Mutations in the genes

August 12, 2017 17:51 | Genetic Diseases


became clear from the above that the genes do, it should also be clear that the change in structure of the gene nucleotide sequence may lead to changes in the protein encoded by the gene.Changes in the structure of the gene are called mutations.These changes in the structure of the gene can occur for a variety of reasons, ranging from random errors in DNA and ending doubling effect of ionizing radiation on gene or specific chemicals, called mutagens.The first type of change leads to so-called spontaneous mutations, and the second - to the induced mutations.Mutations can occur in genes in the germ cells, and then they are transmitted to the next generation, and some of them will lead to the development of a genetic disease.Mutations also occur in genes in somatic cells.In this case, they will inherit only in a particular cell lineage, which originated from the mutant cells.It is known that mutations in the genes somatic cells in some cases, can cause cancer.

types of gene mutations

One of the most common types of mutation is the substitution of a single base pair.Such substitution can not have any effect on the structure of the polypeptide chain encoded by the gene, due to the degeneracy of the genetic code.Replacement of the third nitrogen base in the triplet will almost certainly never have any consequences.Such mutations are called silent substitutions.At the same time, single nucleotide replacements can cause the substitution of one amino acid for another due to changes in the genetic code, a mutant triplet.

single nucleotide base substitution in the triplet can turn it into a stop codon.Since these stop codons of mRNA translation of the polypeptide chain, the polypeptide chain is synthesized is shortened as compared with the normal chain.Mutations causing the formation of a stop codon are called nonsense mutations.As a result

nonsense mutation in which substitution occurs at the A-T-C T in the DNA molecule in the synthesis of the polypeptide chain is terminated at a stop codon.

single nucleotide substitution in the normal stop codon is located, on the contrary, can make it meaningful, then the mutant mRNA and then the mutant polypeptide are longer than normal.

next class of molecular mutation - a deletion (loss) or insertions (insertions) nucleotides.When deletiruetsya or inserted nucleotides triple, then, if this triplet is encoded as part of a polypeptide or a certain amino acid disappears, or there is a new amino acid.However, if the result of the deletion or insertion is inserted or removed numbers of nucleotides is not a multiple of three, then the meaning is lost or changed for all the other following the insertion or deletion of codons of the mRNA molecule.Such mutations are called a frame shift mutations.They often lead to the formation of a stop codon following the insertion or deletion of nucleotide sequence of mRNA.

Gene conversion - this is a direct transfer of a fragment of one allele to a different allele or fragment pseudogene in the gene.Since pseudogenes there are many mutations, such a transfer violates the normal gene structure and may be considered as a mutation.For the implementation of gene conversion between gene and pseudogene needed their mating and subsequent atypical crossover, during which there are breaks in the DNA strands.

recently opened a new and completely unexpected type of mutations, which manifests an increase in the number of repeats (often trinucleotide), but also described cases of increasing the number of repetitions, consisting of 5 or even 12 nucleotides located in the gene exons and introns or untranslatedgene regions.These mutations are called dynamic or unstable.Most of the diseases caused by mutations associated with the expansion zone repetitions - hereditary neurological diseases.This Huntington's disease, spinal and bulbar muscular atrophy, spinocerebellar ataxia, myotonic dystrophy, Friedreich's ataxia.

extension mechanism repeats zone is not completely understood.In a population of healthy individuals generally observed some variability in the number of nucleotide repeats found in different genes.The number of nucleotide repeats in generations inherited as well as during division of somatic cells.However, after the number of repetitions is different for different genes, exceeds a certain critical threshold, which is also different for different genes, they tend to become unstable and may either grow in size during meiosis, or first cleavage divisions of a fertilized ovum.


gene mutation phenotypic effects of mutations can be expressed either in loss of function, or in the acquisition of new functions.

Most of autosomal recessive diseases is a consequence of the loss of function of the corresponding mutant gene.It shows sharp decrease in the activity of enzymes (mostly), which may be due to either a decrease in their synthesis or their stability.In the case where the function of the corresponding protein is completely absent, the gene mutation such effect is called a null allele.The same mutation in different individuals can manifest differently regardless of what level assess its effects: molecular, biochemical or phenotypic.The reasons for these differences may be as in effect on the expression of other gene mutations, and of exogenous reasons, if they are understood widely enough.

Among mutations with loss of function is accepted to allocate a dominant negative mutation.These include such mutations, which not only lead to a reduction or loss of their own product features, but also disrupt the function of the corresponding normal allele.Most manifestations often exhibit dominant negative mutations in proteins, consisting of two or more polypeptide chains, such as collagens.

It was natural to expect that when DNA replication that occurs during each cell division should occur quite a lot of molecular mutations.However, this is in fact not, as occurs in the cells of the repair of DNA damage.Several dozens of enzymes involved in this process.They recognize the modified base, remove it by cutting the DNA strand and replaced by a regular basis, using the complementary DNA strand intact.

Recognition repair enzymes modified base in the DNA chain is due to the fact that correct pairing is broken modified nucleotide with a complementary base of the second DNA strand.There are also repair mechanisms and other types of DNA damage.It is believed that normally is repaired more than 99% of all emerging molecular mutations.If, however, the mutations occur in genes that control the synthesis of enzymes repair, the frequency of spontaneous and induced mutations increases dramatically, and this increases the risk of various cancers.

Changing the structure of the gene nucleotide sequence may lead to changes in the protein encoded by the gene.Changes in the structure of the gene are called mutations.Mutations can occur for various reasons, ranging from random errors in DNA doubling and ending with the influence of ionizing radiation on the gene or specific chemicals are called mutagens.

Mutations can be classified depending on the nature of changes in the nucleotide sequence. Deletions, insertions, substitutions, etc., or the nature of the changes in protein biosynthesis:. Missense, nonsense mutations shift the reading frame etc.

There are also mutations stable and dynamic.

Phenotypic effects of mutations can be expressed either in loss of function, or to acquire new functions.

Most emerging mutations corrected by DNA repair enzymes.

monogenic diseases

In somatic cells, organs and tissues each gene is represented by two copies (each copy is called an allele).The total number of genes of about 30,000 (the exact number of genes in the human genome is unknown).


at the organismal level mutant genes alter a phenotype individuals.

Under phenotype understand the sum of all the external characteristics of a person, and when we talk about the external characteristics, that at the same time, we have in mind not only do external signs, such as height or eye color, but also a variety of physiological and biochemical characteristics that may change in theresult of the action of genes.

Phenotypic features dealt with by medical genetics, is the hereditary diseases and hereditary diseases symptoms.It is obvious that between the symptoms of hereditary diseases, such as, say, the absence of the pinna, seizures, mental retardation, cysts in the kidneys, and the change of the protein as a result of mutations in any particular gene is a huge distance.

mutant protein, which is the product of the mutant gene, must somehow interact with hundreds or even thousands of other proteins encoded by other genes that eventually changed to some normal or pathological sign appeared.In addition, gene products involved in the development of any phenotypic trait may interact with environmental factors and modified under their influence.Unlike phenotype genotype may change throughout life, while genotype remains constant.The most striking evidence of this - our own ontogeny.Throughout life we ​​are changing outwardly, aging, and genotype - not.For the same phenotype can be different genotypes, and, conversely, when the same genotype phenotype may vary.The latter statement is supported by the results of the study of monozygotic twins.Their genotypes are identical, but they may differ phenotypically by body weight, growth, behavior and other characteristics.However, when we are dealing with monogenic hereditary diseases, we see that the effect of the mutant gene usually is not hiding his numerous interactions pathological product with products of other genes or environmental factors.