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  1. AU="Manuel de Villena, Fernando Pardo"
  2. AU=Anand B S
  3. AU="Pandeya, Sarbesh R"
  4. AU="Parra Viviane M."
  5. AU="Anetsberger, Daniel"
  6. AU="Novizio, Nunzia"
  7. AU="Elizabeth Sweeney"
  8. AU="Carrigan, M"
  9. AU="Majid T Noghani"
  10. AU="Hanh, Bui Thi Bich"
  11. AU="Hyun Chul Song"
  12. AU="Cottraux, Jean"
  13. AU=Mauro Michael J
  14. AU="Labate, Demetrio"
  15. AU=Ahmad S

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  1. Artikel ; Online: A mutation in Themis contributes to anaphylaxis severity following oral peanut challenge in CC027 mice.

    Risemberg, Ellen L / Smeekens, Johanna M / Cruz Cisneros, Marta C / Hampton, Brea K / Hock, Pablo / Linnertz, Colton L / Miller, Darla R / Orgel, Kelly / Shaw, Ginger D / Manuel de Villena, Fernando Pardo / Burks, A Wesley / Valdar, William / Kulis, Michael D / Ferris, Martin T

    The Journal of allergy and clinical immunology

    2024  

    Abstract: Background: The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized CC027/GeniUnc (CC027) mice develop ... ...

    Abstract Background: The development of peanut allergy is due to a combination of genetic and environmental factors, although specific genes have proven difficult to identify. Previously, we reported that peanut-sensitized CC027/GeniUnc (CC027) mice develop anaphylaxis upon oral challenge to peanut, unlike C3H/HeJ (C3H) mice.
    Objective: To determine the genetic basis of orally-induced anaphylaxis to peanut in CC027 mice.
    Methods: A genetic mapping population between CC027 and C3H mice was designed to identify the genetic factors that drive oral anaphylaxis. A total of 356 CC027xC3H backcrossed mice were generated, sensitized to peanut, then challenged to peanut by oral gavage. Anaphylaxis and peanut-specific IgE were quantified for all mice. T-cell phenotyping was conducted on CC027 and five additional CC strains.
    Results: Anaphylaxis to peanut was absent in 77% of backcrossed mice, with 19% showing moderate anaphylaxis, and 4% having severe anaphylaxis. A total of eight genetic loci were associated with variation in response to peanut challenge, six associated with anaphylaxis (temperature decrease) and two associated with peanut-specific IgE levels. There were two major loci that impacted multiple aspects of the severity of acute anaphylaxis, at which the CC027 allele was associated with worse outcome. At one of these loci, CC027 has a private genetic variant in the Themis (thymocyte-expressed molecule involved in selection) gene. Consistent with Themis' described functions, we found that CC027 have more immature T cells with fewer CD8+, CD4+, and CD4+CD25+CD127- regulatory T cells.
    Conclusion: Our results demonstrate a key role for Themis in the orally-reactive CC027 mouse model of peanut allergy.
    Sprache Englisch
    Erscheinungsdatum 2024-04-24
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2024.03.027
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Dissecting the genetic architecture of cystatin C in diversity outbred mice

    Huda, M. Nazmul / Verhague, Melissa / Smallwood, Tangi / Bell, Timothy A / Que, Excel / Miller, D. R / Roshanravan, Baback / Allayee, Hooman / Manuel de Villena, Fernando Pardo / Bennett, Brian J

    G3. 2020, v. 10, no. 7

    2020  

    Abstract: Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerularfiltration rate in thekidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysCconcentration. To do so we perform Quantitative Trait Loci ( ...

    Abstract Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerularfiltration rate in thekidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysCconcentration. To do so we perform Quantitative Trait Loci (QTL) and expression QTL (eQTL) analysis of120 Diversity Outbred (DO) female mice, 56 weeks of age. We performed network analysis of kidney geneexpression to determine if the gene modules with common functions are associated with kidney biomarkersof chronic kidney diseases. Our data demonstrates that plasma concentrations and kidney mRNA levelsof CysC are associated with genetic variation and are transcriptionally coregulated by immune genes.Specifically, Type-I interferon signaling genes are coexpressed withCst3mRNA levels and associatedwith CysC concentrations in plasma. Ourfindings demonstrate the complex control of CysC by geneticpolymorphisms and inflammatory pathways
    Schlagwörter biomarkers ; females ; genes ; genetic variation ; interferons ; kidneys ; quantitative traits ; transcription (genetics)
    Sprache Englisch
    Umfang p. 2529-2541.
    Dokumenttyp Artikel
    Anmerkung NAL-AP-2-clean
    ZDB-ID 2629978-1
    ISSN 2160-1836
    ISSN 2160-1836
    DOI 10.1534/g3.120.401275
    Datenquelle NAL Katalog (AGRICOLA)

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  3. Artikel ; Online: Dissecting the Genetic Architecture of Cystatin C in Diversity Outbred Mice.

    Huda, M Nazmul / VerHague, Melissa / Albright, Jody / Smallwood, Tangi / Bell, Timothy A / Que, Excel / Miller, Darla R / Roshanravan, Baback / Allayee, Hooman / Manuel de Villena, Fernando Pardo / Bennett, Brian J

    G3 (Bethesda, Md.)

    2020  Band 10, Heft 7, Seite(n) 2529–2541

    Abstract: Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerular filtration rate in the kidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysC concentration. To do so we perform Quantitative Trait ... ...

    Abstract Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerular filtration rate in the kidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysC concentration. To do so we perform Quantitative Trait Loci (QTL) and expression QTL (eQTL) analysis of 120 Diversity Outbred (DO) female mice, 56 weeks of age. We performed network analysis of kidney gene expression to determine if the gene modules with common functions are associated with kidney biomarkers of chronic kidney diseases. Our data demonstrates that plasma concentrations and kidney mRNA levels of CysC are associated with genetic variation and are transcriptionally coregulated by immune genes. Specifically, Type-I interferon signaling genes are coexpressed with
    Mesh-Begriff(e) Animals ; Biomarkers ; Collaborative Cross Mice ; Cystatin C/genetics ; Female ; Mice ; Quantitative Trait Loci
    Chemische Substanzen Biomarkers ; Cystatin C
    Sprache Englisch
    Erscheinungsdatum 2020-07-07
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1534/g3.120.401275
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Antipsychotic Behavioral Phenotypes in the Mouse Collaborative Cross Recombinant Inbred Inter-Crosses (RIX).

    Giusti-Rodríguez, Paola / Xenakis, James G / Crowley, James J / Nonneman, Randal J / DeCristo, Daniela M / Ryan, Allison / Quackenbush, Corey R / Miller, Darla R / Shaw, Ginger D / Zhabotynsky, Vasyl / Sullivan, Patrick F / Manuel de Villena, Fernando Pardo / Zou, Fei

    G3 (Bethesda, Md.)

    2020  Band 10, Heft 9, Seite(n) 3165–3177

    Abstract: Schizophrenia is an idiopathic disorder that affects approximately 1% of the human population, and presents with persistent delusions, hallucinations, and disorganized behaviors. Antipsychotics are the standard pharmacological treatment for schizophrenia, ...

    Abstract Schizophrenia is an idiopathic disorder that affects approximately 1% of the human population, and presents with persistent delusions, hallucinations, and disorganized behaviors. Antipsychotics are the standard pharmacological treatment for schizophrenia, but are frequently discontinued by patients due to inefficacy and/or side effects. Chronic treatment with the typical antipsychotic haloperidol causes tardive dyskinesia (TD), which manifests as involuntary and often irreversible orofacial movements in around 30% of patients. Mice treated with haloperidol develop many of the features of TD, including jaw tremors, tongue protrusions, and vacuous chewing movements (VCMs). In this study, we used genetically diverse Collaborative Cross (CC) recombinant inbred inter-cross (RIX) mice to elucidate the genetic basis of antipsychotic-induced adverse drug reactions (ADRs). We performed a battery of behavioral tests in 840 mice from 73 RIX lines (derived from 62 CC strains) treated with haloperidol or placebo in order to monitor the development of ADRs. We used linear mixed models to test for strain and treatment effects. We observed highly significant strain effects for almost all behavioral measurements investigated (
    Mesh-Begriff(e) Animals ; Antipsychotic Agents/adverse effects ; Dyskinesia, Drug-Induced ; Haloperidol/adverse effects ; Humans ; Mastication ; Mice ; Phenotype
    Chemische Substanzen Antipsychotic Agents ; Haloperidol (J6292F8L3D)
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-09-02
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1534/g3.120.400975
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: A Mutation in the Borcs7 Subunit of the Lysosome Regulatory BORC Complex Results in Motor Deficits and Dystrophic Axonopathy in Mice.

    Snouwaert, John N / Church, Rachel J / Jania, Leigh / Nguyen, MyTrang / Wheeler, Matthew L / Saintsing, Andrew / Mieczkowski, Piotr / Manuel de Villena, Fernando Pardo / Armao, Diane / Moy, Sheryl S / Lorenzo, Damaris N / Koller, Beverly H

    Cell reports

    2018  Band 24, Heft 5, Seite(n) 1254–1265

    Abstract: Lysosomes play a critical role in maintenance of the integrity of neuronal function, and mutations in genes that contribute to lysosome formation, transport, and activity are associated with neurodegenerative disorders. Recently, the multisubunit complex, ...

    Abstract Lysosomes play a critical role in maintenance of the integrity of neuronal function, and mutations in genes that contribute to lysosome formation, transport, and activity are associated with neurodegenerative disorders. Recently, the multisubunit complex, BLOC-one-related complex (BORC), has been shown to be involved in positioning lysosomes within the cytoplasm, although the consequences of altered BORC function in adult animals have not been established. We show that a spontaneous truncation mutation in the mouse Borcs7 gene, identified through whole-genome sequencing followed by genetic complementation, results in progressive axonal dystrophy with dramatic impairment of motor function. Furthermore, mice homozygous for deletion of the entire Borcs7 coding sequence die shortly after birth, and neurons cultured from these animals show impaired centrifugal transport of lysosomes. This identifies BORCS7 as a central factor in axonal transport of lysosomes and a possible target for improving disease-related disturbances in this important function.
    Mesh-Begriff(e) Animals ; Axonal Transport ; Female ; Locomotion ; Loss of Function Mutation ; Lysosomal Membrane Proteins/genetics ; Lysosomes/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neuroaxonal Dystrophies/genetics ; Neurons/metabolism
    Chemische Substanzen Borcs7 protein, mouse ; Lysosomal Membrane Proteins
    Sprache Englisch
    Erscheinungsdatum 2018-07-26
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2018.06.118
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection.

    Chesler, Elissa J / Gatti, Daniel M / Morgan, Andrew P / Strobel, Marge / Trepanier, Laura / Oberbeck, Denesa / McWeeney, Shannon / Hitzemann, Robert / Ferris, Martin / McMullan, Rachel / Clayshultle, Amelia / Bell, Timothy A / Manuel de Villena, Fernando Pardo / Churchill, Gary A

    G3 (Bethesda, Md.)

    2016  Band 6, Heft 12, Seite(n) 3893–3902

    Abstract: Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding ... ...

    Abstract Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility.
    Mesh-Begriff(e) Alleles ; Animals ; Breeding ; Computational Biology/methods ; Crosses, Genetic ; Female ; Gene Frequency ; Genetic Loci ; Genetic Variation ; Genetics, Population ; Genome ; Genomics/methods ; Haplotypes ; Male ; Mice ; Mitochondria/genetics ; Molecular Sequence Annotation ; Mutation ; Phenotype ; Selection, Genetic ; Sex Chromosome Aberrations ; Sex Ratio
    Sprache Englisch
    Erscheinungsdatum 2016-12-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1534/g3.116.035527
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Annotation of long non-coding RNAs expressed in collaborative cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts.

    Josset, Laurence / Tchitchek, Nicolas / Gralinski, Lisa E / Ferris, Martin T / Eisfeld, Amie J / Green, Richard R / Thomas, Matthew J / Tisoncik-Go, Jennifer / Schroth, Gary P / Kawaoka, Yoshihiro / Manuel de Villena, Fernando Pardo / Baric, Ralph S / Heise, Mark T / Peng, Xinxia / Katze, Michael G

    RNA biology

    2014  Band 11, Heft 7, Seite(n) 875–890

    Abstract: The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). ... ...

    Abstract The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions of host lncRNAs in response to influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) based on their similarity in expression with genes of known function. We performed total RNA-Seq on viral-infected lungs from eight mouse strains, yielding a large data set of transcriptional responses. Overall 5,329 lncRNAs were differentially expressed after infection. Most of the lncRNAs were co-expressed with coding genes in modules enriched in genes associated with lung homeostasis pathways or immune response processes. Each lncRNA was further individually annotated using a rank-based method, enabling us to associate 5,295 lncRNAs to at least one gene set and to predict their potential cis effects. We validated the lncRNAs predicted to be interferon-stimulated by profiling mouse responses after interferon-α treatment. Altogether, these results provide a broad categorization of potential lncRNA functions and identify subsets of lncRNAs with likely key roles in respiratory virus pathogenesis. These data are fully accessible through the MOuse NOn-Code Lung interactive database (MONOCLdb).
    Mesh-Begriff(e) Animals ; Antiviral Agents/administration & dosage ; Antiviral Agents/pharmacology ; Cell Line ; Female ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Influenza A virus/drug effects ; Influenza A virus/physiology ; Interferon-alpha/administration & dosage ; Interferon-alpha/pharmacology ; Lung/metabolism ; Lung/virology ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Annotation ; RNA Virus Infections/drug therapy ; RNA Virus Infections/genetics ; RNA Virus Infections/virology ; RNA, Long Noncoding/genetics ; Severe acute respiratory syndrome-related coronavirus/drug effects ; Severe acute respiratory syndrome-related coronavirus/physiology ; Sequence Analysis, RNA
    Chemische Substanzen Antiviral Agents ; Interferon-alpha ; RNA, Long Noncoding
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2014-06-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2159587-2
    ISSN 1555-8584 ; 1555-8584
    ISSN (online) 1555-8584
    ISSN 1555-8584
    DOI 10.4161/rna.29442
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Content and Performance of the MiniMUGA Genotyping Array: A New Tool To Improve Rigor and Reproducibility in Mouse Research.

    Sigmon, John Sebastian / Blanchard, Matthew W / Baric, Ralph S / Bell, Timothy A / Brennan, Jennifer / Brockmann, Gudrun A / Burks, A Wesley / Calabrese, J Mauro / Caron, Kathleen M / Cheney, Richard E / Ciavatta, Dominic / Conlon, Frank / Darr, David B / Faber, James / Franklin, Craig / Gershon, Timothy R / Gralinski, Lisa / Gu, Bin / Gaines, Christiann H /
    Hagan, Robert S / Heimsath, Ernest G / Heise, Mark T / Hock, Pablo / Ideraabdullah, Folami / Jennette, J Charles / Kafri, Tal / Kashfeen, Anwica / Kulis, Mike / Kumar, Vivek / Linnertz, Colton / Livraghi-Butrico, Alessandra / Lloyd, K C Kent / Lutz, Cathleen / Lynch, Rachel M / Magnuson, Terry / Matsushima, Glenn K / McMullan, Rachel / Miller, Darla R / Mohlke, Karen L / Moy, Sheryl S / Murphy, Caroline E Y / Najarian, Maya / O'Brien, Lori / Palmer, Abraham A / Philpot, Benjamin D / Randell, Scott H / Reinholdt, Laura / Ren, Yuyu / Rockwood, Steve / Rogala, Allison R / Saraswatula, Avani / Sassetti, Christopher M / Schisler, Jonathan C / Schoenrock, Sarah A / Shaw, Ginger D / Shorter, John R / Smith, Clare M / St Pierre, Celine L / Tarantino, Lisa M / Threadgill, David W / Valdar, William / Vilen, Barbara J / Wardwell, Keegan / Whitmire, Jason K / Williams, Lucy / Zylka, Mark J / Ferris, Martin T / McMillan, Leonard / Manuel de Villena, Fernando Pardo

    Genetics

    2020  Band 216, Heft 4, Seite(n) 905–930

    Abstract: The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse ... ...

    Abstract The laboratory mouse is the most widely used animal model for biomedical research, due in part to its well-annotated genome, wealth of genetic resources, and the ability to precisely manipulate its genome. Despite the importance of genetics for mouse research, genetic quality control (QC) is not standardized, in part due to the lack of cost-effective, informative, and robust platforms. Genotyping arrays are standard tools for mouse research and remain an attractive alternative even in the era of high-throughput whole-genome sequencing. Here, we describe the content and performance of a new iteration of the Mouse Universal Genotyping Array (MUGA), MiniMUGA, an array-based genetic QC platform with over 11,000 probes. In addition to robust discrimination between most classical and wild-derived laboratory strains, MiniMUGA was designed to contain features not available in other platforms: (1) chromosomal sex determination, (2) discrimination between substrains from multiple commercial vendors, (3) diagnostic SNPs for popular laboratory strains, (4) detection of constructs used in genetically engineered mice, and (5) an easy-to-interpret report summarizing these results. In-depth annotation of all probes should facilitate custom analyses by individual researchers. To determine the performance of MiniMUGA, we genotyped 6899 samples from a wide variety of genetic backgrounds. The performance of MiniMUGA compares favorably with three previous iterations of the MUGA family of arrays, both in discrimination capabilities and robustness. We have generated publicly available consensus genotypes for 241 inbred strains including classical, wild-derived, and recombinant inbred lines. Here, we also report the detection of a substantial number of
    Mesh-Begriff(e) Animals ; Female ; Genome-Wide Association Study/methods ; Genome-Wide Association Study/standards ; Genotype ; Genotyping Techniques/methods ; Genotyping Techniques/standards ; Male ; Mice/genetics ; Mice, Inbred C57BL ; Oligonucleotide Array Sequence Analysis/methods ; Oligonucleotide Array Sequence Analysis/standards ; Polymorphism, Genetic ; Reproducibility of Results ; Sex Determination Processes
    Sprache Englisch
    Erscheinungsdatum 2020-10-16
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2167-2
    ISSN 1943-2631 ; 0016-6731
    ISSN (online) 1943-2631
    ISSN 0016-6731
    DOI 10.1534/genetics.120.303596
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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