Genetics and exercise: an introduction
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
We have already mentioned that DNA sequence variants influence body height, strength, VO2max trainability or disease risk. We will now discuss how variations in the DNA sequence occur, the different types of DNA variants and their frequency in human populations. But first we need to explain the vocabulary used to define DNA variants. A mutation is an event that changes a DNA sequence. The consequence of a mutation is a DNA variant. For example, a mutation may change a “…CTGT…” to a “…CTAT…” sequence resulting in a G/A DNA variant. Alleles are DNA variants of a given sequence. For example, assume that 20% of a population have a “CTGT” and 80% a “CTAT” DNA sequence in the myostatin gene (important in muscle mass regulation, covered in Chapter 4 and 8); the CTGT variant would be the minor (frequency) allele, whereas the CTAT variant would be the major (frequency) allele. Alleles with a frequency of less than 1% are referred to as rare alleles, whilst those in the range of 1–5% are known as low frequency alleles. DNA variants with a minor allele carried by 5% and more of the population are labelled as common alleles. If a one-base substitution occurs in at least 1% of a population, then it is termed a single-nucleotide polymorphism and is abbreviated as SNP. SNPs are the most studied DNA variants.
Genetic and genomic investigations
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
One should make a mention here of terminology. The word ‘mutation’ can refer here either to the process of change in the genome (a mutational event) or to that which is thereby produced (the mutated copy of the gene). The first sense of the word continues as a useful term. The second sense has become entangled in an unhelpful assumption: it has often been assumed, in the past, that the mutant version of the gene you have sequenced, in a patient affected by the corresponding disease, will of course be the cause of their disease. Given the introduction of exome and genome sequencing, however, many variant sequences are now discovered that may be quite unrelated to the disease in question. They may be completely benign, or they may indicate a risk of a different, (co)incidental disease. For the second sense of the word ‘mutation’, therefore, it is good practice to use the word ‘variant’ instead and to specify a variant as being pathogenic if there is good evidence of that (see Richards et al., 2015). The point is to avoid the inadvertent drawing of false conclusions from unwarranted assumptions.
Cancer Epidemiology
Peter G. Shields in Cancer Risk Assessment, 2005
1. Spontaneous. Often overlooked are the spontaneous causes of cancer. By spontaneous, what is meant is that a certain amount of cancer is due to “spontaneous” or “background” mutation rates (51). These mutations generally show a different pattern of DNA lesions compared to those induced by carcinogens. The exact causes of these mutations are not known, but are likely due to things such as background cosmic radiation and body temperature, and reflect the instability of DNA as a result of oxidative damage and other cellular processes. These factors would be expected to show little or no variability in terms of geographical distribution, and thus there will always be a certain background level of cancer in any population. Doll and Peto (9) have also termed this “chance,” or more simply good or bad luck. At the level of the individual, spontaneous causes of cancer may play an important explanatory role. Knudson (51) has estimated that approximately 15% of cancer may be explained by spontaneous factors.
Histopathology of the Conduction System in Long QT Syndrome
Published in Fetal and Pediatric Pathology, 2022
Alexandra Rogers, Rachel Taylor, Janet Poulik, Bahig M. Shehata
At least 16 genotypically different subtypes of Long QT Syndrome (LQTS) have been identified to date (ex: LQT1, LQT2, LQT3). About 75% of these cases are caused by mutations in one of three major genes, 5% are attributable to mutations in one of 10 minor genes, 5–10% are caused by de novo germline mutations, and the remaining 10–15% of diagnoses are due to unidentified causes [2]. Most cases of LQTS are inherited in an autosomal dominant pattern, underlying the importance of a thorough family history in the evaluation of presenting patients. Most of the mutations are single nucleotide substitutions or insertions/deletions [2]. While a majority of patients harbor only a single mutation in one of the three major genes, a small percentage, roughly 5% to 10%, show multiple mutations. These patients tend to demonstrate a more severe disease phenotype with an earlier age of onset [2].
Early flowering, good grain quality mutants through gamma rays and EMS for enhancing per day productivity in rice (Oryza sativa L.)
Published in International Journal of Radiation Biology, 2021
Vinithashri Gautam, Manonmani Swaminathan, Manoharan Akilan, Anand Gurusamy, Meena Suresh, Bhuvaneswari Kaithamalai, A. John Joel
Mutation breeding mainly involves physical mutagens like gamma rays, electron beam, and chemical mutagens like Ethyl Methane Sulfonate (EMS), Sodium Azide (SA) and Methyl nitroso urea for generating variability in crop plants. The effects of mutation range from single nucleotide changes to large deletions or chromosomal rearrangements. For the past 80 years, the creation of hereditary aberrations and the development of more than 70 percent of mutant varieties were achieved using ionizing radiations (Mba 2013). Gamma rays have a shorter wavelength and penetrate deeper into the plant tissues. The mutagenic effect is reflected because of Deoxyribonucleic acid (DNA) double-strand breaks. Point mutations created by the chemical mutagens leads to both losses of function and gain of function phenotypes as in the cases of tolerance to the herbicide glyphosate (Bradshaw et al. 1997) and sulfonyl urea in the legume group Medicago truncatula (Oldach et al. 2008). In case of rice, EMS mutagenesis was employed to isolate Herbicide Tolerant Mutant-22 (HTM-22) which confers tolerance against broad-spectrum herbicide Imazethapyr (Shoba et al. 2017). Any genotype can be mutagenized and the distribution of mutation is random in the genome. Genome wide saturation mutagenesis can be attained by using a small mutant population because of high concentration of mutation. Response of plants to mutagens is influenced by genotypes. Frequency of mutations tends to differ across physical, chemical and combination treatments across different genotypes.
Genetic variation patterns of β-thalassemia in Western Andalusia (Spain) reveal a structure of specific mutations within the Iberian Peninsula
Published in Annals of Human Biology, 2021
Luis J. Sánchez-Martínez, Candela L. Hernández, Juan N. Rodríguez, Jean M. Dugoujon, Andrea Novelletto, Paloma Ropero, Luisa Pereira, Rosario Calderón
Haemoglobin diseases represent some of the most common pathologies of the human population; ∼7% of people are carriers of mutations in certain genes in the α- and β-globin chains that cause abnormal synthesis or structure of the tetramers of normal haemoglobin A (HbA, α2 β2) in adults (Weatherall 2010). At present, 733 mutations causing α- or β-thalassemia are registered in the IthaGenes (Ithanet) database, and nearly 419 have been identified at the β-globin gene locus (HBB). Most of these mutations are point mutations either within the HBB gene or in the nearest flanking sequence as a result of the substitution of one single nucleotide by another (SNPs, single nucleotide polymorphisms). Only a small fraction of mutations have been identified as deletions or insertions of one or a few nucleotide base pairs in a DNA sequence. These changes in the globin chains cause clinical manifestations of congenital haemolytic anaemias, with a variable degree of severity.