Chromosomal mutations

August 12, 2017 17:51 | Genetic Diseases

There are two basic types of chromosomal mutations: numerical chromosomal mutations and structural chromosome mutations.In turn, the numerical mutations are divided into aneuploidy when mutations are expressed in the loss or the appearance of an additional one or more chromosomes, polyploidy, when an increasing number of haploid sets of chromosomes.The loss of one chromosome is called monosomy, and the emergence of an extra chromosome in each pair of chromosomes - trisomy.Structural chromosome mutations presented translocations, deletions, insertions, inversions, rings and isochromosome.

Numerical chromosomal mutations

Trisomy. called trisomy appearance of an extra chromosome karyotype.The most famous example of trisomy is Down syndrome, which is often called trisomy chromosome 21. The result of trisomy on chromosome 13 is Patau syndrome and chromosome 18 - Edwards syndrome.All called trisomy - autosomal.Other trisomies autosomes for viable, and die in utero, appears to be lost in the form of spo

ntaneous abortions.Viable are individuals with additional sex chromosomes.Moreover, additional clinical manifestations X or Y chromosomes can be quite small.

Usually trisomy arise from the violation of divergence of homologous chromosomes at anaphase of meiosis I. As a result, one daughter cell enter both homologous chromosomes, and the second daughter cell does not fit one of the bivalent chromosomes.Sometimes, however, trisomy may be the result of a violation of divergence of sister chromatids in meiosis II.In this case, one gamete get two identical chromosomes that in case of fertilization, normal sperm will trisomic zygote.This type of chromosomal mutations that lead to trisomy, called nondisjunction.Autosomal trisomy arise due to non-disjunction of chromosomes, which is observed mainly in oogenesis, but also in spermatogenesis nondisjunction autosomes may also be.nondisjunction of chromosomes can occur in the early stages of crushing of a fertilized egg.In this case the body is present in the clone of the mutant cells which can capture a larger or smaller portion of organs and tissues, and sometimes give clinical manifestations are similar to those observed during normal trisomy.

nondisjunction reasons remain unclear.Known fact communication between nondisjunction of chromosomes (chromosome 21 in particular) and the age of the mother still has no unambiguous interpretation.

monosomy .The absence of any autosomes is in most cases be incompatible with normal development and results in early spontaneous abortion.Very rare exception - monosomy for chromosome 21 monosomy may be the result of non-disjunction of chromosomes or chromosome loss during its movement to the pole of the cell in anaphase.

Aneuploidy by sex chromosomes. monosomy for sex chromosomes leads to the formation of the body with karyotype XO, which is the clinical manifestation of Turner syndrome.In 80% of cases of monosomy X chromosome is the result of a violation of meiosis in the father (nondisjunction of the X and Y chromosomes).Most of the XO-zygotes die in utero.

Trisomy on sex chromosomes can be of three types - a karyotype 47, XXY, 47, XXX and 47, XYY.Trisomy 47, XXY is known as Klinefelter's syndrome.Approximately 50% of the cause of the syndrome is an X chromosome nondisjunction in oogenesis, the other 50% of cases are due to nondisjunction of chromosome X and Y spermatogenesis.Aborts about 50% of the embryos with the karyotype.Trisomy 47, XXX is in most cases the result of nondisjunction in gametogenesis mother.On the contrary, trimosiya 47, XYY is a result of violation of meiosis in gametogenesis father.This disorder can occur only as a result of meiosis II nondisjunction Y. Trisomy 47, XXX and 47, XYY occur with a frequency of 1: 1000 for women and men, respectively, they appear relatively minor phenotypic changes and are usually found in the form of random finds.

Polyploidy .Polyploid cells have triple or quadruple haploid set of chromosomes.The man triploidy detected sometimes spontaneous abortions, also known several cases of live births, but the patients died within 1 month of life.Triploids may be due to a violation of meiotic differences in all sets of chromosomes in meiosis of female or male sex cells.As a result, either the egg or the sperm are diploid.As triploidy mechanism are also considering the possibility of fertilization of eggs by two sperm.In the case where due to triploidy paternal diploid set of chromosomes, there is cystic degeneration of placenta, the so-called molar pregnancy.

structural chromosomal mutations

Structural chromosome mutations can occur only as a result of rupture of chromosomes, followed by the reunion, accompanied by violation of the original chromosome configuration.Such mutations can be balanced or unbalanced.When balanced chromosomal mutations is no loss or excess of genetic material, so they have no phenotypic manifestations, except for those cases where the gene is functionally important as a result of the chromosomes divide at the break.At the same time, carriers of balanced chromosomal mutations may be generated by unbalanced chromosomal set of gametes, and, as a result, the fetus arising from a gamete fertilization, chromosome set would also unbalanced.When unbalanced chromosomal at a fetus develop severe clinical manifestations of disease, usually in the form of a complex congenital malformations.

deletions. Deletion means the loss of chromosome region.Terminal deletions occur as a result of a break in the chromosome of the chromosome itself is shortened, and the fragment is usually lost in the next cell division.Other deletions, termed interstitial arise as a result of two discontinuities in the chromosome.Deletion of chromosome region makes monosomy on this site, which usually turns out to be lethal.It is believed that the deletion of more than 2% of chromosomal material from the haploid be lethal.At the same time, some deletion syndromes compatible with life.These include the Wolf-Hirschhorn syndrome, a syndrome of "cat's cry."

Duplications .Duplication - doubling the DNA region may also be a duplication of part of chromosome material, involved in the translocation.Mikroduplikatsii may also be the result of unequal crossing-over in homologous chromosomes.Usually, the duplication does not lead to the emergence of such a pronounced developmental abnormalities, as deletions.

Translocation. translocation called the transfer of genetic material from one chromosome to another.If gaps appear at the same time in two chromosomes exchange formed last and free segments, such translocation is called reciprocal.In this case, the karyotype is presented 46 chromosomes, and the translocation can be detected only with a detailed analysis of chromosomes.Reciprocal translocation is not usually accompanied by phenotypic manifestations.Reciprocal translocations lead to the formation of unbalanced gametes when they pass meiosis.Typically, the following two possibilities are realized: in one gamete get two normal, and in another - two translocated (this type of discrepancy is called alternative) chromosomes in both gametes and get one normal and one translocated chromosome.In the second case there are two combinations of normal and translocated chromosomes.Theoretically, all 4 types of differences should be realized with equal probability.

special kind of reciprocal translocations are so-called Robertsonian translocation.In this case, two gaps acrocentric chromosome centromeres are localized in, or in close proximity thereto.The long arm of chromosomes fuse and short lost.Since the short arm of acrocentric chromosomes contain genes rRNA, their loss does not manifest as multiple copies of these genes are also found in other acrocentric chromosomes.Therefore Robertsonian translocation is balanced functional.The karyotype of the chromosome number is reduced to 45. As in the case of reciprocal translocations, the risk of unbalanced gametes due to the fact as meiosis occurs in carriers of Robertsonian translocations.

possible formation of 6 types of gametes resulting in different ways of chromosomes involved in the translocation Robertsonian:

1) gametes with normal chromosomes;

2) complementary to their gametes with Robertsonian translocation (both types of gametes balanced);

3) gametes, bearing one normal and translocated chromosome;

4) gametes, bearing a second normal and translocated chromosome;

5) gametes, bearing only one normal chromosome;

6) gametes carrying only the second normal chromosome.

In the case where the Robertsonian translocation is the result of the merger of the long arms of chromosomes 21, all gametes are unbalanced.In a family in which one parent is a carrier of this translocation, all children with Down syndrome.

Insertions. When a segment of one chromosome is transferred and inserted into another chromosome, such restructuring is called insertion.To insertion occurred must have at least three chromosome breaks.As in case of the insertion is not lost and is not added new genetic material, such restructuring is considered balanced.However, such media insertion 50% gametes will unbalanced because they will be either chromosome deletion or insertion with.As a result, the zygote will be formed with partial monosomy or partial trisomy.

Inversions. inversion of the chromosomal mutation is called when, after two one chromosome breaks in chromosome segment located between the discontinuities, rotated 180 °, and takes the inverted position.If the inverted segment gets the centromere, it is called a pericentric inversion, and if a segment of chromosome inversion occurs within one shoulder - paracentric.When inversion is no loss of genetic material, except when chromosomes break can affect functionally important gene.So both types of carriers have inversions typically any pathological symptoms.Moreover, some of inversion, such pericentric inversion on chromosome 9, as a normal common characteristic with relatively high frequency in some ethnic groups.As with other balanced rearrangements, inversions in meiosis can lead to the formation of unbalanced gametes.

isochromosome. isochromosome arise in those cases where the centromere is not divided longitudinally and transversely.As a result, one of the arms is lost, and the second is doubled.Most often detected isochromosome composed of the long arm of chromosome X. In this case, the individual media such isochromosome X, exhibit symptoms of Turner's syndrome.

Ring chromosome. This type of chromosomal mutation occurs when gaps occur in both arms of some chromosomes.Acentric fragments are lost, and the central part forms a ring chromosome.If such a ring chromosome is formed from the autosomes, that due to lack of a significant proportion of the genetic material of the chromosomes gametes and zygote are unbalanced, which should lead to early loss of an embryo with a ring chromosome.If, nevertheless, the embryo is formed, the ring chromosome tends to be lost during mitoticheskihdeleny cells.As a consequence, there is the presence of mosaicism for chromosomes in cells of the ring.