DNA Variant
A DNA variant refers to a specific difference in the genetic sequence of an organism compared to a reference sequence. These variants can be single nucleotide changes, insertions, deletions, or larger structural alterations. They contribute to genetic diversity and can impact an individual's traits, susceptibility to diseases, and response to medications.
5 Key excerpts on "DNA Variant"
eBook - ePubThe Human Genome in Health and Disease
A Story of Four Letters
- Tore Samuelsson(Author)
- 2019(Publication Date)
- Garland Science(Publisher)
...5 Variants in the Human Genome Sequence and Their Biological Significance T his chapter covers some more background as to the human genome, before we go on to discuss the role of the protein coding sequences in Chapter 6. The genomes of humans and all other living organisms are not static over time but are subject to changes. We refer to such alterations of the nucleotide sequence as mutations or variants. Mutations are necessary for evolution to proceed, but sometimes they are harmful. One example of such a mutation is the A to T nucleotide substitution associated with sickle cell anemia. Throughout this book, we examine the effect of mutations in the human genome, because they give important clues as to the normal function of different sequence elements. In this chapter, we look into the consequences of mutations in the human genome. Human individuals are genetically different, and we need to understand the nature of these differences. Next, we see how the human genome sequence is related to disorders and traits. We also discuss cancer, one important category of serious diseases with a genetic background. But first we examine some general aspects of mutations and their molecular causes. Types of Mutations Mutations involve one or a few nucleotides only or they may involve larger regions (say 1,000 nucleotides or more) of DNA sequence. The mechanisms by which these two categories of mutations arise are different. In this chapter, we focus on the smaller changes that may be classified into substitution mutations (or point mutations), where one nucleotide is replaced with another, and insertions / deletions, also known as indels where a small number of nucleotides (mean length about 10, median 6) are inserted or deleted as compared to the original sequence. Throughout this book a mutation is represented with an expression like “A > G,” meaning that an A has changed into G...
eBook - ePub- George P. Patrinos, Wilhelm Ansorge, Phillip B. Danielson(Authors)
- 2016(Publication Date)
- Academic Press(Publisher)
...Definitions 2.4.1. Principles To prevent confusion, the recommendations avoid the use of ambiguous terms like “polymorphism” and “mutation.” Polymorphism refers to “a sequence variant” in some disciplines and to “a variant found at a frequency of 1% or higher in a population” in other disciplines. Similarly, mutation is avoided since it is used to indicate both a “change” and a “disease-causing change.” HGVS therefore only uses neutral terms like “variant,” “alteration,” and “change.” To facilitate the computational analysis and description of sequence variants, the basic types of variants have been precisely defined (see the following) and prioritized as (1) deletion, (2) inversion, (3) duplication, (4) conversion, and (5) insertion. • Substitution: a change in a specific sequence where, compared to the reference sequence, one nucleotide is replaced by one other nucleotide • Deletion: a change in a specific sequence where, compared to the reference sequence, one or more nucleotides are not present (deleted) • Duplication: a change in a specific sequence where, compared to the reference sequence, a copy of one or more nucleotides is inserted directly 3′ of the original copy of that sequence • Insertion: a change in a specific sequence where, compared to the reference sequence, one or more nucleotides are inserted in a sequence and where the insertion is not a copy of a sequence immediately 5′ from the insertion location • Deletion-Insertion (indel): a change in a specific sequence where, compared to the reference sequence, one or more nucleotides are replaced by one or more other nucleotides and which is not a substitution, inversion, or...
eBook - ePub- Rajesh V. Thakker, Michael P. Whyte, John Eisman, Takashi Igarashi(Authors)
- 2017(Publication Date)
- Academic Press(Publisher)
...Genetic changes are irreversible alterations of the DNA sequence that are heritable somatically and through the germline. These alterations include single nucleotide variants or polymorphisms, tandem repeats (short tandem repeats or variable number of tandem repeats), small indels (insertions or deletions of short DNA sequences), large deletions or duplications that alter the copy number of DNA segments, and chromosomal rearrangements associated with inversions and translocations (copy-neutral variations). 1 A vast majority of the genetic variations observed in the human population are well tolerated and do not adversely affect phenotype or normal functions. Genetic variations that cannot be tolerated can cause susceptibility to various disease states and abnormal functions. Genetic linkage studies and targeted sequencing together with recent advances, such as genome-wide association study and next-generation sequencing approaches have provided valuable insight into normal and abnormal genetic variations (see Chapter 3). Translation of the same genetic information (genotype) to produce cell-type-specific phenotype is achieved by epigenetic control mechanisms that establish, regulate, and maintain specialized gene expression programs without altering the underlying DNA sequence...
eBook - ePubFrom Genes to Genomes
Concepts and Applications of DNA Technology
- Jeremy W. Dale, Malcolm von Schantz, Nicholas Plant(Authors)
- 2011(Publication Date)
- Wiley(Publisher)
...Or we can compare the genetic composition of members of different species – even over wide taxonomic ranges – which can throw invaluable light on the processes of evolution as well as helping to define the taxonomic relationship between species. Some methods of comparing genomes were considered in Chapter 8; we now want to look further at some methods that can be applied to the analysis of variation within a species. The words polymorphism and mutation are often used in an interchangeable fashion as descriptors of genetic variants; however, it is important to recognize that they do have precise definitions. Formally, a polymorphism is the stable, multi-generational existence of multiple alleles at a gene locus (i.e., different versions of the gene). By comparison, a mutation is an individual event leading to an alteration in base sequence in one individual. In practice, the word polymorphism is used to describe a variant that occurs quite frequently (e.g., >1%) in a population, whereas mutation is used to describe rarer variants. Thus, by this definition, there is no fundamental difference between the two; every polymorphism, no matter how frequent it is today, will have started off as a mutation in one single individual before it became fixed in the population. However, the word mutation is also often used to describe alleles that cause disease. Most of these are rare enough to fit below the 1% cut-off, but some, such as the mutation in beta-globin that causes sickle-cell anaemia, are not. As we will see later, where we set the boundary is largely a matter of convenience. It is easier to screen for the more common polymorphisms (>1%), but the rarer ones (0.5%, or even less frequent) may be more informative. When studying genetic variation, it is important to keep in mind the differences that diploidy makes in species such as our own...
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...
