1,067,945 results match your criteria genetic disease

Immunological lessons from genome-wide association studies of infections.

Curr Opin Immunol 2021 Apr 17;72:87-93. Epub 2021 Apr 17.

School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address:

Over the past few years, genome-wide association studies (GWAS) have been increasingly applied to identify host genetic factors influencing clinical and laboratory traits related to immunity and infection, and to understand the interplay between the host and the microbial genomes. By screening large cohorts of individuals suffering from various infectious diseases, GWAS explored resistance against infection, natural history of the disease, development of life-threatening clinical signs, and innate and adaptive immune responses. These efforts provided fundamental insight on the role of major genes in the interindividual variability in the response to infection and on the mechanisms of the immune response against human pathogens both at the individual and population levels. Read More

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Strain-specific alterations in the skeletal response to adenine-induced chronic kidney disease are associated with differences in parathyroid hormone levels.

Bone 2021 Apr 17:115963. Epub 2021 Apr 17.

Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Medicine - Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, United States; Department of Biomedical Engineering, Indiana University Purdue University of Indianapolis, Indianapolis, IN, United States; Roudebush Veterans Administration Medical Center, Indianapolis, IN, United States. Electronic address:

Chronic kidney disease (CKD) leads to loss of cortical bone through cortical thinning and the development of cortical porosity. The goal of this current study was to assess cortical bone alterations to adenine-induced chronic kidney disease (CKD) in two strains of mice with known genetic differences in cortical thickness. We hypothesized that C3H mice with thicker cortices and baseline levels of intracortical remodeling would have greater cortical porosity in response to adenine-induced CKD compared to B6 animals. Read More

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Genome-based local dynamics of canine rabies virus epidemiology, transmission, and evolution in Davao City, Philippines, 2018-2019.

Infect Genet Evol 2021 Apr 17:104868. Epub 2021 Apr 17.

Department of Biological Sciences and Environmental Studies, University of the Philippines Mindanao, Tugbok District, Mintal, Davao City, Philippines; Philippine Genome Center Mindanao, University of the Philippines Mindanao, Tugbok District, Mintal, Davao City, Philippines. Electronic address:

Rabies is a fatal zoonotic and neglected tropical disease caused by the rabies virus (RABV) and is associated with neuronal dysfunction and death, with dogs as the predominant carrier. The Philippines plans to eradicate rabies by 2022, but this is challenged with sub-optimal coverage of vaccination programs coupled with sustained transmission chains, making it unable to eradicate the disease. We investigated the dynamics of canine rabies in the highly urbanized Davao City of the Philippines and its neighboring localities by assessing genetic relationships, transmission patterns, selection pressure, and recombination events using the whole genome sequence of 49 RABV cases from June 2018 to May 2019, majority of which (46%) were from the district of Talomo, Davao City. Read More

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A machine learning approach to unmask novel gene signatures and prediction of Alzheimer's disease within different brain regions.

Genomics 2021 Apr 17. Epub 2021 Apr 17.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2033, Australia. Electronic address:

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose aetiology is currently unknown. Although numerous studies have attempted to identify the genetic risk factor(s) of AD, the interpretability and/or the prediction accuracies achieved by these studies remained unsatisfactory, reducing their clinical significance. Here, we employ the ensemble of random-forest and regularized regression model (LASSO) to the AD-associated microarray datasets from four brain regions - Prefrontal cortex, Middle temporal gyrus, Hippocampus, and Entorhinal cortex- to discover novel genetic biomarkers through a machine learning-based feature-selection classification scheme. Read More

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PcALF5 inhibits the proliferation of microbiota by binding to RPS4 and MscL of E. coli.

Dev Comp Immunol 2021 Apr 17:104106. Epub 2021 Apr 17.

College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian, 271018, China. Electronic address:

Antimicrobial peptides (AMPs), most of which are small proteins, are necessary for innate immunity against pathogens. Anti-lipopolysaccharide factor (ALF) with a conserved lipopolysaccharide binding domain (LBD) can bind to lipopolysaccharide (LPS) and neutralize LPS activity. The antibacterial mechanism of ALF, especially its role in bacteria, needs to be further investigated. Read More

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Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer.

Mol Cell 2021 Apr 10. Epub 2021 Apr 10.

Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. Electronic address:

Even though SYK and ZAP70 kinases share high sequence homology and serve analogous functions, their expression in B and T cells is strictly segregated throughout evolution. Here, we identified aberrant ZAP70 expression as a common feature in a broad range of B cell malignancies. We validated SYK as the kinase that sets the thresholds for negative selection of autoreactive and premalignant clones. Read More

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General characteristics, features of cultivation and antibiotic resistance representatives of mycobacterium fortuitum group representatives (review of literature).

Klin Lab Diagn 2021 Apr;66(4):223-228

Samara State Medical University.

Recently, more and more scientific works have been devoted to non-tuberculous mycobacteria, both by domestic and foreign researchers. One of the main reasons for this is the increase in patients with immunosuppression of various origins, improvement of the quality of laboratory and instrumental diagnostics of mycobacteriosis. This article focuses on the representatives of the M. Read More

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Secondary CoQ deficiency, bioenergetics unbalance in disease and aging.

Biofactors 2021 Apr 20. Epub 2021 Apr 20.

Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC-JA, Sevilla, Spain.

Coenzyme Q (CoQ ) deficiency is a rare disease characterized by a decreased accumulation of CoQ in cell membranes. Considering that CoQ synthesis and most of its functions are carried out in mitochondria, CoQ deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ supplementation. Read More

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Tracing Clostridium perfringens strains along the chicken production chain from farm to slaughter by multilocus sequence typing.

Zoonoses Public Health 2021 Apr 20. Epub 2021 Apr 20.

Weifang customs of the People's Republic of China, Weifang, China.

The current study is undertaken to characterize the prevalence, genotypes distribution, antibiotic resistance and genetic diversity of Clostridium perfringens (C. perfringens) collected from different stages of a chicken production chain. In total, 579 samples from a broiler farm and 378 samples from the slaughterhouse were collected from a large-scale rearing and slaughter one-stop enterprise in Weifang, China, between June and July 2019, of which 30. Read More

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Marfan syndrome resulting from a rare pathogenic FBN1 variant, ascertained through a proband with IgG4-related arteriopathy.

Am J Med Genet A 2021 Apr 20. Epub 2021 Apr 20.

Cardiac and Critical Care, Division of Medicine, Flinders Medical Center, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.

A 57-year-old man with a family history of aortic aneurysm was found, during assessment of unexplained fever, to have an infrarenal aortic aneurysm requiring immediate repair. Dilatation of popliteal and iliac arteries was also present. Progressive aortic root dilatation with aortic regurgitation was documented from 70 years leading to valve-sparing aortic root replacement at 77 years, at which time genetic studies identified a likely pathogenic FBN1 missense variant c. Read More

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Cis-epistasis at the LPA locus and risk of cardiovascular diseases.

Cardiovasc Res 2021 Apr 20. Epub 2021 Apr 20.

Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, 80636, Munich, Germany.

Aims: Coronary artery disease (CAD) has a strong genetic predisposition. However, despite substantial discoveries made by genome-wide association studies (GWAS), a large proportion of heritability awaits identification. Non-additive genetic-effects might be responsible for part of the unaccounted genetic variance. Read More

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Predicting the animal hosts of coronaviruses from compositional biases of spike protein and whole genome sequences through machine learning.

PLoS Pathog 2021 Apr 20;17(4):e1009149. Epub 2021 Apr 20.

Department of Health Data Science, University of Liverpool, Brownlow Street, Liverpool, United Kingdom.

The COVID-19 pandemic has demonstrated the serious potential for novel zoonotic coronaviruses to emerge and cause major outbreaks. The immediate animal origin of the causative virus, SARS-CoV-2, remains unknown, a notoriously challenging task for emerging disease investigations. Coevolution with hosts leads to specific evolutionary signatures within viral genomes that can inform likely animal origins. Read More

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AAV9-mediated FIG4 delivery prolongs life span in Charcot Marie Tooth disease type 4J mouse model.

J Clin Invest 2021 Apr 20. Epub 2021 Apr 20.

Genetic Resource Science, The Jackson Laboratory, Bar Harbor, United States of America.

Charcot-Marie-Tooth disease type 4J (CMT4J) is caused by recessive, loss-of-function mutations in FIG4, encoding a phosphoinositol(3,5)P2-phosphatase. CMT4J patients have both neuron loss and demyelination in the peripheral nervous system, with vacuolization indicative of endosome/lysosome trafficking defects. Although the disease is highly variable, the onset is often in childhood and FIG4 mutations can dramatically shorten lifespan. Read More

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c.1905 + 1G>A Promotes Fluoropyrimidine-Induced Anemia, a Prognostic Factor in Disease-Free Survival, in Colorectal Cancer.

Genet Test Mol Biomarkers 2021 Apr;25(4):276-283

Department of Medical Oncology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey.

In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase ( gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Read More

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ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease.

J Clin Oncol 2021 Apr 20:JCO2002754. Epub 2021 Apr 20.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: The rho-associated coiled-coil-containing protein kinase-2 (ROCK2) signaling pathway regulates the Th17/regulatory T cells balance and controls profibrotic pathways. Selective ROCK2 inhibition with belumosudil (KD025) may offer a novel approach to the management of chronic graft-versus-host disease (cGVHD).

Patients And Methods: A phase IIa, open-label, dose-finding study of belumosudil enrolled 54 patients with cGVHD who had received one to three prior lines of therapy (LOTs). Read More

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Electrophysiological Approaches for the Study of Ion Channel Function.

Methods Mol Biol 2021 ;2302:49-67

Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory + Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Ion channels play crucial roles in cell physiology, and are a major class of targets for clinically relevant pharmaceuticals. Because they carry ionic current, the function and pharmacology of ion channels can be studied using electrophysiological approaches that range in resolution from the single molecule to many millions of molecules. This chapter describes electrophysiological approaches for the study of one representative ion channel that is defective in a genetic disease, and that is the target of so-called highly effective modulator therapies now used in the clinic: the cystic fibrosis transmembrane conductance regulator (CFTR). Read More

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January 2021

Long-term follow-up of a patient with JAG1-associated retinopathy.

Doc Ophthalmol 2021 Apr 20. Epub 2021 Apr 20.

Newcastle Eye Centre, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK.

Purpose: To report the long-term structural and functional changes in the posterior segments of an adult with an unusual retinal dystrophy caused by a novel mutation in JAG1.

Methods: A 33-year-old female underwent comprehensive ophthalmic examination, including best corrected visual acuity (BCVA) measurement, dilated fundus imaging (wide-angle fundus colour and short wavelength autofluorescence imaging), macular and peripheral spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG) at baseline and 10 years later at the age of 43. The patient also underwent systemic review with detailed cardiac, brain and renal investigations. Read More

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Dystonia and leveraging oral pharmacotherapy.

J Neural Transm (Vienna) 2021 Apr 20. Epub 2021 Apr 20.

Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.

Dystonia is a clinically diverse disorder, characterized by sustained or intermittent muscle contractions causing abnormal and often repetitive movements and/or postures. Accurate clinical diagnosis is tantamount to effective dystonia management. Current guidelines in the treatments of dystonia, including oral therapy, are prescribed to improve symptoms and to restore functional capacity. Read More

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Infectious bursal disease in Nigeria: continuous circulation of reassortant viruses.

Trop Anim Health Prod 2021 Apr 20;53(2):271. Epub 2021 Apr 20.

Department of Veterinary Microbiology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria.

Outbreaks of infectious bursal disease (IBD), a highly contagious immunosuppressive disease of young chickens, are still reported globally despite vaccination efforts. This study investigated the genetic characteristics of infectious bursal disease virus (IBDV) from 26 reported outbreaks in 2019 in Nigeria. Nucleotide sequences of VP2 hypervariable (hvVP2) region (n=26) and VP1 (n=23) of Nigerian IBDVs were determined. Read More

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Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster.

G3 (Bethesda) 2019 Jul;9(7):2225-2234

Faculty of Medicine and Health Technology, FI-331014, University of Tampere, Finland.

Drosophila melanogaster, like most animal species, displays considerable genetic variation in both nuclear and mitochondrial DNA (mtDNA). Here we tested whether any of four natural mtDNA variants was able to modify the effect of the phenotypically mild, nuclear tko25t mutation, affecting mitochondrial protein synthesis. When combined with tko25t, the mtDNA from wild strain KSA2 produced pupal lethality, accompanied by the presence of melanotic nodules in L3 larvae. Read More

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Humans and Chimpanzees Display Opposite Patterns of Diversity in Arylamine N-Acetyltransferase Genes.

G3 (Bethesda) 2019 Jul;9(7):2199-2224

Department of Genetics and Evolution, Anthropology Unit, University of Geneva, Switzerland.

Among the many genes involved in the metabolism of therapeutic drugs, human arylamine N-acetyltransferases (NATs) genes have been extensively studied, due to their medical importance both in pharmacogenetics and disease epidemiology. One member of this small gene family, NAT2, is established as the locus of the classic human acetylation polymorphism in drug metabolism. Current hypotheses hold that selective processes favoring haplotypes conferring lower NAT2 activity have been operating in modern humans' recent history as an adaptation to local chemical and dietary environments. Read More

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Sequencing of a Wild Apple (Malus baccata) Genome Unravels the Differences Between Cultivated and Wild Apple Species Regarding Disease Resistance and Cold Tolerance.

G3 (Bethesda) 2019 Jul;9(7):2051-2060

College of Life Sciences, Northwest A&F University, Yangling 712100, Shannxi, China.

Malus baccata is one of four wild apple species that can hybridize with the cultivated apple species (Malus domestica). It is widely used in high-latitude apple-producing areas as a rootstock and breeding resource because of its disease resistance, and cold tolerance. A lack of a reference genome has limited the application of M. Read More

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Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas.

G3 (Bethesda) 2019 Jul;9(7):2267-2276

Physiological Chemistry, Biocenter, University of Wuerzburg, 97074 Wuerzburg, Germany.

Small aquarium fish models provide useful systems not only for a better understanding of the molecular basis of many human diseases, but also for first-line screening to identify new drug candidates. For testing new chemical substances, current strategies mostly rely on easy to perform and efficient embryonic screens. Cancer, however, is a disease that develops mainly during juvenile and adult stage. Read More

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Prevalence, predictors, and outcomes of clonal hematopoiesis in individuals aged ≥80 years.

Blood Adv 2021 Apr;5(8):2115-2122

Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Clonal hematopoiesis (CH), characterized by a fraction of peripheral blood cells carrying an acquired genetic variant, emerges with age. Although in general CH is associated with increased mortality and morbidity, no higher risk of death was observed for individuals ≥80 years. Here, we investigated CH in 621 individuals aged ≥80 years from the population-based LifeLines cohort. Read More

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COVID-19 Vaccine Concerns: Fact or Fiction?

Antoine Barbari

Exp Clin Transplant 2021 Mar 31. Epub 2021 Mar 31.

From the Rafik Hariri University Hospital, Bir Hassan, Beirut, Lebanon.

One year has elapsed since a team of Chinese scientists reported the first case of COVID-19 in Wuhan, China on January 8, 2020, after sequencing the first viral genetic material. Since then, many vaccines were rushed into testing, bypassing animal experimentations, with more than 200 pharma companies in different countries declaring the development of different vaccines, each with their own strategy for generating immunity, despite the arguments of many infectious disease experts that 18 months for a first vaccine is an incredibly aggressive schedule because it takes an average of 10 years to develop a vaccine. Ten vaccine candidates have already entered phase 3 clinical trials in humans. Read More

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Physiopathology of late-onset fetal growth restriction.

Minerva Obstet Gynecol 2021 Apr 20. Epub 2021 Apr 20.

Department of Obstetrics, Paulista School of Medicine - Federal University of São Paulo (EPM-UNIFESP), São Paulo-SP, Brazil.

Fetal growth restriction (FGR) is defined as the inability of the fetus to reach its potential for genetic determination. FGR can have several causes, including genetic syndromes, chromosomal diseases, and infections; however, a vast majority of cases are probably attributed to impaired uterine and placental circulation. The relationships between abnormal placental development and FGR are complex, and studies are generally few, presenting confounding factors. Read More

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UNC13B variants associated with partial epilepsy with favourable outcome.

Brain 2021 Apr 20. Epub 2021 Apr 20.

Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), that is highly expressed in the brain-predominantly in the cerebral cortex-and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of UNC13B mutation in human disease is not known. In this study we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. Read More

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Expression of tissue factor and thrombomodulin in the placentas of pregnancies affected by early-onset and late-onset preeclampsia.

J Obstet Gynaecol Res 2021 Apr 19. Epub 2021 Apr 19.

Department of Pathology. Faculty of Medicine, Pontificia Universidad Javeriana, Hospital Universitario San Ignacio, Bogotá, Colombia.

Aim: To analyze the differential genetic expression and protein localization of thrombomodulin (THBD) and tissue factor (F3) in the placentas of pregnancies affected by preeclampsia.

Methods: We assessed the expression of THBD and F3 by immunohistochemistry and real-time polymerase chain reaction (PCR) in placentas from 20 PE cases: 10 early-onset PE placentas, 10 late-onset PE placentas, and 10 control cases (normal pregnancies).

Results: In cases, we found higher THBD and F3 RNA levels in placental tissue. Read More

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Universal access to genetic counseling for women with epithelial ovarian cancer in Nova Scotia: Evaluating a new collaborative care model.

J Genet Couns 2021 Apr 19. Epub 2021 Apr 19.

Division of Gynaecologic Oncology, Dalhousie University, Halifax, NS, Canada.

Women with pathogenic variants in BRCA1/2 have a significantly increased lifetime risk of breast and ovarian cancers. The availability of genetic testing to identify BRCA1/2 carriers is imperative to disease prevention and treatment. We evaluated the effectiveness of a new collaborative care model in Nova Scotia, involving the integration of genetic counselors into tumor board rounds, reduction in time allotted for initial genetic counseling appointments from 60 to 45 min, and a standardized dictation template, to increase referral rate for genetic counseling. Read More

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