7,826 results match your criteria PLoS Genetics [Journal]


CD34 defines melanocyte stem cell subpopulations with distinct regenerative properties.

PLoS Genet 2019 Apr 24;15(4):e1008034. Epub 2019 Apr 24.

Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.

Melanocyte stem cells (McSCs) are the undifferentiated melanocytic cells of the mammalian hair follicle (HF) responsible for recurrent generation of a large number of differentiated melanocytes during each HF cycle. HF McSCs reside in both the CD34+ bulge/lower permanent portion (LPP) and the CD34- secondary hair germ (SHG) regions of the HF during telogen. Using Dct-H2BGFP mice, we separate bulge/LPP and SHG McSCs using FACS with GFP and anti-CD34 to show that these two subsets of McSCs are functionally distinct. Read More

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http://dx.plos.org/10.1371/journal.pgen.1008034
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April 2019
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Infection mechanisms and putative effector repertoire of the mosquito pathogenic oomycete Pythium guiyangense uncovered by genomic analysis.

PLoS Genet 2019 Apr 24;15(4):e1008116. Epub 2019 Apr 24.

College of Plant Protection, Nanjing Agricultural University, Nanjing, China.

Pythium guiyangense, an oomycete from a genus of mostly plant pathogens, is an effective biological control agent that has wide potential to manage diverse mosquitoes. However, its mosquito-killing mechanisms are almost unknown. In this study, we observed that P. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008116DOI Listing

The Noonan Syndrome-linked Raf1L613V mutation drives increased glial number in the mouse cortex and enhanced learning.

PLoS Genet 2019 Apr 24;15(4):e1008108. Epub 2019 Apr 24.

School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America.

RASopathies are a family of related syndromes caused by mutations in regulators of the RAS/Extracellular Regulated Kinase 1/2 (ERK1/2) signaling cascade that often result in neurological deficits. RASopathy mutations in upstream regulatory components, such as NF1, PTPN11/SHP2, and RAS have been well-characterized, but mutation-specific differences in the pathogenesis of nervous system abnormalities remain poorly understood, especially those involving mutations downstream of RAS. Here, we assessed cellular and behavioral phenotypes in mice expressing a Raf1L613V gain-of-function mutation associated with the RASopathy, Noonan Syndrome. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008108DOI Listing

Destabilization of chromosome structure by histone H3 lysine 27 methylation.

PLoS Genet 2019 Apr 22;15(4):e1008093. Epub 2019 Apr 22.

Environmental Genomics, Christian-Albrechts University, Kiel, Germany.

Chromosome and genome stability are important for normal cell function as instability often correlates with disease and dysfunction of DNA repair mechanisms. Many organisms maintain supernumerary or accessory chromosomes that deviate from standard chromosomes. The pathogenic fungus Zymoseptoria tritici has as many as eight accessory chromosomes, which are highly unstable during meiosis and mitosis, transcriptionally repressed, show enrichment of repetitive elements, and enrichment with heterochromatic histone methylation marks, e. Read More

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http://dx.plos.org/10.1371/journal.pgen.1008093
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April 2019
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Osmolyte accumulation regulates the SUMOylation and inclusion dynamics of the prionogenic Cyc8-Tup1 transcription corepressor.

PLoS Genet 2019 Apr 22;15(4):e1008115. Epub 2019 Apr 22.

Department of Pharmacology, University of Washington, Seattle, WA, United States of America.

Environmental stressors can severely perturb cellular homeostasis and compromise viability. To cope with environmental stressors, eukaryotes have developed distinct signaling programs that allow for adaptation during different stress conditions. These programs often require a host of post-translational modifications that alter proteins to elicit appropriate cellular responses. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008115DOI Listing

The complex genetic architecture of shoot growth natural variation in Arabidopsis thaliana.

PLoS Genet 2019 Apr 22;15(4):e1007954. Epub 2019 Apr 22.

Institut Jean-Pierre Bourgin, INRA, AgroParisTech, CNRS, Université Paris-Saclay, 78000, Versailles, France.

One of the main outcomes of quantitative genetics approaches to natural variation is to reveal the genetic architecture underlying the phenotypic space. Complex genetic architectures are described as including numerous loci (or alleles) with small-effect and/or low-frequency in the populations, interactions with the genetic background, environment or age. Linkage or association mapping strategies will be more or less sensitive to this complexity, so that we still have an unclear picture of its extent. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007954DOI Listing

A small RNA controls bacterial sensitivity to gentamicin during iron starvation.

PLoS Genet 2019 Apr 22;15(4):e1008078. Epub 2019 Apr 22.

Aix Marseille Univ-CNRS, UMR 7243, Laboratoire de Chimie Bactérienne, Institut de Microbiologie de la Méditerranée, Marseille, France.

Phenotypic resistance describes a bacterial population that becomes transiently resistant to an antibiotic without requiring a genetic change. We here investigated the role of the small regulatory RNA (sRNA) RyhB, a key contributor to iron homeostasis, in the phenotypic resistance of Escherichia coli to various classes of antibiotics. We found that RyhB induces phenotypic resistance to gentamicin, an aminoglycoside that targets the ribosome, when iron is scarce. Read More

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http://dx.plos.org/10.1371/journal.pgen.1008078
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April 2019
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Expression estimation and eQTL mapping for HLA genes with a personalized pipeline.

PLoS Genet 2019 Apr 22;15(4):e1008091. Epub 2019 Apr 22.

Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.

The HLA (Human Leukocyte Antigens) genes are well-documented targets of balancing selection, and variation at these loci is associated with many disease phenotypes. Variation in expression levels also influences disease susceptibility and resistance, but little information exists about the regulation and population-level patterns of expression. This results from the difficulty in mapping short reads originated from these highly polymorphic loci, and in accounting for the existence of several paralogues. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008091DOI Listing
April 2019
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Discovery and characterization of variance QTLs in human induced pluripotent stem cells.

PLoS Genet 2019 Apr 19;15(4):e1008045. Epub 2019 Apr 19.

Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America.

Quantification of gene expression levels at the single cell level has revealed that gene expression can vary substantially even across a population of homogeneous cells. However, it is currently unclear what genomic features control variation in gene expression levels, and whether common genetic variants may impact gene expression variation. Here, we take a genome-wide approach to identify expression variance quantitative trait loci (vQTLs). Read More

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http://dx.plos.org/10.1371/journal.pgen.1008045
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April 2019
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Varicose veins of lower extremities: Insights from the first large-scale genetic study.

PLoS Genet 2019 Apr 18;15(4):e1008110. Epub 2019 Apr 18.

Laboratory of Theoretical and Applied Functional Genomics, Novosibirsk State University, Novosibirsk, Russia.

Varicose veins of lower extremities (VVs) are a common multifactorial vascular disease. Genetic factors underlying VVs development remain largely unknown. Here we report the first large-scale study of VVs performed on a freely available genetic data of 408,455 European-ancestry individuals. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008110DOI Listing
April 2019
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Ribosomal RNA gene repeats associate with the nuclear pore complex for maintenance after DNA damage.

PLoS Genet 2019 Apr 18;15(4):e1008103. Epub 2019 Apr 18.

Laboratory of Genome Regeneration, Institute for Quantitative Biosciences (IQB), Bunkyo-ku, Japan.

The ribosomal RNA genes (rDNA) comprise a highly repetitive gene cluster. The copy number of genes at this locus can readily change and is therefore one of the most unstable regions of the genome. DNA damage in rDNA occurs after binding of the replication fork blocking protein Fob1 in S phase, which triggers unequal sister chromatid recombination. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008103DOI Listing
April 2019
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A stress-response-related inter-compartmental signalling pathway regulates embryonic cuticle integrity in Arabidopsis.

PLoS Genet 2019 Apr 18;15(4):e1007847. Epub 2019 Apr 18.

Laboratoire Reproduction et Développement des Plantes, Univ Lyon, ENS de Lyon, CNRS, INRA, Lyon, France.

The embryonic cuticle is necessary for normal seed development and seedling establishment in Arabidopsis. Although mutants with defective embryonic cuticles have been identified, neither the deposition of cuticle material, nor its regulation, has been described during embryogenesis. Here we use electron microscopy, cuticle staining and permeability assays to show that cuticle deposition initiates de novo in patches on globular embryos. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007847DOI Listing

Schwann cells ER-associated degradation contributes to myelin maintenance in adult nerves and limits demyelination in CMT1B mice.

PLoS Genet 2019 Apr 17;15(4):e1008069. Epub 2019 Apr 17.

Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

In the peripheral nervous system (PNS) myelinating Schwann cells synthesize large amounts of myelin protein zero (P0) glycoprotein, an abundant component of peripheral nerve myelin. In humans, mutations in P0 cause the demyelinating Charcot-Marie-Tooth 1B (CMT1B) neuropathy, one of the most diffused genetic disorders of the PNS. We previously showed that several mutations, such as the deletion of serine 63 (P0-S63del), result in misfolding and accumulation of P0 in the endoplasmic reticulum (ER), with activation of the unfolded protein response (UPR). Read More

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http://dx.plos.org/10.1371/journal.pgen.1008069
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April 2019
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Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.

PLoS Genet 2019 Apr 16;15(4):e1007739. Epub 2019 Apr 16.

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, United States of America.

Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007739DOI Listing
April 2019
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Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae.

PLoS Genet 2019 Apr 15;15(4):e1008114. Epub 2019 Apr 15.

Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia.

Klebsiella pneumoniae has emerged as an important cause of two distinct public health threats: multi-drug resistant (MDR) healthcare-associated infections and drug susceptible community-acquired invasive infections. These pathotypes are generally associated with two distinct subsets of K. pneumoniae lineages or 'clones' that are distinguished by the presence of acquired resistance genes and several key virulence loci. Read More

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http://dx.plos.org/10.1371/journal.pgen.1008114
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April 2019
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Correction: Genetic variants influence on the placenta regulatory landscape.

PLoS Genet 2019 Apr 12;15(4):e1008118. Epub 2019 Apr 12.

[This corrects the article DOI: 10.1371/journal.pgen. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008118DOI Listing

FOXO3 directly regulates an autophagy network to functionally regulate proteostasis in adult neural stem cells.

PLoS Genet 2019 Apr 11;15(4):e1008097. Epub 2019 Apr 11.

Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island, United States of America.

Maintenance of a healthy proteome is essential for cellular homeostasis and loss of proteostasis is associated with tissue dysfunction and neurodegenerative disease. The mechanisms that support proteostasis in healthy cells and how they become defective during aging or in disease states are not fully understood. Here, we investigate the transcriptional programs that are essential for neural stem and progenitor cell (NSPC) function and uncover a program of autophagy genes under the control of the transcription factor FOXO3. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008097DOI Listing

Somatic LINE-1 retrotransposition in cortical neurons and non-brain tissues of Rett patients and healthy individuals.

PLoS Genet 2019 Apr 11;15(4):e1008043. Epub 2019 Apr 11.

Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Mounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism in the brain and other somatic tissues of an individual. However, the genomic distribution of somatic human-specific LINE-1 (L1Hs) insertions and their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 somatic insertions from 20 postmortem tissues from five Rett patients and their matched healthy controls. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008043DOI Listing

Loss of atrx cooperates with p53-deficiency to promote the development of sarcomas and other malignancies.

PLoS Genet 2019 Apr 10;15(4):e1008039. Epub 2019 Apr 10.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States of America.

The SWI/SNF-family chromatin remodeling protein ATRX is a tumor suppressor in sarcomas, gliomas and other malignancies. Its loss of function facilitates the alternative lengthening of telomeres (ALT) pathway in tumor cells, while it also affects Polycomb repressive complex 2 (PRC2) silencing of its target genes. To further define the role of inactivating ATRX mutations in carcinogenesis, we knocked out atrx in our previously reported p53/nf1-deficient zebrafish line that develops malignant peripheral nerve sheath tumors and gliomas. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008039DOI Listing
April 2019
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The H3K27me3 demethylase REF6 promotes leaf senescence through directly activating major senescence regulatory and functional genes in Arabidopsis.

PLoS Genet 2019 Apr 10;15(4):e1008068. Epub 2019 Apr 10.

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

The roles of histone demethylation in the regulation of plant flowering, disease resistance, rhythmical response, and seed germination have been elucidated recently; however, how histone demethylation affects leaf senescence remains largely unclear. In this study, we exploited yeast one-hybrid (Y1H) to screen for the upstream regulators of NONYELLOWING1 (NYE1), and identified RELATIVE OF EARLY FLOWERING6 (REF6), a histone H3 lysine 27 tri-methylation (H3K27me3) demethylase, as a putative binding protein of NYE1 promoter. By in vivo and in vitro analyses, we demonstrated that REF6 directly binds to the motif CTCGYTY in NYE1/2 promoters through its zinc finger domain and positively regulates their expression. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008068DOI Listing

Novel AU-rich proximal UTR sequences (APS) enhance CXCL8 synthesis upon the induction of rpS6 phosphorylation.

PLoS Genet 2019 Apr 10;15(4):e1008077. Epub 2019 Apr 10.

Department of Biological Sciences, National University of Singapore, Singapore.

The role of ribosomal protein S6 (rpS6) phosphorylation in mRNA translation remains poorly understood. Here, we reveal a potential role in modulating the translation rate of chemokine (C-X-C motif) ligand 8 (CXCL8 or Interleukin 8, IL8). We observed that more CXCL8 protein was being secreted from less CXCL8 mRNA in primary macrophages and macrophage-like HL-60 cells relative to other cell types. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008077DOI Listing

An experimental assay of the interactions of amino acids from orthologous sequences shaping a complex fitness landscape.

PLoS Genet 2019 Apr 10;15(4):e1008079. Epub 2019 Apr 10.

Institute of Science and Technology Austria, Am Campus 1, Klosterneuburg, Austria.

Characterizing the fitness landscape, a representation of fitness for a large set of genotypes, is key to understanding how genetic information is interpreted to create functional organisms. Here we determined the evolutionarily-relevant segment of the fitness landscape of His3, a gene coding for an enzyme in the histidine synthesis pathway, focusing on combinations of amino acid states found at orthologous sites of extant species. Just 15% of amino acids found in yeast His3 orthologues were always neutral while the impact on fitness of the remaining 85% depended on the genetic background. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008079DOI Listing

Precise staging of beetle horn formation in Trypoxylus dichotomus reveals the pleiotropic roles of doublesex depending on the spatiotemporal developmental contexts.

PLoS Genet 2019 Apr 10;15(4):e1008063. Epub 2019 Apr 10.

Division of Evolutionary Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Japan.

Many scarab beetles have sexually dimorphic exaggerated horns that are an evolutionary novelty. Since the shape, number, size, and location of horns are highly diverged within Scarabaeidae, beetle horns are an attractive model for studying the evolution of sexually dimorphic and novel traits. In beetles including the Japanese rhinoceros beetle Trypoxylus dichotomus, the sex differentiation gene doublesex (dsx) plays a crucial role in sexually dimorphic horn formation during larval-pupal development. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008063DOI Listing

Temporal and spatial regulation of protein cross-linking by the pre-assembled substrates of a Bacillus subtilis spore coat transglutaminase.

PLoS Genet 2019 Apr 8;15(4):e1007912. Epub 2019 Apr 8.

Microbial Development Group, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, ITQB-NOVA, Oeiras, Portugal.

In many cases protein assemblies are stabilized by covalent bonds, one example of which is the formation of intra- or intermolecular ε-(γ-glutamyl)lysil cross-links catalyzed by transglutaminases (TGases). Because of the potential for unwanted cross-linking reactions, the activities of many TGases have been shown to be tightly controlled. Bacterial endospores are highly resilient cells in part because they are surrounded by a complex protein coat. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007912DOI Listing
April 2019
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Reverse GWAS: Using genetics to identify and model phenotypic subtypes.

PLoS Genet 2019 Apr 5;15(4):e1008009. Epub 2019 Apr 5.

Department of Medicine, UCSF, San Francisco, California, United States of America.

Recent and classical work has revealed biologically and medically significant subtypes in complex diseases and traits. However, relevant subtypes are often unknown, unmeasured, or actively debated, making automated statistical approaches to subtype definition valuable. We propose reverse GWAS (RGWAS) to identify and validate subtypes using genetics and multiple traits: while GWAS seeks the genetic basis of a given trait, RGWAS seeks to define trait subtypes with distinct genetic bases. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008009DOI Listing
April 2019
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Floral regulators FLC and SOC1 directly regulate expression of the B3-type transcription factor TARGET OF FLC AND SVP 1 at the Arabidopsis shoot apex via antagonistic chromatin modifications.

PLoS Genet 2019 Apr 4;15(4):e1008065. Epub 2019 Apr 4.

Department of Plant Developmental Biology, Max-Planck-Institute for Plant Breeding, Cologne, Germany.

Integration of environmental and endogenous cues at plant shoot meristems determines the timing of flowering and reproductive development. The MADS box transcription factor FLOWERING LOCUS C (FLC) of Arabidopsis thaliana is an important repressor of floral transition, which blocks flowering until plants are exposed to winter cold. However, the target genes of FLC have not been thoroughly described, and our understanding of the mechanisms by which FLC represses transcription of these targets and how this repression is overcome during floral transition is still fragmentary. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008065DOI Listing
April 2019
3 Reads

DSB structure impacts DNA recombination leading to class switching and chromosomal translocations in human B cells.

PLoS Genet 2019 Apr 4;15(4):e1008101. Epub 2019 Apr 4.

Department of Immunology, University of Toronto, Toronto, Ontario, Canada.

Class switch recombination (CSR) requires activation-induced cytidine deaminase (AID) to trigger DNA double strand breaks (DSBs) at the immunoglobulin heavy chain (IGH) in B cells. Joining of AID-dependent DSBs within IGH facilitate CSR and effective humoral immunity, but ligation to DSBs in non-IGH chromosomes leads to chromosomal translocations. Thus, the mechanism by which AID-dependent DSBs are repaired requires careful examination. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008101DOI Listing
April 2019
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Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis.

PLoS Genet 2019 Apr 4;15(4):e1008038. Epub 2019 Apr 4.

Department of Internal Medicine, Division of Rheumatology, Celal Bayar University, Manisa, Turkey.

Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008038DOI Listing
April 2019
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Genes influence facial attractiveness through intricate biological relationships.

PLoS Genet 2019 Apr 4;15(4):e1008030. Epub 2019 Apr 4.

Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania, United States of America.

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http://dx.doi.org/10.1371/journal.pgen.1008030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448827PMC
April 2019
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In vivo recombination of Saccharomyces eubayanus maltose-transporter genes yields a chimeric transporter that enables maltotriose fermentation.

PLoS Genet 2019 Apr 4;15(4):e1007853. Epub 2019 Apr 4.

Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629HZ Delft, The Netherlands.

Saccharomyces eubayanus is the non-S. cerevisiae parent of the lager-brewing hybrid S. pastorianus. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448828PMC

Evolution of a novel chimeric maltotriose transporter in Saccharomyces eubayanus from parent proteins unable to perform this function.

PLoS Genet 2019 Apr 4;15(4):e1007786. Epub 2019 Apr 4.

Laboratory of Genetics, Microbiology Doctoral Training Program, Genome Center of Wisconsin, Wisconsin Energy Institute, J. F. Crow Institute for the Study of Evolution, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

At the molecular level, the evolution of new traits can be broadly divided between changes in gene expression and changes in protein-coding sequence. For proteins, the evolution of novel functions is generally thought to proceed through sequential point mutations or recombination of whole functional units. In Saccharomyces, the uptake of the sugar maltotriose into the cell is the primary limiting factor in its utilization, but maltotriose transporters are relatively rare, except in brewing strains. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448821PMC
April 2019
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Genome-wide association study reveals sex-specific genetic architecture of facial attractiveness.

PLoS Genet 2019 04 4;15(4):e1007973. Epub 2019 Apr 4.

Department of Statistics, University of Wisconsin-Madison, Madison, WI, United States of America.

Facial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 4,383 samples in the Wisconsin Longitudinal Study. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448826PMC

What is mutation? A chapter in the series: How microbes "jeopardize" the modern synthesis.

PLoS Genet 2019 Apr 1;15(4):e1007995. Epub 2019 Apr 1.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.

Mutations drive evolution and were assumed to occur by chance: constantly, gradually, roughly uniformly in genomes, and without regard to environmental inputs, but this view is being revised by discoveries of molecular mechanisms of mutation in bacteria, now translated across the tree of life. These mechanisms reveal a picture of highly regulated mutagenesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments-when stressed-potentially accelerating adaptation. Mutation is also nonrandom in genomic space, with multiple simultaneous mutations falling in local clusters, which may allow concerted evolution-the multiple changes needed to adapt protein functions and protein machines encoded by linked genes. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443146PMC
April 2019
2 Reads

Zebrafish Klf4 maintains the ionocyte progenitor population by regulating epidermal stem cell proliferation and lateral inhibition.

PLoS Genet 2019 Apr 1;15(4):e1008058. Epub 2019 Apr 1.

Institute of Cellular and Organismic Biology (ICOB), Academia Sinica, Taipei, Taiwan, Republic of China.

In the skin and gill epidermis of fish, ionocytes develop alongside keratinocytes and maintain body fluid ionic homeostasis that is essential for adaptation to environmental fluctuations. It is known that ionocyte progenitors in zebrafish embryos are specified from p63+ epidermal stem cells through a patterning process involving DeltaC (Dlc)-Notch-mediated lateral inhibition, which selects scattered dlc+ cells into the ionocyte progenitor fate. However, mechanisms by which the ionocyte progenitor population is modulated remain unclear. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008058DOI Listing
April 2019
2 Reads

Quantitative mapping of DNA phosphorothioatome reveals phosphorothioate heterogeneity of low modification frequency.

PLoS Genet 2019 Apr 1;15(4):e1008026. Epub 2019 Apr 1.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Phosphorothioate (PT) modifications of the DNA backbone, widespread in prokaryotes, are first identified in bacterial enteropathogens Escherichia coli B7A more than a decade ago. However, methods for high resolution mapping of PT modification level are still lacking. Here, we developed the PT-IC-seq technique, based on iodine-induced selective cleavage at PT sites and high-throughput next generation sequencing, as a mean to quantitatively characterizing the genomic landscape of PT modifications. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008026DOI Listing
April 2019
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Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures.

PLoS Genet 2019 03 29;15(3):e1008076. Epub 2019 Mar 29.

cpo-Cellular Phenomics & Oncology Berlin-Buch GmbH, Berlin, Germany.

Organoid cultures derived from colorectal cancer (CRC) samples are increasingly used as preclinical models for studying tumor biology and the effects of targeted therapies under conditions capturing in vitro the genetic make-up of heterogeneous and even individual neoplasms. While 3D cultures are initiated from surgical specimens comprising multiple cell populations, the impact of tumor heterogeneity on drug effects in organoid cultures has not been addressed systematically. Here we have used a cohort of well-characterized CRC organoids to study the influence of tumor heterogeneity on the activity of the KRAS/MAPK-signaling pathway and the consequences of treatment by inhibitors targeting EGFR and downstream effectors. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008076DOI Listing
March 2019
2 Reads

Functional analysis of BARD1 missense variants in homology-directed repair and damage sensitivity.

PLoS Genet 2019 03 29;15(3):e1008049. Epub 2019 Mar 29.

Department of Biomedical Informatics, Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, United States of America.

The BARD1 protein, which heterodimerizes with BRCA1, is encoded by a known breast cancer susceptibility gene. While several BARD1 variants have been identified as pathogenic, many more missense variants exist that do not occur frequently enough to assign a clinical risk. In this paper, whole exome sequencing of over 10,000 cancer samples from 33 cancer types identified from somatic mutations and loss of heterozygosity in tumors 76 potentially cancer-associated BARD1 missense and truncation variants. Read More

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http://dx.plos.org/10.1371/journal.pgen.1008049
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http://dx.doi.org/10.1371/journal.pgen.1008049DOI Listing
March 2019
2 Reads

Antero-posterior ectoderm patterning by canonical Wnt signaling during ascidian development.

PLoS Genet 2019 03 29;15(3):e1008054. Epub 2019 Mar 29.

Sorbonne Université, CNRS, Biologie Intégrative des Organismes Marins (BIOM), Banyuls/Mer, France.

Wnt/β-catenin signaling is an ancient pathway in metazoans and controls various developmental processes, in particular the establishment and patterning of the embryonic primary axis. In vertebrates, a graded Wnt activity from posterior to anterior endows cells with positional information in the central nervous system. Recent studies in hemichordates support a conserved role for Wnt/β-catenin in ectoderm antero-posterior patterning at the base of the deuterostomes. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008054DOI Listing

The p38/HOG stress-activated protein kinase network couples growth to division in Candida albicans.

PLoS Genet 2019 03 28;15(3):e1008052. Epub 2019 Mar 28.

Institute for Research in Immunology and Cancer (IRIC), Department of Medicine, Université de Montréal, Montréal, Québec, Canada.

Cell size is a complex trait that responds to developmental and environmental cues. Quantitative size analysis of mutant strain collections disrupted for protein kinases and transcriptional regulators in the pathogenic yeast Candida albicans uncovered 66 genes that altered cell size, few of which overlapped with known size genes in the budding yeast Saccharomyces cerevisiae. A potent size regulator specific to C. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008052DOI Listing
March 2019
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The meiotic phosphatase GSP-2/PP1 promotes germline immortality and small RNA-mediated genome silencing.

PLoS Genet 2019 03 28;15(3):e1008004. Epub 2019 Mar 28.

Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Germ cell immortality, or transgenerational maintenance of the germ line, could be promoted by mechanisms that could occur in either mitotic or meiotic germ cells. Here we report for the first time that the GSP-2 PP1/Glc7 phosphatase promotes germ cell immortality. Small RNA-induced genome silencing is known to promote germ cell immortality, and we identified a separation-of-function allele of C. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008004DOI Listing

Errors in translational decoding: tRNA wobbling or misincorporation?

PLoS Genet 2019 03 28;15(3):e1008017. Epub 2019 Mar 28.

Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.

As the central dogma of molecular biology, genetic information flows from DNA through transcription into RNA followed by translation of the message into protein by transfer RNAs (tRNAs). However, mRNA translation is not always perfect, and errors in the amino acid composition may occur. Mistranslation is generally well tolerated, but once it reaches superphysiological levels, it can give rise to a plethora of diseases. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438450PMC

Genomic inversions and GOLGA core duplicons underlie disease instability at the 15q25 locus.

PLoS Genet 2019 03 27;15(3):e1008075. Epub 2019 Mar 27.

Dipartimento di Biologia, Università degli Studi di Bari "Aldo Moro", Bari, Italy.

Human chromosome 15q25 is involved in several disease-associated structural rearrangements, including microdeletions and chromosomal markers with inverted duplications. Using comparative fluorescence in situ hybridization, strand-sequencing, single-molecule, real-time sequencing and Bionano optical mapping analyses, we investigated the organization of the 15q25 region in human and nonhuman primates. We found that two independent inversions occurred in this region after the fission event that gave rise to phylogenetic chromosomes XIV and XV in humans and great apes. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436712PMC

Intercellular communication is required for trap formation in the nematode-trapping fungus Duddingtonia flagrans.

PLoS Genet 2019 03 27;15(3):e1008029. Epub 2019 Mar 27.

Department of Microbiology, Karlsruhe Institute of Technology (KIT)-South Campus, Institute for Applied Biosciences, Karlsruhe, Germany.

Nematode-trapping fungi (NTF) are a large and diverse group of fungi, which may switch from a saprotrophic to a predatory lifestyle if nematodes are present. Different fungi have developed different trapping devices, ranging from adhesive cells to constricting rings. After trapping, fungal hyphae penetrate the worm, secrete lytic enzymes and form a hyphal network inside the body. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453484PMC

The Plight of Muntaser Ibrahim.

PLoS Genet 2019 03 25;15(3):e1008100. Epub 2019 Mar 25.

Department of Biology and the Integrative Program for Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

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http://dx.plos.org/10.1371/journal.pgen.1008100
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http://dx.doi.org/10.1371/journal.pgen.1008100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433285PMC
March 2019
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A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in Labrador and Golden Retrievers.

PLoS Genet 2019 03 22;15(3):e1007967. Epub 2019 Mar 22.

Animal Health Trust, Newmarket, United Kingdom.

Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447235PMC

Hypomorphic mutation of the mouse Huntington's disease gene orthologue.

PLoS Genet 2019 03 21;15(3):e1007765. Epub 2019 Mar 21.

Molecular Neurogenetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States of America.

Rare individuals with inactivating mutations in the Huntington's disease gene (HTT) exhibit variable abnormalities that imply essential HTT roles during organ development. Here we report phenotypes produced when increasingly severe hypomorphic mutations in the murine HTT orthologue Htt, (HdhneoQ20, HdhneoQ50, HdhneoQ111), were placed over a null allele (Hdhex4/5). The most severe hypomorphic allele failed to rescue null lethality at gastrulation, while the intermediate, though still severe, alleles yielded recessive perinatal lethality and a variety of fetal abnormalities affecting body size, skin, skeletal and ear formation, and transient defects in hematopoiesis. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445486PMC

Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing.

PLoS Genet 2019 03 20;15(3):e1007810. Epub 2019 Mar 20.

Center for Reproductive Genomics, Cornell University, Ithaca, NY, United States of America.

Spermatogenesis is the process by which male gametes are formed from a self-renewing population of spermatogonial stem cells (SSCs) residing in the testis. SSCs represent less than 1% of the total testicular cell population in adults, but must achieve a stable balance between self-renewal and differentiation. Once differentiation has occurred, the newly formed and highly proliferative spermatogonia must then enter the meiotic program in which DNA content is doubled, then halved twice to create haploid gametes. Read More

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http://dx.doi.org/10.1371/journal.pgen.1007810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443194PMC

Deletion of Cdkn1b in ACI rats leads to increased proliferation and pregnancy-associated changes in the mammary gland due to perturbed systemic endocrine environment.

PLoS Genet 2019 03 20;15(3):e1008002. Epub 2019 Mar 20.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.

Mammary epithelial progenitors are the normal cell-of-origin of breast cancer. We previously defined a population of p27+ quiescent hormone-responsive progenitor cells in the normal human breast whose frequency associates with breast cancer risk. Here, we describe that deletion of the Cdkn1b gene encoding the p27 cyclin-dependent kinase inhibitor in the estrogen-induced mammary tumor-susceptible ACI rat strain leads to a decrease in the relative frequencies of Cd49b+ mammary luminal epithelial progenitors and pregnancy-related differentiation. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443185PMC
March 2019
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A missense variant in FTCD is associated with arsenic metabolism and toxicity phenotypes in Bangladesh.

PLoS Genet 2019 03 20;15(3):e1007984. Epub 2019 Mar 20.

Department of Public Health Sciences, The University of Chicago, Chicago, IL, United States of America.

Inorganic arsenic (iAs) is a carcinogen, and exposure to iAs via food and water is a global public health problem. iAs-contaminated drinking water alone affects >100 million people worldwide, including ~50 million in Bangladesh. Once absorbed into the blood stream, most iAs is converted to mono-methylated (MMA) and then di-methylated (DMA) forms, facilitating excretion in urine. Read More

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http://dx.plos.org/10.1371/journal.pgen.1007984
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http://dx.doi.org/10.1371/journal.pgen.1007984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443193PMC
March 2019
14 Reads