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Biomedical subjects

Tetsushi Yada

Publications and source records attributed to Tetsushi Yada.

5 recordsLinked to original sources

Analysis of the promoter of mutated human whey acidic protein (WAP) gene.

Although whey acidic protein (WAP) has been identified in the milk of a range of species, it has been predicted that WAP is not secreted into human milk as a result of critical point mutations within the coding region. In the present study, we first investigated computationally the promoter region of mutated human WAP genes by comparing with those of other known WAP genes. Computational database analyses showed that the human WAP promoter region was highly conserved, as in other species with milk WAP. Next, we evaluated the activity of the human WAP promoter (2.6 kb) using a reporter gene assay. MCF-7 cells were stably transfected with the hWAP/hGH (human growth hormone) fusion gene, cultured on Matrigel, and treated with lactogenic hormones. Radioimmunoassay detected hGH in the culture medium, indicating that the human WAP promoter was responsible for the lactogenic hormones. The human WAP promoter was significantly more active in MCF-7 cells than the mouse WAP promoter (2.4 kb). The present results provide us with important information on the molecular evolution of milk protein genes.

Cell Line, Tumor↗

Chromosome-wide assessment of replication timing for human chromosomes 11q and 21q: disease-related genes in timing-switch regions.

The completion of the human genome sequence will greatly accelerate development of a new branch of bioscience and provide fundamental knowledge to biomedical research. We used the sequence information to measure replication timing of the entire lengths of human chromosomes 11q and 21q. Megabase-sized zones that replicate early or late in S phase (thus early/late transition) were defined at the sequence level. Early zones were more GC-rich and gene-rich than were late zones, and early/late transitions occurred primarily at positions identical to or near GC% transitions. We also found the single nucleotide polymorphism (SNP) frequency was high in the late-replicating and replication-transition regions. In the early/late transition regions, concentrated occurrence of cancer-related genes that include CCND1 encoding cyclin D1 (BCL1), FGF4 (KFGF), TIAM1 and FLI1, was observed. The transition regions contained other disease-related genes including APP associated with familial Alzheimer's disease (AD1), SOD1 associated with familial amyotrophic lateral sclerosis (ALS1) and PTS associated with phenylketonuria. These findings are discussed with respect to the prediction that increased DNA damage occurs in replication-transition regions. We propose that genome-wide assessment of replication timing serves as an efficient strategy for identifying disease-related genes.

Alzheimer Disease↗

A novel index which precisely derives protein coding regions from cross-species genome alignments.

We introduce here a novel index which precisely derives protein coding regions from cross-species genome alignments. The index is deeply related to frame recovery observed in coding sequence alignments, that is, if insertions or deletions of nucleotides causes frame shifts in coding regions, other in-dels which recover the reading frames will be often observed in the vicinity. In contrast, such frame recoveries are not observed in other conserved regions. We prepared two gene models: a model which finds gene by using sequence similarity and intrinsic gene measures (basic model), and the other model which finds gene by using frame recovery index in addition to sequence similarity and intrinsic gene measures (frame recovery model). We evaluated the prediction accuracies of the two models, and our benchmark test revealed that frame recovery model significantly improved the prediction accuracy in comparison with basic model.

Abstracting and Indexing↗