How can an unequal distribution of chromosomes during meiosis lead to conditions such as Down syndrome?

Conditions such as Down syndrome arise from an unequal distribution of chromosomes during meiosis, a process known as nondisjunction.12

During normal meiosis, homologous chromosomes separate so that each gamete (egg or sperm) receives a single copy of each chromosome. Nondisjunction occurs when this separation fails, resulting in gametes that are oversupplied or undersupplied with genetic material. When an abnormal gamete containing an extra chromosome 21 is fertilized by a normal gamete, the resulting zygote possesses three copies of that chromosome instead of the typical two, a condition called trisomy 21.3124

This genomic imbalance disrupts typical development, leading to the physical and cognitive characteristics associated with Down syndrome. While the exact biochemical triggers for these errors remain unknown, the risk of meiotic nondisjunction increases significantly with maternal age, particularly after age 35. Most conceptions involving such chromosomal abnormalities do not result in live births, but trisomy 21 is one of the few autosomal trisomies compatible with full-term pregnancy.3412