Multi‐Omic Approaches to Identify Genetic Factors in Metabolic Syndrome

Clark, Karen C; Kwitek, Anne E.

doi:10.1002/cphy.c210010

Cited by 5 publications

(7 citation statements)

References 361 publications

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“…Multiple lines of computational evidence predict that this variant is probably damaging to the protein structure, function, or protein–protein interaction. The pathogenic variant identified in the GBE1 gene is relevant to the patient’s phenotype, including unexplained progressive neurogenic bladder, gait difficulties from mixed upper and lower motor neuron involvement, sensory loss, predominantly in the distal lower extremities, autonomic dysfunction and mild cognitive difficulties [ 28 , 29 ].…”

Section: Resultsmentioning

confidence: 99%

Identification of Novel and Recurrent Variants in BTD, GBE1, AGL and ASL Genes in Families with Metabolic Disorders in Saudi Arabia

Latif,

Hashmi,

Alayoubi

et al. 2024

JCM

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Background and Objectives: Inherited metabolic disorders (IMDs) are a group of genetic disorders characterized by defects in enzymes or transport proteins involved in metabolic processes. These defects result in an abnormal accumulation of metabolites and thus interfere with the body’s metabolism. A variety of IMDs exist and differential diagnosis is often challenging. Our objective was to gain insight into the genetic basis of IMDs and the correlations between specific genetic mutations and clinical presentations in patients admitted at various hospitals in the Madinah region of the Kingdom of Saudi Arabia. Material and Methods: Whole exome sequencing (WES) has emerged as a powerful tool for diagnosing IMDs and allows for the identification of disease-causing genetic mutations in individuals suspected of IMDs. This ensures accurate diagnosis and appropriate management. WES was performed in four families with multiple individuals showing clinical presentation of IMDs. Validation of the variants identified through WES was conducted using Sanger sequencing. Furthermore, various computational analyses were employed to uncover the disease gene co-expression and metabolic pathways. Results: Exome variant data analysis revealed missense variants in the BTD (c.1270G > C), ASL (c.1300G > T), GBE1 (c.985T > G) and AGL (c.113C > G) genes. Mutations in these genes are known to cause IMDs. Conclusions: Thus, our data showed that exome sequencing, in conjunction with clinical and biochemical characteristics and pathological hallmarks, could deliver an accurate and high-throughput outcome for the diagnosis and sub-typing of IMDs. Overall, our findings emphasize that the integration of WES with clinical and pathological information has the potential to improve the diagnosis and understanding of IMDs and related disorders, ultimately benefiting patients and the medical community.

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Section: Resultsmentioning

confidence: 99%

Identification of Novel and Recurrent Variants in BTD, GBE1, AGL and ASL Genes in Families with Metabolic Disorders in Saudi Arabia

Latif,

Hashmi,

Alayoubi

et al. 2024

JCM

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“…However, there is not yet a consensus on the identity of the "primary" trigger mechanism. We can safely assume that even if we do not accept the 'planned obsolescence' hypothesis, we can forfeit the redundant 'planned' (since all gene-related mechanisms areconceptually-genetically planned, in line with what we know of MS genetics [33,35,1018]) but the obsolescence case remains, in part, unexplained/unjustified by non-steroidal hormone alternative mechanisms. In addition, there are partially superimposable mechanisms to compare (i.e., menopause) which produce deep alterations: functional, metabolic, and behavioral, but which do not share the decimating effect observed in mature and old men.…”

Section: Discussionmentioning

confidence: 99%

The Metabolic Syndrome, a Human Disease

Alemany

2024

IJMS

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This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy of associated diseases/disorders, or just a syndrome of related but rather independent pathologies. The human nature of MS (its exceptionality in Nature and its close interdependence with human action and evolution) is presented and discussed. The text also describes the close interdependence of its components, with special emphasis on the description of their interrelations (including their syndromic development and recruitment), as well as their consequences upon energy handling and partition. The main theories on MS’s origin and development are presented in relation to hepatic steatosis, type 2 diabetes, and obesity, but encompass most of the MS components described so far. The differential effects of sex and its biological consequences are considered under the light of human social needs and evolution, which are also directly related to MS epidemiology, severity, and relations with senescence. The triggering and maintenance factors of MS are discussed, with especial emphasis on inflammation, a complex process affecting different levels of organization and which is a critical element for MS development. Inflammation is also related to the operation of connective tissue (including the adipose organ) and the widely studied and acknowledged influence of diet. The role of diet composition, including the transcendence of the anaplerotic maintenance of the Krebs cycle from dietary amino acid supply (and its timing), is developed in the context of testosterone and β-estradiol control of the insulin-glycaemia hepatic core system of carbohydrate-triacylglycerol energy handling. The high probability of MS acting as a unique complex biological control system (essentially monophyletic) is presented, together with additional perspectives/considerations on the treatment of this ‘very’ human disease.

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“…The development of high-resolution proteomic screening has led to advances in the development of biomarkers based on metabolomic profiling [ 15 ] and the detection of temporal events, which can be implicated in the development of MD [ 16 ]. All of these developments have led to the synthesis of information derived from multi-omic studies [ 17 , 18 , 19 ] with the objective of arriving at a definitive and comprehensive overview of the regulatory factors involved in the development of MDs. The rapid advances of microbial metagenomics [ 20 , 21 , 22 ] and the correlation between microbial metabolites secreted in the gut and MDs [ 23 , 24 , 25 , 26 ] have led researchers to propose novel alternative therapies including the use of bacterial inoculum as dietary supplements [ 27 ] as well as dietary supplements that favor the establishment of a healthy gut microbiome [ 28 ], has led to the dawn of a new era in the management of diet and microbial populations in order to ameliorate the deleterious effects of MDs in a sustainable manner.…”

Section: Introductionmentioning

confidence: 99%

Current Understanding on the Genetic Basis of Key Metabolic Disorders: A Review

Rodrigues

Yong

Bhuiyan

et al. 2022

Biology

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Advances in data acquisition via high resolution genomic, transcriptomic, proteomic and metabolomic platforms have driven the discovery of the underlying factors associated with metabolic disorders (MD) and led to interventions that target the underlying genetic causes as well as lifestyle changes and dietary regulation. The review focuses on fourteen of the most widely studied inherited MD, which are familial hypercholesterolemia, Gaucher disease, Hunter syndrome, Krabbe disease, Maple syrup urine disease, Metachromatic leukodystrophy, Mitochondrial encephalopathy lactic acidosis stroke-like episodes (MELAS), Niemann-Pick disease, Phenylketonuria (PKU), Porphyria, Tay-Sachs disease, Wilson’s disease, Familial hypertriglyceridemia (F-HTG) and Galactosemia based on genome wide association studies, epigenetic factors, transcript regulation, post-translational genetic modifications and biomarker discovery through metabolomic studies. We will delve into the current approaches being undertaken to analyze metadata using bioinformatic approaches and the emerging interventions using genome editing platforms as applied to animal models.

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Multi‐Omic Approaches to Identify Genetic Factors in Metabolic Syndrome

Cited by 5 publications

References 361 publications

Identification of Novel and Recurrent Variants in BTD, GBE1, AGL and ASL Genes in Families with Metabolic Disorders in Saudi Arabia

Identification of Novel and Recurrent Variants in BTD, GBE1, AGL and ASL Genes in Families with Metabolic Disorders in Saudi Arabia

The Metabolic Syndrome, a Human Disease

Current Understanding on the Genetic Basis of Key Metabolic Disorders: A Review

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