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Genomic Informatics in the Healthcare System
Published in Salvatore Volpe, Health Informatics, 2022
It is challenging to understand the phenotype-genotype correlation and phenotypic variability of individuals with a specific genetic variant. Many alternative explanations for differing phenotypes among cases with the same genetic variant have been proposed. One consideration is the presence of another genetic variant that affects disease presentation. A true digenic disorder requires the inheritance of a distinct heterozygous mutation in two genes that, when inherited separately, do not cause a phenotype. The broader term of epistasis refers to possible interactions between genes. Determining genetic epistasis is complex and requires an appropriate pedigree, which includes more than one gene mutated in a single pedigree, a range of genetic permutations, and at least one member with wild type (WT) alleles in both genes.
Bias, Conflict of Interest, Ignorance, and Uncertainty
Published in Ted W. Simon, Environmental Risk Assessment, 2019
The phenotypic fate of developing cells depends on activation of coordinated programs of gene expression during the appropriate time window. The state of chromatin is a significant factor in enabling these programs to occur. DNA methylation, histone alteration, and movement of chromosomes within the nucleus to bring appropriate genes into the transcription compartment all play a role.24–28 Epistasis occurs when the expression of a gene at a specific locus is dependent on the ongoing genetic background: in other words, the interaction between different genes that affects gene expression. Epistasis occurs during both normal development and tumorigenesis.29,30 The use of big data on gene expression and machine learning is revealing epistatic interactions underlying a variety of diseases.31 Cancer cells rely more heavily on glycolysis than on oxidative phosphorylation for their energy needs, and in terms of energetics, resemble single-celled organisms during the early history of the earth when oxygen was absent. As life on earth evolved, the transition to aerobic metabolism also occurred, with the concomitant development of anti-oxidant systems to prevent the toxicity of reactive oxygen species generated by aerobic metabolism. Unlimited growth capacity was a feature of these early organisms, and is shared with cancer cells.32
Genetic Principles
Published in Gail S. Anderson, Biological Influences on Criminal Behavior, 2019
Epistasis occurs when one gene alters the way another gene is expressed. An example is coat color in Labrador retrievers. These dogs come in black, brown, and golden. Black coat color (B) is dominant to brown (b), or chocolate, as we refer to it. To be chocolate, a Labrador must have two recessive alleles (bb). The two alleles for color produce black or chocolate melanin (dark pigment). Sounds simple, but there is another gene (E) that determines whether the dog will deposit melanin in the coat hairs or not. This E gene is epistatic, controlling the other gene. If the dog has a dominant E, then it will produce the color the allele suggests—either black or chocolate, as melanin will be deposited in the coat hairs. However, if the dog has a recessive e, then this will act on the other gene and prevent it from resulting in the deposition of melanin in the coat hairs, whether black or chocolate, and the resulting dog will be golden. Note, however, that melanin is only blocked from forming in the coat, as the dog still has melanin deposited in the dark nose and eyes; the gene only affects the deposition in the coat.2
Association between endothelial nitric oxide synthase and the renin-angiotensin-aldosterone system polymorphisms, blood pressure and training status in normotensive/pre-hypertension and hypertensive older adults: a pilot study
Published in Clinical and Experimental Hypertension, 2021
Roberta Fernanda da Silva, Riccardo Lacchini, Lucas Cezar Pinheiro, Letícia Perticarrara Ferezin, José Eduardo Tanus-Santos, Marcelo Rizzatti Luizon, Thiago José Dionísio, Carlos Ferreira Santos, Thaís Amanda Reia, André Mourão Jacomini, Ana Maria Guilmo Moreno, Anderson Saranz Zago
In general, the literature have shown that eNOS and RAAS polymorphisms are associated with greater risk of developing HT. However, the results of the current study demonstrated that isolated eNOS or RAAS allele or genotype were not associated with HT. Conversely, when epistasis analysis is performed, it shows a significant interaction between polymorphisms of different systems. These results emphasize the importance of studies that consider the risk of developing HT with the combination of polymorphism instead of isolated polymorphism. Furthermore, these results contribute for a better understanding of how the genetic associations of the vasodilation and vasoconstriction mechanisms influence the level of HT in older adults. It also highlight the importance of maintaining good levels of TS through an active lifestyle, in order to improve health-related parameters, contributing to better hemodynamic and humoral control and lower cardiovascular risk profile.
The spermatogenesis-associated protein-7 (SPATA7) gene – an overview
Published in Ophthalmic Genetics, 2020
However, certain common characteristics have been suggested to be present in SPATA7-associated ciliopathy. Based on the analysis of multiple families with mutations in this gene, these include narrow arterioles, a well-preserved macula, widespread RPE atrophy, and mottled hypopigmentation of the mid-peripheral retina. Alongside these similarities, the same set of families are noted to have wide differences in the manifestations of the disease such as visual acuity, varying from light perception to nearly normal acuity; and age at onset, at infancy in some patients, to after the second decade in others (7). The phenotypic differences may also be also evident between siblings, thus complicating genotype-phenotype correlations. Epistatic effects and modifiers have been suggested to be the basis behind variations of phenotypes. An example of such difference is that phenotypes such as cone-rod dystrophy (CRD) are associated to a SPATA7 mutation of Arg85Ter (13), in addition to LCA (12).
Case-only analysis of gene–gene interactions in inflammatory bowel disease
Published in Scandinavian Journal of Gastroenterology, 2020
Milda Aleknonytė-Resch, Sandra Freitag-Wolf, Stefan Schreiber, Michael Krawczak, Astrid Dempfle
Originally, the term ‘epistasis’ was used to refer to the ability of one or more genotypes of a gene, say A, to mask the phenotypic effects of another gene, B [5]. Over time, however, epistasis has become more or less synonymous of gene–gene interaction in general [6], where it is important to distinguish between biological and statistical interaction. The former is usually postulated when the gene products in question share some common role in the disease etiology, i.e., if they either interact physically with one another or if they impede upon one and the same, disease-relevant biological pathway. Statistical interaction, on the other hand, is defined as the lack of additivity of the genotype-associated disease risk difference, measured on a particular scale (usually linear, log or logit). Notably, absence of statistical interaction on one scale implies the presence of interaction on all other scales, i.e., there is no such thing as a lack of statistical gene–gene interaction. Statistical interaction can also be interpreted as ‘effect modification’ in that the risk difference associated with a given genotype of gene A, scaled correspondingly (i.e., risk difference, relative risk, or odds ratio), depends upon the genotype of gene B. While certain types of biological interaction result in statistical interaction on a certain scale, the presence of statistical interaction does not necessarily imply the concurrent presence of any meaningful biological interaction [7].