A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms

Nat Genet. 2009 Apr;41(4):450-4. doi: 10.1038/ng.341. Epub 2009 Mar 15.


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 JAK2(V617F) oncogenic mutation between two parental alleles of the JAK2 gene. We identified a haplotype that preferentially acquires JAK2(V617F) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution*
  • Base Sequence
  • Chromosome Mapping
  • Female
  • Germ-Line Mutation
  • Haplotypes / genetics*
  • Hematologic Neoplasms / enzymology
  • Hematologic Neoplasms / genetics*
  • Heterozygote
  • Homozygote
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Pedigree
  • Polycythemia Vera / enzymology
  • Polycythemia Vera / genetics*
  • Polymorphism, Single Nucleotide*
  • Thrombocythemia, Essential / enzymology
  • Thrombocythemia, Essential / genetics*


  • JAK2 protein, human
  • Janus Kinase 2