Comparative genomics on Wnt9a orthologs.

WNT, Hedgehog and Notch signaling pathways network together during carcinogenesis and embryogenesis. WNT3A-WNT9A (WNT14) locus at chromosome 1q42.13 and WNT3-WNT9B (WNT14B) locus at chromosome 17q21.31 are paralogous regions within the human genome. WNT9A mRNA is expressed in various types of human cancer, such as gastric cancer, pancreatic cancer, and breast cancer. In addition, Wnt9a gene is implicated in chondrogenesis and joint formation during embryogenesis. Here we identified and characterized rat Wnt9a gene by using bioinformatics. Rat Wnt9a gene, consisting of four exons, was located within AC121055.4 and AC133374.2 genome sequences. Rat Wnt9a protein (365 aa) with N-terminal signal peptide, 24 Cys residues and one Asn-linked glycosylation site showed 100%, 98.1% and 82.5% total amino-acid identity with mouse Wnt9a, human WNT9A and chicken wnt9a, respectively. Exonic regions except 3'-UTR were well conserved between human WNT9A and rodent Wnt9a genes; however, 5'-flanking promoter region was not well conserved. Transcription-factor-binding sites conserved between human WNT9A and rodent Wnt9a 5'-flanking promoter regions were not identified by using the Match program. Although the amino-acid sequence was highly conserved among mammalian Wnt9a orthologs, the 5'-flanking promoter region was significantly divergent between human WNT9A and rodent Wnt9a genes. This is the first report on rat Wnt9a gene as well as on comparative genomics for Wnt9a orthologs.