Biomedical subjects

Hidehiko Sugino

Publications and source records attributed to Hidehiko Sugino.

7 recordsLinked to original sources

PubMed2007

Comparative genomic analysis of the mouse and rat amylase multigene family.

The rat and mouse amylase gene families were characterized using sequence data from the UCSC genome assembly. We found that the rat genome contains one amylase-1 and two amylase-2 genes, lying close to one another on the same chromosome. Detailed analysis revealed at least six additional amylase pseudogenes in the rat genome in the region adjacent to the amylase-2 genes. In contrast, the mouse has one amylase-1 gene and five amylase-2 genes; the latter are tandemly and systematically arranged on the same chromosome and were generated by segmental duplication. Detailed analysis revealed that the mouse has two amylase pseudogenes, located 5' to the five amylase-2 segments. Thus, the amylase genes of mouse and rat tend to be amplified; the sequences of some of them are fixed while others have become pseudogenes during evolution. This is the second report of amylase genomic organization in mammals and the first in the rodents.

Amylases↗

PubMed2005

ICAM-3, a ligand for DC-SIGN, was duplicated from ICAM-1 in mammalian evolution, but was lost in the rodent genome.

ICAM-3 is a DC-SIGN ligand that is constitutively expressed on resting leukocytes, and is thus an important molecule for the first immune response. But, ICAM-3 has not been isolated form rodents. Thus, we compare the ICAM gene clusters in human, dog, mouse, and rat. ICAM-1, -4, -5 and -3 are located close to one another on the same chromosome and show genomic synteny in human and dog. Almost the same ICAM gene clusters were found in rodent genome, but only the ICAM-3 was not present. A phylogenetic tree plotting the cDNAs of human, dog, mouse, rat, and bovine suggested that ICAM-3 was made from a duplication of ICAM-1. Thus, ICAM-3 arose from ICAM-1 in the mammalian evolution, but was lost in the rodent's genome. Our study suggests the different immune response in the rodents in comparison with other mammals.

Animals↗

PubMed2004

Genomic organization and transcripts of the zebrafish Protocadherin genes.

We have examined the protocadherin (Pcdh) gene clusters of the zebrafish (Danio rerio). At least three sets of the Pcdh gene cluster were found in the zebrafish genome. Here, we describe the complete organization of the DrPcdh2 gene clusters. Classification by phylogenetic and transcript analyses revealed 7 DrPcdh2omicron, 20 DrPcdh2alphaa, 12 DrPcdh2alphab, and 1 DrPcdh2alphac variable exons upstream of the DrPcdh2alpha constant region exons in the DrPcdh2 gene cluster. The constant regions of the DrPcdh1alpha and DrPcdh2alpha genes in zebrafish were orthologs of those of the mammalian Pcdhalpha. These exons all encoded plural PXXP motifs in their cytoplasmic tails. The sequences of the variable exons were highly conserved within each family: DrPcdh2omicron, DrPcdh2alphaa, and DrPcdh2alphab. Transcript analysis revealed that zebrafish Pcdhs had alternatively spliced variants in the constant region that were not found in mammals. More gene clusters, more variable exons, and more alternative splicing variants were found in zebrafish than in mammals. Thus, although the Pcdhalpha families were common to diverse vertebrates, their gene number, structure, and transcripts were different between teleosts and mammals.

Alternative Splicing↗

PubMed2004

Negative and positive effects of an IAP-LTR on nearby Pcdaalpha gene expression in the central nervous system and neuroblastoma cell lines.

Intracisternal A-particles (IAPs) are defective retrovirions encoded by members of a large family of endogenous proviral elements in the murine genome. An intact IAP element was found in the protocadherin alpha (Pcdhalpha) gene cluster of five laboratory mouse strains. However, IAP insertion was not detected in three wild mouse strains we investigated. This IAP insertion caused the disruption of one variable exon of laboratory mouse and down-regulated expression of the Pcdhalpha v8 exon, which is located just downstream of the IAP in the brain following the methylation of 5' regulatory region of Pcdhalpha v8. In contrast, the Pcdhalpha v8 exon was highly expressed in mouse neuroblastoma cell lines. This suggested that the IAP insertion activates the expression of the nearby Pcdhalpha v8 exon in these cell lines. In fact, the Pcdhalpha v8 exon expression was driven by the IAP-long terminal repeat (LTR) following the de-methylation of 5' regulatory region of Pcdhalpha v8. To investigate the promoter activity of the IAP, we constructed an IAP-LTR-ECFP reporter gene and introduced it into neuroblastoma, melanoma, lymphoma, and plasmacytoma cell lines. Interestingly, ECFP-positive cells were observed only in the neuroblastoma cell lines. Moreover, there were no differences in the promoter activities of the IAP-LTR whether it was in the sense or complimentary orientation. Thus, this IAP-LTR has negative and positive regulation on near by gene expression in the brain and neuroblastoma cell lines.

Animals↗

PubMed2004

Distinct genomic sequence of the CNR/Pcdhalpha genes in chicken.

CNR/Pcdhalpha family proteins have been first identified as a receptor family that corporate with Fyn, a family of the Src family of tyrosine kinase, and known as synaptic cadherins. Here we report the complete genomic sequence and organization of the chicken (Gallus gallus) CNR/Pcdhalpha The total length of chicken CNR/Pcdhalpha is 177kb. The chicken CNR/Pcdhalpha cluster encodes 12 variable and 3 constant exons. The genomic organizations of the chicken, rat, mouse, and human CNR/Pcdhalpha are basically orthologous. The constant-region exons (CP1, CP2, and CP3) are highly conserved between chicken and mammals, with percent identities of 90.9%, 90.7%, and 91.8% at the amino-acid level for chicken versus rat, mouse, and human, respectively. In contrast, the percent identities of the variable-region exons between chicken and mammals were lower: 51.8%, 51.3%, and 52.7%, on average, for chicken versus rat, mouse, and human, respectively, at the amino-acid level. Moreover, the chicken variable-region exons (from v1 to v12) are highly conserved paralogously (91.4%: nucleic acid, 92.4%: amino acid) in comparison with those of mammals. The CG content of each variable exon in the chicken (v1 to v12) is 74% on average and the CpG dinucleotide frequency in each variable-region exon is twice that of mammals. Due to the high CG content, chicken variable exons (from v1 to v12) encode 3 to 4 frame-shifted open reading frames, which span 1.5-3.0kb, in both the sense and anti-sense orientations.

Animals↗

PubMed2004

Intron-less processed Pcdhalpha genes in the central nervous system.

The genomic organization of the Pcdhalpha is remarkably similar to those of T-cell receptor and immunoglobulin genes. To elucidate the somatic rearrangements of the genomic DNAs of Pcdhalphas in the central nervous system, we screened a genomic brain library of the C57BL/6 mouse strain. From this screening we isolated an unusual, rearranged genomic Pcdhalpha DNA. This clone contained an intron-less Pcdhalpha v6 gene resembling the cDNA generated from its mRNA, inserted into the 28S rDNA gene locus. The intron-less Pcdhalpha v6 gene possessed a putative promoter region and 10 nucleotide substitutions but no poly(A) signal. Both edges of the integration site had additional 5-bp duplicated sequences. PCRs that were performed using primers for intron-less Pcdhalphas amplified products from genomic DNAs only in the brain; moreover, using the size-fractionated genomic DNA by sucrose density gradient centrifugation, intron-less Pcdhalpha is mainly amplified in the small size fraction of the genomic DNA. Inverted PCR for this small size fraction also amplifies the Pcdhalphas connecting the both ends with repeat sequences. These features suggest the somatic reverse-transcription, circularization, and rare occasion of integration into the genome of Pcdhalpha in the brain.

Animals↗

PubMed2004

Genomic sequence and organization of the family of CNR/Pcdhalpha genes in rat.

CNR/Pcdhalpha family proteins are known as synaptic cadherins and Reelin receptors. Here we report the complete genomic sequence and organization of the rat CNR. The rat CNR cluster encodes 15 variable and 3 constant exons. The genomic organizations of the rat, mouse, and human CNR/Pcdhalpha are orthologous. The percentage identity of the coding regions between the rat and the mouse is 93.6% on average at the nucleic acid level, and between rat and human it is 82.8%. The rat CNRs (v1-v13) also contain an RGD motif in the extracellular cadherin 1 domains and cysteine repeats that are characteristic of the transmembrane and cytoplasmic domains of CNR proteins. The number of variable exons in the rat CNR cluster is identical to that of the human. The rat CNR cluster has one more variable exon than is found in laboratory mouse strains, because in the mouse a variable exon located between v7 and v8 is divided by the insertion of a retrotransposon. This exon is not disrupted in the rat, in which it is transcribed. By in silico analysis, CNR/Pcdhalpha was also mapped to rat chromosome 18, but the orientation was opposite for the mouse CNR/Pcdhalpha gene cluster. The relative expression profiles of the rat CNRs (v1-v13) show that all the CNRs are transcribed, but there are variations in the expression ratios among the CNRs.

Amino Acid Motifs↗