Biomedical subjects

Shinji Harihara

Publications and source records attributed to Shinji Harihara.

7 recordsLinked to original sources

PubMed2006

Identification of novel functional variants of the melanocortin 1 receptor gene originated from Asians.

Human melanocortin 1 receptor (MC1R) is a seven transmembrane G-coupled protein receptor that upregulates the cAMP pathway. Several functional variants of MC1R that show an impaired ability to activate the cAMP pathway are strongly associated with fair skin and red hair in Europeans and European descendants. The sequence variations of the MC1R gene were repeatedly investigated against worldwide populations; however, there was no evidence that functional variant of MC1R exists in non-European descendants. We report the presence of novel functional variants of MC1R with Asian origins. Three novel variants of MC1R, Phe147Delta, Thr157Ile, and Pro159Thr, were identified in our screening for the sequence variations of the MC1R gene against 995 individuals from 30 Asian and Oceanian populations; there was a single case for the Pro159Thr variant allele and two instances of Phe147Delta and Thr157Ile variant alleles. Our pharmacological assay revealed that Phe147Delta, Thr157Ile, and Pro159Thr variant showed similar or more dramatically impaired activities in comparison with Arg151Cys, which is a major functional variant of MC1R in Europeans. These functional variant alleles were geographically localized in relatively high latitudes, which suggest that the adaptation to ambient UV light intensity may play an important role in shaping the geographical distribution of MC1R alleles in Asia and Oceania.

Animals↗

PubMed2005

Dual origins of the Japanese: common ground for hunter-gatherer and farmer Y chromosomes.

Historic Japanese culture evolved from at least two distinct migrations that originated on the Asian continent. Hunter-gatherers arrived before land bridges were submerged after the last glacial maximum (>12,000 years ago) and gave rise to the Jomon culture, and the Yayoi migration brought wet rice agriculture from Korea beginning approximately 2,300 years ago. A set of 81 Y chromosome single nucleotide polymorphisms (SNPs) was used to trace the origins of Paleolithic and Neolithic components of the Japanese paternal gene pool, and to determine the relative contribution of Jomon and Yayoi Y chromosome lineages to modern Japanese. Our global sample consisted of >2,500 males from 39 Asian populations, including six populations sampled from across the Japanese archipelago. Japanese populations were characterized by the presence of two major (D and O) and two minor (C and N) clades of Y chromosomes, each with several sub-lineages. Haplogroup D chromosomes were present at 34.7% and were distributed in a U-shaped pattern with the highest frequency in the northern Ainu and southern Ryukyuans. In contrast, haplogroup O lineages (51.8%) were distributed in an inverted U-shaped pattern with a maximum frequency on Kyushu. Coalescent analyses of Y chromosome short tandem repeat diversity indicated that haplogroups D and C began their expansions in Japan approximately 20,000 and approximately 12,000 years ago, respectively, while haplogroup O-47z began its expansion only approximately 4,000 years ago. We infer that these patterns result from separate and distinct genetic contributions from both the Jomon and the Yayoi cultures to modern Japanese, with varying levels of admixture between these two populations across the archipelago. The results also support the hypothesis of a Central Asian origin of Jomonese ancestors, and a Southeast Asian origin of the ancestors of the Yayoi, contra previous models based on morphological and genetic evidence.

Biological Evolution↗

PubMed2004

Characteristic beta-globin gene cluster haplotypes of Evenkis and Oroqens in north China.

Haplotype frequencies of the beta-globin gene cluster were estimated for 114 Evenkis and 81 Oroqens from northeast China, and their characteristics were compared with those in Japanese, Koreans, and three Colombian Amerindian groups of South America (Wayuu, Kamsa, and Inga tribes). A major 5' subhaplotype (5' to the delta-globin gene) was + - - - - in Evenkis, whereas + - - - -, - + + - +, and - + - + + were the major subhaplotypes in Oroqens. One possible candidate for an ancestral 5' subhaplotype, - - - - -, was found in one Evenki (0.5%) and three Oroqen chromosomes (2.0%). They were observed as heterozygous forms for + ---- and -----. Major haplotypes were +-----+, + -----+-, and + - - - - + + in Evenkis, whereas they were +-----+,-++-+-+, +----+-, and -+-++-+ in Oroqens. The lowest Nei's genetic distance values of Evenkis or Oroqens based on the 5' subhaplotype frequency distributions were observed in relation to the Wayuu or Koreans, respectively, but those of Evenkis and Oroqens based on the haplotype frequency distributions were found in relation to Koreans.

Asian People↗

PubMed2003

The mitochondrial DNA A3243G mutation in Werner's syndrome.

OBJECTIVE: The contribution of the A3243G mutation in mitochondria DNA (mtDNA) to diabetes mellitus (DM) in Werner's syndrome (WS) was studied. PATIENTS AND METHOD: DNA samples from peripheral white blood cells (WBCs) originating from 24 Japanese WS patients aged 30-56 were used. For control, 239 subjects aged 15-95 were also used. The mtDNA was amplified using specific primers. After HaeIII digestion, the ratio of the A3243G mutation was compared. RESULTS: The ratio of the A3243G mutation is 0.45+/-0.13% in WS, which is statistically insignificant from those in the control groups at various age. The mutation types of WRN in genomic DNA did not affect the ratio of the A3243G mtDNA mutation. No significant difference was observed concerning to the ratios among the WS patients with and without DM, and also controls. Furthermore, no significant difference was observed in the ratios of A3243G mutation among controls from various age groups. CONCLUSION: The A3243G mutation in mtDNA does not accumulated in WBCs from WS. Mitochondria A3243G mutation may not contribute to the pathogenesis of DM observed in WS.

Adult↗

PubMed2003

Single nucleotide polymorphisms in the human complement C6 and C7 genes.

We analyzed the single nucleotide polymorphisms (SNPs) in the sixth (C6) and the seventh (C7) component genes of the complement system in a sample of the Japanese population, using polymerase chain reaction (PCR)-based methods and PCR direct sequencing. SNPs in the C6 gene studied here are as follows: A413C in exon 3, T1674C in exon 10, T7145A in exon 13, G[357+32]A in intron 2, and G[503-78]A in intron 3. We confirmed that nt413A and nt413C were associated with C6A and C6B, respectively. The result of the nt2145 typing showed that two subtypes exist in the C6B allotype. The SNP of G[357+32]A in intron 2 could be analyzed by using the PCR-RFLP method with HinfI. Allele frequencies in the Japanese population were found to be *G=0.920 and *A=0.080. SNPs in the C7 gene are as follows: T382C in exon 4, G1166C and A1258C in exon 9, and G[+10]A in intron 13. Nt382C and nt1258C would be responsible for C7-5 (=C7-3) and C7-4 allotypes, respectively.

Complement C6↗

PubMed2002

Comparison of the level of mitochondrial DNA A3243G mutation in esophageal epithelium and myocardium from individuals of very advanced age.

The A3243G mutation, one of the changes of human mitochondrial DNA (mtDNA) that accumulates in cells during aging, is a useful marker for investigating the aging of cells. We measured the mutation level of the mtDNA A3243G mutation using DNAs from two different tissues (esophageal epithelium and myocardium) from advanced elderly individuals. The mean level of the A3243G mutation for the esophageal epithelium was 0.0063+/-0.0019, and that for the myocardium was 0.0098+/-0.0031. The mutation level in the myocardium was significantly higher than that in the esophageal epithelium, indicating that more mtDNA A3243G mutations accumulated in the myocardium than in the esophageal epithelium. Since the myocardium is static with respect to cell turnover, but in the esophageal epithelium renewal is very rapid, it is possible that the mtDNA A3243G mutation in the myocardium accumulates more rapidly than in the esophageal epithelium. This phenomenon may reflect the difference in the longevity of cells in each of these tissues and their different levels of oxidative stress.

Aged↗

PubMed2002

Apolipoprotein E and H polymorphisms in Mongolian Buryat: allele frequencies and relationship with plasma lipid levels.

A Buryat population consisting of seven tribal groups in eastern Mongolia has been screened to determine the frequency distribution of different apolipoprotein E and H alleles (APOE and APOH, genes) coding for common isoforms and their association with quantitative plasma lipid levels. Allele frequencies at the APOE locus in 125 healthy Buryat aged 17 to 73 years were highest for APOE*3 (0.804), followed by APOE*4 (0.164) and APOE*2 (0.032). The APOH locus had high frequencies of APOH*2 (0.912) and APOH*3 (0.088). APOH*1 was not detected. No significant differences were observed in the overall APOE allele frequencies between the Buryat and the Siberian Evenki, Inuits, and Indians in Asia, or with some European whites. The frequency distribution of the overall APOH alleles of the Buryat was similar to that of the Japanese in Asia. Overall plasma lipid levels of the Buryat (males aged 20 to 73 years, females aged 21 to 64 years) were considerably lower, comparable to those of the Evenki. The APOE*4/E*3 males had significantly high total- and LDL-cholesterol levels compared with the APOE*3/E*3 males (p < 0.025 and p < 0.01, respectively). No significant effects of the APOH genotypes on any of the plasma lipid levels were observed. In particular, our data regarding APOE suggest that the Buryat are genetically close in allele frequencies to the Evenki and Inuits, but differ from them in the association of genotype APOE*4/E*3 with cholesterol levels.

Adolescent↗