Mutation


A Mutation is a change in genetic information.  It is caused by various influences - the most common mutagens are:
* physical factors (UV and ionizing radiation);
* chemical factors' (e.g. planar aromatic compounds, strong oxidant, radical initiators);
* biological factors (viral infections etc.).

This is a random process, but at the same time it has been proven that in some areas of the genome, mutations occur more often and are referred to as 'hot-spots.

The mutation, if manifested (see below), can cause serious disease, either various birth defects or neoplasia.  However, it is also considered one of the mechanisms of evolution.

Mutations are prevented by DNA repair processes, or so-called ``back mutations.  The increased incidence of mutations occurs with a defect in the genes encoding repair enzymes (mutator genes), which is the basis of various diseases (e.g. Fanconi pancytopenia, xeroderma pigmentosum, Cockayne syndrome).

Distribution of mutations

According to the cell line affected by the mutation:
* somatic mutations' — mutations that are not inherited from parents and cannot be passed on to offspring (they do not affect sex cells);

Mutation in the p53 gene in an intestinal adenoma cell, causing its transition to colorectal cancer.

* germ cell mutations (germline mutations) — mutations that can be inherited from parents and can be passed on to offspring (affect germ cells)

Mutations in the germ cell APC gene causing familial adenomatous polyposis.

By genome region and expression:
* coding regions — mostly cause pathology, depending on what change has occurred (see below);
* non-coding regions — usually they do not show up and these are so-called silent mutations, if the change did not occur in the following non-coding regions:
:* promoters, enhancers and silencers — affect gene expression;  incorrect expression of proto-oncogenes and onco-suppressor genes is then the cause of tumor growth;
:* introns — so-called exonization of an intron can occur and then these are 'splicing mutations;  they stand out in particular.
* Cryptic mutations — in regions very similar to splice sites.

According to the change of genetic information:
* point mutations' — a change in one nucleotide: it can be:
:* deletions (analogous to mutations of larger areas),
:* "advertising" (also),
:* substitution:
:*# transition — change of purine to purine or pyrimidineu to pyrimidine (C → T, T → C, A → G, G → A);
:*# transversion — change of purine to pyrimidine or vice versa (A → T, T → A, C → A, A → C, G → T, T → G, G → C, C → G)  .
::* manifestations depend on whether the codon with the swapped base codes for the amino acid the same, a different one, or none:
:::# samesense (silent) — this is a so-called silent mutation (the same amino acid is included);
:::# missense — another amino acid is inserted and the function of the gene product can be changed or even disabled;
:::# nonsense — the substitution will cause a new stop codon and thus a shorter gene product, which will probably be non-functional.

First definition of ecotoxicology (1969): René Truhaut: the study of the adverse effects of chemicals with the aim of protecting natural species and communities. Rachel Carson (1962): the memoir The Silent Spring highlights the use of pesticides , especially DDT and other agrochemicals. The book led to the establishment of the US Environmental Protection Agency (EPA) in the USA. Introduction of methods describing the toxic effects of human-produced substances on the environment and the organisms contained therein. Systematic implementation of fish toxicity testing methods. In addition to direct toxic effects, the effects of bioconcentration and bioaccumulation are studied – increases in the concentration of foreign substances in the tissues of organisms as a result of exposure from the environment.

2004 EC ratification: Persistent Organic Pollutants Protocol to the 1979 Convention on Long-Range Transboundary Air Pollution The aim of the protocol is to limit, reduce or eliminate the discharge, emissions and losses of persistent organic pollutants that have significant adverse effects on human health or the environment due to long-range transboundary air transport.

In 2006 , Regulation No. 166/2006 of the European Parliament and the EC Council was issued, establishing the European Register of Releases and Transfers of Pollutants . It represents a publicly accessible database of pollutant releases into the air, water and soil, information on wastewater, information on pollutant releases from dispersed sources.

In 2003 , the proposal for a new framework for legislation covering the safety of chemicals REACH (Registration, Evaluation and Authorization of Chemicals) was accepted by the European Commission and approved by the European Parliament . Enterprises and firms that import more than 1 ton of a chemical compound per year will be forced to register this chemical in a central data bank. The aim is to improve the protection of the health of nature, including people, to increase the innovation capacity and the ability of the chemical industry to compete in the European Union. The new measures concern not only new chemical substances introduced to the market, but also substances that have been used for a long time. The program aims to ensure that by 2020 at the latest, only chemical substances with known properties and in a way that does not harm human health and the environment are used.

mutace rozsáhlejších oblastí:
- delece — způsobí, že bude ve výsledném proteinu méně aminokyselin. Zároveň, pokud počet deletovaných nukleotidů není násobek tří, dochází k frameshiftu – s velkou pravděpodobností se v blízkém okolí vyskytne nově vzniklý stop kodon a protein bude nejspíše nefunkční;
- inzerce — do výsledného proteinu se zařadí více aminokyselin, obdobně jako u delece může docházet k frameshiftu;
- jiné strukturní chromosomové aberace.

800px|střed|Příklady klinicky významných mutací Template:Pahýl

Odkazy

Související články

Použitá literatura

Reference

[[Kategorie:Genetika] Kategorie:Molekulární biologie Kategorie:Chemie Kategorie:Biochemie * Tumors

References

{{#switch: book

|book =

  Incomplete publication citation. SOUKUPOVÁ, Milena and Francis SUM. Chapters from medical biology and genetics II. Prague : Karolinum, 1997. 86 s. pp. 63 – 66. 978-80-7262-438-6.

|collection =

  Incomplete citation of contribution in proceedings. SOUKUPOVÁ, Milena and Francis SUM. Chapters from medical biology and genetics II. Prague : Karolinum, 1997. 86 s. pp. 63 – 66. {{
  #if: 80-7184-581-7 |978-80-7262-438-6} }
  |article = 
  Incomplete article citation.  SOUKUPOVÁ, Milena and Francis SUM. 1997, year 1997, pp. 63 – 66,

|web =

  Incomplete site citation. SOUKUPOVÁ, Milena and Francis SUM. Karolinum, ©1997.

|cd =

  Incomplete carrier citation. SOUKUPOVÁ, Milena and Francis SUM. Karolinum, ©1997.

|db =

  Incomplete database citation. Karolinum, ©1997.

|corporate_literature =

  SOUKUPOVÁ, Milena and Francis SUM. Chapters from medical biology and genetics II. Prague : Karolinum, 1997. 86 s. 978-80-7262-438-6} }, s. 63 – 66.

References