Calvin Bridges and Thomas Hunt Morgan are credited with discovering nondisjunction in Drosophila melanogaster sex chromosomes in the spring of 1910, while working in the Zoological Laboratory of Columbia University.
[4] In general, nondisjunction can occur in any form of cell division that involves ordered distribution of chromosomal material.
[citation needed] Ovulated eggs become arrested in metaphase II until fertilization triggers the second meiotic division.
Chromosome bridges occur when sister chromatids are held together post replication by DNA-DNA topological entanglement and the cohesion complex.
[11] The spindle assembly checkpoint (SAC) is a molecular safe-guarding mechanism that governs proper chromosome segregation in eukaryotic cells.
[12] SAC inhibits progression into anaphase until all homologous chromosomes (bivalents, or tetrads) are properly aligned to the spindle apparatus.
[citation needed] Surveys of cases of human aneuploidy syndromes have shown that most of them are maternally derived.
The most obvious difference between female oogenesis and male spermatogenesis is the prolonged arrest of oocytes in late stages of prophase I for many years up to several decades.
Failures of recombination or inappropriately located crossovers have been well documented as contributors to the occurrence of nondisjunction in humans.
[5] Due to the prolonged arrest of human oocytes, weakening of cohesive ties holding together chromosomes and reduced activity of the SAC may contribute to maternal age-related errors in segregation control.
[6][13] The cohesin complex is responsible for keeping together sister chromatids and provides binding sites for spindle attachment.
The prolonged arrest of human oocytes prior to completion of meiosis I may therefore result in considerable loss of cohesin over time.
Loss of cohesin is assumed to contribute to incorrect microtubule-kinetochore attachment and chromosome segregation errors during meiotic divisions.
[citation needed] The only known survivable monosomy in humans is Turner syndrome, where the affected individual is monosomic for the X chromosome (see below).
[15] It is well documented that advanced maternal age is associated with greater risk of meiotic nondisjunction leading to Down syndrome.
As a consequence, the organism evolves as a mixture of cell lines with differing ploidy (number of chromosomes).
By this combination of lesions, affected cells completely lose expression of functioning tumor suppressor protein.
PGD is considered difficult due to it being both time consuming and having success rates only comparable to routine IVF.
[17] Karyotyping involves performing an amniocentesis in order to study the cells of an unborn fetus during metaphase 1.
[18] Polar body diagnosis (PBD) can be used to detect maternally derived chromosomal aneuploidies as well as translocations in oocytes.