Nondisjunction is primarily caused by errors during cell division (meiosis or mitosis) where chromosomes fail to separate properly. This results in daughter cells with an abnormal number of chromosomes (aneuploidy).
Nondisjunction in Meiosis
Nondisjunction occurs most commonly during meiosis, the cell division process that creates gametes (sperm and egg cells). There are two phases where it can occur:
- Meiosis I: Homologous chromosomes (pairs of chromosomes with the same genes) fail to separate during anaphase I. This means that both chromosomes of a pair end up in one daughter cell, and neither ends up in the other.
- Meiosis II: Sister chromatids (identical copies of a single chromosome, joined at the centromere) fail to separate during anaphase II. This results in one daughter cell with an extra copy of the chromosome and another daughter cell missing that chromosome.
Nondisjunction in Mitosis
Nondisjunction can also occur during mitosis, the process of cell division for growth and repair in somatic (non-sex) cells. Although less common, mitotic nondisjunction can lead to mosaicism, where some cells have a normal chromosome number and others have an abnormal number. According to the provided reference, Mitotic nondisjunction can occur due to the inactivation of either topoisomerase II, condensin, or separase. This results in 2 aneuploid daughter cells.
Factors Contributing to Nondisjunction:
While the exact mechanisms behind nondisjunction are complex, several factors are known to increase the risk:
- Maternal Age: The risk of nondisjunction increases significantly with increasing maternal age. This is particularly true for trisomy 21 (Down syndrome). This is thought to be due to the prolonged arrest of oocytes (immature egg cells) in prophase I of meiosis.
- Genetic Factors: Some genetic predispositions or mutations in genes involved in chromosome segregation may increase the likelihood of nondisjunction.
- Environmental Factors: Exposure to certain environmental toxins or radiation may potentially disrupt chromosome segregation and increase the risk of nondisjunction.
- Problems with Proteins: As indicated in the short answer, issues with topoisomerase II, condensin, or separase can cause nondisjunction. These proteins are vital to proper chromosome separation.
Consequences of Nondisjunction:
The consequences of nondisjunction vary depending on the chromosome involved and whether it occurs in meiosis or mitosis.
- Meiotic Nondisjunction: Can lead to gametes with an extra or missing chromosome. If such a gamete participates in fertilization, it can result in a zygote (fertilized egg) with aneuploidy. Common examples include trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome), and sex chromosome aneuploidies like Turner syndrome (XO) and Klinefelter syndrome (XXY). Many aneuploidies are lethal, resulting in miscarriage.
- Mitotic Nondisjunction: Results in mosaicism, where some cells have the normal chromosome number and others have an abnormal chromosome number. The severity of the consequences depends on the proportion of cells affected and the specific chromosome involved.
In summary, nondisjunction is caused by the failure of chromosomes or sister chromatids to separate properly during cell division, resulting in cells with an abnormal chromosome number. It is more common in meiosis, particularly with increasing maternal age, but can also occur in mitosis. Disruptions of key proteins, like topoisomerase II, condensin, or separase, may also cause nondisjunction in mitosis.
