If you just learned about your diagnosis of inherited thrombophilia, which is actually thrombophilic gene mutation, you might wonder how such mutations arise. Hopefully, this article will help you understand how mutations are distinguished generally and what mutations types exist.
Classification of mutations can be through many aspects, depending on what the purpose of classification.
We distinguish these mutations types:
a) According to causal terms – spontaneous and induced mutation
b) According to the nature, scale of disturbances DNA – genetic mutations, structural chromosomal aberrations and genomic mutations (numerical chromosome aberrations).
c) Depending on the type of affected cells – somatic mutations and gametic mutations
d) According to the degree of cell damage – mutations vital and lethal
etc.
Spontaneous mutations
The causal relationship to exogenous factors is not known yet. Spontaneous mutations types occur in different genes with different constant frequency for a given gene. The probability that a mutation occurs in a cell is directly proportional to for example the extent of its genome and the duration of the cell cycle.
Induced mutations
In this case, the relation to external factors can be experimentally proved. Occurrence of mutations can be substantially enhanced by the effects of certain physical factors or chemicals. This is used for breeding purposes and for research purposes. Factors causing mutations are called mutagens or inductive factors. The most common physical mutagenic factor is a shortwave, ionizing radiation, particularly X-ray radiation and radioactive radiation, (causing radio mutations). However, mutations can also be caused by thermal shock or ultrasound. It is known that a great deal of chemical mutagens (substances genotoxic) are dangerous to man. About 60 basic types of chemicals have been identified, they are mainly:
- Deaminase agents (e.g. nitrites)
- Alkylating agents (e.g. dimethylsulfate)
- Strong oxidizing agents (e.g. peroxides)
- Aromatic amines (e.g. benzidine)
- Nitro compounds, azo dyes etc.
There are even epigenetic mutagens, e.g.: nickel, arsenic, manganese, or antibiotics (actinomycin D, mitomycin). These are substances that do not damage DNA directly, but disrupt the function of enzymes required for replication or DNA repair. At least 80% of mutagens acting simultaneously carcinogenic (cancer-causing). From this point of view is the formation of the tumor caused by somatic mutation. Today is constantly increasing concentrations of mutagens around us (emissions from energy, industry, exhaust fumes, substances used in agriculture to protect plants etc.)
Gene mutation
Standard allele of the gene may be mutated in a different one by interference at any point of its length. This change may have various manifestations. Most often it is one of the changes on the base. Gene is essentially a sentence formed from the bases A, T, G and C. This DNA segment is responsible for how the protein is to be formed. Any change in the sentence may change its meaning and thus change the protein produced or the way in which cells produce the protein. Just as there are many different ways to change the gene, so there are many ways of doing typos in sentences.
Among the mutations are included also the changes in which bases are not changed, but there is a change in of carbohydrates or phosphate nucleotides. All these mutations are called point mutations. Point change may also lead to a frameshift mutation, in the case if there are changes in the “reading” of the triplets from the mutated point to the end of the gene. It is a severe type of mutation because the result will change the amino acid sequence. This mutation changes the protein which is synthesized according to the gene information, because the mutant mRNA enters into it erroneous amino acids. However, if the mutated point (triplet) is just before the end of the gene, the mutation may not manifest. The structure of the protein (i.e. also the enzyme) also shows its function, and therefore can cause a change in the structure or the concentration of a number of other substances, and thus multiply phenotypic effects. Mutation in a location of a protein molecule that is not important for the function, will not manifest phenotypically – so called “the silent mutations”. It is the same in the case that mutation changes codon in a different one, synonymous – coding the same amino acid.
There are also conditional mutations, which are very interesting subjects for research. These conditional mutations manifest phenotypically only under certain external conditions, e.g. temperature-sensitive mutations, which occur only at elevated temperatures, will not manifest in normal ambient temperature.
Structural aberrations of chromosomes
Structural aberrations are characterized by the structural change of the chromosome or multiple chromosomes. Any change in the standard structure of a chromosome is associated with changing the order or the number of genes in it because this change is the result of significant deterioration of its DNA. Chromosome breakage in one or more locations induces structural chromosome aberrations. Chromosome is shortened by break and divided into two parts; fragment with centromere and a fragment without centromere, which is lost in the next nuclear division (together with its genes) – deletion.
Compared to gene mutations types are structural chromosomal aberrations often hindrance in the normal course of meiosis. Gametes bearing the aberrant chromosome tend to have a limited ability to participate in fertilization and in the case of successful fertilization can cause lifelessness zygote.
Numerical aberrations of chromosomes
The principle of these aberrations lies in a change of the standard number of chromosomes in the cell. Eukaryotic cell then does not have 2n chromosomes, but more or less. A typical numerical aberration is Down syndrome.
Somatic mutations and gamete
In somatic mutations, mutation take place in the somatic, i.e. diploid body cell. Gamete mutations take place in haploid gamete. Under Mendelian laws each gametic mutation is then transferred to the next generation (found in gametes and is transmitted to all cells of offspring). Somatic mutation arose in somatic cells at different levels of postzygotic evolution of an individual. Mutated allele can be compared to other alleles be recessive or dominant. Loss mutations are recessive. Dominant mutations that bring the body’s ability to perform a certain new function, are rare.
Mutations vital and lethal
Viable mutations allow the survival of the organism, at least till the reproductive age. Lethal mutations types are not compatible with life. Mutant allele of a gene can be exceptionally later mutated again in the opposite direction, back to the standard allele. This process is referred to as reversion mutation, mutations backward.