Letter abstract

Nature Genetics 41, 450 - 454 (2009)
Published online: 15 March 2009 | doi:10.1038/ng.341

A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms

Damla Olcaydu1, Ashot Harutyunyan1, Roland Jäger1, Tiina Berg1, Bettina Gisslinger2, Ingrid Pabinger2, Heinz Gisslinger2 & Robert Kralovics1,2


Genome-wide association studies have identified a number of new disease susceptibility loci that represent haplotypes defined by numerous SNPs. SNPs within a disease-associated haplotype are thought to influence either the expression of genes or the sequence of the proteins they encode. In a series of investigations of the JAK2 gene in myeloproliferative neoplasms, we uncovered a new property of haplotypes that can explain their disease association. We observed a nonrandom distribution of the somatic JAK2V617F oncogenic mutation between two parental alleles of the JAK2 gene. We identified a haplotype that preferentially acquires JAK2V617F and confers susceptibility to myeloproliferative neoplasms. One interpretation of our results is that a certain combination of SNPs may render haplotypes differentially susceptible to somatic mutagenesis. Thus, disease susceptibility loci may harbor somatic mutations that have a role in disease pathogenesis.

  1. Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  2. Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria.

Correspondence to: Robert Kralovics1,2 e-mail: robert.kralovics@cemm.oeaw.ac.at