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991.
Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility
Astuti D Morris MR Cooper WN Staals RH Wake NC Fews GA Gill H Gentle D Shuib S Ricketts CJ Cole T van Essen AJ van Lingen RA Neri G Opitz JM Rump P Stolte-Dijkstra I Müller F Pruijn GJ Latif F Maher ER 《Nature genetics》2012,44(3):277-284
Perlman syndrome is a congenital overgrowth syndrome inherited in an autosomal recessive manner that is associated with Wilms tumor susceptibility. We mapped a previously unknown susceptibility locus to 2q37.1 and identified germline mutations in DIS3L2, a homolog of the Schizosaccharomyces pombe dis3 gene, in individuals with Perlman syndrome. Yeast dis3 mutant strains have mitotic abnormalities. Yeast Dis3 and its human homologs, DIS3 and DIS3L1, have exoribonuclease activity and bind to the core RNA exosome complex. DIS3L2 has a different intracellular localization and lacks the PIN domain found in DIS3 and DIS3L1; nevertheless, we show that DIS3L2 has exonuclease activity. DIS3L2 inactivation was associated with mitotic abnormalities and altered expression of mitotic checkpoint proteins. DIS3L2 overexpression suppressed the growth of human cancer cell lines, and knockdown enhanced the growth of these cells. We also detected evidence of DIS3L2 mutations in sporadic Wilms tumor. These observations suggest that DIS3L2 has a critical role in RNA metabolism and is essential for the regulation of cell growth and division. 相似文献
992.
Parallel domestication of the Shattering1 genes in cereals 总被引:3,自引:0,他引:3
Lin Z Li X Shannon LM Yeh CT Wang ML Bai G Peng Z Li J Trick HN Clemente TE Doebley J Schnable PS Tuinstra MR Tesso TT White F Yu J 《Nature genetics》2012,44(6):720-724
993.
The history of the Greenlandic mineral cryolite is outlined from its discovery in late-eighteenth century to the mid-nineteenth century, when its potential for industrial use was first recognized by the Danish chemist Julius Thomsen. During the 1850s, several attempts were made to exploit cryolite for the production of soda and/or aluminium, of which only the soda process became implemented on an industrial scale. The main part of the paper examines the early cryolite soda manufacture, its chemical basis as well as its industrial significance. The focus is thus the intersection of chemical science and technology. It is argued that Thomsen's process depended intimately on current chemical knowledge, and that, with regard to the science-technology relationship, the cryolite soda manufacture signified a new kind of industrial chemistry. 相似文献
994.
995.
Weedon MN Lango H Lindgren CM Wallace C Evans DM Mangino M Freathy RM Perry JR Stevens S Hall AS Samani NJ Shields B Prokopenko I Farrall M Dominiczak A;Diabetes Genetics Initiative;Wellcome Trust Case Control Consortium Johnson T Bergmann S Beckmann JS Vollenweider P Waterworth DM Mooser V Palmer CN Morris AD Ouwehand WH;Cambridge GEM Consortium Zhao JH Li S Loos RJ Barroso I Deloukas P Sandhu MS Wheeler E Soranzo N Inouye M Wareham NJ Caulfield M Munroe PB Hattersley AT McCarthy MI Frayling TM 《Nature genetics》2008,40(5):575-583
Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait. 相似文献
996.
997.
Nearly 30 years ago, Cavalli-Sforza et al. pioneered the use of principal component analysis (PCA) in population genetics and used PCA to produce maps summarizing human genetic variation across continental regions. They interpreted gradient and wave patterns in these maps as signatures of specific migration events. These interpretations have been controversial, but influential, and the use of PCA has become widespread in analysis of population genetics data. However, the behavior of PCA for genetic data showing continuous spatial variation, such as might exist within human continental groups, has been less well characterized. Here, we find that gradients and waves observed in Cavalli-Sforza et al.'s maps resemble sinusoidal mathematical artifacts that arise generally when PCA is applied to spatial data, implying that the patterns do not necessarily reflect specific migration events. Our findings aid interpretation of PCA results and suggest how PCA can help correct for continuous population structure in association studies. 相似文献
998.
Aitman TJ Critser JK Cuppen E Dominiczak A Fernandez-Suarez XM Flint J Gauguier D Geurts AM Gould M Harris PC Holmdahl R Hubner N Izsvák Z Jacob HJ Kuramoto T Kwitek AE Marrone A Mashimo T Moreno C Mullins J Mullins L Olsson T Pravenec M Riley L Saar K Serikawa T Shull JD Szpirer C Twigger SN Voigt B Worley K 《Nature genetics》2008,40(5):516-522
The rat is an important system for modeling human disease. Four years ago, the rich 150-year history of rat research was transformed by the sequencing of the rat genome, ushering in an era of exceptional opportunity for identifying genes and pathways underlying disease phenotypes. Genome-wide association studies in human populations have recently provided a direct approach for finding robust genetic associations in common diseases, but identifying the precise genes and their mechanisms of action remains problematic. In the context of significant progress in rat genomic resources over the past decade, we outline achievements in rat gene discovery to date, show how these findings have been translated to human disease, and document an increasing pace of discovery of new disease genes, pathways and mechanisms. Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research. 相似文献
999.
Benzinou M Creemers JW Choquet H Lobbens S Dina C Durand E Guerardel A Boutin P Jouret B Heude B Balkau B Tichet J Marre M Potoczna N Horber F Le Stunff C Czernichow S Sandbaek A Lauritzen T Borch-Johnsen K Andersen G Kiess W Körner A Kovacs P Jacobson P Carlsson LM Walley AJ Jørgensen T Hansen T Pedersen O Meyre D Froguel P 《Nature genetics》2008,40(8):943-945
Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity. 相似文献
1000.
Hollox EJ Huffmeier U Zeeuwen PL Palla R Lascorz J Rodijk-Olthuis D van de Kerkhof PC Traupe H de Jongh G den Heijer M Reis A Armour JA Schalkwijk J 《Nature genetics》2008,40(1):23-25
Psoriasis is a common inflammatory skin disease with a strong genetic component. We analyzed the genomic copy number polymorphism of the beta-defensin region on human chromosome 8 in 179 Dutch individuals with psoriasis and 272 controls and in 319 German individuals with psoriasis and 305 controls. Comparisons in both cohorts showed a significant association between higher genomic copy number for beta-defensin genes and risk of psoriasis. 相似文献