Meiotic non-disjunction, miscarriage and aneuploidy
In meiosis, the cell division that makes eggs and sperm, non-disjunction (failure of chromosomes to separate correctly) gives gametes with one extra or one missing chromosome.
Remember
Non-disjunction in meiosis gives gametes with the wrong number of chromosomes, so if one of them is fertilised, the embryo is aneuploid (it has an abnormal number of chromosomes), and the most characteristic consequence is miscarriage.
Meiosis is the cell division that makes eggs and sperm, and each gamete should receive one copy of every chromosome (23 in all). A failure of chromosomes to separate properly is called non-disjunction, or mis-segregation. One gamete then receives an extra chromosome and another is missing one.
After fertilisation, the embryo is aneuploid, which means it carries an abnormal number of chromosomes. It has either a trisomy (three copies of a chromosome) or a monosomy (one copy). The number of copies of each gene is then wrong across a whole chromosome, and most aneuploid embryos cannot develop normally. The commonest result is early pregnancy loss, or miscarriage, and errors in meiotic chromosome separation are linked with about a third of identified miscarriages. A few embryos survive to birth, such as trisomy 21 (Down's syndrome). Meiotic errors are also linked with infertility (abnormal gametes reduce the chance of a successful pregnancy), and they are a leading cause of intellectual disability.
How many gametes are affected depends on when the error occurs. A mistake in meiosis I (the first division) affects every gamete from that cell, so no zygote is normal. A mistake in meiosis II (the second division) affects half of them, so two of the four gametes are normal. Most errors come from maternal meiosis I (the first division in the egg), and the risk rises with maternal age. The rise in risk with age is partly because oocytes (immature eggs) wait in meiosis for years.
Key facts
- Non-disjunction
- the failure of chromosomes to separate correctly in meiosis, also called mis-segregation
- In the gametes
- some have an extra chromosome and some are missing one
- In the embryo
- after fertilisation, a trisomy (three copies of a chromosome) or a monosomy (one copy)
- Main outcome
- aneuploidy is the leading genetic cause of miscarriage
- Timing
- an error in meiosis I affects every gamete from that cell, whereas one in meiosis II affects half of them
- Down's syndrome
- 96% of cases are caused by non-disjunction in meiosis
Exam traps
- Mosaicism, a mix of normal and abnormal cell lines, is not the direct result of a meiotic error, because it arises from an error in mitosis after fertilisation, whereas a meiotic error is present in every cell from the start.
- Meiotic errors do not explain most congenital heart defects, because heart defects have many causes and meiotic errors explain only a minority of them.
- Non-disjunction does not raise the risk of single-gene disorders in offspring, because it changes the number of whole chromosomes, whereas single-gene disorders come from mutations within the DNA sequence of one gene.
Read the full notes
Tested in 6 SimpleMed+ questions
Practice it in Genetics, with the answer and a full explanation after every question.
Practice these questions