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Volume 464 Issue 7289, 1 April 2010

The working draft of the human genome sequence was released nearly 10 years ago, with the much-heralded announcement of its completion taking place in June 2000. For much of the decade, casual observers might have wondered what all the fuss was about. But the biology and technology were developing all the time, and with the recent publication of a series of major genome-wide association studies, a flood of human sequences and the advent of 'personal genomics', it's a good time to take stock. See the Editorial for a full list of human genome features in this issue, and the web special on www.nature.com/humangenome. To tell us what you think the human genome's greatest impact has been complete our survey (go.nature.com/KL4gK1) by 30 April. Cover illustration by Jonathan Burton

Editorial

  • Nearly a decade on from the completion of the draft sequence of the human genome, researchers should work with the same intensity and focus to apply the results to health.

    Editorial

    Advertisement

  • The time is right to revitalize US agricultural research.

    Editorial
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Research Highlights

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Journal Club

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News

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Correction

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News Feature

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Column

  • The US defence department should be at the centre of the nation's energy policy, says Daniel Sarewitz.

    • Daniel Sarewitz
    Column
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Correspondence

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Opinion

  • Looking back over the past decade of human genomics, Francis Collins finds five key lessons for the future of personalized medicine — for technology, policy, partnerships and pharmacogenomics.

    • Francis Collins
    Opinion
  • Genomic data will soon become a commodity; the next challenge — linking human genetic variation with physiology and disease — will be as great as the one genomicists faced a decade ago, says J. Craig Venter.

    • J. Craig Venter
    Opinion
  • There is little to show for all the time and money invested in genomic studies of cancer, says Robert Weinberg — and the approach is undermining tried-and-tested ways of doing, and of building, science. This Opinion piece is part of a linked pair; see also Counterpoint: Data First by Todd Golub.

    • Robert Weinberg
    Opinion
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Books & Arts

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News & Views

  • An exceptionally large-scale project aimed at assigning function to all protein-coding genes in the human genome is reported on page 721 by Neumann et al.1. Here are two complementary views on the experimental design and analysis, and on how useful the findings will be to cell biologists.

    • Jason R. Swedlow
    • Cecilia Cotta-Ramusino
    • Stephen J. Elledge
    News & Views
  • Researchers have long wanted to be able to control macroscopic mechanical objects in their smallest possible state of motion. Success in achieving that goal heralds a new generation of quantum experiments.

    • Markus Aspelmeyer
    News & Views
  • Different types of stem cell maintain the skin's epidermis and contribute to its healing after damage. The identity of a stem-cell type that gives rise to different epidermal-cell lineages has just been revealed.

    • Cédric Blanpain
    News & Views
  • Given that the Sun was dimmer in its youth, our planet should have been frozen over for much of its early history. That it evidently wasn't is a puzzle that continues to engage the attention of Earth scientists.

    • James F. Kasting
    News & Views
  • The addition of a fatty acid to certain proteins is vital for the survival of protozoa that cause sleeping sickness and of their mammalian hosts. Compounds that target this process in the protozoa are now reported.

    • George A. M. Cross
    News & Views
  • Why metabolic rates do not vary in direct proportion to body mass has long been the subject of debate. Progress has been made with the realization that no universal scaling exponent can be applied to them.

    • Craig R. White
    News & Views
  • Non-Abelian anyons are hypothesized particles that, if found, could form the basis of a fault-tolerant quantum computer. The theoretical finding that they may turn up in three dimensions comes as a surprise.

    • Chetan Nayak
    News & Views
  • Meteorologist who brought the study of clouds to the forefront of Earth science.

    • Robert A. Houze Jr
    News & Views
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Article

  • Quantum mechanics provides an accurate description of a wide variety of physical systems but it is very challenging to prove that it also applies to macroscopic (classical) mechanical systems. This is because it has been impossible to cool a mechanical mode to its quantum ground state, in which all classical noise is eliminated. Recently, various mechanical devices have been cooled to a near-ground state, but this paper demonstrates the milestone result of a piezoelectric resonator with a mechanical mode cooled to its quantum ground state.

    • A. D. O’Connell
    • M. Hofheinz
    • A. N. Cleland
    Article
  • Much genetic variation among humans can be accounted for by structural DNA differences that are greater than 1 kilobase in size. Here, using tiling oligonucleotide arrays and HapMap samples, a map of 11,700 copy number variations (CNVs) bigger than 443 base pairs has been generated. About half of these CNVs were also genotyped in individuals of different ancestry. The results offer insight into the relative prevalence of mechanisms that generate CNVs, their evolution, and their contribution to complex genetic diseases.

    • Donald F. Conrad
    • Dalila Pinto
    • Matthew E. Hurles
    Article
  • Copy number variants (CNVs) account for a major proportion of human genetic diversity and may contribute to genetic susceptibility to disease. Here, a large, genome-wide study of association between common CNVs and eight common human diseases is presented. The study provides a wealth of technical insights that will inform future study design and analysis. The results also indicate that common CNVs that can be 'typed' on existing platforms are unlikely to contribute much to the genetic basis of common diseases.

    • Nick Craddock
    • Matthew E. Hurles
    • Peter Donnelly
    Article
  • High-throughput microscopy combined with gene silencing by RNA interference is a powerful method for studying gene function. Here, a genome-wide method is presented for phenotypic screening of each of the 21,000 human protein-coding genes, using two-day imaging of dividing cells with fluorescently labelled chromosomes. The method enabled the identification of hundreds of genes involved in biological functions such as cell division, migration and survival.

    • Beate Neumann
    • Thomas Walter
    • Jan Ellenberg
    Article
  • African sleeping sickness, caused by Trypanosoma brucei species, is responsible for some 30,000 human deaths each year. Available treatments are limited by poor efficacy and safety profiles. However, a new molecular target for potential treatments has now been identified. The protein target is T. brucei N-myristoyltransferase. In further experiments, lead compounds have been discovered that inhibit this protein, kill trypanosomes in vitro and in vivo, and can cure trypanosomiasis in mice.

    • Julie A. Frearson
    • Stephen Brand
    • Paul G. Wyatt
    Article
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Letter

  • Massive galaxies in the early Universe have been shown to be forming stars at high rates. Probing the properties of individual star-forming regions is beyond the resolution and sensitivity of existing telescopes. Here, however, observations are reported of the galaxy SMMJ2135–0102 at redshift z=2.3259, which has been gravitationally magnified by a factor of 32 by a galaxy cluster lens in the foreground. The physics underlying star formation here is similar to that in local galaxies, but the energetics are very different.

    • A. M. Swinbank
    • I. Smail
    • J. D. Younger
    Letter
  • Light beams can be engineered to carry orbital angular momentum, with application as, for instance, optical 'spanners' — essentially a 'twisted' variant of the more familiar optical tweezers. Here it is shown that it is, in principle, possible to engineer similar behaviour into an electron beam. Such a beam could find use in a variety of spectroscopy and microscopy techniques.

    • Masaya Uchida
    • Akira Tonomura
    Letter
  • Our current concepts of abrupt climate change are influenced by palaeoclimate evidence for events such as the Younger Dryas cold interval, in which massive climate changes occurred essentially instantaneously. It is thought that an injection of fresh water from the retreating Laurentide Ice Sheet altered the Atlantic meridional overturning circulation and triggered the Younger Dryas, but convincing geological evidence has been elusive. Here, a major flood event that is chronologically consistent with the Younger Dryas has been identified—through the MacKenzie River into the Arctic Ocean.

    • Julian B. Murton
    • Mark D. Bateman
    • Zhirong Yang
    Letter
  • It has been inferred that, during the Archaean eon, there must have been a high concentration of atmospheric CO2 and/or CH4, causing a greenhouse effect that would have compensated for the lower solar luminosity at the time and allowed liquid water to be stable in the hydrosphere. Here it is shown, however, that the mineralogy of Archaean sediments is inconsistent with such high concentrations of greenhouse gases. Instead it is proposed that a lower albedo on the Earth helped to moderate surface temperature.

    • Minik T. Rosing
    • Dennis K. Bird
    • Christian J. Bjerrum
    Letter
  • Evidence for hominin activity on Flores, Indonesia, has been thought to go back at least 800,000 years, as shown by fission-track dating at Mata Menge in the Soa Basin. However, new research at another locality in the Soa Basin uses the more accurate technique of 40Ar/39Ar dating to show that hominins were living on Flores at least a million years ago.

    • Adam Brumm
    • Gitte M. Jensen
    • Michael Storey
    Letter
  • It has been thought that the basal metabolic rate of organisms increases as body mass is raised to some power, p. But the value of p has proved controversial, with both 2/3 and 3/4 being proposed. It is found here that the relationship between mass and metabolic rate does not follow a pure power law at all, and requires a quadratic term to account for curvature. Taking temperature and phylogeny into account, this explains why different data sets have produced different exponents when a power law has been fitted.

    • Tom Kolokotrones
    • Van Savage
    • Walter Fontana
    Letter
  • The genome of the zebra finch — a songbird and a model for studying the vertebrate brain, behaviour and evolution — has been sequenced. Comparison with the chicken genome, the only other bird genome available, shows that genes that have neural function and are implicated in the cognitive processing of song have been evolving rapidly in the finch lineage. Moreover, vocal communication engages much of the transcriptome of the zebra finch brain.

    • Wesley C. Warren
    • David F. Clayton
    • Richard K. Wilson
    Letter Open Access
  • A deletion on human chromosome 22 (22q11.2) is one of the largest genetic risk factors for schizophrenia. Mice with a corresponding deletion have problems with working memory, one feature of schizophrenia. It is now found that these mice also show disruptions in synchronous firing between neurons of the prefrontal cortex and of the hippocampus, an electrophysiological phenomenon that has been linked to learning and memory and which is also thought to be disrupted in schizophrenia patients.

    • Torfi Sigurdsson
    • Kimberly L. Stark
    • Joshua A. Gordon
    Letter
  • There is much interest in understanding the genetic mechanisms that underlie individual variations in gene expression. Here, RNA sequencing has been used to study gene expression in lymphoblastoid cell lines derived from Nigerian individuals for whom extensive genotype information is known. Numerous genetic determinants of variation in gene expression were identified, including variation in transcription, splicing and allele-specific expression.

    • Joseph K. Pickrell
    • John C. Marioni
    • Jonathan K. Pritchard
    Letter
  • Here, sequencing has been used to characterize the mRNA fraction of the transcriptome in Caucasian individuals, to provide a fine-scale view of transcriptomes and to identify genetic variants that affect alternative splicing. Measuring allele-specific expression identified rare expression quantitative trait loci (eQTLs) and allelic differences in transcript structure, revealing new properties of genetic effects on the transcriptome.

    • Stephen B. Montgomery
    • Micha Sammeth
    • Emmanouil T. Dermitzakis
    Letter
  • In multicellular organisms, apoptotic cells are removed from tissues by phagocytes, which recognize and engulf the dying cells. The molecular mechanisms underlying the subsequent degradation of the cells have been unclear. Here, two evolutionarily conserved genes have been identified that are required for such processing in Caenorhabditis elegans and mammals. An understanding of these events could lead to new treatments for diseases associated with poor engulfment and destruction of dying cells.

    • Jason M. Kinchen
    • Kodi S. Ravichandran
    Letter
  • Signalling through the epidermal growth factor receptor (EGFR) is preceded by its dimerization, which has typically been thought to occur through a ligand-induced conformational change. Here, the dimerization dynamics of individual EGFR molecules have been determined in living cells in real time, using a quantum-dot-based approach. Unliganded EGFR molecules undergo spontaneous and reversible dimerization; these pre-formed dimers are primed for ligand binding and signalling and are enriched at the cell periphery.

    • Inhee Chung
    • Robert Akita
    • Ira Mellman
    Letter
  • In plants, the hormone jasmonoyl-isoleucine (JA-Ile) regulates growth, development and defence against pathogens. Proteins of the JAZ family repress JA-Ile-dependent gene expression, but the mechanism has been unclear. Here, an adaptor protein, NINJA, has been identified, which recruits co-repressor proteins that are known to mediate auxin-responsive gene expression as well. Hence these co-repressors are part of general repression complexes that are recruited to several different signalling pathways.

    • Laurens Pauwels
    • Gemma Fernández Barbero
    • Alain Goossens
    Letter
  • The amino-terminal tails of histone proteins are subject to a variety of post-translational modifications; addition or removal of these 'marks' facilitates gene activation or silencing. Here, a mechanism is defined that modulates the activity of the dual-specificity histone demethylase LSD1 during androgen-dependent transcription. Androgen-dependent signalling through protein kinase C beta I leads to phosphorylation of a histone amino acid, which prevents demethylation of an adjacent amino acid by LSD1.

    • Eric Metzger
    • Axel Imhof
    • Roland Schüle
    Letter
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News

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Prospects

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Careers and Recruitment

  • It takes a special combination of thick skin and scientific enthusiasm to be a journal editor. Kendall Powell gets tips from a chosen few.

    • Kendall Powell
    Careers and Recruitment
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Futures

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Brief Communications Arising

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