Abstract:
:Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts.
journal_name
Naturejournal_title
Natureauthors
Dickinson ME,Flenniken AM,Ji X,Teboul L,Wong MD,White JK,Meehan TF,Weninger WJ,Westerberg H,Adissu H,Baker CN,Bower L,Brown JM,Caddle LB,Chiani F,Clary D,Cleak J,Daly MJ,Denegre JM,Doe B,Dolan ME,Edie SM,Fuchsdoi
10.1038/nature19356subject
Has Abstractpub_date
2016-09-22 00:00:00pages
508-514issue
7621eissn
0028-0836issn
1476-4687pii
nature19356journal_volume
537pub_type
杂志文章相关文献
NATURE文献大全abstract::A 12 amino-acid synthetic peptide (NANP)3 comprising the immunodominant epitope of Plasmodium falciparum circumsporozoite protein was conjugated to tetanus toxoid (TT), adjuvanted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. No...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/328257a0
更新日期:1987-07-16 00:00:00
abstract::The GAL4 protein activates transcription of the genes required for galactose utilization in Saccharomyces cerevisiae. The protein, consisting of 881 amino acids, is dimeric when bound to one of the approximately twofold symmetrical DNA sites present in the galactose upstream activating sequence (UASG). Here we use two...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/356450a0
更新日期:1992-04-02 00:00:00
abstract::The formation of disulphide bonds is essential to the structure and function of proteins. These bonds rapidly form either cotranslationally or immediately post-translationally in the lumen of the endoplasmic reticulum. Native disulphide pairing for such proteins has been achieved in vitro; however, the rates of reasse...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/317267a0
更新日期:1985-09-19 00:00:00
abstract::Extant vertebrates form two clades, the jawless Cyclostomata (lampreys and hagfishes) and the jawed Gnathostomata (all other vertebrates), with contrasting facial architectures. These arise during development from just a few key differences in the growth patterns of the cranial primordia: notably, the nasal sacs and h...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12980
更新日期:2014-03-27 00:00:00
abstract::Few intergalactic, plausibly primordial clouds of neutral atomic hydrogen (H(i)) have been found in the local Universe, suggesting that such structures have either dispersed, become ionized or produced a stellar population on gigayear timescales. The Leo ring, a massive (M(H(i)) approximately 1.8 x 10(9)M[symbol: see ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07780
更新日期:2009-02-19 00:00:00
abstract::Human apolipoprotein E has three isoforms: APOE2, APOE3 and APOE4. APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage. Neurovascular dysfunction is present in normal APOE4 carriers and i...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11087
更新日期:2012-05-16 00:00:00
abstract::Environmental change has altered the phenology, morphological traits and population dynamics of many species. However, the links underlying these joint responses remain largely unknown owing to a paucity of long-term data and the lack of an appropriate analytical framework. Here we investigate the link between phenoty...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09210
更新日期:2010-07-22 00:00:00
abstract::The orexin (also known as hypocretin) G protein-coupled receptors (GPCRs) respond to orexin neuropeptides in the central nervous system to regulate sleep and other behavioural functions in humans. Defects in orexin signalling are responsible for the human diseases of narcolepsy and cataplexy; inhibition of orexin rece...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14035
更新日期:2015-03-12 00:00:00
abstract::Endothelial cells line the inner surface of blood vessels and act as the main barrier to the passage of cells and large molecules from the blood stream to the tissues. Recent interest in the part played by the endothelium in regulating vascular tone has focused on the synthesis and secretion of prostacyclin and an end...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/325811a0
更新日期:1987-02-26 00:00:00
abstract::On 12 May 2008, the devastating magnitude 7.9 (Wenchuan) earthquake struck the eastern edge of the Tibetan plateau, collapsing buildings and killing thousands in major cities aligned along the western Sichuan basin in China. After such a large-magnitude earthquake, rearrangement of stresses in the crust commonly leads...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07177
更新日期:2008-07-24 00:00:00
abstract::Networks of interacting proteins orchestrate the responses of living cells to a variety of external stimuli, but how sensitive is the functioning of these protein networks to variations in their biochemical parameters? One possibility is that to achieve appropriate function, the reaction rate constants and enzyme conc...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/16483
更新日期:1999-01-14 00:00:00
abstract::The angle between the spin of a star and the orbital planes of its planets traces the history of the planetary system. Exoplanets orbiting close to cool stars are expected to be on circular, aligned orbits because of strong tidal interactions with the stellar convective envelope. Spin-orbit alignment can be measured w...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature24677
更新日期:2018-01-25 00:00:00
abstract::Transmission of obligate bacterial symbionts between generations is vital for the survival of the host. Although the larvae of certain hydrothermal vent tubeworms (Vestimentifera, Siboglinidae) are symbiont-free and possess a transient digestive system, these structures are lost during development, resulting in adult ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04793
更新日期:2006-05-18 00:00:00
abstract::Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis. However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma. Moreover, lymphatic vessels collapse and become dysfunctio...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature22977
更新日期:2017-06-28 00:00:00
abstract::The death of massive stars produces a variety of supernovae, which are linked to the structure of the exploding stars. The detection of several precursor stars of type II supernovae has been reported (see, for example, ref. 3), but we do not yet have direct information on the progenitors of the hydrogen-deficient type...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05825
更新日期:2007-06-14 00:00:00
abstract::Intensive fisheries have reduced fish biodiversity and abundance in aquatic ecosystems worldwide1-3. 'No-take' marine reserves have become a cornerstone of marine ecosystem-based fisheries management4-6, and their benefits for adjacent fisheries are maximized when reserve design fosters synergies among nearby reserves...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2944-y
更新日期:2020-12-01 00:00:00
abstract::The embryos and larvae of stalked crinoids, which are considered the most basal group of extant echinoderms, have not previously been described. In contrast, much is known about the development of the more accessible stalkless crinoids (feather stars), which are phylogenetically derived from stalked forms. Here we des...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01236
更新日期:2003-01-09 00:00:00
abstract::Most Oryza sativa cultivars die within a week of complete submergence--a major constraint to rice production in south and southeast Asia that causes annual losses of over US 1 billion dollars and affects disproportionately the poorest farmers in the world. A few cultivars, such as the O. sativa ssp. indica cultivar FR...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04920
更新日期:2006-08-10 00:00:00
abstract::Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains. These antibodies all exhibit an unusually high level of somat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10660
更新日期:2011-11-30 00:00:00
abstract::Guard cells are located in the epidermis of plant leaves, and in pairs surround stomatal pores. These control both the influx of CO2 as a raw material for photosynthesis and water loss from plants through transpiration to the atmosphere. Guard cells have become a highly developed system for dissecting early signal tra...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/35066500
更新日期:2001-03-15 00:00:00
abstract::Since the discovery that epidermal growth factor (EGF) can accelerate opening of the eyelids, the EGF receptor (EGF-R) has been extensively studied and is now considered to be a prototype tyrosine kinase receptor. Binding of EGF or of transforming growth factor-alpha (TGF-alpha) or other related factors activates the ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/376337a0
更新日期:1995-07-27 00:00:00
abstract::With the discovery1 of superconductivity at 203 kelvin in H3S, attention returned to conventional superconductors with properties that can be described by the Bardeen-Cooper-Schrieffer and the Migdal-Eliashberg theories. Although these theories predict the possibility of room-temperature superconductivity in metals th...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1201-8
更新日期:2019-05-01 00:00:00
abstract::Exploring visual illusions reveals fundamental principles of cortical processing. Illusory motion perception of non-moving stimuli was described almost a century ago by Gestalt psychologists. However, the underlying neuronal mechanisms remain unknown. To explore cortical mechanisms underlying the 'line-motion' illusio...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature02396
更新日期:2004-03-25 00:00:00
abstract::Y chromosomes underlie sex determination in mammals, but their repeat-rich nature has hampered sequencing and associated evolutionary studies. Here we trace Y evolution across 15 representative mammals on the basis of high-throughput genome and transcriptome sequencing. We uncover three independent sex chromosome orig...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13151
更新日期:2014-04-24 00:00:00
abstract::The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication. Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an i...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14498
更新日期:2015-06-18 00:00:00
abstract::Protein structures are stabilized by hydrophobic and van der Waals forces, and by hydrogen bonds. The relation between these thermodynamic quantities and the actual three-dimensional structure of proteins can not be calculated precisely. However, certain empirical relations have been discovered. Hydrophobic energy is ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/328834a0
更新日期:1987-08-27 00:00:00
abstract::The inner ear is capable of highly selective frequency discrimination. This is achieved not only by the travelling wave of the basilar membrane in the cochlear partition, but also by the active participation of nonlinear and vulnerable elements that enhance frequency selectivity. It has been shown that isolated mammal...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/342814a0
更新日期:1989-12-14 00:00:00
abstract::It has long been known that the 5' to 3' polarity of DNA synthesis results in both a leading and lagging strand at all replication forks. Until now, however, there has been no evidence that leading or lagging strands are spatially organized in any way within a cell. Here we show that chromosome segregation in Escheric...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07282
更新日期:2008-10-30 00:00:00
abstract::The eight catalytic subunits of the mammalian phosphoinositide-3-OH kinase (PI(3)K) family form the backbone of an evolutionarily conserved signalling pathway; however, the roles of most PI(3)K isoforms in organismal physiology and disease are unknown. To delineate the role of p110alpha, a ubiquitously expressed PI(3)...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04694
更新日期:2006-05-18 00:00:00
abstract::About one-third of the carbon dioxide (CO(2)) released into the atmosphere as a result of human activity has been absorbed by the oceans, where it partitions into the constituent ions of carbonic acid. This leads to ocean acidification, one of the major threats to marine ecosystems and particularly to calcifying organ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10295
更新日期:2011-08-03 00:00:00