Definition – What is meant by a chromosomal mutation?
The human genome, i.e. the totality of genes, is divided into chromosomes. Chromosomes are very long DNA chains that can be distinguished from each other in the metaphase of cell division. The genes are arranged on the chromosomes in a fixed order.
In the case of chromosomal mutations, microscopically visible changes in this order occur, which are caused by relatively large damage to the chromosomes. These damages can be distinguished in different forms. Some forms remain undiscovered, but others cause serious disease patterns. Which disease develops depends on which form of damage is present and on which chromosome it is located.
Causes – Why do they arise?
Chromosomal mutations arise in half of the people affected by mutations that are created “de novo”. De-novo means that the mutation was only created in the germ cells of the parents, i.e. egg or sperm cells. Certain toxins can cause chromosomal mutations.
These so-called clastogens cause the chromosomes to break and thus cause the various forms of chromosomal mutations. Man has two types of chromosomes, one maternal and one paternal. When the germ cell is formed, the maternal and paternal genetic material is mixed.
This process is called “crossing over”. Normally there is only mixing between chromosomes of the same type. In the case of chromosomal mutation, this crossing-over is defective.
It occurs when parts of a chromosome are incorporated into a chromosome that is not of the same type. In addition, parts of chromosomes may be inserted upside down. Sometimes, however, a section of the chromosome in a germ cell is completely lost.
How do you recognize a chromosomal mutation?
In the presence of malformations or mental retardation, chromosome analyses can be performed to confirm a genetic cause. In order to carry out a chromosome analysis, cells are taken from the affected person to examine the chromosomes of the latter. The most common cells used for analysis are lymphocytes, i.e. cells of the immune system circulating in the blood.
In principle, however, all cells that have a cell nucleus can be used. Chromosomal mutations are associated with changes, some of which can be detected under the light microscope. The different chromosomes have a very specific shape.
In addition, it is possible to stain the chromosomes using a special technique. This staining creates so-called bands. By identifying the special bands, it is possible to determine which of the 23 pairs of chromosomes is involved. By this banding technique, changes in the respective chromosomes can also be determined.
Which chromosomal mutations are there?
In chromosomal mutations, a distinction is made between different forms of mutation. With deletion, a section of the chromosome is lost. The affected chromosome is shortened at the corresponding location.
In the case of deletion, genes are lost, and the effects can vary depending on the section. In contrast to deletion, insertion involves the insertion of a section of chromosome into another chromosome. If the section originates in another cell nucleus, the genes of this section are duplicated.
Under certain circumstances, an overproduction of the gene product may occur. In the case of inversion, a segment is inserted in the correct chromosome, but in the reverse order. Duplication can also occur, in which a part of the chromosome is duplicated.
The most significant chromosome mutation is translocation. In this case, chromosomal parts of 2 different chromosomes exchange their places. If this exchange is not accompanied by a loss of genes, it is called a balanced translocation.
Carriers of balanced translocations do not normally show any abnormality, but they have more frequent miscarriages. In addition, the offspring are often carriers of unbalanced translocations. In these cases genetic material is lost and the offspring are restricted.
In reciprocal translocation, parts of two different chromosomes are exchanged between them. In reciprocal translocation, it is important that the total content of genetic material in the cell remains the same. However, those affected have problems with the formation of germ cells.
If there is a chromosome in the developing germ cell in which a piece has been exchanged, then this cell is not viable. However, it may also be the case that the two chromosomes in which a piece has been exchanged end up in a germ cell. Then only the normal chromosomes end up in the other germ cell.
If this is the case, only half of the germ cells are not viable. The other half contains a normal set of chromosomes. Reciprocal translocation can lead to various genetic diseases.
One of them is, for example, chronic myeloid lekemia, where a high number of Philadelphia chromosomes can be detected. The Cat Screaming Syndrome, or Cri-du-Chat Syndrome, is so called because toddlers scream very high and cat-like. These high cries are caused by a malformation of the larynx.
The cause of the cri-du-chat syndrome is a deletion on the short arm of chromosome 5. The affected children are severely retarded in their development and mentally handicapped. The mental retardation is however very variable.
They have a small head and the growth is disturbed. In addition, there are other physical malformations. Changes of the internal organs occur only very rarely. Life expectancy is therefore not significantly limited.
