Changes

In [[biology]], '''mutations''' are  changes to the [[base pair]] sequence of [[genetic material]] (either [[DNA]] or [[RNA]]). Mutations can be caused by copying errors in the genetic material during [[cell division]] and by exposure to [[ultraviolet]] or [[ionizing radiation|ionizing]] radiation, chemical [[mutagens]], or [[virus (biology)|viruses]], or can occur deliberately under cellular control during processes such as [[meiosis]] or [[hypermutation]]. In multicellular organisms, mutations can be subdivided into ''[[germline mutation]]s'', which can be passed on to descendants, and ''[[somatic mutation]]s''. The somatic mutations cannot be transmitted to descendants in animals. Plants sometimes can transmit somatic mutations to their descendants asexually or sexually (in case when flower buds develop in somatically mutated part of plant).

In [[biology]], '''mutations''' are  changes to the [[base pair]] sequence of [[genetic material]] (either [[DNA]] or [[RNA]]). Mutations can be caused by copying errors in the genetic material during [[cell division]] and by exposure to [[ultraviolet]] or [[ionizing radiation|ionizing]] radiation, chemical [[mutagens]], or [[virus (biology)|viruses]], or can occur deliberately under cellular control during processes such as [[meiosis]] or [[hypermutation]]. In multicellular organisms, mutations can be subdivided into ''[[germline mutation]]s'', which can be passed on to descendants, and ''[[somatic mutation]]s''. The somatic mutations cannot be transmitted to descendants in animals. Plants sometimes can transmit somatic mutations to their descendants asexually or sexually (in case when flower buds develop in somatically mutated part of plant).

==Classification==

==Classification==

===By effect on structure===

===By effect on structure===

The sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins. Structurally, mutations can be classified as:

The sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins. Structurally, mutations can be classified as:

* '''Loss-of-function mutations''' are the result of gene product having less or no function. When the allele has a complete loss of function ([[null allele]]) it is often called an '''[[Muller's morphs|amorphic]] mutation'''. Phenotypes associated with such mutations are most often [[recessive]]. Exceptions are when the organism is [[haploid]], or when the reduced dosage of a normal gene product is not enough for a normal phenotype (this is called [[haploinsufficiency]]).

* '''Loss-of-function mutations''' are the result of gene product having less or no function. When the allele has a complete loss of function ([[null allele]]) it is often called an '''[[Muller's morphs|amorphic]] mutation'''. Phenotypes associated with such mutations are most often [[recessive]]. Exceptions are when the organism is [[haploid]], or when the reduced dosage of a normal gene product is not enough for a normal phenotype (this is called [[haploinsufficiency]]).

* '''Gain-of-function mutations''' change the gene product such that it gains a new and abnormal function. These mutations usually have [[dominant gene|dominant]] phenotypes. Often called a [[Muller's morphs|neomorphic]] mutation.

* '''Gain-of-function mutations''' change the gene product such that it gains a new and abnormal function. These mutations usually have [[dominant gene|dominant]] phenotypes. Often called a [[Muller's morphs|neomorphic]] mutation.

* '''Dominant negative mutations''' (also called '''[[Muller's morphs|antimorphic]] mutations''') have an altered gene product that acts antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often inactive) and are characterised by a [[Dominant gene|dominant]] or [[incomplete dominance|semi-dominant]] phenotype. In humans, [[Marfan syndrome]] is an example of a dominant negative mutation occurring in an [[autosomal dominant]] disease. In this condition, the defective glycoprotein product of the fibrillin gene (FBN1) antagonizes the product of the normal allele.

* '''Dominant negative mutations''' (also called '''[[Muller's morphs|antimorphic]] mutations''') have an altered gene product that acts antagonistically to the wild-type allele. These mutations usually result in an altered molecular function (often inactive) and are characterized by a [[Dominant gene|dominant]] or [[incomplete dominance|semi-dominant]] phenotype. In humans, [[Marfan syndrome]] is an example of a dominant negative mutation occurring in an [[autosomal dominant]] disease. In this condition, the defective glycoprotein product of the fibrillin gene (FBN1) antagonizes the product of the normal allele.

*'''Lethal mutations''' are mutations that lead to a phenotype incapable of effective reproduction.

*'''Lethal mutations''' are mutations that lead to a phenotype incapable of effective reproduction.

===Special classes===

===Special classes===

*'''Conditional mutation''' is a mutation that has wild-type (or less severe) phenotype under certain "permissive" environmental conditions and a mutant phenotype under certain "restrictive" conditions. For example, a temperature-sensitive mutation can cause cell death at high temperature (restrictive condition), but might have no deletirious consequences at a lower temperature (permissive condition).

*'''Conditional mutation''' is a mutation that has wild-type (or less severe) phenotype under certain "permissive" environmental conditions and a mutant phenotype under certain "restrictive" conditions. For example, a temperature-sensitive mutation can cause cell death at high temperature (restrictive condition), but might have no deleterious consequences at a lower temperature (permissive condition).

===Causes of mutation===

===Causes of mutation===

Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by [[mutagen]]s.  

Two classes of mutations are spontaneous mutations (molecular decay) and induced mutations caused by [[mutagen]]s.  

'''Spontaneous mutations''' on the molecular level include:

'''Spontaneous mutations''' on the molecular level include:

* [[Tautomerism]] - A base is changed by the repositioning of a hydrogen atom.

* Tautomerism - A base is changed by the repositioning of a hydrogen atom.

* [[Depurination]] - Loss of a purine base (A or G).

* Depurination - Loss of a purine base (A or G).

* [[Deamination]] - Changes a normal base to an atypical base; C → U, (which can be corrected by DNA repair mechanisms), or spontaneous deamination of 5-methycytosine (irreparable), or A → HX (hypoxanthine).

* Deamination - Changes a normal base to an atypical base; C → U, (which can be corrected by DNA repair mechanisms), or spontaneous deamination of 5-methycytosine (irreparable), or A → HX (hypoxanthine).

* Transition - A purine changes to another purine, or a pyrimidine to a pyrimidine.

* Transition - A purine changes to another purine, or a pyrimidine to a pyrimidine.

* Transversion - A purine becomes a pyrimidine, or vice versa.

* Transversion - A purine becomes a pyrimidine, or vice versa.

'''Induced mutations''' on the molecular level can be caused by:

'''Induced mutations''' on the molecular level can be caused by:

** DNA intercalating agents (e.g. [[ethidium bromide]])

** DNA intercalating agents (e.g. [[ethidium bromide]])

** [[DNA crosslinker]] (e.g. [[platinum]])

** [[DNA crosslinker]] (e.g. [[platinum]])

** Oxidative damage caused by [[oxygen]](O)] [[Radical (chemistry)|radical]]s

** Oxidative damage caused by [[oxygen]](O) [[Radical (Chemistry)|radical]]s

* Radiation

* Radiation

** [[Ultraviolet]] radiation (nonionizing radiation) - excites electrons to a higher energy level. DNA absorbs one form, ultraviolet light. Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.  

** [[Ultraviolet]] radiation (nonionizing radiation) - excites electrons to a higher energy level. DNA absorbs one form, ultraviolet light. Two nucleotide bases in DNA - cytosine and thymine-are most vulnerable to excitation that can change base-pairing properties. UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.  

==Beneficial mutations==

==Beneficial mutations==

A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a specfic 32 base pair deletion in human CCR5 (CCR5-32) confers [[HIV]] resistance to [[Zygosity|homozygotes]] and delays [[AIDS]] onset in [[Zygosity|heterozygotes]].<ref>[http://www.cdc.gov/genomics/hugenet/factsheets/FS_CCR5.htm]</ref> The CCR5 mutation is more common in those of European descent. One theory for the [[etiology]] of the relatively high frequency of CCR5-32 in the euopean population is that is conferred resistance to the [[bubonic plague]] in mid-14th century Europe.<ref>[http://www.pbs.org/wnet/secrets/case_plague/clues.html]</ref>

A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a specific 32 base pair deletion in human CCR5 (CCR5-32) confers [[HIV]] resistance to [[Zygosity|homozygotes]] and delays [[AIDS]] onset in [[Zygosity|heterozygotes]].<ref>[https://www.cdc.gov/genomics/hugenet/factsheets/FS_CCR5.htm]</ref> The CCR5 mutation is more common in those of European descent. One theory for the [[etiology]] of the relatively high frequency of CCR5-32 in the European population is that it conferred resistance to the [[bubonic plague]] in mid-14th century Europe.<ref>[https://www.pbs.org/wnet/secrets/case_plague/clues.html]</ref>

 

==References==

==References==

* Taggart R. Starr C. ''Biology The Unity and Diversity of Life: Mutated Genes and Their Protein Products''.  14.4:227. Thompson Brooks/Cole 2006.

* Taggart R. Starr C. ''Biology The Unity and Diversity of Life: Mutated Genes and Their Protein Products''.  14.4:227. Thompson Brooks/Cole 2006.

===Online books===

===Online books===

* Chapter 7, [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=mutation+AND+mga%5Bbook%5D+AND+110363%5Buid%5D&rid=mga.section.996 The Molecular Basis of Mutation] in ''Modern Genetic Analysis'' by Anthony J. F. Griffiths, William M. Gelbart, Jeffrey H. Miller and [[Richard Lewontin|Richard C. Lewontin]] (1999) published by W. H. Freeman and Company ISBN 0-7167-3597-0.

* Chapter 7, [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=mutation+AND+mga%5Bbook%5D+AND+110363%5Buid%5D&rid=mga.section.996 The Molecular Basis of Mutation] in ''Modern Genetic Analysis'' by Anthony J. F. Griffiths, William M. Gelbart, Jeffrey H. Miller and [[Richard Lewontin|Richard C. Lewontin]] (1999) published by W. H. Freeman and Company ISBN 0-7167-3597-0.

* Chapter 9, [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hmg.section.1050 Instability of the human genome: mutation and DNA repair] in ''Human Molecular Genetics 2'' by Tom Strachan and  Andrew P. Read (1999) published by John Wiley & Sons, Inc.

* Chapter 9, [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hmg.section.1050 Instability of the human genome: mutation and DNA repair] in ''Human Molecular Genetics 2'' by Tom Strachan and  Andrew P. Read (1999) published by John Wiley & Sons, Inc.

* ''[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.preface.91 Genes and Disease]'' from the [[National Library of Medicine]] provides descriptions of mutations that cause human diseases. For example, a common mutation associated with [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=mutation+AND+gnd%5Bbook%5D+AND+138070%5Buid%5D&rid=gnd.section.207 Huntington disease] is an increased number of copies of repeated CGA triplets in the [[Huntingtin]] gene.

* ''[https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.preface.91 Genes and Disease]'' from the [[National Library of Medicine]] provides descriptions of mutations that cause human diseases. For example, a common mutation associated with [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=mutation+AND+gnd%5Bbook%5D+AND+138070%5Buid%5D&rid=gnd.section.207 Huntington disease] is an increased number of copies of repeated CGA triplets in the [[Huntingtin]] gene.

* ''[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gene GeneReviews]'' by Roberta A. Pagon, Editor-in-chief is made available by the [[University of Washington]] and contains peer-reviewed descriptions of heritable diseases written by experts. For example, [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gene.chapter.brca1 BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer] describes mutations in [[BRCA1]] and [[BRCA2]] that are associated with  predispositions to cancer.

* ''[https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gene GeneReviews]'' by Roberta A. Pagon, Editor-in-chief is made available by the [[University of Washington]] and contains peer-reviewed descriptions of heritable diseases written by experts. For example, [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gene.chapter.brca1 BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer] describes mutations in [[BRCA1]] and [[BRCA2]] that are associated with  predispositions to cancer.

==External links==

==External links==

* [http://www.gate.net/~rwms/EvoMutations.html Examples of Beneficial Mutations]

* [http://www.gate.net/~rwms/EvoMutations.html Examples of Beneficial Mutations]

* [http://www.q-pharm.com/home/contents/drug_d/order_form/online_services/mutagenesis  Software for Mutated Proteins' Activity Prediction]

* [http://www.q-pharm.com/home/contents/drug_d/order_form/online_services/mutagenesis  Software for Mutated Proteins' Activity Prediction]

[[Category:Genetics]]

[[Category:Genetics]]