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, Lydia A. Polyakova, Sonny O. Ang, Yves D. Pastore, Katerina Jedlickova, Terry R.J. Lappin, Victor Gordeuk, Josef T. Prchal

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


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 8 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 healthy unrelated individuals from Chuvash and other ethnic groups. The differences in allele frequencies for each of the 8 markers between 447 healthy 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, was spread from a single founder 14 000 to 62 000 years ago.

Original languageEnglish
Pages (from-to)1937-1940
Number of pages4
Issue number5
StatePublished - Mar 1 2004


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