Browsing by Author "Young, D."
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Item Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans(Nature Genetics, 2013-09) Comas, I.; Coscolla, M.; Luo, T.; Borrell, S.; Holt, K.E.; Kato-Maeda, M.; Parkhill, J.; Malla, B.; Berg, S.; Thwaites, G.; Yeboah-Manu, D.; Bothamley, G.; Mei, J.; Wei, L.; Bentley, S.; Harris, S.R.; Niemann, S.; Diel, R.; Aseffa, A.; Gao, Q.; Young, D.; Gagneux, S.Tuberculosis caused 20% of all human deaths in the Western world between the seventeenth and nineteenth centuries and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. We analyzed the whole genomes of 259 M. Tuberculosis complex (MTBC) strains and used this data set to characterize global diversity and to reconstruct the evolutionary history of this pathogen. Coalescent analyses indicate that MTBC emerged about 70,000 years ago, accompanied migrations of anatomically modern humans out of Africa and expanded as a consequence of increases in human population density during the Neolithic period. This long coevolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low and high host densities. © 2013 Nature America, Inc. All rights reserved.Item TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and Ameta-Analysis of Racial Differences(American Journal of Epidemiology, 2017-06) Zhou, C.K.; Young, D.; Yeboah, E.D.; Coburn, S.B.; Tettey, Y.; Biritwum, R.B.; Adjei, A.A.; Tay, E.; Niwa, S.; Truelove, A.; Welsh, J.; Mensah, J.E.; Hoover, R.N.; Sesterhenn, I.A.; Hsing, A.W.; Srivastava, S.; Cook, M.B.The prevalence of TMPRSS2-ERG fusions in prostate cancer varies by race. However, such somatic aberration and its association with prognostic factors have neither been studied in a West African population nor been systematically reviewed in the context of racial differences. We used immunohistochemistry to assess ERG expression as the established surrogate of ERG fusion genes among 262 prostate cancer biopsies from the Ghana Prostate Study. Poisson regression with robust variance estimation provided prevalence ratios and 95% confidence intervals of ERG expression in relation to patients' characteristics. We found 47 of 262 (18%) prostate cancers were ERG-positive, and negative ERG staining was associated with higher Gleason score. We further conducted a systematic review and meta-analysis of TMPRSS2-ERG fusions in relation to race, Gleason score, and tumor stage, combining results from Ghana with 40 additional studies. Meta-analysis showed the prevalence of TMPRSS2-ERG fusions in prostate cancer to be highest in men of European descent (49%) followed by Asian (27%) and then African (25%). The lower prevalence of TMPRSS2-ERG fusions in men of African descent implies that alternative genomic mechanisms might explain the disproportionately high prostate cancer burden in such populations.