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Badano JL Leitch CC Ansley SJ May-Simera H Lawson S Lewis RA Beales PL Dietz HC Fisher S Katsanis N 《Nature》2006,439(7074):326-330
Epistatic interactions have an important role in phenotypic variability, yet the genetic dissection of such phenomena remains challenging. Here we report the identification of a novel locus, MGC1203, that contributes epistatic alleles to Bardet-Biedl syndrome (BBS), a pleiotropic, oligogenic disorder. MGC1203 encodes a pericentriolar protein that interacts and colocalizes with the BBS proteins. Sequencing of two independent BBS cohorts revealed a significant enrichment of a heterozygous C430T mutation in patients, and a transmission disequilibrium test (TDT) showed strong over-transmission of this variant. Further analyses showed that the 430T allele enhances the use of a cryptic splice acceptor site, causing the introduction of a premature termination codon (PTC) and the reduction of steady-state MGC1203 messenger RNA levels. Finally, recapitulation of the human genotypes in zebrafish shows that modest suppression of mgc1203 exerts an epistatic effect on the developmental phenotype of BBS morphants. Our data demonstrate how the combined use of biochemical, genetic and in vivo tools can facilitate the dissection of epistatic phenomena, and enhance our appreciation of the genetic basis of phenotypic variability. 相似文献
63.
Sebastian SE Harrison N Batista CD Balicas L Jaime M Sharma PA Kawashima N Fisher IR 《Nature》2006,441(7093):617-620
Competition between electronic ground states near a quantum critical point (QCP)--the location of a zero-temperature phase transition driven solely by quantum-mechanical fluctuations--is expected to lead to unconventional behaviour in low-dimensional systems. New electronic phases of matter have been predicted to occur in the vicinity of a QCP by two-dimensional theories, and explanations based on these ideas have been proposed for significant unsolved problems in condensed-matter physics, such as non-Fermi-liquid behaviour and high-temperature superconductivity. But the real materials to which these ideas have been applied are usually rendered three-dimensional by a finite electronic coupling between their component layers; a two-dimensional QCP has not been experimentally observed in any bulk three-dimensional system, and mechanisms for dimensional reduction have remained the subject of theoretical conjecture. Here we show evidence that the Bose-Einstein condensate of spin triplets in the three-dimensional Mott insulator BaCuSi2O6 (refs 12-16) provides an experimentally verifiable example of dimensional reduction at a QCP. The interplay of correlations on a geometrically frustrated lattice causes the individual two-dimensional layers of spin-(1/2) Cu2+ pairs (spin dimers) to become decoupled at the QCP, giving rise to a two-dimensional QCP characterized by linear power law scaling distinctly different from that of its three-dimensional counterpart. Thus the very notion of dimensionality can be said to acquire an 'emergent' nature: although the individual particles move on a three-dimensional lattice, their collective behaviour occurs in lower-dimensional space. 相似文献
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During the 1930s and 1940s, American physical organic chemists employed electronic theories of reaction mechanisms to construct models offering explanations of organic reactions. But two molecular rearrangements presented enormous challenges to model construction. The Claisen and Cope rearrangements were predominantly inaccessible to experimental investigation and they confounded explanation in theoretical terms. Drawing on the idea that models can be autonomous agents in the production of scientific knowledge, I argue that one group of models in particular were functionally autonomous from the Hughes–Ingold theory. Cope and Hardy’s models of the Claisen and Cope rearrangements were resources for the exploration of the Hughes–Ingold theory that otherwise lacked explanatory power. By generating ‘how-possibly’ explanations, these models explained how these rearrangements could happen rather than why they did happen. Furthermore, although these models were apparently closely connected to theory in terms of their construction, I argue that partial autonomy issued in extra-logical factors concerning the attitudes of American chemists to the Hughes–Ingold theory. And in the absence of a complete theoretical hegemony, a degree of consensus was reached concerning modelling the Claisen rearrangement mechanism. 相似文献
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We investigated localities from which Eutamias atristriatus Bailey, 1913 (= Tamias minimus atristriatus ) and Zapus luteus Miller, 1911 (= Zapus hudsonius luteus ) were collected during a 1902 survey in the Sacramento Mountains, New Mexico, by the United States Biological Survey. The locality from which the holotype of Eutamias atristriatus was collected is restricted to James Canyon rather than the Rio Pe?asco. Locality records indicate that the historical distribution of Zapus hudsonius luteus and its obligate wetland habitat were broader than currently realized. 相似文献
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Emerging fungal threats to animal, plant and ecosystem health 总被引:7,自引:0,他引:7
Fisher MC Henk DA Briggs CJ Brownstein JS Madoff LC McCraw SL Gurr SJ 《Nature》2012,484(7393):186-194
The past two decades have seen an increasing number of virulent infectious diseases in natural populations and managed landscapes. In both animals and plants, an unprecedented number of fungal and fungal-like diseases have recently caused some of the most severe die-offs and extinctions ever witnessed in wild species, and are jeopardizing food security. Human activity is intensifying fungal disease dispersal by modifying natural environments and thus creating new opportunities for evolution. We argue that nascent fungal infections will cause increasing attrition of biodiversity, with wider implications for human and ecosystem health, unless steps are taken to tighten biosecurity worldwide. 相似文献
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Females often mate with several males before producing offspring. Field studies of vertebrates suggest, and laboratory experiments on invertebrates confirm, that even when males provide no material benefits, polyandry can enhance offspring survival. This enhancement is widely attributed to genetic benefits that arise whenever paternity is biased towards males that sire more viable offspring. Field studies suggest that post-mating sexual selection biases fertilization towards genetically more compatible males and one controlled experiment has shown that, when females mate with close kin, polyandry reduces the relative number of inbred offspring. Another potential genetic benefit of polyandry is that it increases offspring survival because males with more competitive ejaculates sire more viable offspring. Surprisingly, however, there is no unequivocal evidence for this process. Here, by experimentally assigning mates to females, we show that polyandry greatly increases offspring survival in the Australian marsupial Antechinus stuartii. DNA profiling shows that males that gain high paternity under sperm competition sire offspring that are more viable. This beneficial effect occurs in both the laboratory and the wild. Crucially, there are no confounding non-genetic maternal effects that could arise if polyandry increases female investment in a particular reproductive event because A. stuartii is effectively semelparous. Our results therefore show that polyandry improves female lifetime fitness in nature. The threefold increase in offspring survival is not negated by a decline in maternal lifespan and is too large to be offset by an equivalent decline in the reproductive performance of surviving offspring. 相似文献