Errors in segregation

We learned in week one that during cell division, most dividing cells go through a process called Mitosis. This is true for all cells, other than the sperm and egg cells, which go through Meiosis. During cell division and prior to both Mitosis and Meiosis, cells go through a phase where the chromosomes replicate so that each chromosome consists of identical sister chromatids. Separation of the sister chromatids occurs in both Mitosis and Meiosis 2. Separation of homologous chromosomes occurs in Meiosis I. The process of separating the tips or pairs of homologous chromosomes is known as segregation. When segregation goes wrong, such that either both chromosomes or chromatids go to one pole and not to the other, this is known as nondisjunction.

In nondisjunction, the daughter cells will either have too many or too few chromosomes. When nondisjunction occurs in Meiosis, the resulting gametes, the sperm or the eggs, are chromosomally unbalanced. If those gametes go on to participate in fertilisation, the resulting foetus will have too many or too few of one or all chromosomes. Areas of ploidy refers to a rare situation where there are the wrong number of whole sets of chromosomes, such as triploidy, where there are 69 chromosomes. However, the main focus of this presentation is on the aneuploisies, where there is a single extra or missing chromosome. For example, a female with Turner’s syndrome has only one X chromosome. Someone with Patau’s syndrome has an extra 13, or trisomy 13.

Someone with Edward’s syndrome has trisomy 18, and someone with Down syndrome has trisomy 21. Turner’s syndrome often presents in adolescence, with failure to menstruate and short stature. It can also present in infancy, or even antenatally, with characteristic features, such as puffy feet and webbed neck. Babies with trisomy 13, or Patau’s Syndrome, have complex malformations of the heart, abdominal wall, and brain. And many are stillborn or survive for just hours or days after birth, Similarly, over 95% of foetuses with trisomy 18 or Edward’s Syndrome, die in utero. They also have complex heart and brain abnormalities and characteristic skeletal changes. The trisomy you are likely to be most familiar with is Down syndrome, or trisomy 21.

Many people with Down syndrome have fulfilling and happy lives. However, there is also an increased chance that they will have certain health problems, including congenital heart problems, disorders of the digestive tract, vision and hearing problems, and an increased risk of leukaemia. Nondisjunction can happen in both men and women. However, most cases of trisomy take place because of nondisjunction of Meiosis 1 in the mother. This is likely to be due to the fact that this stage is very long in women, starting before birth and ending at ovulation. For this reason, the risk of most aneuploidies increases with maternal age, which is also why the risk of miscarriage increases in older women.