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Pulmonology 2020Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and multisystemic disease with progressive increasing morbidity and mortality. COPD is now widely... (Review)
Review
Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and multisystemic disease with progressive increasing morbidity and mortality. COPD is now widely accepted as a heterogeneous condition with multiple phenotypes and endotypes. This review will discuss the old and new concepts for the different types of COPD phenotypes, as well as the inclusion of them in current guidelines. Phenotypical approach to COPD is having huge impact on everyday practice and changed nonpharmacological and pharmacological management of COPD in last decade. However, phenotypical approach is small step to precision medicine in COPD management in the absence of big, specific and well-designed COPD trials with exact identification of phenotypes for more personalization of the treatment of COPD.
Topics: Humans; Phenotype; Practice Guidelines as Topic; Precision Medicine; Pulmonary Disease, Chronic Obstructive
PubMed: 31740261
DOI: 10.1016/j.pulmoe.2019.10.006 -
Journal of Clinical Immunology Jan 2020Since 2013, the International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) has published an updated phenotypic...
Since 2013, the International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) has published an updated phenotypic classification of IEI, which accompanies and complements their genotypic classification into ten tables. This phenotypic classification is user-friendly and serves as a resource for clinicians at the bedside. There are now 430 single-gene IEI underlying phenotypes as diverse as infection, malignancy, allergy, autoimmunity, and autoinflammation. We herein report the 2019 phenotypic classification, including the 65 new conditions. The diagnostic algorithms are based on clinical and laboratory phenotypes for each of the ten broad categories of IEI.
Topics: Autoimmunity; Genotype; Hereditary Autoinflammatory Diseases; Humans; Hypersensitivity; Immunity; Immunologic Deficiency Syndromes; Phenotype
PubMed: 32048120
DOI: 10.1007/s10875-020-00758-x -
Plant Biotechnology Journal Jul 2020Genotyping-by-sequencing has enabled approaches for genomic selection to improve yield, stress resistance and nutritional value. More and more resource studies are... (Review)
Review
Genotyping-by-sequencing has enabled approaches for genomic selection to improve yield, stress resistance and nutritional value. More and more resource studies are emerging providing 1000 and more genotypes and millions of SNPs for one species covering a hitherto inaccessible intraspecific genetic variation. The larger the databases are growing, the better statistical approaches for genomic selection will be available. However, there are clear limitations on the statistical but also on the biological part. Intraspecific genetic variation is able to explain a high proportion of the phenotypes, but a large part of phenotypic plasticity also stems from environmentally driven transcriptional, post-transcriptional, translational, post-translational, epigenetic and metabolic regulation. Moreover, regulation of the same gene can have different phenotypic outputs in different environments. Consequently, to explain and understand environment-dependent phenotypic plasticity based on the available genotype variation we have to integrate the analysis of further molecular levels reflecting the complete information flow from the gene to metabolism to phenotype. Interestingly, metabolomics platforms are already more cost-effective than NGS platforms and are decisive for the prediction of nutritional value or stress resistance. Here, we propose three fundamental pillars for future breeding strategies in the framework of Green Systems Biology: (i) combining genome selection with environment-dependent PANOMICS analysis and deep learning to improve prediction accuracy for marker-dependent trait performance; (ii) PANOMICS resolution at subtissue, cellular and subcellular level provides information about fundamental functions of selected markers; (iii) combining PANOMICS with genome editing and speed breeding tools to accelerate and enhance large-scale functional validation of trait-specific precision breeding.
Topics: Breeding; Genome-Wide Association Study; Genomics; Genotype; Phenotype; Polymorphism, Single Nucleotide
PubMed: 32163658
DOI: 10.1111/pbi.13372 -
Trends in Ecology & Evolution Jan 2020Genetically identical individuals can be phenotypically variable, even in constant environmental conditions. The ubiquity of this phenomenon, known as 'intra-genotypic... (Review)
Review
Genetically identical individuals can be phenotypically variable, even in constant environmental conditions. The ubiquity of this phenomenon, known as 'intra-genotypic variability', is increasingly evident and the relevant mechanistic underpinnings are beginning to be understood. In parallel, theory has delineated a number of formal expectations for contexts in which such a feature would be adaptive. Here, we review empirical evidence across biological systems and theoretical expectations, including nonlinear averaging and bet hedging. We synthesize existing results to illustrate the dependence of selection outcomes both on trait characteristics, features of environmental variability, and species' demographic context. We conclude by discussing ways to bridge the gap between empirical evidence of intra-genotypic variability, studies demonstrating its genetic component, and evidence that it is adaptive.
Topics: Biological Evolution; Genotype; Humans; Phenotype; Selection, Genetic
PubMed: 31519463
DOI: 10.1016/j.tree.2019.08.005 -
Emerging Topics in Life Sciences Dec 2023Repeat expansion disorders (REDs) are monogenic diseases caused by a sequence of repetitive DNA expanding above a pathogenic threshold. A common feature of the REDs is a...
Repeat expansion disorders (REDs) are monogenic diseases caused by a sequence of repetitive DNA expanding above a pathogenic threshold. A common feature of the REDs is a strong genotype-phenotype correlation in which a major determinant of age at onset (AAO) and disease progression is the length of the inherited repeat tract. Over a disease-gene carrier's life, the length of the repeat can expand in somatic cells, through the process of somatic expansion which is hypothesised to drive disease progression. Despite being monogenic, individual REDs are phenotypically variable, and exploring what genetic modifying factors drive this phenotypic variability has illuminated key pathogenic mechanisms that are common to this group of diseases. Disease phenotypes are affected by the cognate gene in which the expansion is found, the location of the repeat sequence in coding or non-coding regions and by the presence of repeat sequence interruptions. Human genetic data, mouse models and in vitro models have implicated the disease-modifying effect of DNA repair pathways via the mechanisms of somatic mutation of the repeat tract. As such, developing an understanding of these pathways in the context of expanded repeats could lead to future disease-modifying therapies for REDs.
Topics: Mice; Animals; Humans; Trinucleotide Repeat Expansion; Age of Onset; Genetic Association Studies; Phenotype; Disease Progression
PubMed: 37861103
DOI: 10.1042/ETLS20230015 -
Journal of Animal Science Feb 2021Genetic strategies aimed at improving general immune competence (IC) have the potential to reduce the incidence and severity of disease in beef production systems, with...
Genetic strategies aimed at improving general immune competence (IC) have the potential to reduce the incidence and severity of disease in beef production systems, with resulting benefits of improved animal health and welfare and reduced reliance on antibiotics to prevent and treat disease. Implementation of such strategies first requires that methodologies be developed to phenotype animals for IC and demonstration that these phenotypes are associated with health outcomes. We have developed a methodology to identify IC phenotypes in beef steers during the yard weaning period, which is both practical to apply on-farm and does not restrict the future sale of tested animals. In the current study, a total of 838 Angus steers, previously IC phenotyped at weaning, were categorized as low (n = 98), average (n = 653), or high (n = 88) for the IC phenotype. Detailed health and productivity data were collected on all steers during feedlot finishing, and associations between IC phenotype, health outcomes, and productivity were investigated. A favorable association between IC phenotype and number of mortalities during feedlot finishing was observed with higher mortalities recorded in low IC steers (6.1%) as compared with average (1.2%, P < 0.001) or high (0%, P = 0.018) IC steers. Disease incidence was numerically highest in low IC steers (15.3 cases/100 animals) and similar in average IC steers (10.1 cases/100 animals) and high IC steers (10.2 cases/100 animals); however, differences between groups were not significant. No significant influence of IC phenotype on average daily gain was observed, suggesting that selection for improved IC is unlikely to incur a significant penalty to production. The potential economic benefits of selecting for IC in the feedlot production environment were calculated. Health-associated costs were calculated as the sum of lost production costs, lost capital investment costs, and disease treatment costs. Based on these calculations, health-associated costs were estimated at AUS$103/head in low IC steers, AUS$25/head in average IC steers, and AUS$4/head in high IC steers, respectively. These findings suggest that selection for IC has the potential to reduce mortalities during feedlot finishing and, as a consequence, improve the health and welfare of cattle in the feedlot production environment and reduce health-associated costs incurred by feedlot operators.
Topics: Animal Feed; Animals; Cattle; Diet; Phenotype; Weaning
PubMed: 33476384
DOI: 10.1093/jas/skab016 -
Journal of the American College of... Aug 2022
Topics: Humans; Hypertension, Pulmonary; Phenotype; Pulmonary Artery
PubMed: 35953137
DOI: 10.1016/j.jacc.2022.05.039 -
Journal of Biosciences 2022Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as nongenetic/ non-mutational heterogeneity. Such heterogeneity... (Review)
Review
Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as nongenetic/ non-mutational heterogeneity. Such heterogeneity - a ubiquitous nature of biological systems - has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systemslevel approach integrating mathematical modeling and in () experiments can map the diverse phenotypic repertoire and identify therapeutic vulnerabilities of an otherwise clonal cell population.
Topics: Clone Cells; Gene Regulatory Networks; Humans; Models, Biological; Neoplasms; Phenotype; Tumor Microenvironment
PubMed: 36210746
DOI: No ID Found -
ELife Sep 2023Experiments on worms suggest that a statistical measure called the G matrix can accurately predict how phenotypes will adapt to a novel environment over multiple...
Experiments on worms suggest that a statistical measure called the G matrix can accurately predict how phenotypes will adapt to a novel environment over multiple generations.
Topics: Phenotype; Biological Evolution; Adaptation, Biological; Animals
PubMed: 37671937
DOI: 10.7554/eLife.91450 -
Journal of Neurology, Neurosurgery, and... Apr 2022Neurometabolic diseases are a group of individually rare but numerous and heterogeneous genetic diseases best known to paediatricians. The more recently reported adult... (Review)
Review
Neurometabolic diseases are a group of individually rare but numerous and heterogeneous genetic diseases best known to paediatricians. The more recently reported adult forms may present with phenotypes strikingly different from paediatric ones and may mimic other more common neurological disorders in adults. Furthermore, unlike most neurogenetic diseases, many neurometabolic diseases are treatable, with both conservative and more recent innovative therapeutics. However, the phenotypical complexity of this group of diseases and the growing number of specialised biochemical tools account for a significant diagnostic delay and underdiagnosis. We reviewed all series and case reports of patients with a confirmed neurometabolic disease and a neurological onset after the age of 10 years, with a focus on the 36 treatable ones, and classified these diseases according to their most relevant clinical manifestations. The biochemical diagnostic approach of neurometabolic diseases lays on the use of numerous tests studying a set of metabolites, an enzymatic activity or the function of a given pathway; and therapeutic options aim to restore the enzyme activity or metabolic function, limit the accumulation of toxic substrates or substitute the deficient products. A quick diagnosis of a treatable neurometabolic disease can have a major impact on patients, leading to the stabilisation of the disease and cease of repeated diagnostic investigations, and allowing for familial screening. For the aforementioned, in addition to an exhaustive and clinically meaningful review of these diseases, we propose a simplified diagnostic approach for the neurologist with the aim to help determine when to suspect a neurometabolic disease and how to proceed in a rational manner. We also discuss the place of next-generation sequencing technologies in the diagnostic process, for which deep phenotyping of patients (both clinical and biochemical) is necessary for improving their diagnostic yield.
Topics: Child; Delayed Diagnosis; High-Throughput Nucleotide Sequencing; Humans; Nervous System Diseases; Phenotype
PubMed: 35140137
DOI: 10.1136/jnnp-2021-328045