Physiological genomics
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The novel coronavirus SARS-CoV-2 was identified as the causative agent for a series of atypical respiratory diseases in the Hubei Province of Wuhan, China in December of 2019. The disease SARS-CoV-2, termed COVID-19, was officially declared a pandemic by the World Health Organization on March 11, 2020. SARS-CoV-2 contains a single-stranded, positive-sense RNA genome surrounded by an extracellular membrane containing a series of spike glycoproteins resembling a crown. ⋯ COVID-19 infection causes imbalances in ACE2 and induces an inflammatory immune response, known as a cytokine storm, both of which amplify comorbidities within the host. Herein, we discuss the genetics, pathogenesis, and possible therapeutics of COVID-19 infection along with secondary complications associated with disease progression, including ARDS and pulmonary fibrosis. Understanding the mechanisms of COVID-19 infection will allow the development of vaccines or other novel therapeutic approaches to prevent transmission or reduce the severity of infection.
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Physiological genomics · Sep 2017
ReviewEpigenetic research in multiple sclerosis: progress, challenges, and opportunities.
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis, and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. ⋯ A growing body of evidence supports a role of epigenetic processes in the mechanisms underlying immune pathogenesis and nervous system dysfunction in MS. However, disparities between studies shed light on the need to consider possible confounders and methodological limitations for a better interpretation of the data. Nevertheless, translational use of epigenetics might offer new opportunities in epigenetic-based diagnostics and therapeutic tools for a personalized care of MS patients.
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Physiological genomics · Feb 2017
ReviewPharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia.
A review of the pharmacogenetics (PGt) and pathophysiology of calcium voltage-gated channel subunit alpha1 S (CACNA1S) mutations in malignant hyperthermia susceptibility type 5 (MHS5; MIM #60188) is presented. Malignant hyperthermia (MH) is a life-threatening hypermetabolic state of skeletal muscle usually induced by volatile, halogenated anesthetics and/or the depolarizing neuromuscular blocker succinylcholine. ⋯ At present, one or at most six CACNA1S mutations display significant linkage or association either to clinically diagnosed MH or to MHS as determined by contracture testing. Additional pathogenic variants in CACNA1S, either alone or in combination with genes affecting Ca2+ homeostasis, are likely to be discovered in association to MH as whole exome sequencing becomes more commonplace.
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Physiological genomics · Nov 2014
ReviewmiR-21 in ischemia/reperfusion injury: a double-edged sword?
MicroRNAs (miRNAs or miRs) are endogenous, small RNA molecules that suppress expression of targeted mRNA. miR-21, one of the most extensively studied miRNAs, is importantly involved in divergent pathophysiological processes relating to ischemia/reperfusion (I/R) injury, such as inflammation and angiogenesis. The role of miR-21 in renal I/R is complex, with both protective and pathological pathways being regulated by miR-21. Preconditioning-induced upregulation of miR-21 contributes to the protection against subsequent renal I/R injury through the targeting of genes such as the proapoptotic gene programmed cell death 4 and interactions between miR-21 and hypoxia-inducible factor. Conversely, long-term elevation of miR-21 may be detrimental to the organ by promoting the development of renal interstitial fibrosis following I/R injury. miR-21 is importantly involved in several pathophysiological processes related to I/R injury including inflammation and angiogenesis as well as the biology of stem cells that could be used to treat I/R injury; however, the effect of miR-21 on these processes in renal I/R injury remains to be studied.