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Altuna Akalin Matthias Kormaksson Sheng Li Francine E Garrett-Bakelman Maria E Figueroa Ari Melnick Christopher E Mason 《Genome biology》2012,13(10):R87
DNA methylation is a chemical modification of cytosine bases that is pivotal for gene regulation,
cellular specification and cancer development. Here, we describe an R package, methylKit, that
rapidly analyzes genome-wide cytosine epigenetic profiles from high-throughput methylation and
hydroxymethylation sequencing experiments. methylKit includes functions for clustering, sample
quality visualization, differential methylation analysis and annotation features, thus automating
and simplifying many of the steps for discerning statistically significant bases or regions of DNA
methylation. Finally, we demonstrate methylKit on breast cancer data, in which we find statistically
significant regions of differential methylation and stratify tumor subtypes. methylKit is available
at http://code.google.com/p/methylkit. 相似文献
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Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk 下载免费PDF全文
García-Closas M Malats N Real FX Yeager M Welch R Silverman D Kogevinas M Dosemeci M Figueroa J Chatterjee N Tardón A Serra C Carrato A García-Closas R Murta-Nascimento C Rothman N Chanock SJ 《PLoS genetics》2007,3(2):e29
Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs) in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5′ UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 × 10−5). To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5′ UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651) were associated with increased risk for bladder cancer: odds ratio (95% confidence interval): 2.52 (1.06–5.97), 2.74 (1.26–5.98), and 3.02 (1.36–6.63), respectively; and a polymorphism in intron 2 (rs3024994) was associated with reduced risk: 0.65 (0.46–0.91). Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5′ UTR (global p = 0.02 and 0.009, respectively). These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5′ UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk. 相似文献
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Soodabeh Sahba Alex Nechiporuk Karla P. Figueroa Tamilla Nechiporuk Stefan-M. Pulst 《Genomics》1998,47(3):359
Spinocerebellar ataxia type 2 (SCA2) is a member of a group of neurodegenerative diseases that are caused by instability of a DNA CAG repeat. We report the genomic structure of theSCA2gene. Its 25 exons, encompassing approximately 130 kb of genomic DNA, were mapped onto the physical map of the region. Exonic sizes varied from 37 to 890 bp, and intronic sizes ranged from 323 bp to more than 15 kb. The CAG repeat was contained in the 5′ coding region of the gene in exon 1. Determination of the splice junction sequences indicated the presence of only one deviation from the GT-AG rule at the donor splice site of intron 9, which contained a GC instead of a GT dinucleotide. Exon 10, immediately downstream from this rare splice donor site, was alternatively spliced. Alternative splicing does not affect the reading frame and is predicted to encode an isoform containing 70 amino acids less. 相似文献
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Susana Redondo-Gómez Manuel Cantos Enrique Mateos-Naranjo M. Enrique Figueroa Antonio Troncoso 《Soil & Sediment Contamination》2009,18(3):320-327
Soils from four estuaries of SW Iberian Peninsula, affected by anthropogenic influence (urban, industrial and agricultural activities), were analyzed for the occurrence of a variety of metals and trace elements including Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, S and Zn. The soils presented very high levels of salinity (high concentrations of Na, K and Mg), organic matter and, consequently, of C and N concentrations. In contrast, very low values of CaCO3, Ca and P were found. In addition, it should be highlighted that in certain localities (Piedras 1 and 2 and Guadiana in Huelva, Spain, and Ria Formosa, Faro, Portugal) the concentrations of Pb, S and Zn were extremely high, reaching levels of pollution. 相似文献
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