77,321 results match your criteria variants genes


Systematic interrogation of mutation groupings reveals divergent downstream expression programs within key cancer genes.

BMC Bioinformatics 2021 May 6;22(1):233. Epub 2021 May 6.

Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.

Background: Genes implicated in tumorigenesis often exhibit diverse sets of genomic variants in the tumor cohorts within which they are frequently mutated. For many genes, neither the transcriptomic effects of these variants nor their relationship to one another in cancer processes have been well-characterized. We sought to identify the downstream expression effects of these mutations and to determine whether this heterogeneity at the genomic level is reflected in a corresponding heterogeneity at the transcriptomic level. Read More

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First report of a bla metallo-β-lactamase-possessing Klebsiella michiganensis.

J Glob Antimicrob Resist 2021 May 3. Epub 2021 May 3.

Institute for Infectious Diseases (IFIK), University of Bern. Electronic address:

Background: Klebsiella michiganensis is an emerging pathogen. As for Klebsiella pneumoniae, this species is able to acquire antibiotic resistance genes (ARGs) via mobile genetic elements. In this context, K. Read More

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Diagnostic Yield of Whole Exome Sequencing for Adults with Ataxia: a Brazilian Perspective.

Cerebellum 2021 May 6. Epub 2021 May 6.

Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126. Cidade Universitária "Zeferino Vaz", Campinas, SP, 13083-887, Brazil.

Previous studies using whole exome sequencing (WES) have shown that a significant proportion of adult patients with undiagnosed ataxia in European and North American cohorts have a known genetic cause. Little is known about the diagnostic yield of WES in non-Caucasian ataxic populations. Herein, we used WES to investigate a Brazilian cohort of 76 adult patients with idiopathic ataxia previously screened for trinucleotide expansions in known ataxia genes. Read More

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Group B Streptococcus chimeric capsular polysaccharides as novel multivalent vaccine candidates.

Glycoconj J 2021 May 6. Epub 2021 May 6.

GSK, Siena, Italy.

The capsular polysaccharide of the human pathogen Group B Streptococcus is a key virulence factor and vaccine candidate that induces protective antibodies when conjugated to carrier proteins. It consists of long polymeric chains of oligosaccharide repeating units, and each of the ten capsular serotypes described so far presents a unique chemical structure with distinct antigenic properties; therefore, broad protection against this pathogen could be achieved by a combination of ten glycoconjugates. Capsular polysaccharide biosynthesis and assembly follow a polymerase-dependent pathway that is widespread in encapsulated bacteria and is encoded by a polycistronic operon. Read More

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BRASSINOSTEROID-SIGNALLING KINASES 7 and 8 associate with the FLS2 immune receptor and are required for flg22-induced PTI responses.

Mol Plant Pathol 2021 May 6. Epub 2021 May 6.

School of Plant Sciences and Food Security, Tel-Aviv University, Tel-Aviv, Israel.

Pattern-triggered immunity (PTI) is typically initiated in plants by recognition of pathogen- or damage-associated molecular patterns (PAMP/DAMPs) by cell surface-localized pattern recognition receptors (PRRs). Here, we investigated the role in PTI of Arabidopsis thaliana brassinosteroid-signalling kinases 7 and 8 (BSK7 and BSK8), which are members of the receptor-like cytoplasmic kinase subfamily XII. BSK7 and BSK8 localized to the plant cell periphery and interacted in yeast and in planta with FLS2, but not with other PRRs. Read More

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Polymorphisms in eicosanoid-related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti-inflammatory drug hypersensitivity.

Br J Dermatol 2021 May 6. Epub 2021 May 6.

Allergy Research Group, Instituto de Investigación Biomédica de Málaga-IBIMA, ARADyAL, Malaga, Spain.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs), probably the most consumed medicines, are the main triggers of drug hypersensitivity, being NSAID-induced acute urticaria/angioedema (NIUA) the most frequent phenotype. NSAID-hypersensitivity is bred by cyclooxygenase (COX)-1 inhibition, which leads to an imbalance in prostaglandin (PG) and cysteinyl-leukotriene (CysLT) synthesis. As only susceptible individuals develop NSAID-hypersensitivity, genetic factors are believed to participate; however, no study has assessed the overall genetic variability of key enzymes in PG and CysLT synthesis in NSAID-hypersensitivity. Read More

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An update on genetic basis of generalized pustular psoriasis (Review).

Int J Mol Med 2021 Jun 6;47(6). Epub 2021 May 6.

Department of Laboratory Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.

Generalized pustular psoriasis (GPP) is a rare and severe auto‑inflammatory skin disease that is characterized by recurrent, acute onset, and generalized pustular eruptions on erythematous, inflamed skin. GPP is traditionally classified as a variant of psoriasis vulgaris, even though recent clinical, histological and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, variants of , , and genes have been identified as causative or contributing to genetic defects in a proportion of patients affected by GPP. Read More

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Metabolic source isotopic pair labeling and genome-wide association are complementary tools for the identification of metabolite-gene associations in plants.

Plant Cell 2021 May;33(3):492-510

Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.

The optimal extraction of information from untargeted metabolomics analyses is a continuing challenge. Here, we describe an approach that combines stable isotope labeling, liquid chromatography- mass spectrometry (LC-MS), and a computational pipeline to automatically identify metabolites produced from a selected metabolic precursor. We identified the subset of the soluble metabolome generated from phenylalanine (Phe) in Arabidopsis thaliana, which we refer to as the Phe-derived metabolome (FDM) In addition to identifying Phe-derived metabolites present in a single wild-type reference accession, the FDM was established in nine enzymatic and regulatory mutants in the phenylpropanoid pathway. Read More

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Evaluation of the Association of Polymorphisms With Palbociclib-Induced Neutropenia: Pharmacogenetic Analysis of PALOMA-2/-3.

Oncologist 2021 May 5. Epub 2021 May 5.

Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Background: The most frequently reported treatment-related adverse event in clinical trials with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib is neutropenia. Allelic variants in ABCB1 and ERCC1 might be associated with early occurrence (ie, end of Week 2 treatment) of grade 3/4 neutropenia. Pharmacogenetic analyses were performed to uncover associations between single nucleotide polymorphisms (SNPs) in these genes, patient baseline characteristics, and early occurrence of grade 3/4 neutropenia. Read More

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Molecular Diagnosis of Inherited Cardiac Diseases in the Era of Next-Generation Sequencing: A Single Center's Experience Over 5 Years.

Mol Diagn Ther 2021 May 5. Epub 2021 May 5.

Laboratoire de Cardiogénétique Moléculaire, Centre de Biologie et Pathologie Est, Hospices Civils de Lyon, Bron Cedex, 69677, Lyon, France.

Background And Objective: Molecular diagnosis in inherited cardiac diseases is challenging because of the significant genetic and clinical heterogeneity. We present a detailed molecular investigation of a cohort of 4185 patients with referrals for inherited cardiac diseases.

Methods: Patients suffering from cardiomyopathies (3235 probands), arrhythmia syndromes (760 probands), or unexplained sudden cardiac arrest (190 cases) were analyzed using a next-generation sequencing (NGS) workflow based on a panel of 105 genes involved in sudden cardiac death. Read More

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Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients with RAG1/2 Mutations: First Cases Series from Mexico and Description of Two Novel Mutations.

J Clin Immunol 2021 May 5. Epub 2021 May 5.

Facultad de Medicina, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico.

Mutations in recombinase activating genes 1 and 2 (RAG1/2) result in human severe combined immunodeficiency (SCID). The products of these genes are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Mutations resulting in null-recombination activity in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with hypomorphic mutations may develop leaky SCID, including Omenn syndrome (OS). Read More

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Comparison of the Full Distribution of Fitness Effects of New Amino Acid Mutations Across Great Apes.

Genetics 2019 Nov;213(3):953-966

Bioinformatics Research Centre, Aarhus University, DK-8000 Aarhus C, Denmark.

Castellano et al. provide the first comparison of the full distribution of fitness effects (including deleterious, neutral but also beneficial mutations) in the great apes. The authors investigate which aspects of the full DFE are likely. Read More

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November 2019

Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains.

Genetics 2019 Nov;213(3):1079-1092

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.

To identify genes involved in cerebral infarction, we have employed a forward genetic approach in inbred mouse strains, using quantitative trait loci (QTL) mapping for cerebral infarct volume after middle cerebral artery occlusion. We had previously observed that infarct volume is inversely correlated with cerebral collateral vessel density in most strains. In this study, we expanded the pool of allelic variation among classical inbred mouse strains by utilizing the eight founder strains of the Collaborative Cross and found a wild-derived strain, WSB/EiJ, that breaks this general rule that collateral vessel density inversely correlates with infarct volume. Read More

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November 2019

Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains.

Genetics 2019 Nov;213(3):1079-1092

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.

To identify genes involved in cerebral infarction, we have employed a forward genetic approach in inbred mouse strains, using quantitative trait loci (QTL) mapping for cerebral infarct volume after middle cerebral artery occlusion. We had previously observed that infarct volume is inversely correlated with cerebral collateral vessel density in most strains. In this study, we expanded the pool of allelic variation among classical inbred mouse strains by utilizing the eight founder strains of the Collaborative Cross and found a wild-derived strain, WSB/EiJ, that breaks this general rule that collateral vessel density inversely correlates with infarct volume. Read More

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November 2019

Comparison of the Full Distribution of Fitness Effects of New Amino Acid Mutations Across Great Apes.

Genetics 2019 Nov;213(3):953-966

Bioinformatics Research Centre, Aarhus University, DK-8000 Aarhus C, Denmark.

Castellano et al. provide the first comparison of the full distribution of fitness effects (including deleterious, neutral but also beneficial mutations) in the great apes. The authors investigate which aspects of the full DFE are likely. Read More

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November 2019

Genetic Architecture Modulates Diet-Induced Hepatic mRNA and miRNA Expression Profiles in Diversity Outbred Mice.

Genetics 2020 Sep;216(1):241-259

Western Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture, Davis, California 95616.

Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression. Read More

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September 2020

Genetic Signatures of Drug Response Variability in Drosophila melanogaster.

Genetics 2019 Oct;213(2):633-650

Section for Biology and Environmental Science, Department of Chemistry and Bioscience, Aalborg University, 9220, Denmark.

Individuals may respond differently to the same medical treatment because of genetic differences. Such genetic control constitutes both a challenge and an opportunity for improved effectiveness of medical treatment: a challenge because patients with the same diagnosis respond.. Read More

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October 2019

Interpreting Coronary Artery Disease Risk Through Gene-Environment Interactions in Gene Regulation.

Genetics 2019 Oct;213(2):651-663

Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Epidemiological and genome-wide association studies have identified environmental and genetic risk factors for CVD. Using human vascular endothelial cells treated with dexamethasone, retinoic acid, caffeine, and selenium. Read More

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October 2019

Interpreting Coronary Artery Disease Risk Through Gene-Environment Interactions in Gene Regulation.

Genetics 2019 Oct;213(2):651-663

Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan 48201.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Epidemiological and genome-wide association studies have identified environmental and genetic risk factors for CVD. Using human vascular endothelial cells treated with dexamethasone, retinoic acid, caffeine, and selenium. Read More

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October 2019

Genetic Signatures of Drug Response Variability in Drosophila melanogaster.

Genetics 2019 Oct;213(2):633-650

Section for Biology and Environmental Science, Department of Chemistry and Bioscience, Aalborg University, 9220, Denmark.

Individuals may respond differently to the same medical treatment because of genetic differences. Such genetic control constitutes both a challenge and an opportunity for improved effectiveness of medical treatment: a challenge because patients with the same diagnosis respond.. Read More

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October 2019

Inferring the Nature of Missing Heritability in Human Traits Using Data from the GWAS Catalog.

Genetics 2019 Jul;212(3):891-904

Departamento de Bioquímica, Genética e Inmunología, Universidade de Vigo, 36310, Spain.

Here, López-Cortegano and Caballero carried out a meta-analysis using records from a database of genome-wide studies in order to investigate the nature of missing heritability in humans... Read More

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Comprehensive Multiple eQTL Detection and Its Application to GWAS Interpretation.

Genetics 2019 Jul;212(3):905-918

School of Biological Sciences and Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, Georgia 30332.

Expression QTL (eQTL) detection has emerged as an important tool for unraveling the relationship between genetic risk factors and disease or clinical phenotypes. Most studies are predicated on the assumption that only a single causal variant explains the association signal in each interval. This greatly simplifies the statistical modeling, but is liable to biases in scenarios where multiple local causal-variants are responsible. Read More

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Comprehensive Multiple eQTL Detection and Its Application to GWAS Interpretation.

Genetics 2019 Jul;212(3):905-918

School of Biological Sciences and Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, Georgia 30332.

Expression QTL (eQTL) detection has emerged as an important tool for unraveling the relationship between genetic risk factors and disease or clinical phenotypes. Most studies are predicated on the assumption that only a single causal variant explains the association signal in each interval. This greatly simplifies the statistical modeling, but is liable to biases in scenarios where multiple local causal-variants are responsible. Read More

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Inferring the Nature of Missing Heritability in Human Traits Using Data from the GWAS Catalog.

Genetics 2019 Jul;212(3):891-904

Departamento de Bioquímica, Genética e Inmunología, Universidade de Vigo, 36310, Spain.

Here, López-Cortegano and Caballero carried out a meta-analysis using records from a database of genome-wide studies in order to investigate the nature of missing heritability in humans... Read More

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Binding and Regulation of Transcription by Yeast Ste12 Variants To Drive Mating and Invasion Phenotypes.

Genetics 2020 Feb;214(2):397-407

Department of Genome Sciences, University of Washington, Seattle, Washington 98195.

Here, Zhou et al. took advantage of Saccharomyces cerevisiae and its well-characterized mating and invasion pathways to explain how transcription factor variants alter motif recognition and gene expression, and ultimately, organismal phenotypes.. Read More

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February 2020

Pathogen Genetic Control of Transcriptome Variation in the Arabidopsis thaliana - Botrytis cinerea Pathosystem.

Genetics 2020 May;215(1):253-266

Department of Plant Sciences, University of California, Davis, California 95616.

Disease arises from the interaction of two genomes, host and pathogen genomes. To highlight these genomic interactions, Soltis et al. performed genome-wide association (GWA) based on genetic variation in the pathogen. Read More

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The Association of Polymorphisms in and Genes Involved in Redox Homeostasis in the Development and Progression of Clear Cell Renal Cell Carcinoma.

Oxid Med Cell Longev 2021 17;2021:6617969. Epub 2021 Apr 17.

Institute of Medical and Clinical Biochemistry, 11000, Serbia.

Deleterious effects of SNPs found in genes encoding transcriptional factors, as well as antioxidant and detoxification enzymes, are disputable; however, their functional significance seems to modify the risk for clear cell renal cell carcinoma (ccRCC) development and progression. We investigated the effect of specific , , gene variants and haplotype on ccRCC risk and prognosis and evaluated the association between GSTP1 and regulatory (JNK1/2) and executor (caspase-3) apoptotic molecule expression in ccRCC tissue samples and the presence of GSTP1 : JNK1/2 protein : protein interactions. Genotyping was performed in 223 ccRCC patients and 336 matched controls by PCR-CTTP and qPCR. Read More

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Genetic Predictors of Mortality in Patients with Multiple Myeloma.

Appl Clin Genet 2021 29;14:241-254. Epub 2021 Apr 29.

Department of Hematology and Medical Oncology, Boston University Medical Center, Boston, MA, USA.

Multiple myeloma (MM) is a heterogeneous disease featured by clonal plasma cell proliferation and genomic instability. The advent of next-generation sequencing allowed unraveling the complex genomic landscape of the disease. Several recurrent genomic aberrations including immunoglobulin genes translocations, copy number abnormalities, complex chromosomal events, transcriptomic and epigenomic deregulation, and mutations define various molecular subgroups with distinct outcomes. Read More

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A high-quality bonobo genome refines the analysis of hominid evolution.

Nature 2021 May 5. Epub 2021 May 5.

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.

The divergence of chimpanzee and bonobo provides one of the few examples of recent hominid speciation. Here we describe a fully annotated, high-quality bonobo genome assembly, which was constructed without guidance from reference genomes by applying a multiplatform genomics approach. We generate a bonobo genome assembly in which more than 98% of genes are completely annotated and 99% of the gaps are closed, including the resolution of about half of the segmental duplications and almost all of the full-length mobile elements. Read More

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Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas.

Leukemia 2021 May 5. Epub 2021 May 5.

University of Duesseldorf, Medical Faculty, Department of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Düsseldorf, Germany.

B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR. Read More

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