (a failure of sister chromatids to seperate), this results in one gamete with an extra chromosome 21.