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Small-scale mutations affecting one or a few nucleotides, including:

Point mutations, often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide for another. Most common is the transition that exchanges a purine for a purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔ T). A transition can be caused by nitrous acid, base mispairing, or mutagenic base analogs such as 5-bromo-2-deoxyuridine (BrdU). Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). A point mutation can be reversed by another point mutation, in which the nucleotide is changed back to its original state (true reversion) or by second-site reversion (a complementary mutation elsewhere that results in regained gene functionality). These changes are classified as transitions or transversions. An example of a transversion is adenine (A) being converted into a cytosine (C). There are also many other examples that can be found. Point mutations that occur within the protein coding region of a gene may be classified into three kinds, depending upon what the erroneous codon codes for:

Silent mutations: which code for the same amino acid.

Missense mutations: which code for a different amino acid.

Nonsense mutations: which code for a stop and can truncate the protein.

Insertions add one or more extra nucleotides into the DNA. They are usually caused by transposable elements, or errors during replication of repeating elements (e.g. AT repeats). Insertions in the coding region of a gene may alter splicing of the mRNA (splice site mutation), or cause a shift in the reading frame (frameshift), both of which can significantly alter the gene product. Insertions can be reverted by excision of the transposable element.

Deletions remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. They are irreversible.

Large-scale mutations in chromosomal structure, including:

Amplifications (or gene duplications) leading to multiple copies of chromosomal regions, increasing the dosage of the genes located within them.

Deletions of large chromosomal regions, leading to loss of the genes within those regions.

Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct fusion genes (e.g. bcr-abl). These include:

Chromosomal translocations: interchange of genetic parts from nonhomologous chromosomes.

Interstitial deletions: removing regions of DNA from a single chromosome, thereby apposing previously distant genes (e.g. fig-ros).

Chromosomal inversions: reversing the orientation of a chromosomal segment.

Loss of heterozygosity: loss of one allele, either by a deletion or recombination event, in organisms which previously had two.

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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 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 phenotypes. Often called a neomorphic mutation.

Dominant negative mutations (also called 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 or 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.

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Morphological mutations usually affect the outward appearance of an individual. Mutations can change the height of a plant or change it from smooth to rough seeds.

Biochemical mutations result in lesions stopping the enzymatic pathway. Often, morphological mutants are the direct result of a mutation due to the enzymatic pathway.

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Conditional mutation is a mutation that has wild-type phenotype under certain environmental conditions and a mutant phenotype under certain selective conditions. Conditional mutations may also be lethal.

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

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).

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

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

Chemicals

Nitrosoguanidine (NTG)

Base analogs (e.g. BrdU)

Simple chemicals (e.g. acids)

Alkylating agents (e.g. ''N''-ethyl-''N''-nitrosourea (ENU)) These agents can mutate both replicating and non-replicating DNA. In contrast, a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA. Each of these classes of chemical mutagens has certain effects that then lead to transitions, transversions, or deletions.

Methylating agents (e.g. ethane methyl sulfonate (EMS))

Polycyclic hydrocarbons (e.g. benzpyrenes found in internal combustion engine exhaust)

DNA intercalating agents (e.g. ethidium bromide)

DNA crosslinker (e.g. platinum)

Oxidative damage caused by oxygen radicals

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.

Ionizing radiation

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Homeobox

Macromutation

Mutant

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Chapter 7, The Molecular Basis of Mutation in Modern Genetic Analysis by Anthony J. F. Griffiths, William M. Gelbart, Jeffrey H. Miller and Richard C. Lewontin (1999) published by W. H. Freeman and Company ISBN 0-7167-3597-0.

Chapter 9, 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.

Genes and Disease from the National Library of Medicine provides descriptions of mutations that cause human diseases. For example, a common mutation associated with Huntington disease is an increased number of copies of repeated CGA triplets in the Huntingtin 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, BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer describes mutations in BRCA1 and BRCA2 that are associated with predispositions to cancer.