Comprehensive analysis of 300 KAO-NASHI (Face less) genes.

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The human genome project has provided a computer-estimation of 23,000 protein-coding genes in the human genome. However, many of these protein-coding genes are not fully proven for their existence by experimental evidence. In general, proteins with known motifs are readily classified, but substantial numbers of protein have no obvious motifs in their sequences. We designated these genes/proteins without obvious motifs as KAO-NASHI (Face-less) and initiated a project to unveil their face (kao) by comparative genomics and knock-down analysis.We extracted 1,000 KAO-NASHI genes from human genome sequence by step-wise filtration with InterPro motif analysis, BLAST homology search and PubMed document search. A small fish medaka (Oryzias latipes) was chosen as an experimental system to knock-down medaka orthologs of human KAO-NASHI genes with morpholino-antisense oligos. As an initial study, we designed antisense oligos to target translation initiation sites of 130 medaka kao-nashi genes. When these antisense oligos were micro-injected into medaka embryos, their morphogenesis at early developmental stages was disturbed and morphological changes were observed at certain rates. Thus, we obtained initial sketchy information how these medaka kao-nashi genes are involved in the embryonic process of patterning and organ formation. To date, 60 genes were found to cause embryonic defects and these were further classified in terms of developmental sub-stages and expression profiles. Thus, our approach using medaka seems effective and it will eventually provide functional information on the human KAO-NASHI genes/proteins.