Anti-WNT7B (aa 87-307) polyclonal antibody

The WNT family of secreted proteins is a group of signaling molecules that control a diverse range of developmental processes including cell proliferation and tumorigenesis. We have constructed a subtracted full-length cDNA library from a human gastric cell line SNU5 using the capping and subtraction method and isolated and characterized the full-length cDNA of human WNT7b. Cloned cDNA sequence comprised 1440 bp including the 5'-noncoding region of 374 bp, an ORF of 1050 bp and the 3'-noncoding region of 16 bp. The ORF could encode a protein of 349 amino acids. Analysis of deduced amino acid sequence showed a conserved WNT signature sequence (CKCHGvSGSC), characteristic 25 cysteine residues and three different N-glycosylation sites at 83, 127, and 295 of asparagines. Comparison of cloned WNT7b with previously reported human WNT7b revealed that cloned WNT7b has 100% identity with nucleotide sequence in coding sequence but has more 279 bp than that in 5'-noncoding region. Also, comparison of cloned WNT7b with mouse WNT7b showed 91% identity in nucleotide sequence and 99% in amino acid sequence. Furthermore, a phylogeny of WNT7b in relation to other known WNT proteins revealed that human WNT7b has a close paralog with other WNT7b proteins across the different species and genus, not with human WNT7a. Besides, expression profiles in different gastric cell lines by RT-PCR showed higher expression of human WNT7b in cancer cell lines than in normal cells, suggesting that human WNT7b has a crucial role in gastric tumorigenesis.

BACKGROUND Dupuytren's disease is a benign fibromatosis of the hands and fingers that leads to flexion contractures. We hypothesized that multiple genetic and environmental factors influence susceptibility to this disease and sought to identify susceptibility genes to better understand its pathogenesis. METHODS We conducted a genomewide association study of 960 Dutch persons with Dupuytren's disease and 3117 controls (the discovery set) to test for association between the disease and genetic markers. We tested the 35 single-nucleotide polymorphisms (SNPs) most strongly associated with Dupuytren's disease (P< 1x10-4) in the discovery set in three additional, independent case series comprising a total of 1365 affected persons and 8445 controls from Germany, the United Kingdom, and the Netherlands. RESULTS Initially, we observed a significant genomewide association between Dupuytren's disease and 8 SNPs at three loci. Tests of replication and joint analysis of all data from 2325 patients with Dupuytren's disease and 11,562 controls yielded an association with 11 SNPs from nine different loci (P< 5.0x10(-8)). Six of these loci contain genes known to be involved in the Wnt-signaling pathway: WNT4 (rs7524102) (P = 2.8x10(-9); odds ratio, 1.28), SFRP4 (rs16879765) (P = 5.6x10-39; odds ratio, 1.98), WNT2 (rs4730775) (P = 3.0x10(-8); odds ratio, 0.83), RSPO2 (rs611744) (P = 7.9x10(-15); odds ratio, 0.75), SULF1 (rs2912522) (P = 2.0x10(-13); odds ratio, 0.72), and WNT7B (rs6519955) (P = 3.2x10(-33); odds ratio, 1.54). CONCLUSIONS This study implicates nine different loci involved in genetic susceptibility to Dupuytren's disease. The fact that six of these nine loci harbor genes encoding proteins in the Wnt-signaling pathway suggests that aberrations in this pathway are key to the process of fibromatosis in Dupuytren's disease.