The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.

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This report describes the isolation of the genes encoding allantoicase (DAL2) and ureidoglycolate hydrolase (DAL3), which are components of the large DAL gene cluster on the right arm of chromosome IX of Saccharomyces cerevisiae. During this work a new gene (DAL7) was identified and found to be regulated in the manner expected for an allantoin pathway gene. Its expression was (i) induced by allophanate, (ii) sensitive to nitrogen catabolite repression, and (iii) responsive to mutation of the DAL80 and DAL8J loci, which have previously been shown to regulate the allantoin degradation system. Hybridization probes generated from these cloned genes were used to analyze expression of the allantoin pathway genes in wild-type and mutant cells grown under a variety of physiological conditions. When comparison was possible, the patterns of mRNA and enzyme levels observed in various strains and physiological conditions were very similar, suggesting that the system is predominantly regulated at the level of gene expression. Although all of the genes seem to be controlled by a common mechanism, their detailed patterns of expression were, at the same time, highly individual and diverse.

Cancer is a very complicated process, characterized by the uncontrolled, unbalanced overgrowth of malignant cells. The complexity of oncogenic processes and cancer progressions has demanded the discovery of biomarkers with a high sensitivity and specificity for diagnosis, prognosis, diseases monitoring, and therapeutic response prediction. Unfortunately, a discrete biomarker for colon cancer has yet to be discovered, although nearly 800,000 new colorectal cancer cases are thought to globally occur each year, which account for ϳ10% of all incident cancers, and the mortality from colorectal cancer is estimated at nearly 450,000 per year (1). MLI1 and MSH genes are associated with hereditary non-polyposis colon cancer (2), and the APC gene is associated with familial adenomatous polyposis (3), but those factors fail to account for an occurrence of wide range of colon cancer. Moreover, colon cancer is one of the epithelium-derived cancers in which the circumstantial factors govern over hereditary genetic factors. These require a clear marker that serves as tracer molecule for the efficacious treatment of colon cancer.Recent proteomics have focused on a dynamic alteration of post-translational modification of proteins, and many lines of evidence indicate that changes in post-translational modification of proteins are closely associated with the pathogenic processes of cells. An aberrant glycosylation induced by Nacetylglucosaminyltransferase V (GnT-V), 1 is a representative example of such protein modification as is implicated in tumor progression. An increase in ␤1,6-branching on N-linked glycans is associated with metastatic potential of cancer cells (4). Several target molecules for GnT-V were proposed to be involved in cancer progressions, including matriptase (5), ␤ 1 integrin (6), and N-cadherin (7). However, those proteins are membrane-bound proteins and were not demonstrated to be aberrantly glycosylated in sera or tissues of cancer patients. Recent work stresses the discrete roles of the microenviron-

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