What is non-disjunction?
Meiosis is a very complex type of cell division and requires precision at each step. However, mistakes or errors during meiosis are not so rare in humans. The main cause of these errors is the failure of separation of homologous chromosomes during meiosis I, or the failure of separation of sister chromatids during meiosis II, and both these cases are called non-disjunction of chromosomes.
Non-disjunction of chromosomes leads to the formation of gametes that contain an abnormal number of chromosomes – either an extra copy of a chromosome or a missing chromosome. When these abnormal gametes fuse with a normal gamete, this fusion leads to the formation of a zygote having an abnormal number of chromosomes, which can cause serious consequences.
In most cases, these abnormal zygotes develop into an abnormal embryo by division, but fail to develop into a complete offspring at some stage of development. However, in a few cases, the zygote develops into an offspring having a different number of chromosomes from the usual number in its species. This condition is called aneuploidy.
Do not confuse the two: the gain or loss of one or a few chromosomes (due to non-disjunction) is aneuploidy. Failure of cytokinesis after telophase, which increases a whole set of chromosomes, is polyploidy – often seen in plants.
Types of aneuploidy
- Monosomy (2n−1) – cells with one chromosome of a homologous pair missing.
- Double monosomy (2n−1−1) – cells with one chromosome missing from 2 homologous pairs.
- Nullisomy (2n−2) – cells with both chromosomes of a homologous pair missing.
- Trisomy (2n+1) – cells with one extra copy of a chromosome.
Consequences of aneuploidy
The consequences of aneuploidy depend on which chromosome or chromosomes are affected.
The absence of one autosomal chromosome (monosomy) is always lethal, regardless of the affected chromosome number, either during embryonic development or during fetal development. The reason is that the absence of a chromosome results in the absence of the 2nd set of alleles of the genes on that chromosome. This results in the expression of all the genes of that chromosome, whether dominant or recessive. This may lead to the expression of harmful mutations that otherwise could not be expressed in normal conditions.
The gain of a chromosome (trisomy) does not have any survival advantage either. Out of the 22 autosomal chromosomes in humans, only zygotes with trisomy of the 21st chromosome can survive beyond the first few weeks or months of life. Babies with trisomy of chromosomes 13 and 18 are born alive, but do not survive more than a few weeks due to severe abnormalities.
However, an abnormal number of sex chromosomes does not have such lethal effects on human development.
Chances of aneuploidy
The chances of non-disjunction leading to the development of abnormal gametes are higher in females than in males. As the age of the female increases, the chances of giving birth to an abnormal offspring increase too. For Down’s syndrome, it increases from 0.05% in 19-year-old mothers to more than 3% in mothers aged 45 years or older.
Non-disjunction is more commonly observed during meiosis I than during meiosis II. According to one hypothesis, the reason is that the older oocytes of females remain arrested in meiosis I for so long that the meiotic spindles are less able to hold together a weakly constructed bivalent. There is also a possibility that cohesin, which prevents chiasmata from sliding off the end of the chromosome, cannot be maintained for extended periods, resulting in the premature separation of homologous chromosomes.
More than 25% of fetuses that are spontaneously aborted carry a chromosomal trisomy.
In humans, more than 20% of oocytes are aneuploid.
Examples of trisomy (47 chromosomes)
Down’s syndrome
Discovered by Langdon Down in 1866, it occurs due to trisomy of the 21st chromosome. Chromosome number 21 is the smallest chromosome in humans, having approximately 400 genes. The additional copy of the chromosome leads to abnormal expression of the genes of the 21st chromosome. It can also affect the expression of genes on other chromosomes, as many of its genes code for proteins/ enzymes involved in regulating genes present on other chromosomes.
Symptoms of Down’s syndrome are:
- Intellectual disability
- Short stature
- Small round head
- Protruding tongue
- Open mouth
- Multiple finger loops
- Broad palm with characteristic palm crease
- Congenital heart disease
- Increased susceptibility to infectious diseases
- High risk of leukaemia
- Early onset of Alzheimer’s disease
- Males are usually sterile; females may be fertile
Klinefelter’s syndrome
Klinefelter’s syndrome is a trisomy of the sex chromosomes, in which a male is born with an extra copy of the X chromosome, resulting in a 44AA + XXY organisation of chromosomes.
Symptoms of Klinefelter’s syndrome are:
- Male with female-like characters
- Gynaecomastia – development of breasts in males
- Under-development of genitalia
- Sterile males
- Female pattern of pubic hair growth
Jacob’s syndrome
A trisomy of the sex chromosomes, resulting in a chromosomal organisation of 44AA + XYY. Males are taller than average. Other features, like aggressive, antisocial and criminal behaviour, are only hypotheses.
Example of monosomy (45 chromosomes)
Turner’s syndrome
A monosomy of the sex chromosomes, resulting in a chromosomal organisation of 44AA + XO, i.e. females having only one copy of the X chromosome.
Symptoms of Turner’s syndrome are:
- Short stature and webbed neck
- Arrested development of genitalia
- Rudimentary (poorly developed) ovaries, so the females are sterile
- Lack of other secondary sexual characters
Quick revision: Down’s – 47, trisomy 21; Klinefelter’s – 47, XXY (sterile male); Turner’s – 45, XO (sterile female, as the ovaries are rudimentary, with a lack of other secondary sexual characters). NCERT describes Down’s syndrome as having a small round head, furrowed tongue, partially open mouth, and a broad palm with a characteristic palm crease.