Types of Mutations

11 Key excerpts on "Types of Mutations"

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  eBook - PDF

  Genetic Theory and Analysis

  Finding Meaning in a Genome

  • Danny E. Miller, Angela L. Miller, R. Scott Hawley(Authors)
  • 2023(Publication Date)
  • Wiley

    (Publisher)

  Genetic Theory and Analysis: Finding Meaning in a Genome, Second Edition. Danny E. Miller, Angela L. Miller, and R. Scott Hawley. © 2023 John Wiley & Sons, Inc. Published 2023 by John Wiley & Sons, Inc. 1 A mutation is a stable and potentially heritable change in a DNA sequence. Mutations may occur in the soma of an organism, affecting only a particular cell or lineage of cells, or they may occur in the germline of an organism and be passed to all of that organism’s offspring. Mutations that occur within or near a gene may create a phenotype different from that normally expressed by the wildtype allele of that gene. A number of different Types of Mutations have been found to cause changes in phenotype. These mutations can be changes in individual base pairs, such as substitutions (e.g. C →T), insertions or deletions of DNA, or they may be chromosomal aberrations such as inversions, translocations, or copy number variants near or within genes. Because this book is fundamentally about mutational analysis, we need to spend some time considering the Types of Mutations that can occur, both at the molecular level and in terms of the effects they can have. We also need to review the various systems that exist to classify mutations. Such a review is all the more critical because the nomenclature systems that geneticists have developed are keyed to the structure and effects of the mutants they name. Thus, the things themselves – and our names for them – are inextricably intertwined. 1.1 Types of Mutations Most introductory genetics texts classify mutations simply as recessive or dominant. A mutation (m1) is said to be recessive if m1/m1 organisms display a mutant phenotype, but m1/+ organisms are wildtype. (Note: the symbol “+” denotes the wildtype, or normal, allele of a given gene.) Conversely, a mutation (M2) is said to be dominant if M2/+ organisms display a mutant phenotype while +/+ organisms are normal.

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  Molecular Biology

  • David P. Clark(Author)
  • 2009(Publication Date)
  • Academic Cell

    (Publisher)

  Many different types of mutation occur. Some affect a single base, others affect large segments of DNA.

  The sequence of a DNA molecule may be altered in many different ways. Such mutations have a variety of outcomes that depend in part on the nature of the change and in part on the role of the DNA sequence that was altered. The major types of sequence alteration are as follows, and will be discussed separately below:

  Base substitution: one base is replaced by another base.

  Insertion: one or more bases are inserted into the DNA sequence.

  Deletion: one or more bases are deleted from the DNA sequence.

  Inversion: a segment of DNA is inverted, but remains at the same overall location.

  Duplication: a segment of DNA is duplicated; the second copy usually remains at the same location as the original.

  Translocation: a segment of DNA is transferred from its original location to another position either on the same DNA molecule or on a different DNA molecule.

  Much of the discussion below considers what happens when mutations occur within genes that encode proteins. However it is important to realize that mutations may also occur within those genes whose products are tRNA, rRNA, or other non-translated RNA molecules. Alterations in these molecules may have drastic effects on ribosome function, splicing or other vital processes. Furthermore, mutations may also fall within promoter sequences or other regulatory sites on the DNA that do not actually encode any gene product. Nonetheless, such regulatory sites are important for gene expression and altering them may have major effects.

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  Molecular Pathology

  • Antoni Horst(Author)
  • 2018(Publication Date)
  • CRC Press

    (Publisher)

  Chapter 8 MUTATION

  Mutation is any heritable change in the genetic material (not caused by genetic segregation or genetic recombination) which is transmitted to daughter cells and even to succeeding generations giving rise to mutant cells or mutant individuals (provided it does not act as a dominant lethal factor). Mutations in the germ line may be transmitted by the gametes to the next generation resulting in an individual with the mutant condition either in germ or somatic cells. Mutation usually affects the carrier of genetic information, i.e., DNA, affecting its chemical or physical constitution, mutability, replication, phenotypic function or recombination. The essence of mutation depends on nucleotides that may be added, deleted, substituted, inverted or transposed to other positions with or without inversion. Mutation may occur spontaneously or can be induced by mutagens. Spontaneous mutations are probably the result of several unknown and ubiquitous mutagens or mutagenic effects. A considerable number of spontaneous mutations seems to be the result of intracellular production of mutagens and antimutagens (e.g., free radicals or free radical scavengers). The number of spontaneous mutations is probably high, but usually they become repaired before they have time to be expressed.

  Mutations can be divided into gene mutations involving only a single gene, and chromosomal mutations involving a part or whole chromosome with more than one gene. Since a functional gene consists of larger or smaller DNA fragments, and many sites may be involved in a single gene mutation, the consequences of a mutation vary dependent on the particular sites of mutation, e.g., mutations of the particular exons or introns, flanking sequences containing regulatory sequences like TATA box, upstream regulatory sequences, enhancers, etc.

  On the molecular basis, gene mutations usually depend on substitution of a purine or pyrimidine base. Substitutions of a purine base on another purine base (adenine for guanine or vice versa) or a pyrimidine base on another pyrimidine base (thymine for cytosine or vice versa) are named transitions, and substitutions of a pyrimidine base on a purine base, and vice versa, are called transversions. Gene mutations also may be caused by deletion or insertion (addition) of a single or of multiple nucleotides.

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  Medical Genetics at a Glance

  • Dorian J. Pritchard, Bruce R. Korf(Authors)
  • 2013(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  25 Types of genetic alterations

  Overview

  Mutations are permanent modifications in the base sequence of DNA. They can occur at the level of one or a few bases of DNA, as point mutations involving substitution, deletion or insertion. Substitution of a purine by another purine or of a pyrimidine by another primidine is a transition, exchanges of purines and pyrimidines are transversions. At the level of a gene, mutations involve dozens to thousands of bases. At the genomic level muta­tions include deletions or dupli­cations of hundreds of thousands to millions of bases, up to chromosome rearrangements and aneuploidies (Chapter 36 ). Copy number variation (CNV) involves large deletions and insertions of various lengths created by unequal crossing over between misaligned segments of repetitious DNA or by non-homologous end-joining. Unequal crossing over is the origin of X-linked anomalous colour vision (see Chapter 11 ).

  Activation of enhancers and silencers (Chapter 21 ) can cause phenotypic variation in expression of the genes they control.

  Dynamic mutations involve expansion of triplet repeat sequences (see Chapter 28 ), and can undergo further expansion or contraction from generation to generation.

  Substitutions, deletions, insertions, frameshifts and duplications

  Substitution involves replacement of a base pair. If the amino acid encoded by the new codon is the same, it is a silent mutation, or if different, a missense mutation (see Figures 25.1, 24.1). Some missense mutations do not alter the chemical properties of the protein (conservative mutations), whereas others have a deleterious effect. In some cases, though, heterozygosity of a deleterious mutation may create selective advantage. A notable example is the substitution of the sixth codon in the β-globin chain responsible for sickle cell anaemia (see Chapter 29 ), which in heterozygotes confers resistance to malaria.

  Substitution can create a STOP codon, causing translation to come to a premature halt. This is called a premature termination or nonsense (‘non-sense’) mutation

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  Characterization of Biomaterials

  • M Jaffe, W. Hammond, P Tolias, T Arinzeh(Authors)
  • 2012(Publication Date)
  • Woodhead Publishing

    (Publisher)

  A mutation is an alteration to the genetic material and its effect on the organism can vary greatly. Many mutations are silent and have no influence at all, while others have such a drastic effect that they compromise the organism’s normal function and even its survival. Mutations can arise in the germ cells and be inherited by future offspring or they can occur in the somatic cells and be the underlying basis for diseases like cancer. They can involve just a single nucleotide pair in the DNA or be the result of changes to enormous amounts of the organism’s genetic material. Regardless of how they arise, they produce their effects by disturbing the normal flow of genetic information from nucleic acid to protein, and since there are so many steps in this central process, it has been found that mutations exert their effects in many different places in the cell’s metabolism.

  7.3.1 Point mutations

  The simplest type of mutation is at the level of one nucleotide pair. Occasionally errors in DNA replication avoid the normal proofreading cellular processes and become fixed in the DNA, resulting in a single nucleotide base substitution. Such a change of an Adenine (A) for a Cytosine (C) or a Guanine (G) to a Thymine (T), is termed a point mutation and it can be passed on to daughter cells in successive divisions. If this mutation affects the genetic code, the change can result in the substitution of one amino acid for an altered one, thereby affecting protein structure and function. Point mutations can also arise because of the influence of outside agents. Various wavelengths of the electromagnetic spectrum, such as X-rays and ultraviolet radiation, are known to alter the structure of nucleic acids and can produce mutations. Also, many chemical agents called mutagens have this nucleotide-altering property. Many mutagens are well known to be cancer-causing agents and are called carcinogens.

  Several different forms of point mutations are well documented, with many examples of mutations that show an insertion, deletion or duplication of a single base into the DNA coding sequence. Such changes can yield (1) substitution of one amino acid by another in the primary sequence of a polypeptide chain (missense mutation), (2) the stoppage of the protein synthesizing process altogether, with the formation of an inappropriate stop codon (nonsense mutation), or (3) the misreading of the genetic code resulting in frame shifts to the normal reading sequence (frame-shift mutations) resulting in the production of an altered or non-functional protein (Fig. 7.3

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  Chemical Mutagens Environmental Effects on Biological Systems

  • L Fishbein(Author)
  • 2012(Publication Date)
  • Academic Press

    (Publisher)

  C H A P T E R Mode of Action and Types of Mutations Induced by Chemicals From the preceding chapter, it follows that mutation involves alterations in D N A ; an alteration of its shape, structure, or con-stituent nucleotides. All three types have been discovered and will be discussed here. There are, however, two main categories into which mutations can be grouped. One is referred to as a point mutation implying a small, submicro-scopic alteration of DNA affecting only one or a very small number of nucleotides. The other category concerns gross chromosomal alterations which can be seen with the light microscope, i.e., chromosomal breaks, deletions, and translocations. From the point of view of molecular mechanisms of action, only point mutations are considered understood. The concept that gross mutations are always a consequence of many point mutations or are caused by point mutations is presently without adequate foundation. In fact, the relationship between the two categories of mutations is obscure. One reason is undoubtedly the necessity of using different biological test systems for each of the two categories : point mutations are most readily tested for in microbial systems while gross mutations are generally observed in higher plants and animals. I. Substitution by Base Analogs The genetic code depends upon a transcription of D N A into RNA such that the RNA represents a complementary copy of its DNA template (its gene). The RNA produced specifies an amino acid sequence for a particular 13 14 3. MODE OF ACTION AND Types of Mutations protein via the protein-synthesizing machinery of the cell which is able to read the RNA by translating groups of three nucleotides (codons) into appropriate amino acids. By substituting one nucleotide for another (for instance, A for G) within a given codon, the code can be changed, and hence a different amino acid may be specified or protein synthesis may be terminated at that point.

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  Genetics of Common Diseases

  Future Therapeutic and Diagnostic Possibilities

  • Ian Day, Prof Steve Humphries(Authors)
  • 2020(Publication Date)
  • Garland Science

    (Publisher)

  de novo mutation in a population depends on the reproductive performance of the carrier individual(s) and on chance. Without mutation there would be no evolution. Unfortunately, this is about the only statement population genetic theorists unanimously accept. How much mutation does evolution require, and how much can a species afford, are still unanswered questions.

  Non-random mutation. With the development of mutation detection methods, geneticists can study and measure the relative occurrence of an ever-increasing number of mutations, and the evidence for a non-random distribution of mutations is accumulating (Boulikas, 1992). Some loci remain unchanged (conserved) for long periods of evolutionary time whereas some loci present intense mutability (Burns and Surridge, 1990; Jolly et al., 1996); these are called mutational hot spots. Some genes mutate more frequently than others (Glickman et al., 1994). Intergenic sequences are more variable than intragenic sequences (Kissi et al., 1995) and transcribed sequences are less variable than non-transcribed ones. These inequalities are usually explained by the theory of natural selection (Moxon et al., 1994) but transcription-dependent repair mechanisms have also been suggested and documented (Selby and Sancar, 1994).

  Some types of mutation occur more, or less, frequently than expected by chance alone. For example, transition (replacement of a purine by another purine, or of a pyrimidine by another pyrimidine) is more common than transversion (replacement of a purine by a pyrimidine, or vice versa) although the prior probability of a transversion is twice as much as the prior probability of a transition (Kumar, 1996). CpG sites are genetically unstable and TpG or CpA mutants are found at exceptionally high frequences in vertebrates. This mutability is associated with methylation, a natural chemical modification of DNA that is also involved in DNA repair and regulation of transcription (Hsieh et al.,

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  Crumbling Genome

  The Impact of Deleterious Mutations on Humans

  • Alexey S. Kondrashov(Author)
  • 2017(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Chapter 8 ). Still, some mutant alleles persist for a long time, reaching substantial frequencies. A very small proportion of mutant, derived alleles eventually become fixed in the population, completely replacing the ancestral alleles. Of course, without such rare allele replacements life would be unable to evolve.

  The key premise of evolutionary biology, common ancestry of different species, implies that mutation is the ultimate cause of not only within‐population variation, but also of between‐species differences. Together with natural selection, mutation is a sine qua non of Darwinian evolution. However, mutant alleles responsible for interspecific differences, which passed the test of natural selection, are different from those responsible for within‐population variation: many of the former are advantageous, and most of the latter, as long as they have any effect on the phenotype, are deleterious (see Chapters 6 , 7 , 9 , and 11 ).

  4.2 Kinds of Mutations

  The mutation process produces a wide variety of changes of DNA sequences. First of all, different mutations involve changes at very different scales. Over 99% of individual mutations are small‐scale, affecting DNA sequence only within the span of, say, less than 50 nucleotides. Among those, a vast majority consists of a simple replacement of one continuous DNA segment, of length L 1 , with another segment, of length L 2 . Among such mutations, single‐nucleotide substitutions (L 1  = L 2  = 1) constitute ~90% of cases, followed by ~6% of deletions (L 1  > 0, L 2  = 0), ~2% of insertions (L 1  = 0, L 2  > 0) and ~2% of complex events (both L 1 and L 2 positive, and at least one of them above 1) (Figure 4.4 ). Exact proportions may be different in different organisms, but the general pattern appears to be universal.

  Figure 4.4

  A single‐nucleotide substitution, a deletion, an insertion, and a complex event. Three nucleotides are shown on each side of each mutation.

  There is a one‐to‐one correspondence between mutations that affect just one segment of the DNA and polymorphisms. To emphasize this point, mutations shown in Figure 4.4 coincide with polymorphisms shown in Figure 2.8 . However, occasionally a mutation results in a mutant allele which is different from the original allele at several distinct segments of the genome (Figure 4.5

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  Population Genetics

  • Matthew B. Hamilton(Author)
  • 2021(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  The following sections will present classical population genetic models for the fate of a new mutation, the impact of mutation on allele fre- quencies in a population, and the predicted balance between the removal of genetic variation by genetic drift and its replacement by mutation. This chapter will also cover several models of the way new alleles are introduced by mutation commonly employed in population genetics, illustrated with applications that highlight the consequences of these models. The final section of the chapter will show how the process of mutation can be incorporated into genea- logical branching models. Mutation is a broad term that encompasses a wide variety of events that lead to alterations in DNA sequences. Point mutations lead to the replace- ment of a single base pair by another nucleotide. Point mutations to chemically similar nucleotides (purine to purine (A G) or pyrimidine to pyrimidine (C T)) are called transitions, while point muta- tions to chemically dissimilar nucleotides (purine to pyrimidine or pyrimidine to purine) are called transversions. Base substitutions that occur within coding genes may or may not alter the protein pro- duced by that gene. Synonymous or silent muta- tions result in the same translation of a DNA sequence into a protein due to the redundant nature of the genetic code, while nonsynonymous or mis- sense mutations result in a codon that does change the resulting amino acid sequence. Mutation can take the form of insertion or dele- tion of DNA sequences, often referred to by the short-hand indels. Indels within coding regions result in frameshift mutations if the change in sequence length is not an even multiple of three, altering the translation of a DNA sequence and possibly creating premature stop codons. Indels may range in size from a single base pair to segments of chromosomes containing many thousands of base Population Genetics, Second Edition.

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  Molecular Evolution and Population Genetics for Marine Biologists

  • Yuri Kartavtsev(Author)
  • 2015(Publication Date)
  • CRC Press

    (Publisher)

  6 GENES, MUTATIONS AND EVOLUTION MAIN GOALS 6.1 Introduction to the Study of Mutation 6.2 Structure and Functions of Genes 6.3 Types of Mutations on DNA Level 6.4 Mutations and Amino Acid Substitutions 6.5 Mutation Rate 6.6 TRAINING COURSE, #6 SUMMARY 1. Mutations lead to the alteration of a current phenotype or to creation of variability, and by this provide a subject for genetic research. Due to this, their importance for genetics and evolution of life in general is obvious. 2. In terms of their function, genes can be classi fi ed into two groups: protein-coding or structural genes and RNA-coding or regulatory genes . Structural genes may participate in regulation too, and in this have no principal difference from the second group of genes. 3. Nucleotide substitutions can be divided into two different classes: transition and transvertion . Transition is the substitution of a purine for another purine (A G) or the substitution of a pyrimidine for another pyrimidine (T C). Transvertions are inverse types of nucleotide substitutions, when a purine is substituted by a pyrimidine and vice versa (G T, A C, C G or A T). 4. Classical geneticists have determined that the rate of mutations, that alter phenotypic characters or induce lethal effects, is of the order of 10 –5 per locus per generation in eukaryotes such as man, Drosophila and corn. The mean rate of amino acid substitution for an average polypeptide is estimated to be 70 Molecular Evolution and Population Genetics for Marine Biologists 4 × 10 –7 per locus per year. Due to the evidences that electrophoresis detects only about one-quarter of all amino acid changes, the rate of amino acid substitutions detectable by electrophoresis is estimated to be about 10 –7 per locus per year. 5. Mutations play the principal role in molecular clocks .

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  Snyder and Champness Molecular Genetics of Bacteria

  • Tina M. Henkin, Joseph E. Peters(Authors)
  • 2020(Publication Date)
  • ASM Press

    (Publisher)

  single mutation if only one error in replication, recombination, or repair has altered the DNA sequence.

  As discussed above, to be considered a mutation, the change in the DNA sequence must be heritable. In other words, the DNA must be able to replicate normally but with the changed sequence. Damage to DNA by itself is not a mutation, but a mutation can occur when the cell attempts to repair damage or replicate over it and a strand of DNA is synthesized that is not completely complementary to the original sequence. The wrong sequence is then replicated, and the resulting DNA carries a mutation. Lethal changes in the DNA sequence (as also mentioned above) do occur but ordinarily cannot be scored as mutations, because these cells by definition do not survive, and other techniques are needed for the study of this kind of mutation (as described above). Sometimes, a situation can be established to search for mutations that are only lethal in combination with another mutation that results, for example, in the absence of another gene product. This is called synthetic lethality and has been used to search for genes whose products can substitute for each other. We talk about selections in subsequent sections of this chapter.

  Properties of Mutations

  The properties and causes of the different Types of Mutations are probably not very different in all organisms, but they are more easily studied with bacteria. A geneticist can often make an educated guess about what type of mutation is causing a mutant phenotype merely by observing some of its properties.

  One property that distinguishes mutations is whether they are leaky . The term “leaky” means something very specific in genetics. It means that in spite of the mutation, the gene product still retains some activity and therefore may result in a partial phenotype.

  Another distinguishing property of mutations is whether they revert . If the sequence has been changed to a different sequence, it can often be changed back to the original sequence by a subsequent mutation. The organism in which a mutation has reverted is called a revertant , and the reversion rate

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