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- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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- O'Brien, Sallyarm L., et al.
(författare)
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CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer
- 2007
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 120:7, s. 1434-1443
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Tidskriftsartikel (refereegranskat)abstract
- DNA microarrays have the potential to classify tumors according to their transcriptome. Tissue microarrays (TMAs) facilitate the validation of biomarkers by offering a high-throughput approach to sample analysis. We reanalyzed a high profile breast cancer DNA microarray dataset containing 96 tumor samples using a powerful statistical approach, between group analyses. Among the genes we identified was centromere protein-F (CENP-F), a gene associated with poor prognosis. In a published follow-up breast cancer DNA microarray study, comprising 295 tumour samples, we found that CENP-F upregulation was significantly associated with worse overall survival (p < 0.001) and reduced metastasis-free survival (p < 0.001). To validate and expand upon these findings, we used 2 independent breast cancer patient cohorts represented on TMAs. CENP-F protein expression was evaluated by immunohistochemistry in 91 primary breast cancer samples from cohort I and 289 samples from cohort II. CENP-F correlated with markers of aggressive tumor behavior including ER negativity and high tumor grade. In cohort I, CENP-F was significantly associated with markers of CIN including cyclin E, increased telomerase activity, c-Myc amplification and aneuploidy. In cohort II CENP-F correlated with VEGFR2, phosphorylated Ets-2 and Ki67, and in multivariate analysis, was an independent predictor of worse breast cancer-specific survival (p = 0.036) and overall survival (p = 0.040). In conclusion, we identified CENP-F as a biomarker associated with poor outcome in breast cancer and showed several novel associations of biological significance. (c) 2007 Wiley-Liss, Inc.
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| 5. |
- Lanigan, Fiona, et al.
(författare)
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Increased claudin-4 expression is associated with poor prognosis and high tumour grade in breast cancer
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:9, s. 2088-2097
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Tidskriftsartikel (refereegranskat)abstract
- The role of intercellular tight junctions in breast epithelia[ cells is traditionaliy thought to be in maintaining polarity and barrier function. However, claudin-4, a tight junction protein, is overexpressed in breast tumour cells compared to normal epithelial cells, which generally corresponds to a loss in polarity. The aim of this study was to investigate the distribution and potential clinical value of claudin-4 in breast cancer, and to evaluate its usefulness as a prognostic and predictive biomarker. Expression of claudin-4 was initially examined by Western blot analysis in a cohort of 88 breast tumours, and was found to correlate positively with tumour grade and negatively with ER. Claudin-4 expression was then evaluated by immunohistochemistry in a larger cohort of 299 tumours represented on a tissue microarray. Claudin-4 expression correlated positively with tumour grade and Hcr2, and negatively with ER. High claudin-4 expression was also associated with worse breast cancer-specific survival (p = 0.0031), recurrence-free survival (P = 0.025) and overall survival (p = 0.034). Multivariate analysis revealed that claudin-4 independently predicted survival in the entire cohort (HR 1.95; 95%CI 1.01-3.79; p = 0.047) and in the ER positive subgroup treated with adjuvant tamoxifen (FIR 4.34; 95%C1 1.14-16.53; p = 0.032). This relationship between increased claudin-4 expression and adverse outcome was validated at the mRNA level in a DNA microarray dataset of 295 breast tumours. We conclude that high levels of claudin-4 protein are associated with adverse outcome in breast cancer patients, including the subgroup of patients treated with adjuvant tamoxifen. (C) 2008 Wiley-Liss, Inc.
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| 10. |
- Hegarty, Peter, 1971, et al.
(författare)
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When Almost All Sets are Difference Dominated
- 2009
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Ingår i: Random Structures and Algorithms. - : Wiley. - 1042-9832 .- 1098-2418. ; 35:1, s. 118-136
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the relationship between the sizes of the sum and difference sets attached to a subset of {0,1,...,N}, chosen randomly according to a binomial model with parameter p(N), with N^{-1} = o(p(N)). We show that the random subset is almost surely difference dominated, as N --> oo, for any choice of p(N) tending to zero, thus confirming a conjecture of Martin and O'Bryant. The proofs use recent strong concentration results. Furthermore, we exhibit a threshold phenomenon regarding the ratio of the size of the difference- to the sumset. If p(N) = o(N^{-1/2}) then almost all sums and differences in the random subset are almost surely distinct, and in particular the difference set is almost surely about twice as large as the sumset. If N^{-1/2} = o(p(N)) then both the sum and difference sets almost surely have size (2N+1) - O(p(N)^{-2}), and so the ratio in question is almost surely very close to one. If p(N) = c N^{-1/2} then as c increases from zero to infinity (i.e., as the threshold is crossed), the same ratio almost surely decreases continuously from two to one according to an explicitly given function of c. We also extend our results to the comparison of the generalized difference sets attached to an arbitrary pair of binary linear forms. For certain pairs of forms f and g, we show that there in fact exists a sharp threshold at c_{f,g} N^{-1/2}, for some computable constant c_{f,g}, such that one form almost surely dominates below the threshold, and the other almost surely above it. The heart of our approach involves using different tools to obtain strong concentration of the sizes of the sum and difference sets about their mean values, for various ranges of the parameter p.
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