A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms
A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms
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DOI：
10.1038/ng.341
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发表时间：
2009-04-01
期刊：
影响因子：
30.8
通讯作者：
Kralovics, Robert
中科院分区：
文献类型：
--
作者：
Olcaydu, Damla;Harutyunyan, Ashot;Kralovics, Robert
全基因组关联研究已经确定了许多新的疾病易感性基因座，这些基因座代表了由许多SNP定义的单倍型。疾病相关单倍型内的SNP被认为影响基因的表达或它们编码的蛋白质的序列。在对JAK2基因在骨髓增生性肿瘤中的一系列研究中，我们发现了单倍型的一个新特性，可以解释它们与疾病的关联。我们观察到JAK2基因的两个亲本等位基因之间的体细胞JAK2（V617F）致癌突变的非随机分布。我们确定了一个单倍型，优先收购JAK2（V617F），并赋予骨髓增生性肿瘤的易感性。我们的研究结果的一种解释是，一定的SNP组合可能使单倍型差异敏感体细胞诱变。因此，疾病易感基因座可能含有在疾病发病机制中起作用的体细胞突变。
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.