Format

Send to

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

A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms.

Author information

1
Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

Abstract

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.

PMID:
19287385
DOI:
10.1038/ng.341
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center