Abstract:
:Estimation of gene diversity (heterozygosity) at 1442 single-nucleotide polymorphism (SNP) loci in an ethnically diverse sample of humans revealed consistently reduced gene diversities at SNP loci causing amino acid changes, particularly those causing amino acid changes predicted to be disruptive to protein structure. The reduction of gene diversity at these SNP loci, in comparison to SNPs in the same genes not affecting protein structure, is evidence that negative natural selection (purifying selection) has reduced the population frequencies of deleterious SNP alleles. This, in turn, suggests that slightly deleterious mutations are widespread in the human population and that estimation of gene diversity even in a sample of modest size can help guide the search for disease-associated genes.
journal_name
Proc Natl Acad Sci U S Aauthors
Hughes AL,Packer B,Welch R,Bergen AW,Chanock SJ,Yeager Mdoi
10.1073/pnas.2536718100keywords:
subject
Has Abstractpub_date
2003-12-23 00:00:00pages
15754-7issue
26eissn
0027-8424issn
1091-6490pii
2536718100journal_volume
100pub_type
杂志文章abstract::We have developed a color complementation assay that allows rapid screening of specific genomic DNA sequences. It is based on the simultaneous amplification of two or more DNA segments with fluorescent oligonucleotide primers such that the generation of a color, or combination of colors, can be visualized and used for...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.23.9178
更新日期:1989-12-01 00:00:00
abstract::Myxococcus xanthus is a Gram-negative bacterium that aggregates to form fruiting bodies when nutrients are limiting. Previous studies showed that the frz mutants that are defective in chemotaxis exhibited irregular and infrequent patterns of cellular reversal. In contrast, wild-type cells, when examined individually, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.9.4142
更新日期:1996-04-30 00:00:00
abstract::Mammalian CLC proteins function as Cl(-) channels or as electrogenic Cl(-)/H(+) exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0606137103
更新日期:2006-09-12 00:00:00
abstract::The ecology of microbes in the gut has been shown to play important roles in the health of the host. To better understand microbial growth and population dynamics in the proximal colon, the primary region of bacterial growth in the gut, we built and applied a fluidic channel that we call the "minigut." This is a chann...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1601306113
更新日期:2016-10-11 00:00:00
abstract::Grain yield in many cereal crops is largely determined by grain size. Here we report the genetic and molecular characterization of GS3, a major quantitative trait locus for grain size. It functions as a negative regulator of grain size and organ size. The wild-type isoform is composed of four putative domains: a plant...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1014419107
更新日期:2010-11-09 00:00:00
abstract::In eukaryotes, RNA polymerase I transcription is controlled by DNA elements located within the spacers that separate the tandemly arranged rRNA genes. Unlike rRNA coding sequences, the intergenic spacers evolve rapidly and have little sequence similarity even among closely related species. Nonetheless, the arrangement...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.16.7528
更新日期:1993-08-15 00:00:00
abstract::One of the core features of human speech is that words cause listeners to retrieve corresponding visual mental images. However, whether vocalizations similarly evoke mental images in animal communication systems is surprisingly unknown. Japanese tits (Parus minor) produce specific alarm calls when and only when encoun...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1718884115
更新日期:2018-02-13 00:00:00
abstract::The photoaffinity labeling agent 5-azidoindole-3-acetic acid, an analog of the endogenous plant hormone indole-3-acetic acid (an auxin), was used to identify indole-3-acetic acid-binding proteins in maize. Two peptides with subunit molecular masses of 24 and 22 kilodaltons are specifically labeled in a saturable manne...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.16.6153
更新日期:1989-08-01 00:00:00
abstract::The 24-hr intracarotid infusion of plasma-treated glycyl-L-glutamine (3 microM) produced significant enhancement of the monomeric G1 and tetrameric G4 forms of acetylcholinesterase of the cat superior cervical ganglion 48 hr after denervation, in comparison with denervated, noninfused controls. No significant effect o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.16.6215
更新日期:1988-08-01 00:00:00
abstract::The genes encoding the histone acetyl-transferases (HATs) CREB binding protein (CREBBP) and EP300 are recurrently mutated in the activated B cell-like and germinal center (GC) B cell-like subtypes of diffuse large B cell lymphoma (DLBCL). Here, we introduced a patient mutation into a human DLBCL cell line using CRISPR...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1619555114
更新日期:2017-09-05 00:00:00
abstract::To study the similarity between a putative cloned mammalian release factor (RF) and tryptophanyl-tRNA synthetase (TRS), a recombinant rabbit RF fusion protein was expressed from prokaryotic expression vectors. Purified fractions of the fusion proteins were tested for TRS and RF activities. Addition of the fusion prote...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.7.2777
更新日期:1994-03-29 00:00:00
abstract::Tumor necrosis factor alpha (TNF-alpha), also known as cachectin, was demonstrated to induce the expression of human immunodeficiency virus (HIV) in a chronically infected T-cell clone (ACH-2). Concentrations of recombinant TNF-alpha as low as 50 pg/ml induced a significant increase over background of HIV expression i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.7.2365
更新日期:1989-04-01 00:00:00
abstract::It is generally believed that serial passage at high multiplicity of infection (moi) is required for the generation of defective interfering (DI) particles. High levels of DI RNAs are found associated with persistent infections initiated with laboratory cultures of cucumber necrosis virus (CNV). Two synthetic CNV tran...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.24.11153
更新日期:1991-12-15 00:00:00
abstract::Facilitation of social attraction and bonding by the evolutionarily conserved neuropeptide oxytocin is well-established in female mammals. However, accumulating behavioral evidence suggests that oxytocin may have evolved sex-specific functional roles in the domain of human social cognition. A critical question is how ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1602620113
更新日期:2016-07-05 00:00:00
abstract::Regulation of the sterol-synthesizing mevalonate pathway occurs in part through feedback-regulated endoplasmic reticulum degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R). In yeast, the Hmg2p isozyme of HMG-R is regulated in this manner. We have tested the involvement of ubiquitination in the regulated d...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.24.12944
更新日期:1997-11-25 00:00:00
abstract::English and Russian color terms divide the color spectrum differently. Unlike English, Russian makes an obligatory distinction between lighter blues ("goluboy") and darker blues ("siniy"). We investigated whether this linguistic difference leads to differences in color discrimination. We tested English and Russian spe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0701644104
更新日期:2007-05-08 00:00:00
abstract::Cellular metabolism alters patterns of gene expression through a variety of mechanisms, including alterations in histone modifications and transcription factor activity. Nicotinamide adenine dinucleotide (NAD)-dependent proteins such as poly(ADP ribose) polymerases (PARPs) and sirtuin deacetylases play important roles...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1002130107
更新日期:2010-12-14 00:00:00
abstract::Despite sharing a common architecture with archetypal voltage-gated ion channels (VGICs), hyperpolarization- and cAMP-activated ion (HCN) channels open upon hyperpolarization rather than depolarization. The basic motions of the voltage sensor and pore gates are conserved, implying that these domains are inversely coup...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1816724116
更新日期:2019-01-08 00:00:00
abstract::Despite its popularity, chromatin immunoprecipitation followed by sequencing (ChIP-seq) remains a tedious (>2 d), manually intensive, low-sensitivity and low-throughput approach. Here, we combine principles of microengineering, surface chemistry, and molecular biology to address the major limitations of standard ChIP-...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1913261117
更新日期:2020-06-16 00:00:00
abstract::The ubiquitin ligase Siah2 has been shown to regulate prolyl hydroxylase 3 (PHD3) stability with concomitant effect on HIF-1alpha availability. Because HIF-1alpha is implicated in tumorigenesis and metastasis, we used SW1 mouse melanoma cells, which develop primary tumors with a propensity to metastasize, in a syngene...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0804063105
更新日期:2008-10-28 00:00:00
abstract::We have recently shown that the Alzheimer disease 40-residue amyloid beta-protein [A beta P-(1-40)] can form cation-selective channels when incorporated into planar lipid bilayers by fusion of liposomes containing the peptide. Since A beta P-(1-40) comprises portions of the putative extracellular and membrane-spanning...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.22.10573
更新日期:1993-11-15 00:00:00
abstract::Severe burn trauma is generally followed by a catabolic response that leads to muscle wasting and weakness affecting skeletal musculature. Here, we perform whole-genome expression and in vivo NMR spectroscopy studies to define respectively the full set of burn-induced changes in skeletal muscle gene expression and the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0501211102
更新日期:2005-04-12 00:00:00
abstract::Electron spectroscopic imaging, a new technique that permits the quantitative detection of the spatial distributions of atomic elements at high resolution, has been applied to the epiphyseal zone of hypertrophy in the mouse for the visualization of calcium, phosphorus, and sulfur. Longitudinally sectioned epiphyseal g...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.5.1322
更新日期:1983-03-01 00:00:00
abstract::The surface layer of the oceans and other aquatic environments contains many bacteria that range in activity, from dormant cells to those with high rates of metabolism. However, little experimental evidence exists about the activity of specific bacterial taxa, especially rare ones. Here we explore the relationship bet...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1101405108
更新日期:2011-08-02 00:00:00
abstract::Escherichia coli cells treated with toluene replicate DNA when they are provided with deoxyribonucleoside 5'-triphosphates, ATP, Mg(++), and K(+). However, when deoxycytidine 5'-triphosphate is replaced by hydroxymethyl deoxycytidine 5'-triphosphate, incorporation of nucleotides into acid-precipitable material by tolu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.10.2527
更新日期:1971-10-01 00:00:00
abstract::Regulated proteolysis is required to execute many cellular programs. In Caulobacter crescentus, timely degradation of the master regulator CtrA by ClpXP protease is essential for cell-cycle progression and requires the colocalization of CtrA and RcdA. Here, we establish a biochemical framework to understand regulated ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0701776104
更新日期:2007-04-17 00:00:00
abstract::The synthesis of a photosensitive blocking group for the carboxyl function of neurotransmitters, in this case glycine, is reported. The compound, 2-methoxy-5-nitrophenyl glycine ester (caged glycine), is photolyzed by a laser pulse at 308 or 337 nm within 3 microseconds and with a product quantum yield of 0.2. The com...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.23.11074
更新日期:1993-12-01 00:00:00
abstract::The role of the mouse tumor necrosis factor (TNF) promoter, 5' untranslated region (UTR), and 3' UTR in TNF gene expression has been examined in three nonmacrophage cell lines (HeLa, NIH 3T3, and L-929). The TNF promoter is not macrophage-specific. On the contrary, it constitutively drives reporter gene expression in ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.2.673
更新日期:1992-01-15 00:00:00
abstract::The activation of plant defensive genes in leaves of tomato plants in response to herbivore damage or mechanical wounding is mediated by a mobile 18-amino acid polypeptide signal called systemin. Systemin is derived from a larger, 200-amino acid precursor called prosystemin, similar to polypeptide hormones and soluble...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.93.22.12053
更新日期:1996-10-29 00:00:00
abstract::The unique ability of bovine papillomavirus (BPV-1) DNA to replicate as a stable, multicopy plasmid in transformed mouse cells has led to its utilization as a eukaryotic cloning vector. One limitation of the system has been the marked reduction in transformation efficiency when BPV-1 DNA or the subgenomic transforming...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.23.7147
更新日期:1982-12-01 00:00:00