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Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma 总被引:20,自引:0,他引:20
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Puigserver P Rhee J Donovan J Walkey CJ Yoon JC Oriente F Kitamura Y Altomonte J Dong H Accili D Spiegelman BM 《Nature》2003,423(6939):550-555
245.
Van Laere AS Nguyen M Braunschweig M Nezer C Collette C Moreau L Archibald AL Haley CS Buys N Tally M Andersson G Georges M Andersson L 《Nature》2003,425(6960):832-836
Most traits and disorders have a multifactorial background indicating that they are controlled by environmental factors as well as an unknown number of quantitative trait loci (QTLs). The identification of mutations underlying QTLs is a challenge because each locus explains only a fraction of the phenotypic variation. A paternally expressed QTL affecting muscle growth, fat deposition and size of the heart in pigs maps to the IGF2 (insulin-like growth factor 2) region. Here we show that this QTL is caused by a nucleotide substitution in intron 3 of IGF2. The mutation occurs in an evolutionarily conserved CpG island that is hypomethylated in skeletal muscle. The mutation abrogates in vitro interaction with a nuclear factor, probably a repressor, and pigs inheriting the mutation from their sire have a threefold increase in IGF2 messenger RNA expression in postnatal muscle. Our study establishes a causal relationship between a single-base-pair substitution in a non-coding region and a QTL effect. The result supports the long-held view that regulatory mutations are important for controlling phenotypic variation. 相似文献
246.
Wiedemann N Kozjak V Chacinska A Schönfisch B Rospert S Ryan MT Pfanner N Meisinger C 《Nature》2003,424(6948):565-571
Mitochondria contain translocases for the transport of precursor proteins across their outer and inner membranes. It has been assumed that the translocases also mediate the sorting of proteins to their submitochondrial destination. Here we show that the mitochondrial outer membrane contains a separate sorting and assembly machinery (SAM) that operates after the translocase of the outer membrane (TOM). Mas37 forms a constituent of the SAM complex. The central role of the SAM complex in the sorting and assembly pathway of outer membrane proteins explains the various pleiotropic functions that have been ascribed to Mas37 (refs 4, 11-15). These results suggest that the TOM complex, which can transport all kinds of mitochondrial precursor proteins, is not sufficient for the correct integration of outer membrane proteins with a complicated topology, and instead transfers precursor proteins to the SAM complex. 相似文献
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A velocity dipole in the distribution of radio galaxies 总被引:1,自引:0,他引:1
The motion of our Galaxy through the Universe is reflected in a systematic shift in the temperature of the cosmic microwave background-because of the Doppler effect, the temperature of the background is about 0.1 per cent higher in the direction of motion, with a correspondingly lower temperature in the opposite direction. This effect is known as dipole anisotropy. If our standard cosmological model is correct, a related dipole effect should also be present as an enhancement in the surface density of distant galaxies in the direction of motion. The main obstacle to finding this signal is the uneven distribution of galaxies in the local supercluster, which drowns out the small cosmological signal. Here we report a detection of the expected cosmological dipole anisotropy in the distribution of galaxies. We use a survey of radio galaxies that are mainly located at cosmological distances, so the contamination from nearby clusters is small. When local radio galaxies are removed from the sample, the resulting dipole is in the same direction as the temperature anisotropy of the microwave background, and close to the expected amplitude. The result therefore confirms the standard cosmological interpretation of the microwave background. 相似文献
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Gardner MJ Hall N Fung E White O Berriman M Hyman RW Carlton JM Pain A Nelson KE Bowman S Paulsen IT James K Eisen JA Rutherford K Salzberg SL Craig A Kyes S Chan MS Nene V Shallom SJ Suh B Peterson J Angiuoli S Pertea M Allen J Selengut J Haft D Mather MW Vaidya AB Martin DM Fairlamb AH Fraunholz MJ Roos DS Ralph SA McFadden GI Cummings LM Subramanian GM Mungall C Venter JC Carucci DJ Hoffman SL Newbold C Davis RW Fraser CM Barrell B 《Nature》2002,419(6906):498-511
The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria. 相似文献