In this article, we look at information about chromosomal aberrations. An analysis of this term and its constituent elements, such as meaning, classification, mechanism, probable conditioning factors, etc., will allow the reader to create a general picture of this natural process.
Introduction
Chromosomal aberration is a mutational rearrangement that changes the structure of chromosomes. In accordance with the classification, the following types are distinguished:
- inversion;
- duplication;
- mutational rearrangement;
- translocation;
- the phenomenon of dicentric and ring chromosomes, isochromosomes.
There is the concept of intrachromosomal and interchromosomal rearrangement. In the first case, a structural change is observed within one chromosome, and in the interchromosomal type, changes occur in different ones. Among the rearrangements, the balanced and unbalanced types are also distinguished. The latter aberration causes a change in the dose ratio between the genes and leads to a serious series of deviations.
The mechanisms of chromosomal aberrations are largely closely related to the evolutionary development and speciation of living organisms, and also occupy a significant place in impaired fertility, the presence of some hereditary diseases. Oncological problems of the body are also considered against the background of chromosomal rearrangements.
Contributing factor
The cause of chromosome aberration is most often the formation of a gap in the DNA chain inside the cell. In this case, a violation of the structure should be observed in both filamentous spirals and lie in the limit of a small number of paired bases. Double-stranded DNA breaking can occur spontaneously, as well as under the influence of a certain number of mutational factors of different nature (physical, biological and chemical). This violation can be observed at certain periods of cell life. These processes include the first prophase of meiosis and the maturation of certain types of lymphocytes during special somatic type recombination. It is a violation of the natural course of these vital cell cycles that leads to rearrangement.
Deletion phenomenon
One type of chromosomal aberration is the deletion process. It can be terminal (the end fragment of the chromosome is lost) and intercalary (loss is observed in the inner regions). If a centromere was formed during the deletion, then as a result of mitotic cell division, it will be passed on to the generation of the daughter organism. At the same time, the site that did not form the centromere will be lost.
Conjugation of a set of chromosomes of a homologous type during meiosis leads to the formation of a deletion loop that compensates for the absence of a deleted fragment. This happens if there is a defect in the chromosome. The location of the violation corresponds to the "site" of intercalar deletion in ordinary chromosomes. In a predominant number of cases, the presence of congenital deletions causes the fetus to die at an early stage of development. An example of chromosomal aberration in a deletion is the development of feline scream syndrome.
Duplication process
Duplications are rearrangements that occur both between chromosomes and within one. Any copying of the chromosomal region can be considered duplication. If such a fragment is located next to the site from which it was duplicated, then this phenomenon is called tandem duplication.
The newly formed “clone” is able to form a small chromosome with personal telomeres. It is also possible to create a centromere. In this case, it will be called free duplication.
The occurrence of tandem duplication can occur during cell division by meiosis. The determining factor is the violation of crossing over. Another reason is non-allelic homologous recombination within a somatic cell. Typically, this phenomenon occurs during the repair of the rupture of two strands of DNA.
Inversion
Chromosomal aberrations are changes in the structure of the chromosome itself, which can have different consequences and causes. Another type of such a phenomenon is inversion.
Inversion is the rotation of a chromosome fragment 180 degrees. There is paracentric and pericentric inversion. The latter is characterized by the location of the inverted fragment on both sides of the centromere. The paracentric type is characterized by the occurrence of an inverted element on one side.
Inversion most often does not affect the phenotypic data of the carrier. Partial elimination of gametes and the formation of germ cells with hereditary material in an unbalanced form can be observed when the inversion of a heterozygous organism during gametogenesis occurs on an inverted site.
Translocation Progress
Another type of chromosomal aberration is translocation, which is represented by the transfer of a fragment of the structure from the chromosome to the chromosome. The phenomenon of reciprocal and Robertson translocation is distinguished.
The reciprocal type of translocation does not lose hereditary material and enters the department of balanced translocations. The phenotype most often does not change. The problem is the unbalanced distribution of genetic data between gametes. About half of the germ cells have a defect that can lead to a decrease in fertility or increase the chance of spontaneous miscarriage. And also a born child may have a number of congenital anomalies. Depending on the nature of the reciprocal type of translocation, the probability of encoding an unbalanced karyotype in a child can reach forty percent.
Chromosomal aberrations in humans as a result of translocation can lead to myeloid leukemia. This disease occurs due to the translocation of the "Philadelphia chromosome" (between the ninth and twenty second chromosomes).
The Robertson form of translocation is one of the most common processes that leads to congenital chromosome abnormalities in humans. According to statistics, approximately every thousandth newborn has a chromosome that is susceptible to translocation.
The concept of isochromosomes
The phenomenon of isochromosomes refers to chromosomal aberrations. These structures are formed by 2 copies taken from one chromosomal arm. Isochromosomes are interconnected by a centromere so that the shoulders are represented in the form of a mirror “reflection” with respect to each other. To some extent, the isochromosome is a huge duplication, which was subject to inversion.
Subjects with 46 chromosomes, among which at least one is the isochromosome, are called monosomics, which is caused by the loss of a gene in the chromosome shoulder. In the case when the patient isochromosome is considered an additional structural unit, it is called tetrasomic. The size of the isochromosma is directly related to genetic abnormalities and imbalance. The smaller it is, the greater the chance of fetal survival. The most common formations of isochromosomes in the shoulders of the fifth, eighth, twelfth and eighteenth chromosomes.
There are two assumptions about the causes of structures such as isochromosomes:
- Cross division of centromeres during cell division is subject to anomaly.
- Incorrect process of fusion of isochromatid ends that were torn in the area of the pericentromere.
Relationship with mutations
There is a well-known phenomenon of chromosomal mutations. Types of chromosomal aberrations are closely interrelated with them. A mutagenic effect can cause rupture of two strands of DNA, leading to the formation of rearrangement in the cell. The best-studied effect is exerted by ionizing radiation.
Karl Sachs is rightly considered the ancestor of cytogenetic radiation science. His fundamental works made it possible to take a fresh look at the relationship of mutations and perestroika. The genetics of medicine has a classification of aberration problems arising on chromosomes, but radio-induced rearrangements only partially coincide with them, and to a greater extent have their own types. Such processes are divided into chromosomal and chromatid ones, and they, in turn, differ in the type of exchange of fragments of chromosomes (simple, stable and unstable). The phase of the cell cycle to a greater extent determines the type of aberration.
If we irradiate cells that are at the stages G0-G1, then we can observe the rearrangement in the chromosome form. The most characteristic representatives are metabolic aberrations, which are divided into two types: dicentric and annular. They can be formed due to the incorrect reunion of breaks in two strands of DNA.
Chromosomes of the dicentric and ring type are most often accompanied by chromosome fragments that do not contain a centromere. Exchange adjustment is part of the group of translocation aberrations. Rupture of DNA strands, which is not subjected to repair, causes the phenomenon of deletion of the chromosome and causes the formation of an acentric chromosome fragment, which can be monitored in the subsequent process of mitotic division. Ring dicentrics and acentric components have a low rate of transmission chance in cell division and may disappear altogether over time. In view of this, they are included in the section of unstable rearrangements of chromosomes. If the process of translocation does not cause loss of gene code material, then it can be transmitted to the daughter cell due to mitosis, and therefore they are referred to as stable aberrations.
Mutational chromosome aberrations are changes in the structure of a chromosome due to the action of certain factors. If the effect of irradiation leads to the appearance of a double-stranded DNA break in that part of the chromosome that has already undergone the doubling process during replication, then most often this leads to the formation of chromatid aberration. The most characteristic form of such a restructuring is tetradial. It is represented by an incorrect articulation of 2 breaks in both DNA strands that are part of chromatids on individual chromosomes.
Identification Methodology
Chromosomal aberrations are rearrangements first discovered in Drosophila flies. The discovery was made through genetic tests. Sometimes the crossing of species led to a ratio of the number of descendants, which were very different from each other and did not fit the expected results. This phenomenon has been explained by aberration in the parent chromosomes.
The presence of deletions, duplications and translocations was discovered by K. Bridges (in the period from 1916 to 1923). The first person to describe the inversion process was A. Stertevant, and he published his work in 1921.
For the first time, observations of cytology revealed the presence of rearrangements in the study of polytene chromosomes taken from the glands responsible for the secretion of saliva in Drosophila. Aberration of the mitotic type of chromosomes was shown much later. The cytological form of rearrangement can be detected during the first division of meiosis, at the prophase stage.
Genetics reveals chromosomal aberrations by analyzing data obtained through cytogenetic agents intended for research. Most often, the study of the processes of adjustment takes place during the metaphase. Currently, the most accessible and widely known method of cytogenetic study of the phenomena considered in the article is represented by differential G-staining of chromosomes, also called G-branding. In the late eighties of the twentieth century, the detection of aberrations was carried out by applying the method of fluorescent hybridization. In the course of such studies, special DNA samples are used that are introduced into individual chromosomal formations or their loci.
The technique of duplication and deletion studies, which allows to determine their presence on the chromosome as accurately as possible, consists in comparing genomic hybridization using metaphase preparations of chromosomes or special DNA microarrays.
One of the most accurate methods for detecting small duplications and deletions at present is the method of comparative genomic hybridization on preparations of metaphase chromosomes or DNA microarrays.
To summarize
Now, having examined the concept of chromosomal aberrations, their types and types, possible causes, methods of detection, etc., we can state the following. This type of phenomena includes rearrangements in the structure of one or more chromosomes, which can lead to negative consequences both for the cell and for the whole organism. Very often, such a biological process causes a number of diseases in humans or leads to death. However, sometimes they do not appear in the subject, but can be transmitted to a subsidiary organism. The classification of chromosomal aberrations includes 5 main forms and is closely interconnected with mutations.
Chromosomal rearrangements play a huge role in evolutionary processes and have a direct impact on speciation of all living things. Various ways of their identification and general study allow a person to better understand the essence of the transmission and coding of hereditary material, as well as the ways of the emergence of new signs, because not all rearrangements lead to death.