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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1937-1940. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-07-2550. This Article Full Text (PDF) All Versions of this Article: 2003-07-2550v1 103/5/1937    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liu, E. Articles by Prchal, J. T Search for Related Content PubMed PubMed Citation Articles by Liu, E. Articles by Prchal, J. T Social Bookmarking                   What's this? Submitted August 7, 2003 Accepted October 26, 2003 The worldwide distribution of the VHL 598C>T mutation indicates a single founding event Enli Liu, Melanie J Percy, Christopher I Amos, Yongli Guan, Sanjay Shete, David W Stockton, Mary F McMullin, Sonny O Ang, Yves D Pastore, Katerina Jedlickova, Terry R Lappin, Victor Gordeuk, and Josef T Prchal* Department of Medicine, Baylor College of Medicine, Houston, TX, USA Belfast City Hospital, Belfast City Hospital, Queen's University, Belfast, United Kingdom Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA Kleberg Genotyping Center, Baylor College of Medicine, Houston, TX, USA Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA Department of Medicine, Howard University, Washington, DC, USA * Corresponding author; email: jprchal{at}bcm.tmc.edu. The first congenital defect of hypoxia sensing - homozygosity for VHL 598C>T mutation was recently identified in Chuvash polycythemia. Subsequently we found this mutation in 11 unrelated individuals of diverse ethnic backgrounds. To address the question of whether the VHL 598C>T substitution occurred in a single founder or resulted from recurrent mutational events in human evolution, we performed haplotype analysis of eight polymorphic markers covering 340 kb spanning the VHL gene on 101 subjects bearing the VHL 598C>T mutation including 72 homozygotes (61 Chuvash and 11 non-Chuvash) and 29 heterozygotes (11 Chuvash and 18 non-Chuvash), and 447 normal unrelated individuals from Chuvash and other ethnic groups. The differences in allele frequencies for each of the eight markers between 447 normal controls (598C) and 101 subjects bearing the 598T allele (P<10-7) showed strong linkage disequilibrium. Haplotype analysis indicated a founder effect. We conclude that the VHL 598C>T mutation, the most common defect of congenital polycythemia yet found, has spread from a single founder 14,000 to 62,000 years ago. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Liu, M. Martini, B. Rocca, C. I. Amos, L. Teofili, F. Giona, J. Ding, H. Komatsu, L. M. Larocca, and R. C. Skoda Evidence for a founder effect of the MPL-S505N mutation in eight Italian pedigrees with hereditary thrombocythemia Haematologica, October 1, 2009; 94(10): 1368 - 1374. [Abstract] [Full Text] [PDF] E. R. Woodward, K. Wall, J. Forsyth, F. Macdonald, and E. R. Maher VHL mutation analysis in patients with isolated central nervous system haemangioblastoma Brain, March 1, 2007; 130(3): 836 - 842. [Abstract] [Full Text] [PDF] S. Perrotta, B. Nobili, M. Ferraro, C. Migliaccio, A. Borriello, V. Cucciolla, V. Martinelli, F. Rossi, F. Punzo, P. Cirillo, et al. Von Hippel-Lindau-dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster Blood, January 15, 2006; 107(2): 514 - 519. [Abstract] [Full Text] [PDF]

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