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排序方式: 共有7211条查询结果,搜索用时 31 毫秒
281.
Stacey SN Gudbjartsson DF Sulem P Bergthorsson JT Kumar R Thorleifsson G Sigurdsson A Jakobsdottir M Sigurgeirsson B Benediktsdottir KR Thorisdottir K Ragnarsson R Scherer D Rudnai P Gurzau E Koppova K Höiom V Botella-Estrada R Soriano V Juberías P Grasa M Carapeto FJ Tabuenca P Gilaberte Y Gudmundsson J Thorlacius S Helgason A Thorlacius T Jonasdottir A Blondal T Gudjonsson SA Jonsson GF Saemundsdottir J Kristjansson K Bjornsdottir G Sveinsdottir SG Mouy M Geller F Nagore E Mayordomo JI 《Nature genetics》2008,40(11):1313-1318
To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide SNP association study of 930 Icelanders with BCC and 33,117 controls. After analyzing 304,083 SNPs, we observed signals from loci at 1p36 and 1q42, and replicated these associations in additional sample sets from Iceland and Eastern Europe. Overall, the most significant signals were from rs7538876 on 1p36 (OR = 1.28, P = 4.4 x 10(-12)) and rs801114 on 1q42 (OR = 1.28, P = 5.9 x 10(-12)). The 1p36 locus contains the candidate genes PADI4, PADI6, RCC2 and ARHGEF10L, and the gene nearest to the 1q42 locus is the ras-homolog RHOU. Neither locus was associated with fair pigmentation traits that are known risk factors for BCC, and no risk was observed for melanoma. Approximately 1.6% of individuals of European ancestry are homozygous for both variants, and their estimated risk of BCC is 2.68 times that of noncarriers. 相似文献
282.
A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse 总被引:1,自引:0,他引:1
Rosengren Pielberg G Golovko A Sundström E Curik I Lennartsson J Seltenhammer MH Druml T Binns M Fitzsimmons C Lindgren G Sandberg K Baumung R Vetterlein M Strömberg S Grabherr M Wade C Lindblad-Toh K Pontén F Heldin CH Sölkner J Andersson L 《Nature genetics》2008,40(8):1004-1009
In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals. 相似文献
283.
High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi 总被引:1,自引:0,他引:1
Holt KE Parkhill J Mazzoni CJ Roumagnac P Weill FX Goodhead I Rance R Baker S Maskell DJ Wain J Dolecek C Achtman M Dougan G 《Nature genetics》2008,40(8):987-993
Isolates of Salmonella enterica serovar Typhi (Typhi), a human-restricted bacterial pathogen that causes typhoid, show limited genetic variation. We generated whole-genome sequences for 19 Typhi isolates using 454 (Roche) and Solexa (Illumina) technologies. Isolates, including the previously sequenced CT18 and Ty2 isolates, were selected to represent major nodes in the phylogenetic tree. Comparative analysis showed little evidence of purifying selection, antigenic variation or recombination between isolates. Rather, evolution in the Typhi population seems to be characterized by ongoing loss of gene function, consistent with a small effective population size. The lack of evidence for antigenic variation driven by immune selection is in contrast to strong adaptive selection for mutations conferring antibiotic resistance in Typhi. The observed patterns of genetic isolation and drift are consistent with the proposed key role of asymptomatic carriers of Typhi as the main reservoir of this pathogen, highlighting the need for identification and treatment of carriers. 相似文献
284.
Zhang Y Goss AM Cohen ED Kadzik R Lepore JJ Muthukumaraswamy K Yang J DeMayo FJ Whitsett JA Parmacek MS Morrisey EE 《Nature genetics》2008,40(7):862-870
Epithelial organs, including the lung, are known to possess regenerative abilities through activation of endogenous stem cell populations, but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung, its absence in Gata6-null lung epithelium leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation. This expansion of BASCs was the result of a pronounced increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the noncanonical Wnt receptor Fzd2 was downregulated in Gata6 mutants and increased Fzd2 or decreased beta-catenin expression rescued, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, canonical Wnt signaling was activated in the niche containing BASCs and forced activation of Wnt signaling led to a large increase in BASC numbers. Moreover, Gata6 was required for proper lung epithelial regeneration, and postnatal loss of Gata6 led to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration. 相似文献
285.
286.
1.INTaODUCTIONThemultilayerfeedforwardneuralnetworks(MFNN)hasbeenwidelyappliedinmanyfieldssuchaspatternrecognition,nonlinearoptimization,systemidentificationandcontrol.Thesimpleback-propagation(BP)learningalgorithmisusuallyadoptedtoupdateitsweights.TheBPalgorithm,however,suffersdrawbacksofslowconvergenceandunpredictablesolutionsduringlearning.Althoughmailyapproachessuchasvariablestepsize,conjugategradient,pseudo-Newtonmethods[4]andothermethods[3,10],havebeendevelopedtoovercometheproble… 相似文献
287.
Bosch-Comas A Lindsten K Gonzàlez-Duarte R Masucci MG Marfany G 《Cellular and molecular life sciences : CMLS》2006,63(6):723-734
The biological functions of the more than one hundred genes coding for deubiquitinating enzymes in the human genome remain
mostly unknown. The USP25 gene, located at 21q11.2, encodes three protein isoforms produced by alternative splicing. While
two of the isoforms are expressed nearly ubiquituously, the expression of the longer USP25 isoform (USP25m) is restricted
to muscular tissues and is upregulated during myogenesis. USP25m interacts with three sarcomeric proteins: actin alpha-1 (ACTA1),
filamin C (FLNC), and myosin binding protein C1 (MyBPC1), which are critically involved in muscle differentiation and maintenance,
and have been implicated in the pathogenesis of severe myopathies. Biochemical analyses demonstrated that MyBPC1 is a short-lived
proteasomal substrate, and its degradation is prevented by over-expression of USP25m but not by other USP25 isoforms. In contrast,
ACTA1 and FLNC appear to be stable proteins, indicating that their interaction with USP25m is not related to their turnover
rate.
Received 7 November 2005; received after revision 7 January 2006; accepted 13 January 2006 相似文献
288.
Liver X receptors in cardiovascular and metabolic disease 总被引:5,自引:0,他引:5
Liver X receptors (LXRs) α and β are nuclear oxysterol receptors and metabolic sensors initially found to regulate cholesterol
metabolism and lipid biosynthesis. Recent studies have elucidated the importance of LXR in the development of cardiovascular
diseases and metabolic disorders. LXR agonists prevent development of atherosclerosis by modulation of metabolic as well as
inflammatory gene expression in rodent models. Moreover, LXR activation inhibits hepatic gluconeogenesis and lowers serum
glucose levels, indicating possible application of LXR activation in the treatment of diabetes mellitus. However, first-generation
LXR agonists elevate hepatic and serum trigylceride levels, making subtype-specific agonists and selective LXR modulators
rather than unselective LXR agonists a potential pharmacological strategy. This review summarizes the multiple physiological
and pathophysiological implications of LXRs and observations that identify LXRs as potential targets for therapeutic interventions
in human cardiovascular and metabolic disease.
Received 30 August 2005; received after revision 10 October 2005; accepted 4 November 2005 相似文献
289.
Greenway MJ Andersen PM Russ C Ennis S Cashman S Donaghy C Patterson V Swingler R Kieran D Prehn J Morrison KE Green A Acharya KR Brown RH Hardiman O 《Nature genetics》2006,38(4):411-413
We recently identified angiogenin (ANG) as a candidate susceptibility gene for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder characterized by adult-onset loss of motor neurons. We now report the finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS. Our findings provide further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration. 相似文献
290.
Gandhi TK Zhong J Mathivanan S Karthick L Chandrika KN Mohan SS Sharma S Pinkert S Nagaraju S Periaswamy B Mishra G Nandakumar K Shen B Deshpande N Nayak R Sarker M Boeke JD Parmigiani G Schultz J Bader JS Pandey A 《Nature genetics》2006,38(3):285-293
We present the first analysis of the human proteome with regard to interactions between proteins. We also compare the human interactome with the available interaction datasets from yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans) and fly (Drosophila melanogaster). Of >70,000 binary interactions, only 42 were common to human, worm and fly, and only 16 were common to all four datasets. An additional 36 interactions were common to fly and worm but were not observed in humans, although a coimmunoprecipitation assay showed that 9 of the interactions do occur in humans. A re-examination of the connectivity of essential genes in yeast and humans indicated that the available data do not support the presumption that the number of interaction partners can accurately predict whether a gene is essential. Finally, we found that proteins encoded by genes mutated in inherited genetic disorders are likely to interact with proteins known to cause similar disorders, suggesting the existence of disease subnetworks. The human interaction map constructed from our analysis should facilitate an integrative systems biology approach to elucidating the cellular networks that contribute to health and disease states. 相似文献