A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk.

Abstract:

:Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches. Here we report the use of integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein-Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration, is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)-a macrophage-associated autoimmune disease-than randomly selected immune response genes (P = 8.85 × 10(-6)). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0 × 10(-10); odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D.

journal_name

Nature

journal_title

Nature

authors

Heinig M,Petretto E,Wallace C,Bottolo L,Rotival M,Lu H,Li Y,Sarwar R,Langley SR,Bauerfeind A,Hummel O,Lee YA,Paskas S,Rintisch C,Saar K,Cooper J,Buchan R,Gray EE,Cyster JG,Cardiogenics Consortium.,Erdmann J,Heng

doi

10.1038/nature09386

subject

Has Abstract

pub_date

2010-09-23 00:00:00

pages

460-4

issue

7314

eissn

0028-0836

issn

1476-4687

pii

nature09386

journal_volume

467

pub_type

杂志文章

相关文献

NATURE文献大全
  • Rejuvenation of metallic glasses by non-affine thermal strain.

    abstract::When a spatially uniform temperature change is imposed on a solid with more than one phase, or on a polycrystal of a single, non-cubic phase (showing anisotropic expansion-contraction), the resulting thermal strain is inhomogeneous (non-affine). Thermal cycling induces internal stresses, leading to structural and prop...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature14674

    authors: Ketov SV,Sun YH,Nachum S,Lu Z,Checchi A,Beraldin AR,Bai HY,Wang WH,Louzguine-Luzgin DV,Carpenter MA,Greer AL

    更新日期:2015-08-13 00:00:00

  • Evolutionary origin of a calcium-dependent protease by fusion of genes for a thiol protease and a calcium-binding protein?

    abstract::Calcium-dependent protease (calcium protease) is apparently involved in a variety of cellular processes. Here we have attempted to clarify the role and regulatory mechanism of calcium protease by analysing its structure. The complete primary structure of calcium protease (relative molecular mass (Mr) 80,000 (80K), 705...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/312566a0

    authors: Ohno S,Emori Y,Imajoh S,Kawasaki H,Kisaragi M,Suzuki K

    更新日期:1984-12-06 00:00:00

  • Computed redox potentials and the design of bioreductive agents.

    abstract::Anti-cancer agents that have been made selective for tumour cells by exploiting the known differences in the availability of oxygen between normal and transformed cells are a promising development in cancer chemotherapy. We have recently suggested a new type of bioreductive activity which would depend on a two-electro...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/334080a0

    authors: Reynolds CA,King PM,Richards WG

    更新日期:1988-07-07 00:00:00

  • Localization of the human GM-CSF receptor gene to the X-Y pseudoautosomal region.

    abstract::Mammalian sex chromosomes share a small terminal region of homologous DNA sequences, which pair and recombine during male meiosis. Alleles in this region can be exchanged between X and Y chromosomes and are therefore inherited as if autosomal. Genes from this so-called pseudoautosomal region (PAR) are present in two d...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/345734a0

    authors: Gough NM,Gearing DP,Nicola NA,Baker E,Pritchard M,Callen DF,Sutherland GR

    更新日期:1990-06-21 00:00:00

  • Single channel recordings of K+ currents in squid axons.

    abstract::Ionic currents from individual K+ channels in squid axon membrane have been recorded. At hyperpolarizing membrane voltages, unit events occur as widely spaced rectangular pulses with short interruptions. The frequency of occurrence of the units increases strongly when the membrane is depolarized. ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/285140a0

    authors: Conti F,Neher E

    更新日期:1980-05-15 00:00:00

  • Evolutionary divergence of the mRNA transcription initiation mechanism in yeast.

    abstract::The promoters of eukaryotic genes are being increasingly defined through the identification of consensus DNA sequences, by mutational analysis, and by in vitro and in vivo studies of transcription. Whereas the TATA sequence (Goldberg-Hogness box) has been largely conserved among protein encoding genes (transcribed by ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/301167a0

    authors: Russell PR

    更新日期:1983-01-13 00:00:00

  • The physical mechanisms of fast radio bursts.

    abstract::Fast radio bursts are mysterious millisecond-duration transients prevalent in the radio sky. Rapid accumulation of data in recent years has facilitated an understanding of the underlying physical mechanisms of these events. Knowledge gained from the neighbouring fields of gamma-ray bursts and radio pulsars has also of...

    journal_title:Nature

    pub_type: 杂志文章,评审

    doi:10.1038/s41586-020-2828-1

    authors: Zhang B

    更新日期:2020-11-01 00:00:00

  • A dominant autoinflammatory disease caused by non-cleavable variants of RIPK1.

    abstract::Activation of RIPK1 controls TNF-mediated apoptosis, necroptosis and inflammatory pathways1. Cleavage of human and mouse RIPK1 after residues D324 and D325, respectively, by caspase-8 separates the RIPK1 kinase domain from the intermediate and death domains. The D325A mutation in mouse RIPK1 leads to embryonic lethali...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-019-1830-y

    authors: Tao P,Sun J,Wu Z,Wang S,Wang J,Li W,Pan H,Bai R,Zhang J,Wang Y,Lee PY,Ying W,Zhou Q,Hou J,Wang W,Sun B,Yang M,Liu D,Fang R,Han H,Yang Z,Huang X,Li H,Deuitch N,Zhang Y,Dissanayake D,Haude K,McWalter K

    更新日期:2020-01-01 00:00:00

  • Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis.

    abstract::Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic1. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory respons...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-020-2600-6

    authors: Carvelli J,Demaria O,Vély F,Batista L,Chouaki Benmansour N,Fares J,Carpentier S,Thibult ML,Morel A,Remark R,André P,Represa A,Piperoglou C,Explore COVID-19 IPH group.,Explore COVID-19 Marseille Immunopole group.,Cordier PY

    更新日期:2020-12-01 00:00:00

  • Inositol phosphates are assembly co-factors for HIV-1.

    abstract::A short, 14-amino-acid segment called SP1, located in the Gag structural protein1, has a critical role during the formation of the HIV-1 virus particle. During virus assembly, the SP1 peptide and seven preceding residues fold into a six-helix bundle, which holds together the Gag hexamer and facilitates the formation o...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-018-0396-4

    authors: Dick RA,Zadrozny KK,Xu C,Schur FKM,Lyddon TD,Ricana CL,Wagner JM,Perilla JR,Ganser-Pornillos BK,Johnson MC,Pornillos O,Vogt VM

    更新日期:2018-08-01 00:00:00

  • A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor.

    abstract::Atrial natriuretic peptide (ANP) is a polypeptide hormone whose effects include the induction of diuresis, natriuresis and vasorelaxation. One of the earliest events following binding of ANP to receptors on target cells is an increase in cyclic GMP concentration, indicating that this nucleotide might act as a mediator...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/338078a0

    authors: Chinkers M,Garbers DL,Chang MS,Lowe DG,Chin HM,Goeddel DV,Schulz S

    更新日期:1989-03-02 00:00:00

  • Control of X chromosome transcription by the maleless gene in Drosophila.

    abstract::In Drosophila, a large group of structural genes exhibit coordinate regulation, not because they function in a common developmental pathway but because they happen to reside on the X chromosome. These genes are subjected to the regulatory mechanism of dosage compensation which insures that their phenotypic products ar...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/285573a0

    authors: Belote JM,Lucchesi JC

    更新日期:1980-06-19 00:00:00

  • Sleep in Drosophila is regulated by adult mushroom bodies.

    abstract::Sleep is one of the few major whole-organ phenomena for which no function and no underlying mechanism have been conclusively demonstrated. Sleep could result from global changes in the brain during wakefulness or it could be regulated by specific loci that recruit the rest of the brain into the electrical and metaboli...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature04811

    authors: Joiner WJ,Crocker A,White BH,Sehgal A

    更新日期:2006-06-08 00:00:00

  • Astronomy (communication arising): black holes, fleas and microlithography.

    abstract::Fresnel lenses allow almost perfect imaging in widely different circumstances, but their focus is perfect only for a single wavelength. Wang et al. have shown how the effective bandpass may be widened for X-ray microscopy by using a compound diffractive/refractive lens near to an absorption edge. A compound lens has a...

    journal_title:Nature

    pub_type: 评论,杂志文章

    doi:10.1038/426245b

    authors: Skinner G,Gorenstein P

    更新日期:2003-11-20 00:00:00

  • Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters.

    abstract::Excitatory amino acids mediate fast synaptic transmission in the central nervous system through the activation of at least three distinct ionotropic receptors: N-methyl-D-aspartate (NMDA), the alpha-amino-3-hydroxy-5-methyl-isoxasole-4-propionate (AMPA)/quisqualate (QUIS) and the kainate subtypes (for reviews, see ref...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/347765a0

    authors: Charpak S,Gähwiler BH,Do KQ,Knöpfel T

    更新日期:1990-10-25 00:00:00

  • Potentiation of neuroblastoma metastasis by loss of caspase-8.

    abstract::Neuroblastoma, the most common paediatric solid tumour, arises from defective neural crest cells. Genetic alterations occur frequently in the most aggressive neuroblastomas. In particular, deletion or suppression of the proapoptotic enzyme caspase-8 is common in malignant, disseminated disease, although the effect of ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature04323

    authors: Stupack DG,Teitz T,Potter MD,Mikolon D,Houghton PJ,Kidd VJ,Lahti JM,Cheresh DA

    更新日期:2006-01-05 00:00:00

  • Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor.

    abstract::T lymphocytes are predisposed to recognition of foreign protein fragments bound to cell-surface molecules encoded by the major histocompatibility complex (MHC). There is now compelling evidence that this specificity is a consequence of a selection process operating on developing T lymphocytes in the thymus. As a resul...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/341746a0

    authors: Kaye J,Hsu ML,Sauron ME,Jameson SC,Gascoigne NR,Hedrick SM

    更新日期:1989-10-26 00:00:00

  • Biomechanics: independent evolution of running in vampire bats.

    abstract::Most tetrapods have retained terrestrial locomotion since it evolved in the Palaeozoic era, but bats have become so specialized for flight that they have almost lost the ability to manoeuvre on land at all. Vampire bats, which sneak up on their prey along the ground, are an important exception. Here we show that commo...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/434292a

    authors: Riskin DK,Hermanson JW

    更新日期:2005-03-17 00:00:00

  • The oyster genome reveals stress adaptation and complexity of shell formation.

    abstract::The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteom...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11413

    authors: Zhang G,Fang X,Guo X,Li L,Luo R,Xu F,Yang P,Zhang L,Wang X,Qi H,Xiong Z,Que H,Xie Y,Holland PW,Paps J,Zhu Y,Wu F,Chen Y,Wang J,Peng C,Meng J,Yang L,Liu J,Wen B,Zhang N,Huang Z,Zhu Q,Feng Y,Mount A

    更新日期:2012-10-04 00:00:00

  • The nature and origin of interstellar diamond.

    abstract::Microscopic diamond was recently discovered in oxidized acid residues from several carbonaceous chondrite meteorites (for example, the C delta component of the Allende meteorite). Some of the reported properties of C delta seem in conflict with those expected of diamond. Here we present high spatial resolution analy...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/332611a0

    authors: Blake DF,Freund F,Krishnan KF,Echer CJ,Shipp R,Bunch TE,Tielens AG,Lipari RJ,Hetherington CJ,Chang S

    更新日期:1988-04-14 00:00:00

  • Myosin from fetal hearts contains the skeletal muscle embryonic light chain.

    abstract::The contractile proteins of adult skeletal and cardiac muscle tissue are very similar. Some of these proteins are identical in amino acid sequence or differ only slightly. Various structural studies have shown that the heavy and light chains of myosin are also homologous in skeletal and cardiac muscles. In developing ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/286731a0

    authors: Whalen RG,Sell SM

    更新日期:1980-08-14 00:00:00

  • Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking.

    abstract::The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours, but our understanding of the interaction between these two brain regions has been limited by the inability to man...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature10194

    authors: Stuber GD,Sparta DR,Stamatakis AM,van Leeuwen WA,Hardjoprajitno JE,Cho S,Tye KM,Kempadoo KA,Zhang F,Deisseroth K,Bonci A

    更新日期:2011-06-29 00:00:00

  • Electrostatic interactions in the assembly of haemoglobin.

    abstract::Haemoglobin is the prototype of an allosteric protein in which cooperative behaviour depends on interaction between unlike subunits. Here we present haematological and biochemical evidence that electrostatic interactions are an important determinant of haemoglobin assembly. Individuals heterozygous for positively char...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/306498a0

    authors: Bunn HF,McDonald MJ

    更新日期:1983-12-01 00:00:00

  • Evidence for two active sites in the spliceosome provided by stereochemistry of pre-mRNA splicing.

    abstract::Excision of introns from nuclear precursors to messenger RNAs (pre-mRNAs) by the spliceosome requires two distinct phosphodiester transfer (transesterification) reactions: exchange of a 3'-5' for a 2'-5' bond in the first step (lariat formation) and exchange of one 3'-5' phosphodiester for another in the second step (...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/365364a0

    authors: Moore MJ,Sharp PA

    更新日期:1993-09-23 00:00:00

  • Immunization to a syngeneic sarcoma by a monoclonal auto-anti-idiotypic antibody.

    abstract::Idiotypic networks regulate the immune response to a variety of antigens. Antibodies generated against other antibodies, called anti-idiotypic antibodies, can themselves mimic antigen and elicit a specific immune response. They have been shown to induce delayed-type hypersensitivity (DTH) to model antigens in the mous...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/303627a0

    authors: Forstrom JW,Nelson KA,Nepom GT,Hellström I,Hellström KE

    更新日期:1983-06-16 00:00:00

  • Decay characteristics of HIV-1-infected compartments during combination therapy.

    abstract::Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insight into the dynamics of human immunodeficiency virus type 1 (HIV-1). The concentration of HIV-1 in plasma drops by approximately 99% in the first two weeks of treatment owing to the rapid eli...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/387188a0

    authors: Perelson AS,Essunger P,Cao Y,Vesanen M,Hurley A,Saksela K,Markowitz M,Ho DD

    更新日期:1997-05-08 00:00:00

  • Genetic evidence for Near-Eastern origins of European cattle.

    abstract::The limited ranges of the wild progenitors of many of the primary European domestic species point to their origins further east in Anatolia or the fertile crescent. The wild ox (Bos primigenius), however, ranged widely and it is unknown whether it was domesticated within Europe as one feature of a local contribution t...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35074088

    authors: Troy CS,MacHugh DE,Bailey JF,Magee DA,Loftus RT,Cunningham P,Chamberlain AT,Sykes BC,Bradley DG

    更新日期:2001-04-26 00:00:00

  • Double-walled polymer microspheres for controlled drug release.

    abstract::One approach to the controlled release of drugs involves incorporation of the drug molecules into the matrix of microscopic polymer spheres or capsules. Existing methods for preparing such microparticles do not, however, always guarantee a constant release rate, for example because drug molecules may be trapped prefer...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/367258a0

    authors: Pekarek KJ,Jacob JS,Mathiowitz E

    更新日期:1994-01-20 00:00:00

  • Modular assembly of the nucleolar pre-60S ribosomal subunit.

    abstract::Early co-transcriptional events during eukaryotic ribosome assembly result in the formation of precursors of the small (40S) and large (60S) ribosomal subunits. A multitude of transient assembly factors regulate and chaperone the systematic folding of pre-ribosomal RNA subdomains. However, owing to a lack of structura...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature26156

    authors: Sanghai ZA,Miller L,Molloy KR,Barandun J,Hunziker M,Chaker-Margot M,Wang J,Chait BT,Klinge S

    更新日期:2018-04-05 00:00:00

  • ATP is a mediator of chemosensory transduction in the central nervous system.

    abstract::Extracellular signalling by the purine nucleotide ATP has long been associated with sensory function. In the periphery, ATP mediates nociception, mechanosensitivity, thermal sensitivity and O2 chemosensitivity. These processes share a common mechanism that involves the release of ATP to excite afferent fibres via acti...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature03690

    authors: Gourine AV,Llaudet E,Dale N,Spyer KM

    更新日期:2005-07-07 00:00:00