Biomedical subjects

Makiko Meguro

Publications and source records attributed to Makiko Meguro.

8 recordsLinked to original sources

PubMed2004

Development and construct validation of the Korean competence scale (KCS).

A comprehensive Korean competence scale (KCS) designed for Korean older adults, was developed and its construct validity evaluated. KCS assesses their higher levels of functional competence than activities of daily livings (ADL), necessary for independence in the home and community. The internal structure of the scale was tested using an exploratory and confirmatory factor analysis with two elderly Korean sample groups. As expected, the exploratory factor analysis result demonstrated a three-factor solution comprised of the following three domains: instrumental self-maintenance, intellectual activity, and social role. The confirmatory factor analysis results showed that an acceptable solution could be estimated for a second-order factor model comprised of these factors. These findings provide evidence for the construct validity of the instrument and have implications for future research on factorial invariance.

Activities of Daily Living↗

PubMed2003

Calcr, a brain-specific imprinted mouse calcitonin receptor gene in the imprinted cluster of the proximal region of chromosome 6.

Expressed sequence tags (ESTs) in the human chromosome 7q21-q31 region were recently used to screen for allelic expression bias in monochromosomal hybrids retaining a paternal or maternal human chromosome 7. Six candidate imprinted genes were identified. In this study, we investigated parent-of-origin-specific expression profiles of their mouse homologues in the proximal region of chromosome 6. An imprinting analysis, using F1 mice from reciprocal crosses between the B6 and JF strains, demonstrated that the mouse calcitonin receptor gene ( Calcr) was expressed preferentially from the maternal allele in brain, whereas no allelic bias was detected in other tissues. Our results indicate that Calcr is imprinted in a tissue-specific manner, with a predominant expression from the maternal allele in the brain.

Animals↗

PubMed2003

Predominant maternal expression of the mouse Atp10c in hippocampus and olfactory bulb.

The human chromosome 15q11-q13 region is one of the most intriguing imprinted domains, and the abnormalities inherited are associated with neurological disorders including Prader-Willi syndrome (PWS), Angelman syndrome (AS) and autism. Recently we have identified a novel maternally expressed gene, ATP10C, that encodes a putative aminophospholipid translocase within this critical region, 200 kb distal to UBE3A in an imprinted domain on human chromosome 15. ATP10C, with UBE3A, displayed tissue-specific imprinting with predominant expression of the maternal allele in the brain. In this study, we demonstrated that the mouse homologue, Atp10c/pfatp, showed tissue-specific maternal expression in the hippocampus and olfactory bulb, which overlapped the region of imprinted Ube3a expression. These data suggest that the imprinted transcript of Atp10c in the specific region of CNS may be associated with neurological disorders including AS and autism.

Adenosine Triphosphatases↗

PubMed2003

A new imprinted cluster on the human chromosome 7q21-q31, identified by human-mouse monochromosomal hybrids.

We have previously established a series of human monochromosomal hybrids containing a single human chromosome of defined parental origin as an in vitro resource for the investigation of human imprinted loci. Using the hybrids with a paternal or maternal human chromosome 7, we determined the allelic expression profiles of 76 ESTs mapped to the human chromosome 7q21-q31. Seven genes/transcripts, including PEG10 which has previously been reported to be imprinted, showed parent-of-origin-specific expression in monochromosomal hybrids. One of the 6 candidate genes/transcripts, i.e., DLX5 was confirmed to be imprinted in normal human lymphoblasts and brain tissues by a polymorphic analysis. Thus, an imprinted domain has been newly defined in the region of human chromosome 7q21-q31 using human-mouse monochromosomal hybrids.

Animals↗

PubMed2003

Discovery of imprinted transcripts in the mouse transcriptome using large-scale expression profiling.

Candidate imprinted transcriptional units in the mouse genome were identified systematically from 27,663 FANTOM2 full-length mouse cDNA clones by expression profiling. Large-scale cDNA microarrays were used to detect differential expression dependent upon chromosomal parent of origin by comparing the mRNA levels in the total tissue of 9.5 dpc parthenogenote and androgenote mouse embryos. Of the FANTOM2 transcripts, 2114 were identified as candidates on the basis of the array data. Of these, 39 mapped to known imprinted regions of the mouse genome, 56 were considered as nonprotein-coding RNAs, and 159 were natural antisense transcripts. The imprinted expression of two transcripts located in the mouse chromosomal region syntenic to the human Prader-Willi syndrome region was confirmed experimentally. We further mapped all candidate imprinted transcripts to the mouse and human genome and were shown in correlation with the imprinting disease loci. These data provide a major resource for understanding the role of imprinting in mammalian inherited traits.

Animals↗

PubMed2002

Identification and characterization of an imprinted antisense RNA (MESTIT1) in the human MEST locus on chromosome 7q32.

Imprinted gene(s) on human chromosome 7 are thought to be involved in Russell-Silver syndrome (RSS), based on the fact that approximately 10% of patients have maternal uniparental disomy of chromosome 7. However, involvement of the known imprinted genes (GRB10 at 7p12, PEG10 at 7q21.3 and MEST at 7q32) in RSS has yet to be established. To screen for new imprinted genes, we are initially using somatic cell hybrids containing a paternal or maternal human chromosome 7. Transcripts located between D7S530 and D7S649 (a 1.5 Mb interval encompassing MEST ) were subjected to RT-PCR analysis using somatic cell hybrids. One transcript named MESTIT1 (for MEST intronic transcript 1) reproducibly showed paternal-specific expression. Upon further analysis, we found MESTIT1 to be (1) paternally (and not maternally) expressed in all fetal tissues and fibroblasts examined, (2) to be located in an intron of one of the two isoforms of MEST but transcribed in the opposite direction, (3) to be composed of at least two exons without any significant open reading frame, and (4) to exist as a 4.2 kb transcript in many fetal and adult tissues. We could also identify two isoforms of the mouse Mest gene as observed in humans, but it is still unknown if a murine ortholog of MESTIT1 exists. We also examined the imprinting status of MEST isoforms as a first step in assessing whether MESTIT1 might influence the allelic expression pattern of the sense transcript. MEST isoform 1 was determined to be exclusively expressed from the paternal allele in all fetal tissues and cell lines examined, whereas MEST isoform 2 was only preferentially expressed from the paternal allele in a tissue/cell-type-specific manner. Our results suggest that MESTIT1 is a paternally expressed non-coding RNA that may be involved in the regulation of MEST expression during development. MESTIT1 (also known as PEG1-AS) is now the third independent transcript (with MEST and COPG2IT1) identified at human chromosome 7q32 demonstrating paternal chromosome-specific expression.

Blotting, Northern↗

PubMed2002

Asb4, Ata3, and Dcn are novel imprinted genes identified by high-throughput screening using RIKEN cDNA microarray.

Genes differentially expressed between parthenogenetic and androgenetic embryos are candidates for the identification of imprinted genes, which are expressed specifically from the maternal or paternal allele. To search for genes differentially expressed between parthenogenetic and androgenetic embryos, we used the RIKEN full-length enriched mouse cDNA microarray. The 25 candidates obtained included 8 known imprinted genes (such as IgfII, Snrpn, and Neuronatin) and 3 new ones--Asb4 (ankyrin repeat and SOCS box-containing protein 4), Ata3 (amino acid transport system A3), and Decorin--which were confirmed by using normal diploid embryos from the reciprocal F1 crosses of B6 and JF1 mice. The 25 candidates also included genes that showed no imprinting-associated expression in normal diploid embryos. We describe a feasible high-throughput method of screening for novel imprinted genes by using the RIKEN cDNA microarray.

Amino Acid Transport System A↗

PubMed2002

Molecular genetic studies of human chromosome 7 in Russell-Silver syndrome.

Russell-Silver syndrome (RSS) is a form of congenital short stature characterized by severe growth retardation and variable dysmorphic features. In some RSS individuals, alterations in imprinted genes may be involved because approximately 7% of sporadic patients have been observed to have maternal uniparental disomy (mUPD) of chromosome 7. RSS patients with structural abnormalities of chromosome 7 have also been described. In these individuals the chromosome rearrangement could disrupt the balance of imprinted genes, contribute to a recessive form of RSS, or lead to haploinsufficiency of a crucial developmental gene product. Because the mechanism and molecular defects on chromosome 7 causing RSS are still unknown, we tested our collection of 77 RSS families for mUPD7 and were able to identify three new cases. We also characterized two RSS patients with de novo cytogenetic abnormalities involving the short arm of chromosome 7. One had a partial duplication [46, XX, dup(7)(p12 p14)] and the second contained a paracentric inversion [46, XY, inv(7)(p14 p21)]. Fluorescence in situ hybridization (FISH) mapping revealed that the breakpoints on 7p14 were localized to the same novel gene, C7orf10, which encompasses >700 kb of DNA. We also identified other transcription units from this immediate region, but all seem to be biallelically expressed when using a somatic cell hybrid assay.

Abnormalities, Multiple↗