Chromosomal Mutations
Chromosomal mutations are changes in the structure or number of chromosomes, which can lead to genetic disorders or variations in an organism. These mutations can occur through processes such as deletion, duplication, inversion, or translocation of genetic material within chromosomes. They can have significant impacts on an organism's development, health, and genetic diversity.
7 Key excerpts on "Chromosomal Mutations"
eBook - ePubAdvanced Molecular Biology
A Concise Reference
- Richard Twyman(Author)
- 2018(Publication Date)
- Garland Science(Publisher)
...Chapter 4 Chromosome Mutation Fundamental concepts and definitions A chromosome mutation (or chromosome aberration) is a mutation involving a large segment of the genome. Such a mutation usually affects many genes and is often observable at the cytogenetic level, i.e. it can be seen with a light microscope. Chromosome mutations are numerical if they involve a deviation from normal chromosome number, and structural if they involve breakage and rearrangement of chromosome segments. Numerical mutations often result from chromosome segregation errors caused by structural mutations, but may also reflect aberrant replication or errors at fertilization. Structural mutations result from the faulty repair of broken chromosomes or from nonallelic recombination events. In mammals and in Drosophila, subtle structural mutations can be detected because they disrupt chromosome banding patterns (q.v.). Structural mutations are balanced if DNA is rearranged but there is no loss or gain of material, or unbalanced if DNA is lost or gained. All numerical mutations are unbalanced. There are four consequences of chromosome mutations disruption, fusion, position and dosage effects. Disruption and fusion effects occur in structural mutations and reflect the nature of the chromosome breakpoints before and after mutation (e.g. a breakpoint can interrupt a gene or separate a gene from its promoter, resulting in loss of gene function, and fusion can join two genes, allowing a composite product to be synthesized, perhaps with novel functions). Position effects also occur in structural mutations and reflect global influences on gene expression conferred by chromatin structure (e.g. a translocation may bring a normally active gene adjacent to a region of heterochromatin causing transcriptional repression; q.v. chromatin domain, position-effect variegation). Dosage effects occur in both structural and numerical mutations and concern the number of copies of each gene in the cell...
eBook - ePub- Antoni Horst(Author)
- 2018(Publication Date)
- CRC Press(Publisher)
...Intrachromosomal changes either involve one arm which is named paracentric, or both arms which are named pericentric mutations. Chromosomal structural changes that cause mutations involve deletions (loss of terminal or intercalary fragments of chromosomes), duplications (presence of additional fragment of a chromosome), inversions (chromosome fragment becomes inverted and reinserted into its original chromosomal position), and translocations (relocation of chromosome fragments within the same or among other chromosomes). Chromosome mutations may result in: 1. Chromosome aberrations in which both chromatids are engaged in aberration formation at identical loci 2. Chromatid aberrations in which mutation concerns only one of the two chromatids of a single chromosome 3. Subchromatid aberration in which a fibrillar subunit (usually half of the chromatid) is involved in the aberration. The chromosomal aberrations are the final results of complicated processes the nature of which are not yet completely clear. Two main processes have been proposed: the breakage-reunion hypothesis and the exchange model. According to the breakage-reunion hypothesis, the primary lesions are breaks that cause discontinuities of chromosomes. These lesions occur spontaneously or may be caused by the action of mutagens. Most of those breaks (90 to 99%) become rejoined by “repair processes” of DNA. Restoration in these cases may be complete without any structural or functional changes, or intra- or inter-changes may occur because of failure to restore the original chromosome structure. The breakage surfaces may stabilize which causes further breaks producing fragments of chromosomes. The breakage may also reunite when two or more breaks interact and join in a new order producing a chromosomal structural change...
eBook - ePub- Chang-Hui Shen(Author)
- 2019(Publication Date)
- Academic Press(Publisher)
...A somatic mutation is a change in the structure of a gene that can arise during DNA replication. It is not inherited from a parent, nor can it be passed to an offspring. The mutation that results in a single base substitution in DNA is known as a somatic point mutation. A loss-of-function variant results from a point mutation that leads to reduced or abolished protein function. Most lost-of-function mutations are recessive, indicating that clinical signs typically are observed only when both chromosomal copies of a gene carry the same mutation. SNP At a given chromosomal site, one individual might have the A nucleotide and the other individual might have the G nucleotide. This type of site in DNA is known as an SNP (Fig. 13.27). If each of the two different DNA sequences at this site can be inherited, this site is part of a gene, and the alternate forms of the DNA sequence is called an allele. Fig. 13.27 An example of SNP containing a difference in a single nucleotide (an A/G polymorphism). Types of Chromosomal Rearrangements Various genomic rearrangements can arise by several mechanisms, including deletions, amplifications, translocations, and inversions of DNA fragments (Fig. 13.28). Deletions occur when a portion of a chromosome is missing or removed. Duplications result from the copying of a portion of a chromosome more than once, producing extra genetic material. Deletions and duplications are known as CNVs. Fig. 13.28 Examples of chromosomal rearrangement. Chromosomal translocation is a common chromosomal mutation. Burkitt's lymphoma (BL) is a heterogeneous group of highly aggressive mature B-cell malignancies. It is characterized by a high rate of turnover of malignant cells and deregulation of the c-myc gene. The histologic hallmark of BL is the presence of apoptotic cells within scattered macrophages, a feature responsible for a “starry sky” microscopic appearance...
eBook - ePub- David P. Clark(Author)
- 2009(Publication Date)
- Academic Cell(Publisher)
...An error in a cell’s genetic material is known as a mutation. As might be expected, many mutations are detrimental. However, detrimental mutations tend to be overestimated because they are more noticeable. Very often the negative effect is minimal, and in fact, the majority of mutations have little or no significant effect on the survival of an organism—they are essentially neutral. Furthermore, occasional mutations may turn out to be beneficial to the survival and reproduction of the organism. The accumulation of such beneficial mutations allows the organism to evolve in response to changing environmental conditions (see Ch. 20). Mutations are heritable alterations in the genetic material of any organism or gene creature. At the molecular level, mutations are alterations in the DNA molecules of which the genes are made. Consequently, when a DNA molecule replicates, any changes due to mutation of the original DNA base sequence will be duplicated and passed on to the next generation of cells. In single-celled organisms, mutations are passed on from one generation to the next when the organism divides. Among multi-cellular organisms, the situation is more complicated. Mutations are inherited by the next generation of organisms only if they occur in the cells of the germ line and are passed on during sexual reproduction. Mutations that occur in somatic cells will only be passed on to the descendents of those cells. Such mutant cell lines will be restricted to the original multi-cellular organism where the mutation occurred. Somatic mutations that result in unregulated cell growth are responsible for the emergence of cancers. Other somatic mutations merely result in particular cell-lines or organs being genetically different from the rest of the body. Since the DNA is used as a template in transcription to make an RNA copy, a mutation in the DNA sequence within a cell will be passed on to the mRNA molecule. Finally, the mRNA is translated to yield protein...
eBook - ePub- Kedar N. Prasad(Author)
- 2020(Publication Date)
- CRC Press(Publisher)
...Duplication This type of chromosomal damage requires one break. The free piece of the chromosome may be added onto another chromosome, so that the cells, after mitosis, contain a duplication for certain genes (Figure 16.4). Duplications are generally more viable than deficiency. Duplication of a large segment of chromosome may cause dominant lethal mutation. Examples of chromosomal damage due to rearrangement of broken fragments of chromosomes are (1) translocation, which requires two breaks; (2) inversion, which requires two breaks (Figure 16.4); and (3) dicentric rings, which require two breaks. b. Translocation The exchange of segments between two or more chromosomal rearrangements is not harmful as long as the normal gene contents are present. However, the gametes of persons having such “balanced” translocations frequently receive only one of the two parts of the rearrangements; and the zygotes produced by such gametes are genetically unbalanced. 2 The nature and the extent of abnormality of the embryo depend upon the particular chromosomal regions that are duplicated or deficient; as well as upon the size of the chromosome. 2 Most of the zygotes having unbalanced genetic materials result in early embryonic death. However, the survivors of such chromosomal damage often have physical abnormalities associated with mental retardation. c. Inversion If the two breaks are in the same chromosome, then the interstitial piece — instead of being deleted — is inverted and reinserted into the chromosome. The frequency of inversion is much less than translocation. 2 The genetic consequence of this type of chromosomal damage is semisterility. However, the extent of the effect depends on the size and location of the chromosomal segment that is inverted. d. Dicentric Ring The rearrangement of chromosomes after two breaks can lead to the configuration of a dicentric ring. These studies show that ionizing radiation can induce deletion, duplication, and rearrangement of chromosomes...
eBook - ePub- Dorian J. Pritchard, Bruce R. Korf(Authors)
- 2013(Publication Date)
- Wiley-Blackwell(Publisher)
...25 Types of g enetic a lterations 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, d eletions, i nsertions, f rameshifts and d uplications 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...
eBook - ePubThe Human Genome in Health and Disease
A Story of Four Letters
- Tore Samuelsson(Author)
- 2019(Publication Date)
- Garland Science(Publisher)
...Insertion, duplication, and inversion events are illustrated. An inversion arises when a piece of DNA changes its orientation relative to its genomic context. Other types of structural variation are changes in chromosome number and chromosomal translocations. Translocations are rearrangements where a portion of one chromosome is moved to another nonhomologous chromosome. Chromosomal translocations are quite frequent during meiosis—they occur in about 1 of 600 human newborns. Sometimes translocations give rise to diseases such as several forms of cancer (see section Cancer—Translocations and More Dramatic Genomic Aberrations) and Down syndrome. However, most translocations are associated with a normal phenotype because they do not disturb the organization and expression of individual genes. How common is structural variation? It has been estimated that the total amount of sequences of the human genome involved in structural variation corresponds to 5%–10% of the genome. Thus, the nucleotide content of structural variation is much larger than that of SNVs. When comparing two unrelated individuals, the fraction of the genome that is different in terms of structural variation is in the order of 1%. Structural variation is not as well studied as SNVs. For elucidation of such variation, we require a careful assembly of the human genome from sequencing reads. However, as this is technically demanding, the most common method of reconstructing a genome is by alignment of sequencing reads to the reference genome. The alignment method has the disadvantage that it is far from ideal for identifying structural variation. Figure 5.15 illustrates the differences observed in human individuals with respect to structural variation. As for SNVs, structural variation is distributed throughout the genome. We also know that there is a substantial structural variation, such as CNVs, between different tissues in a human individual...
