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A prevalent narrative locates the discovery of the statistical phenomenon of regression to the mean in the work of Francis Galton. It is claimed that after 1885, Galton came to explain the fact that offspring deviated less from the mean value of the population than their parents did as a population-level statistical phenomenon and not as the result of the processes of inheritance. Arguing against this claim, we show that Galton did not explain regression towards mediocrity statistically, and did not give up on his ideas regarding an inheritance process that caused offspring to revert to the mean. While the common narrative focuses almost exclusively on Galton’s statistics, our arguments emphasize the anthropological and biological questions that Galton addressed. Galton used regression towards mediocrity to support the claim that some biological types were more stable than others and hence were resistant to evolutionary change. This view had implications concerning both natural selection and eugenics. The statistical explanation attributed to Galton appeared later, during the biometrician-mutationist debate in the early 1900s. It was in the context of this debate and specifically by the biometricians, that the development of the statistical explanation was originally attributed to Galton. 相似文献
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Locasale JW Grassian AR Melman T Lyssiotis CA Mattaini KR Bass AJ Heffron G Metallo CM Muranen T Sharfi H Sasaki AT Anastasiou D Mullarky E Vokes NI Sasaki M Beroukhim R Stephanopoulos G Ligon AH Meyerson M Richardson AL Chin L Wagner G Asara JM Brugge JS Cantley LC Vander Heiden MG 《Nature genetics》2011,43(9):869-874
Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood. Using a metabolomics approach with isotope labeling, we found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase (PHGDH). An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal copy number gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Our findings show that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer. 相似文献
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Bass AJ Lawrence MS Brace LE Ramos AH Drier Y Cibulskis K Sougnez C Voet D Saksena G Sivachenko A Jing R Parkin M Pugh T Verhaak RG Stransky N Boutin AT Barretina J Solit DB Vakiani E Shao W Mishina Y Warmuth M Jimenez J Chiang DY Signoretti S Kaelin WG Spardy N Hahn WC Hoshida Y Ogino S Depinho RA Chin L Garraway LA Fuchs CS Baselga J Tabernero J Gabriel S Lander ES Getz G Meyerson M 《Nature genetics》2011,43(10):964-968
Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of 30.7× and 31.9× coverage, respectively. We identify an average of 75 somatic rearrangements per tumor, including complex networks of translocations between pairs of chromosomes. Eleven rearrangements encode predicted in-frame fusion proteins, including a fusion of VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes TCF4, which cooperates with β-catenin in colorectal carcinogenesis, the fusion lacks the TCF4 β-catenin-binding domain. We found a colorectal carcinoma cell line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage-independent growth using RNA interference-mediated knockdown. This study shows previously unidentified levels of genomic rearrangements in colorectal carcinoma that can lead to essential gene fusions and other oncogenic events. 相似文献