The C allele of JAK2 rs4495487 is an additional candidate locus that contributes to myeloproliferative neoplasm predisposition in the Japanese population

<p>Abstract</p> <p>Background</p> <p>Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are myeloproliferative neoplasms (MPNs) characterized in most cases by a unique somatic mutation, <it>JAK2 </it>V617F. Recent studies revealed that <it>JAK2 </it>V617F occurs more frequently in a specific <it>JAK2 </it>haplotype, named <it>JAK2 </it>46/1 or GGCC haplotype, which is tagged by rs10974944 (C/G) and/or rs12343867 (T/C). This study examined the impact of single nucleotide polymorphisms (SNPs) of the <it>JAK2 </it>locus on MPNs in a Japanese population.</p> <p>Methods</p> <p>We sequenced 24 <it>JAK2 </it>SNPs in Japanese patients with PV. We then genotyped 138 MPN patients (33 PV, 96 ET, and 9 PMF) with known <it>JAK2 </it>mutational status and 107 controls for a novel SNP, in addition to two SNPs known to be part of the 46/1 haplotype (rs10974944 and rs12343867). Associations with risk of MPN were estimated by odds ratios and their 95% confidence intervals using logistic regression.</p> <p>Results</p> <p>A novel locus, rs4495487 (T/C), with a mutated T allele was significantly associated with PV. Similar to rs10974944 and rs12343867, rs4495487 in the <it>JAK2 </it>locus is significantly associated with <it>JAK2</it>-positive MPN. Based on the results of SNP analysis of the three <it>JAK2 </it>locus, we defined the "GCC genotype" as having at least one minor allele in each SNP (G allele in rs10974944, C allele in rs4495487, and C allele in rs12343867). The GCC genotype was associated with increased risk of both <it>JAK2 </it>V617F-positive and <it>JAK2 </it>V617F-negative MPN. In ET patients, leukocyte count and hemoglobin were significantly associated with <it>JAK2 </it>V617F, rather than the GCC genotype. In contrast, none of the <it>JAK2 </it>V617F-negative ET patients without the GCC genotype had thrombosis, and splenomegaly was frequently seen in this subset of ET patients. PV patients without the GCC genotype were significantly associated with high platelet count.</p> <p>Conclusions</p> <p>Our results indicate that the C allele of <it>JAK2 </it>rs4495487, in addition to the 46/1 haplotype, contributes significantly to the occurrence of <it>JAK2 </it>V617F-positive and <it>JAK2 </it>V617F-negative MPNs in the Japanese population. Because lack of the GCC genotype represents a distinct clinical-hematological subset of MPN, analyzing <it>JAK2 </it>SNPs and quantifying <it>JAK2 </it>V617F mutations will provide further insights into the molecular pathogenesis of MPN.</p

Complete mitochondrial DNA sequences of two endemic subspecies, Salvelinus leucomaenis imbrius and Salvelinus leucomaenis pluvius (Salmonid, White spotted charr) in Japan

The complete mitochondrial DNA (mtDNA) sequences of two endemic subspecies of the White spotted charr (Salvelinus leucomaenis) in Japan were determined. The complete mtDNA sequences of two individuals of S. l. imbrius and S. l. pluvicus were analyzed and compared with those of other charrs in GenBank. The whole mtDNA sequences of S. l. imbrius and S. l. pluvicus were 16,655 bp in length. The whole mtDNA sequence comparisons between S. leucomaenis in Japan and other charrs in GenBank, including charrs from East Asia to North American, revealed that S. l. imbrius and S. l. pluvius in Japan belonged to a different group from S. curilus (syn. S. alma krascheninnikovi), which is sympatric with S. leucomaenis in Hokkaido. Furthermore, it was discovered that the Japanese subspecies had 8 nucleotide deletions and four nucleotide insertions compared with S. curilus

Analysis of genetic variation in mitochondrial cytochrome c oxidase subunit 1 between Haemadipsa japonica in Japan and land leeches worldwide

Haemadipsa japonica is the most common land leech species found in Japan. It has been considered to possess genetic variation that limits its habitat range. In the present study, to characterize variation in the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of H. japonica specimens from various locations in Japan, we examined nucleotide sequences of the mitochondrial cox1 gene. We performed PCR of mitochondrial cox1 using 10 H. japonica specimens and compared the result with those of land leeches from around the world using a maximum likelihood (ML) tree. ML tree of H. japonica in Japan showed significant differences between cox1 sequences of specimens from Yakushima and other regions of Japan. ML tree of land leeches from around the world revealed that H. japonica had the closest relationship with H. picta from Borneo

Expression Profile of a γ-Deletion Variant of the Human Telomerase Reverse Transcriptase Gene

The human telomerase reverse transcriptase (hTERT) is an essential component of the holoenzyme complex that adds telomeric repeats to the ends of chromosomes. The hTERT transcript has been shown to have two deletion type alternative splicing sites. One deletion site induces the α-deletion variant, lacking 36 bp from exon 6, and the other induces the β-deletion variant, lacking 182 bp from exons 7 and 8. Here, we identified a novel deletion variant of the hTERT transcript in hepatocellular carcinoma cell lines. The deleted transcript was characterized by an in-frame deletion of 189 bp, spanning nucleotides 2710 to 2898, corresponding to the complete loss of exon 11 (γ-deletion). The region lacking in the γ-deletion lies within RT motifs D and E, suggesting that it is missing conserved residues from the catalytic core of the protein. Both γ- and α-deletion variants were occasionally detected, but the β-deletion variant was frequently observed. Our results may provide important information for more detailed studies on the regulation of telomerase activity