308 results on '"Jun Ohashi"'
Search Results
52. Modern Japanese ancestry-derived variants revealed the formation process of the current Japanese regional gradations
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Jun Ohashi and Yusuke Watanabe
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education.field_of_study ,Geography ,Ancient DNA ,geography.geographical_feature_category ,Evolutionary biology ,Population size ,Haplotype ,Archipelago ,Population ,Single-nucleotide polymorphism ,East Asia ,Mainland ,education - Abstract
SummaryModern Japanese have two major ancestral populations: the indigenous Jomon hunter gatherers and continental East Asian farmers. To figure out the formation process of current Japanese population, we developed a reference-free detection method of variants derived from ancestral populations using a summary statistic, the ancestry-marker index (AMI). We confirmed by computer simulations thatAMIcan detect ancestry-derived variants even in an admixed population of recently diverged source populations with high accuracy, which cannot be achieved by the most widely used statistics, S*, for identifying archaic ancestry. We applied theAMIto modern Japanese samples and identified 208,648 single nucleotide polymorphisms (SNPs) that were likely derived from the Jomon people (Jomon-derived variants). The analysis of Jomon-derived variants in 10,842 modern Japanese individuals recruited from all over Japan revealed that the admixture proportions of the Jomon people varied between prefectures, probably due to the differences of population sizes of immigrants in the final Jomon to the Yayoi period. The estimated allele frequencies of genome-wide SNPs in the ancestral populations of modern Japanese suggested their phenotypic characteristics possibly for adaptation to their respective livelihoods; higher triglycerides and blood sugar for the Jomon ancestry and higher C-reactive protein and eosinophil counts for continental ancestry. According to our findings, we propose a formation model of modern Japanese population; regional variations in admixture proportions of the Jomon people and continental East Asians formed genotypic and phenotypic gradations of current Japanese archipelago populations.
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- 2020
53. Characterization of LILRB3 and LILRA6 allelic variants in the Japanese population
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Gen Hasegawa, Jinwen Sun, Atsushi Tajima, Kouyuki Hirayasu, Jun Ohashi, Yuko Hashikawa, Katsushi Tokunaga, Kazuyoshi Hosomichi, and Rikinari Hanayama
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0301 basic medicine ,DNA Copy Number Variations ,Lineage (evolution) ,Pseudogene ,Population ,030105 genetics & heredity ,Biology ,03 medical and health sciences ,Japan ,Antigens, CD ,Genetics ,Leukocytes ,Humans ,Typing ,Copy-number variation ,Allele ,Receptors, Immunologic ,education ,Gene ,Genetics (clinical) ,Alleles ,Phylogeny ,education.field_of_study ,genomic DNA ,030104 developmental biology ,Genetics, Population ,Multigene Family - Abstract
Leukocyte immunoglobulin (Ig)-like receptors (LILRs) are encoded by members of a human multigene family, comprising 11 protein-coding genes and two pseudogenes. Among the LILRs, LILRB3 and LILRA6 show the highest homology with each other, along with high allelic and copy number variations. Therefore, it has been difficult to discriminate between them, both genetically and functionally, precluding disease association studies of LILRB3 and LILRA6. In this study, we carefully performed variant screening of LILRB3 and LILRA6 by cDNA cloning from Japanese individuals and identified four allelic lineages showing significantly high non-synonymous-to-synonymous ratios in pairwise comparisons. Furthermore, the extracellular domains of the LILRB3*JP6 and LILRA6*JP1 alleles were identical at the DNA level, suggesting that gene conversion-like events diversified LILRB3 and LILRA6. To determine the four allelic lineages from genomic DNA, we established a lineage typing method that accurately estimated the four allelic lineages in addition to specific common alleles from genomic DNA. Analysis of LILRA6 copy number variation revealed one, two, and three copies of LILRA6 in the Japanese-in-Tokyo (JPT) population. Flow cytometric analysis showed that an anti-LILRB3 antibody did not recognize the second most common lineage in the Japanese population, indicating significant amino acid differences across the allelic lineages. Taken together, our findings indicate that our lineage typing is useful for classifying the lineage-specific functions of LILRB3 and LILRA6, serving as the basis for disease association studies.
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- 2020
54. Genetic association study of interferon lambda 3, CD27, and human leukocyte antigen-DPB1 with dengue severity in Thailand
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Izumi Naka, Jintana Patarapotikul, Sumalee Chanama, Pornlada Nuchnoi, Areerat Sa-ngasang, Thareerat Kalambaheti, Unchana Arayasongsak, Suwanna Chaorattanakawee, and Jun Ohashi
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0301 basic medicine ,Male ,Adolescent ,Genotype ,Single-nucleotide polymorphism ,030105 genetics & heredity ,Dengue virus ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Dengue fever ,lcsh:Infectious and parasitic diseases ,Dengue ,03 medical and health sciences ,Severity of illness ,medicine ,Odds Ratio ,Humans ,lcsh:RC109-216 ,Severe Dengue ,IFNL3 ,Child ,Disease severity ,3' Untranslated Regions ,CD27 ,Alleles ,Genetic Association Studies ,HLA-DP beta-Chains ,Genetic association ,business.industry ,Case-control study ,virus diseases ,Odds ratio ,Dengue Virus ,medicine.disease ,Thailand ,Tumor Necrosis Factor Receptor Superfamily, Member 7 ,HLA-DPB1 ,030104 developmental biology ,Infectious Diseases ,Case-Control Studies ,Immunology ,Female ,Interferons ,business ,Research Article - Abstract
Background Dengue patients develop different disease severity ranging from mild (dengue fever [DF]) to severe forms (dengue hemorrhagic fever [DHF] and the fatal dengue shock syndrome [DSS]). Host genetics are considered to be one factor responsible for the severity of dengue outcomes. To identify genes associated with dengue severity that have not been studied yet, we performed genetic association analyses of interferon lambda 3 (IFNL3), CD27, and human leukocyte antigen-DPB1 (HLA-DPB1) genes in Thai dengue patients. Methods A case–control association study was performed in 877 children (age ≤ 15 years) with dengue infection (DF, n = 386; DHF, n = 416; DSS, n = 75). A candidate single nucleotide polymorphism of each of IFNL3, CD27, and HLA-DPB1 was selected to be analyzed. Genotyping was performed by TaqMan real-time PCR assay, and the association with dengue severity was examined. Results The rs9277534 variant of HLA-DPB1 was weakly associated with DHF. The genotype GG and G allele conferred protection against DHF (p = 0.04, odds ratio 0.74 for GG genotype, p = 0.03, odds ratio 0.79 for G allele). The association became borderline significant after adjusting for confounders (p = 0.05, odds ratio 0.82). No association was detected for IFNL3 or CD27. Conclusions The present study demonstrated the weak association of the rs9277534 variant of HLA-DPB1 with protection against DHF. This variant is in the 3′ untranslated region and affects HLA-DPB1 surface protein expression. Our finding suggests that HLA-DPB1 may be involved in DHF pathogenesis.
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- 2020
55. Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals
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Massimo Pizzato, Doreen Kamori, Ai Kawana-Tachikawa, Jun Ohashi, Hiroyuki Gatanaga, Jonathan M. Carlson, Mako Toyoda, Shinichi Oka, Toong Seng Tan, Kageaki Goebuchi, and Takamasa Ueno
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0301 basic medicine ,Cellular immunity ,Viral pathogenesis ,viruses ,030106 microbiology ,lcsh:Medicine ,Viremia ,HIV Infections ,Human leukocyte antigen ,Biology ,Virus-host interactions ,Virus Replication ,Article ,Cell Line ,03 medical and health sciences ,Retrovirus ,Downregulation and upregulation ,medicine ,Humans ,nef Gene Products, Human Immunodeficiency Virus ,lcsh:Science ,Cells, Cultured ,Immune Evasion ,Infectivity ,Multidisciplinary ,Membrane Glycoproteins ,Viral immune evasion ,lcsh:R ,virus diseases ,Membrane Proteins ,Viral Load ,medicine.disease ,biology.organism_classification ,Virology ,030104 developmental biology ,Viral replication ,HLA-B Antigens ,CD4 Antigens ,HIV-1 ,Leukocytes, Mononuclear ,lcsh:Q - Abstract
HIV-1 Nef plays an essential role in enhancing virion infectivity by antagonizing the host restriction molecule SERINC5. Because Nef is highly polymorphic due to the selective forces of host cellular immunity, we hypothesized that certain immune-escape polymorphisms may impair Nef’s ability to antagonize SERINC5 and thereby influence viral fitness in vivo. To test this hypothesis, we identified 58 Nef polymorphisms that were overrepresented in HIV-infected patients in Japan sharing the same HLA genotypes. The number of immune-associated Nef polymorphisms was inversely correlated with the plasma viral load. By breaking down the specific HLA allele-associated mutations, we found that a number of the HLA-B*51:01-associated Y120F and Q125H mutations were most significantly associated with a reduced plasma viral load. A series of biochemical experiments showed that the double mutations Y120F/Q125H, but not either single mutation, impaired Nef’s ability to antagonize SERINC5 and was associated with decreasing virion infectivity and viral replication in primary lymphocytes. In contrast, other Nef functions such as CD4, CCR5, CXCR4 and HLA class I downregulation and CD74 upregulation remained unchanged. Taken together, our results suggest that the differential ability of Nef to counteract SERINC5 by naturally occurring immune-associated mutations was associated with the plasma viral load in vivo.
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- 2020
56. Geographic variation in the polygenic score of height in Japan
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Mariko Isshiki, Yusuke Watanabe, and Jun Ohashi
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Male ,Multifactorial Inheritance ,Population ,Geographic variation ,Genome-wide association study ,Biology ,Population stratification ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Asian People ,Japan ,Genetics ,Humans ,East Asia ,education ,Genetics (clinical) ,030304 developmental biology ,Genetic association ,0303 health sciences ,education.field_of_study ,Geography ,030305 genetics & heredity ,Heritability ,Body Height ,Phenotype ,Polygenic trait ,Female ,Demography ,Genome-Wide Association Study - Abstract
A geographical gradient of height has existed in Japan for approximately 100 years. People in northern Japan tend to be taller than those in southern Japan. The differences in annual temperature and day length between the northern and southern prefectures of Japan have been suggested as possible causes of the height gradient. Although height is well known to be a polygenic trait with high heritability, the genetic contributions to the gradient have not yet been explored. Polygenic score (PS) is calculated by aggregating the effects of genetic variants identified by genome-wide association studies (GWASs) to predict the traits of individual subjects. Here, we calculated the PS of height for 10,840 Japanese individuals from all 47 prefectures in Japan. The median height PS for each prefecture was significantly correlated with the mean height of females and males obtained from another independent Japanese nation-wide height dataset, suggesting genetic contribution to the observed height gradient. We also found that individuals and prefectures genetically closer to continental East Asian ancestry tended to have a higher PS; modern Japanese people are considered to have originated as result of admixture between indigenous Jomon people and immigrants from continental East Asia. Another PS analysis based on the GWAS using only the mainland Japanese was conducted to evaluate the effect of population stratification on PS. The result also supported genetic contribution to height, and indicated that the PS might be affected by a bias due to population stratification even in a relatively homogenous population like Japanese.
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- 2020
57. Prefecture-level population structure of the Japanese based on SNP genotypes of 11,069 individuals
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Yusuke Watanabe, Mariko Isshiki, and Jun Ohashi
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0301 basic medicine ,Mainland China ,Genetic Markers ,Genotype ,Population ,030105 genetics & heredity ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Asian People ,Genetics ,Humans ,East Asia ,Genetic Predisposition to Disease ,education ,Location ,Genetics (clinical) ,Genetic Association Studies ,Genetic association ,education.field_of_study ,Genome, Human ,030104 developmental biology ,Geography ,Genetics, Population ,Genetic marker ,Genetic structure ,Demography - Abstract
We analyzed genome-wide single-nucleotide polymorphism data of 11,069 Japanese individuals recruited from all 47 prefectures of Japan to clarify their genetic structure. The principal component analysis at the prefectural level enabled us to study the relationship between geographical location and genetic differentiation. The results revealed that the mainland Japanese were not genetically homogeneous, and the genetic structure could be explained mainly by the degree of Jomon ancestry and the geographical location. One of the interesting findings was that individuals in the Shikoku region (i.e., Tokushima Prefecture, Kagawa Prefecture, Ehime Prefecture, and Kochi Prefecture) were genetically close to Han Chinese. Therefore, the genetic components of immigrants from continental East Asia in the Yayoi period may have been well maintained in Shikoku. The present results will be useful for understanding the peopling of Japan, and also provide suggestions for recruiting subjects in genetic association studies.
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- 2020
58. Japanese language education and Japanese Studies as intercultural learning
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Jun Ohashi and Hiroko Ohashi
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- 2020
59. Development of a quantitative, portable, and automated fluorescent blue-ray device-based malaria diagnostic equipment with an on-disc SiO2 nanofiber filter
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Hiroaki Oka, Takahiro Nogami, Yusuke Ido, James Kongere, Takuya Hayashi, Kenji Nagatomi, Yasuyuki Sofue, Masatoshi Kataoka, Shouki Yatsushiro, Muneaki Hashimoto, Kaori Abe, Stephen Munga, George Sonye, Toshihiro Mita, Noriko Tamari, Beatrice Awuor, Takeki Yamamoto, Noboru Minakawa, Kazuaki Kajimoto, and Jun Ohashi
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0301 basic medicine ,Blood Platelets ,Male ,Erythrocytes ,030231 tropical medicine ,Plasmodium falciparum ,Nanofibers ,lcsh:Medicine ,Diagnostic system ,Polymerase Chain Reaction ,Article ,Fluorescence ,03 medical and health sciences ,0302 clinical medicine ,Diagnostic equipment ,parasitic diseases ,medicine ,Leukocytes ,Humans ,Malaria, Falciparum ,lcsh:Science ,Child ,Multidisciplinary ,biology ,business.industry ,Diagnostic Tests, Routine ,lcsh:R ,Diagnostic markers ,Translational research ,medicine.disease ,biology.organism_classification ,Silicon Dioxide ,Kenya ,Malaria ,030104 developmental biology ,Fully automated ,Molecular Diagnostic Techniques ,Filter (video) ,Nanofiber ,Child, Preschool ,lcsh:Q ,Female ,business ,Biomedical engineering - Abstract
There is an urgent need to develop an automated malaria diagnostic system that can easily and rapidly detect malaria parasites and determine the proportion of malaria-infected erythrocytes in the clinical blood samples. In this study, we developed a quantitative, mobile, and fully automated malaria diagnostic system equipped with an on-disc SiO2 nanofiber filter and blue-ray devices. The filter removes the leukocytes and platelets from the blood samples, which interfere with the accurate detection of malaria by the blue-ray devices. We confirmed that the filter, which can be operated automatically by centrifugal force due to the rotation of the disc, achieved a high removal rate of leukocytes (99.7%) and platelets (90.2%) in just 30 s. The automated system exhibited a higher sensitivity (100%) and specificity (92.8%) for detecting Plasmodium falciparum from the blood of 274 asymptomatic individuals in Kenya when compared to the common rapid diagnosis test (sensitivity = 98.1% and specificity = 54.8%). This indicated that this system can be a potential alternative to conventional methods used at local health facilities, which lack basic infrastructure.
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- 2020
60. The Origin and Composition of Korean Ethnicity Analyzed by Ancient and Present-Day Genome Sequences
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Asta Blazyte, Fahd Al-Mulla, Sungwon Jeon, Suthat Fucharoen, Jae-Pil Choi, Katsushi Tokunaga, Jong Il Kim, Yeonsu Jeon, Jong Bhak, Jungeun Kim, Jun Ohashi, and Sumio Sugano
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Male ,Pleistocene ,Human Migration ,Population ,Ethnic group ,Present day ,Biology ,DNA, Mitochondrial ,03 medical and health sciences ,variome ,Peninsula ,Republic of Korea ,Genetics ,Ethnicity ,Humans ,East Asia ,DNA, Ancient ,education ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,KoVariome ,0303 health sciences ,Genetic diversity ,education.field_of_study ,geography ,geography.geographical_feature_category ,Chromosomes, Human, Y ,Whole Genome Sequencing ,population study ,Genome, Human ,Genetic Variation ,Korean origin ,Genomics ,Genetics, Population ,paleogenomics ,030301 anatomy & morphology ,Haplotypes ,Evolutionary biology ,Population study ,Korean migration ,Research Article - Abstract
Koreans are thought to be an ethnic group of admixed northern and southern subgroups. However, the exact genetic origins of these two remain unclear. In addition, the past admixture is presumed to have taken place on the Korean peninsula, but there is no genomic scale analysis exploring the origin, composition, admixture, or the past migration of Koreans. Here, 88 Korean genomes compared with 91 other present-day populations showed two major genetic components of East Siberia and Southeast Asia. Additional paleogenomic analysis with 115 ancient genomes from Pleistocene hunter-gatherers to Iron Age farmers showed a gradual admixture of Tianyuan (40 ka) and Devil’s gate (8 ka) ancestries throughout East Asia and East Siberia up until the Neolithic era. Afterward, the current genetic foundation of Koreans may have been established through a rapid admixture with ancient Southern Chinese populations associated with Iron Age Cambodians. We speculate that this admixing trend initially occurred mostly outside the Korean peninsula followed by continuous spread and localization in Korea, corresponding to the general admixture trend of East Asia. Over 70% of extant Korean genetic diversity is explained to be derived from such a recent population expansion and admixture from the South.
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- 2020
61. Genome-wide association study identifies CDH13 as a susceptibility gene for rhododendrol-induced leukoderma
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Hiroshi Nagai, Izumi Naka, Naoki Oiso, Atsushi Tanemura, Ichiro Katayama, Ken Okamura, Yuko Abe, Tamio Suzuki, Yuta Araki, Yutaka Hozumi, Akiko Ito, Jun Ohashi, Kayoko Matsunaga, Yukiko Masui, Toshiharu Yamashita, Chikako Nishigori, Kazuyoshi Fukai, Yumi Aoyama, Masahiro Hayashi, Toru Saito, Yui Kobayashi, and Akiko Yagami
- Subjects
0301 basic medicine ,Tyrosinase ,Leukoderma ,Butanols ,Vitiligo ,Genome-wide association study ,Dermatology ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,medicine ,Humans ,Genetic Predisposition to Disease ,Alleles ,Gene knockdown ,medicine.disease ,Cadherins ,Molecular biology ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Melanocytes ,Epidermis ,Genome-Wide Association Study - Abstract
Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol; trade name: Rhododenol [RD]), which is used in topical skin-lightening cosmetics, was unexpectedly reported in Japan to induce leukoderma or vitiligo called RD-induced leukoderma (RIL) after repeated application. To our knowledge, no studies have investigated chemical-induced vitiligo pathogenesis on a genome-wide scale. Here, we conducted a genome-wide association study (GWAS) for 147 cases and 112 controls. CDH13, encoding a glycosylphosphatidylinositol-anchored protein called T-cadherin (T-cad), was identified as the strongest RIL susceptibility gene. RD sensitivity was remarkably increased by T-cad knockdown in cultured normal human melanocytes. Furthermore, we confirmed tyrosinase upregulation and downregulation of the anti-apoptotic molecules (BCL-2 and BCL-XL), suggesting that T-cad is associated with RD via tyrosinase or apoptotic pathway regulation. Finally, monobenzyl ether of hydroquinone sensitivity also tended to increase with T-cad knockdown, suggesting that the T-cad could be a candidate susceptibility gene for RIL and other chemical-induced vitiligo forms. This is the first GWAS for chemical-induced vitiligo, and it could be a useful model for studying the disease's genetic aspects.
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- 2020
62. Endogenization and excision of human herpesvirus 6 in human genomes
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Chikashi Terao, Yoshiki Kawamura, Koichi Matsuda, Xiaoxi Liu, Hidewaki Nakagawa, Yoshinori Murakami, Gen Tamiya, Kei Sato, Nana Matoba, Yukihide Momozawa, Hiroki Miura, Shunichi Kosugi, Jumpei Ito, Rie Koide, Michiaki Kubo, Tetsushi Yoshikawa, Amr Aswad, Nicholas F. Parrish, Masashi Fujita, Yoichiro Kamatani, Anselmo Jiro Kamada, Jun Ohashi, and Motomichi Matsuzaki
- Subjects
Cancer Research ,Heredity ,Chromosomes, Human, Pair 22 ,Herpesvirus 6, Human ,viruses ,Genome-wide association study ,integration ,QH426-470 ,Genome ,0302 clinical medicine ,Direct repeat ,infections ,RNA, Small Interfering ,Genetics (clinical) ,Data Management ,Genetics ,Viral Genomics ,0303 health sciences ,Chromosome Biology ,transmission ,virus diseases ,Phylogenetic Analysis ,Genomics ,Phylogenetics ,Genetic Mapping ,HHV-6A ,Research Article ,Transposable element ,Chromosome Structure and Function ,Computer and Information Sciences ,Virus Integration ,Locus (genetics) ,Microbial Genomics ,Biology ,Polymorphism, Single Nucleotide ,Microbiology ,Chromosomes ,Human Genomics ,Evolution, Molecular ,03 medical and health sciences ,Asian People ,Virology ,Genome-Wide Association Studies ,Humans ,Evolutionary Systematics ,Molecular Biology ,Germ-Line Mutation ,Ecology, Evolution, Behavior and Systematics ,Taxonomy ,030304 developmental biology ,Evolutionary Biology ,Genome, Human ,association ,Biology and Life Sciences ,Computational Biology ,Human Genetics ,Cell Biology ,DNA ,500 Naturwissenschaften und Mathematik::570 Biowissenschaften ,Biologie::570 Biowissenschaften ,Biologie ,biochemical phenomena, metabolism, and nutrition ,Genome Analysis ,telomeres ,Human genetics ,RNAs ,Haplotypes ,Human genome ,030217 neurology & neurosurgery - Abstract
Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactivate into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association. In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected “solo-DR scar” has not been described in vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines., Author summary Human herpesvirus 6 (HHV-6) infects most people during childhood and can reactivate later in life to contribute to diseases. The HHV-6 genome is also inherited by about 1% of people, included in the end “cap” of one of their 46 chromosomes. Little is known about how HHV-6 genomes entered human genomes, whether or not they still do, and the risk this poses for virus reactivation. We looked for HHV-6 in genome sequences from ~7,500 Japanese people. Most integrated HHV-6 variants have been co-evolving with human chromosomes for many generations. Surprisingly, in almost three-fourths of Japanese people with HHV-6 in their genome, HHV-6 is integrated in the same end of the same chromosome – 22q. Persistence of the HHV-6 genome within the short “cap” that preserves the end of chromosome 22q raises the question of whether the integrated viral sequence has taken on a useful function for this chromosome. Some human genomes harbor only one part of the HHV-6 genome–the same part that remains after experimental HHV-6 reactivation, during which most of the virus is cut out of the genome. This suggests that integration of HHV-6 into inherited human genomes is not irreversible, and possibly leads to production of infectious virus.
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- 2020
- Full Text
- View/download PDF
63. Association of an intronic SNP of the EFEMP1 gene with height in Tongans
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Taro Yamauchi, Yasuhiro Matsumura, Mariko Isshiki, Nao Nishida, Takafumi Ishida, Kazumi Natsuhara, Izumi Naka, Ryosuke Kimura, Ryutaro Ohtsuka, Jun Ohashi, Tsukasa Inaoka, Minato Nakazawa, and Takuro Furusawa
- Subjects
0301 basic medicine ,education.field_of_study ,Population ,Single-nucleotide polymorphism ,Regression analysis ,Biology ,03 medical and health sciences ,030104 developmental biology ,Genetics ,Intronic SNP ,SNP ,Allele ,Human height ,education ,Allele frequency ,Genetics (clinical) ,Demography - Abstract
A common single nucleotide polymorphism (SNP) located in intron 4 of the EFEMP1 gene, rs3791675, has been reported to be associated with human height in European and Asian populations. The objective of this study is to examine the possible association of rs3791675-G with taller height in Oceanian populations. The rs3791675 SNP was genotyped for 636 adult subjects living in Tonga (Tonga population) and Solomon Islands (Munda, Kusaghe, and Rawaki populations). The allele frequency of rs3791675-G ranged from 0.29 to 0.66. A multiple regression analysis adjusted for age and sex was performed to test the association of rs3791675 with height in each population. The results revealed that a single copy of the rs3791675-G allele significantly increased height by 1.2 cm in Tonga population (P-value = 0.031), while no significant association was detected in Munda, Kusaghe, and Rawaki populations. Since the partial regression coefficients of rs3791675-G estimated in regression models were positive in all the populations, the lack of association in the Solomon Islanders may have come from small effect size of rs3791675-G in them as well as small sample size. To confirm the present finding, replication studies in other Oceanian populations are required.
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- 2018
64. Endogenization and excision of human herpesvirus 6 in human genomes
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Chikashi Terao, Yoshinori Murakami, Hiroki Miura, Yoshiki Kawamura, Gen Tamiya, Rie Koide, Xiaoxi Liu, Anselmo Jiro Kamada, Nicholas F. Parrish, Masashi Fujita, Nana Matoba, Michiaki Kubo, Koichi Matsuda, Tetsushi Yoshikawa, Yoichiro Kamatani, Kei Sato, Yukihide Momozawa, Hidewaki Nakagawa, Jumpei Ito, Motomichi Matsuzaki, Jun Ohashi, and Shunichi Kosugi
- Subjects
Genetics ,Transposable element ,Nuclear gene ,viruses ,Direct repeat ,Chromosome ,virus diseases ,Locus (genetics) ,Human genome ,Biology ,Genome ,Telomere - Abstract
The genome of human herpesvirus 6 (HHV-6) is integrated within the nuclear genome of about 1% of humans, but how this came about is not clear. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). piRNAs block integration of transposons in the germline, so piRNA-mediated repression of HHV-6 integration has been suspected. Whether integrated HHV-6 can reactive into an infectious virus is also uncertain. In vitro, recombination of the viral genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected single DR “scar” has not been described in vivo. We analyzed whole-genome sequencing (WGS) data from 13,040 subjects, including 7,485 from Japan. We found an association between integrated HHV-6 and polymorphisms on chr22q in Japanese subjects. However, association with the reported MOV10L1 polymorphism was driven by physical linkage to a single ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. We resolved the junction of the human chromosome with this viral genome using long read sequencing. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a single DR, supporting in vivo excision and viral reactivation. Using WGS data from North American families, we show that the incidence of HHV-6 integration into the germline is lower than its prevalence, and that integrated HHV-6 is not associated with the reported variant in MOV10L1. Together these results explain the recently reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact non-retroviral genome known to be present in human germlines.SIGNIFICANCE STATEMENTHuman herpesvirus 6 (HHV-6) infects most people during childhood, usually only causing fever and rash. Reactivation of HHV-6 has been linked to a number of neurological diseases including encephalitis, Alzheimer’s disease and multiple sclerosis. However, about 1% of people are born with the HHV-6 genome present within their genome, included in the end “cap” of one of their 46 chromosomes. Little is known about how and when HHV-6 genomes entered human genomes, whether or not they still do, and whether or not this poses risk for virus reactivation. We looked for HHV-6 in genome sequences from over 13,000 people. Most HHV-6 variants present in human genomes have been co-evolving with human chromosomes for many generations, and new integration events are rare. Surprisingly, in almost three fourths of Japanese people with HHV-6 in their genome, HHV-6 integrated in the same end of the same chromosome – 22q. Persistence of the HHV-6 genome within the short “cap” that preserves the end of chromosome 22q suggests that the integrated viral sequence may have taken on a useful function for this chromosome. We also found that some human genomes harbor only one part of the HHV-6 genome. This part is the same part that remains after experimental viral reactivation, during which most of the virus is cut out of the genome. This warrants assessment of the risk that integration of HHV-6 into inherited human genomes is not irreversible, and possibly leads to production of infectious virus.
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- 2019
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- View/download PDF
65. Key HLA‐DRB1‐DQB1 haplotypes and role of the BTNL2 gene for response to a hepatitis B vaccine
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Takayo Tsuchiura, Ryo Sumazaki, Hiromi Sawai, Yasuhiro Takikawa, Kazumoto Murata, Keisuke Kakisaka, Nao Nishida, Osamu Yokosuka, Masashi Mizokami, Tatsuo Kanda, Jun Ohashi, Keisuke Hino, Aiko Sakai, Katsushi Tokunaga, Seik-Soon Khor, Sohji Nishina, and Masaya Sugiyama
- Subjects
0301 basic medicine ,musculoskeletal diseases ,Adult ,Male ,HBsAg ,Hepatitis B virus ,Viral Hepatitis ,Human leukocyte antigen ,Biology ,medicine.disease_cause ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Antigen ,Genotype ,medicine ,Humans ,Hepatitis B Vaccines ,030212 general & internal medicine ,HLA-DRB1 ,Hepatology ,Butyrophilins ,Haplotype ,Original Articles ,Hepatitis B ,Middle Aged ,medicine.disease ,3. Good health ,030104 developmental biology ,Immunology ,Original Article ,Female ,Genome-Wide Association Study ,HLA-DRB1 Chains - Abstract
Approximately 5-10% of individuals who are vaccinated with a hepatitis B (HB) vaccine designed based on the hepatitis B virus (HBV) genotype C fail to acquire protective levels of antibodies. Here, host genetic factors behind low immune response to this HB vaccine were investigated by a genome-wide association study (GWAS) and Human Leukocyte Antigen (HLA) association tests. The GWAS and HLA association tests were carried out using a total of 1,193 Japanese individuals including 107 low responders, 351 intermediate responders, and 735 high responders. Classical HLA class II alleles were statistically imputed using the genome-wide SNP typing data. The GWAS identified independent associations of HLA-DRB1-DQB1, HLA-DPB1 and BTNL2 genes with immune response to a HB vaccine designed based on the HBV genotype C. Five HLA-DRB1-DQB1 haplotypes and two DPB1 alleles showed significant associations with response to the HB vaccine in a comparison of three groups of 1,193 HB vaccinated individuals. When frequencies of DRB1-DQB1 haplotypes and DPB1 alleles were compared between low immune responders and HBV patients, significant associations were identified for three DRB1-DQB1 haplotypes, and no association was identified for any of the DPB1 alleles. In contrast, no association was identified for DRB1-DQB1 haplotypes and DPB1 alleles in a comparison between high immune responders and healthy individuals. Conclusion: The findings in this study clearly show the importance of HLA-DR-DQ (i.e., recognition of a vaccine related HB surface antigen (HBsAg) by specific DR-DQ haplotypes) and BTNL2 molecules (i.e., high immune response to HB vaccine) for response to a HB vaccine designed based on the HBV genotype C. (Hepatology 2018).
- Published
- 2018
66. Artemisinin-Resistant Plasmodium falciparum with High Survival Rates, Uganda, 2014–2016
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Alex Olia, Miki Sakurai-Yatsushiro, Toshihiro Horii, Mary A. Auma, Mie Ikeda, Megumi Kaneko, Denis A Anywar, Makoto Hirai, Joseph Okello-Onen, Takafumi Tsuboi, Masatoshi Kataoka, Betty Balikagala, Eisaku Kimura, Shouki Yatsushiro, Osbert T. Katuro, Masato Yamauchi, Makoto Sekihara, Muneaki Hashimoto, Paul S. Obwoya, Toshihiro Mita, Shin-Ichiro Tachibana, Nirianne Marie Q. Palacpac, Nobuyuki Takahashi, Emmanuel I. Odongo-Aginya, and Jun Ohashi
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0301 basic medicine ,Male ,Epidemiology ,lcsh:Medicine ,Drug resistance ,Parasite hosting ,Uganda ,Artemisinin ,Malaria, Falciparum ,biology ,Artemisinins ,Survival Rate ,Infectious Diseases ,Phenotype ,Child, Preschool ,Female ,medicine.drug ,Microbiology (medical) ,medicine.medical_specialty ,Genotype ,Artemisinin-Resistant P. falciparum, Uganda ,030106 microbiology ,Plasmodium falciparum ,malaria ,parasites ,History, 21st Century ,Artemisinin-Resistant Plasmodium falciparum with High Survival Rates, Uganda, 2014–2016 ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Drug treatment ,Antimalarials ,Antibiotic resistance ,parasitic diseases ,medicine ,Humans ,lcsh:RC109-216 ,antimicrobial resistance ,drug resistance ,Whole Genome Sequencing ,Public health ,Research ,lcsh:R ,medicine.disease ,biology.organism_classification ,Virology ,Cross-Sectional Studies ,Mutation ,Malaria - Abstract
Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014-2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage-specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates. Similar rates have been closely associated with delayed parasite clearance after drug treatment and are considered to be a proxy for the artemisinin-resistant phenotype. Of these, the PfKelch13 mutation was observed in only 1 isolate, A675V. Population genetics analysis suggested that these possibly artemisinin-resistant isolates originated in Africa. Large-scale surveillance of possibly artemisinin-resistant parasites in Africa would provide useful information about treatment outcomes and help regional malaria control.
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- 2018
67. An emerging role-identity and honorifics: A longitudinal study of email exchanges in a Japanese community
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Jun Ohashi
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060201 languages & linguistics ,Linguistics and Language ,Honorific ,Social network ,business.industry ,Interpretation (philosophy) ,Social distance ,06 humanities and the arts ,Language and Linguistics ,Linguistics ,Artificial Intelligence ,0602 languages and literature ,Semiotics ,Japanese honorifics ,Sociology ,Affect (linguistics) ,business ,Indexicality - Abstract
The study presents a longitudinal, qualitative and ethnographic investigation of language use and change within an informal Japanese alumni network. It utilises the author's corpus of past email correspondence among a social network of Japanese men between 2006 and 2009, and a subsequent interview in 2012. The study illuminates a struggle over the interpretation of the use of honorifics as a semiotic tool which could affect interpersonal relationships. More specifically, it illustrates the increasing use of honorifics by a member in enacting a social event organiser (幹事Kanji) role in this community and its multiple interpretations by other members reflecting various vantage points. Theoretically, it aims to demonstrate the multiple indexical meanings of Japanese honorifics by exploring the use of honorifics indexing neither deference nor social distance (the traditional interpretations of honorific use) but rather the functional enactment of a recognized social role and its associated register. This use of honorific language as ‘functional rather than relational’ has not been previously emphasised in the literature on Japanese honorific use. It also demonstrates the fundamental indeterminacy of indexical meanings in relation to various interpretive vantage points and evaluative moments.
- Published
- 2018
68. Statistical hypothesis testing in case-control studies on HLA and disease associations
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Jun Ohashi
- Subjects
business.industry ,Immunology ,Case-control study ,Medicine ,Human leukocyte antigen ,Disease ,business ,Statistical hypothesis testing - Published
- 2018
69. Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) polymorphism as a genetic marker of cerebral malaria in Thai population
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Jun Ohashi, Jintana Patarapotikul, Pornlada Nuchnoi, Saw Thu Wah, Hathairad Hananantachai, and Izumi Naka
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Genetics ,Linkage disequilibrium ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Single-nucleotide polymorphism ,Plasmodium falciparum ,General Medicine ,Biology ,biology.organism_classification ,medicine.disease ,thai ,Genotype frequency ,interferon-induced protein with tetratricopeptide repeats 1 ,Genetic marker ,Cerebral Malaria ,parasitic diseases ,medicine ,cerebral malaria ,polymorphisms ,Genotyping ,Malaria - Abstract
Objective: To know whether the effect of interferon-induced protein with tetratricopeptide repeats (IFIT) 1 polymorphism influences the susceptibility of cerebral malaria outcome. Methods: Case-control association study was performed among 314 Thai patients (110 with cerebral malaria and 204 with uncomplicated malaria) infected with Plasmodium falciparum. Genotyping for five tag-single nucleotide polymorphisms of IFIT1 was performed by endpoint genotyping. Results: Genotype frequencies of all tag-SNPs (single nucleotide polymorphisms) showed no association with malaria outcome. However, C allele of rs11203109 was associated with the protection from cerebral malaria (OR=0.62, 95% CI=0.38-0.99, P=0.048). Two single nucleotide polymorphisms (rs5786868 and rs57941432) were in linkage disequilibrium with rs11203109. Conclusions: This suggests that our associated single nucleotide polymorphism (rs11203109) might be a genetic marker of cerebral malaria progression in the Thai population.
- Published
- 2018
70. Recurrent Hypoglycemia Due to a High Titer of Insulin Antibody in Response to Exogenous Insulin Administration in Two Cases of Type 1 Diabetes.
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Ryoichi Kawamura, Satoshi Miyao, Hiroshi Onuma, Yasuko Uchigata, Eiji Kawasaki, Jun Ohashi, Sanshiro Shiraishi, Wataru Nishida, Maki Yokomoto-Umakosh, Yasunori Takata, Haruhiko Osawa, and Hideichi Makino
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- 2022
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71. Evolution of Fseg/Cseg dimorphism in region III of the Plasmodium falciparum eba-175 gene
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Hathairad Hananantachai, Jintana Patarapotikul, Izumi Naka, Yoshiki Yasukochi, and Jun Ohashi
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0301 basic medicine ,Microbiology (medical) ,Plasmodium ,Lineage (genetic) ,Plasmodium falciparum ,030231 tropical medicine ,Population ,Protozoan Proteins ,Gene Expression ,Antigens, Protozoan ,Microbiology ,Evolution, Molecular ,03 medical and health sciences ,0302 clinical medicine ,Molecular evolution ,Databases, Genetic ,parasitic diseases ,Genetics ,Animals ,Humans ,Allele ,education ,Molecular Biology ,Allele frequency ,Alleles ,Phylogeny ,Ecology, Evolution, Behavior and Systematics ,education.field_of_study ,Polymorphism, Genetic ,Base Sequence ,biology ,Nucleic acid sequence ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,GenBank - Abstract
The 175-kDa erythrocyte binding antigen (EBA-175) of the malaria parasite Plasmodium falciparum is important for its invasion into human erythrocytes. The primary structure of eba-175 is divided into seven regions, namely I to VII. Region III contains highly divergent dimorphic segments, termed Fseg and Cseg. The allele frequencies of segmental dimorphism within a P. falciparum population have been extensively examined; however, the molecular evolution of segmental dimorphism is not well understood. A comprehensive comparison of nucleotide sequences among 32 P. falciparum eba-175 alleles identified in our previous study, two Plasmodium reichenowi, and one P. gaboni orthologous alleles obtained from the GenBank database was conducted to uncover the origin and evolutionary processes of segmental dimorphism in P. falciparum eba-175. In the eba-175 nucleotide sequence derived from a P. reichenowi CDC strain, both Fseg and Cseg were found in region III, which implies that the original eba-175 gene had both segments, and deletions of F- and C-segments generated Cseg and Fseg alleles, respectively. We also confirmed the presence of allele with Fseg and Cseg in another P. reichenowi strain (SY57), by re-mapping short reads obtained from the GenBank database. On the other hand, the segmental sequence of eba-175 ortholog in P. gaboni was quite diverged from those of the other species, suggesting that the original eba-175 dimorphism of P. falciparum can be traced back to the stem linage of P. falciparum and P. reichenowi. Our findings suggest that Fseg and Cseg alleles are derived from a single eba-175 allele containing both segments in the ancestral population of P. falciparum and P. reichenowi, and that the allelic dimorphism of eba-175 was shaped by the independent emergence of similar dimorphic lineage in different species that has never been observed in any evolutionary mode of allelic dimorphism at other loci in malaria genomes.
- Published
- 2017
72. Dual Effects of a RETN Single Nucleotide Polymorphism (SNP) at –420 on Plasma Resistin: Genotype and DNA Methylation
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Wataru Nishida, Masaaki Ochi, Haruhiko Osawa, Jun Ohashi, Ryoichi Kawamura, Hiroshi Onuma, Yasumasa Ohyagi, Tatsuya Nishimiya, Yasuharu Tabara, Tetsuro Miki, Katsuhiko Kohara, Yasunori Takata, and Ryuichi Kawamoto
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Genotype ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Bisulfite sequencing ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Biochemistry ,Monocytes ,Body Mass Index ,Cell Line ,Epigenesis, Genetic ,03 medical and health sciences ,Endocrinology ,Asian People ,Japan ,Internal medicine ,medicine ,Humans ,Resistin ,RNA, Messenger ,Epigenetics ,Aged ,Biochemistry (medical) ,Methylation ,DNA Methylation ,Middle Aged ,Molecular biology ,C-Reactive Protein ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,CpG site ,DNA methylation ,CpG Islands ,Female - Abstract
We previously reported that single nucleotide polymorphism (SNP)-420 CG (rs1862513) in the promoter region of RETN was associated with type 2 diabetes. Plasma resistin was tightly correlated with SNP-420 genotypes. SNP-420 is a CpG-SNP affecting the sequence of cytosine-phosphate-guanine dinucleotides.To examine whether methylation at SNP-420 affects plasma resistin, we analyzed plasma resistin and methylation at RETN SNP-420.Genomic DNA was extracted from peripheral white blood cells in 2078 Japanese subjects. Quantification of the methylation was performed by pyrosequencing after DNA bisulfite conversion.Methylation at SNP-420 was highest in the C/C genotype (36.9 ± 5.7%), followed by C/G (21.4 ± 3.5%) and G/G (2.9 ± 1.4%; P0.001). When assessed in each genotype, methylation at SNP-420 was inversely associated with plasma resistin in the C/C (β = -0.134, P0.001) or C/G (β = -0.227, P0.001) genotype. In THP-1 human monocytes intrinsically having the C/C genotype, a demethylating reagent, 5-aza-dC, decreased the methylation at SNP-420 and increased RETN messenger RNA. SNP+1263 (rs3745369), located in the 3' untranslated region of RETN, was also associated with methylation at SNP-420. In addition, highly sensitive C-reactive protein was inversely associated with methylation at SNP-420 in the C/C genotype, whereas body mass index was positively associated.Plasma resistin was inversely associated with the extent of methylation at SNP-420 mainly dependent on the SNP-420 genotype. The association can also be explained partially independent of SNP-420 genotypes. SNP-420 could have dual, genetic and epigenetic effects on plasma resistin.
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- 2016
73. Field evaluation of a quantitative, and rapid malaria diagnostic system using a fluorescent Blue-ray optical device
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Kaori Abe, Stephen Munga, Muneaki Hashimoto, Noboru Minakawa, Noriko Tamari, Yasuyuki Sofue, Masatoshi Kataoka, Takeki Yamamoto, Beatrice Awuor, Shouki Yatsushiro, Yusuke Ido, James Kongere, Hiroaki Oka, George Sonye, Kenji Nagatomi, Jun Ohashi, Takahiro Nogami, Toshihiro Mita, Takuya Hayashi, and Kazuaki Kajimoto
- Subjects
Detection limit ,Rapid diagnostic test ,biology ,business.industry ,Plasmodium falciparum ,Parasitemia ,medicine.disease ,biology.organism_classification ,Diagnostic system ,Confidence interval ,parasitic diseases ,medicine ,Nuclear medicine ,business ,Nested polymerase chain reaction ,Malaria - Abstract
We improved a previously developed quantitative malaria diagnostic system based on fluorescent Blue-ray optical device. Here, we first improved the diagnostic system to enable fully automated operation and the field application was evaluated in Kenya. We detected Plasmodium falciparum in blood samples collected from 288 individuals aged 1-16 years using nested polymerase chain reaction (nPCR), rapid diagnostic test (RDT), and automated system. Compared to RDT, the automated system exhibited a higher sensitivity (100%; 95% confidence interval [CI], 93.3–100%) and specificity (92.8%; 95%CI, 88.5–95.8%). The limit of detection was 0.0061%. Linear regression analysis revealed a correlation between the automated system and microscopic examination for detecting parasitemia (adjusted R2 value=0.63, P=1.13×10−12). The automated system exhibited a stable quantification of parasitemia and a higher diagnostic accuracy for parasitemia than RDT. This indicates the potential of this system as a valid alternative to conventional methods used at local health facilities, which lack basic infrastructure.
- Published
- 2019
74. Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea
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Jun Ohashi, Makoto Hirai, Alyssa E. Barry, Toshiyuki Mori, Francis Hombhanje, Rintis Noviyanti, Toshihiro Mita, Ric N. Price, Masato Yamauchi, Pascal Ringwald, Sarah Auburn, Richard D. Pearson, Mehra Somya, Makoto Sekihara, Roberto Amato, Shin-Ichiro Tachibana, Livingstone Tavul, Moses Laman, Sónia Gonçalves, Dominic P. Kwiatkowski, Olivo Miotto, Mie Ikeda, Jutta Marfurt, Manuel W Hetzel, and Ivo Mueller
- Subjects
Heredity ,Single Nucleotide Polymorphisms ,Genes, Protozoan ,Drug Resistance ,Drug resistance ,medicine.disease_cause ,Identity by descent ,Geographical locations ,Medical Conditions ,0302 clinical medicine ,Anti-Infective Agents ,Medicine and Health Sciences ,Malaria, Falciparum ,Biology (General) ,Artemisinin ,Genetics ,0303 health sciences ,Mutation ,Drugs ,Genomics ,Artemisinins ,3. Good health ,Genetic Mapping ,Research Article ,medicine.drug ,Asia ,Lineage (genetic) ,QH301-705.5 ,Oceania ,Plasmodium falciparum ,030231 tropical medicine ,Immunology ,Biology ,Microbiology ,Deep sequencing ,Papua New Guinea ,Antimalarials ,03 medical and health sciences ,Antibiotic resistance ,Virology ,parasitic diseases ,Parasitic Diseases ,medicine ,Humans ,Gene ,Molecular Biology ,030304 developmental biology ,Pharmacology ,Haplotype ,Biology and Life Sciences ,RC581-607 ,medicine.disease ,biology.organism_classification ,Cross-Sectional Studies ,Haplotypes ,Parasitology ,Indonesia ,People and places ,Immunologic diseases. Allergy ,Malaria - Abstract
The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants’ genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance., Author summary Artemisinin is the most widely used drug against Plasmodium falciparum malaria. In southeast Asia, parasites have evolved genetic changes making them resistant to artemisinin. The elimination of resistant strains is a global priority, since their global spread could result in massive loss of lives. In Papua New Guinea, we found three patients infected with parasites carrying the most widespread resistant variant in southeast Asia, and they were confirmed to be artemisinin resistant. We established that the mutations were not imported from southeast Asia, and found other drug resistance variants in their genetic background, including some shared with parasites in Indonesia. This indicates that artemisinin resistance has emerged in New Guinea separately from southeast Asia, not by a chance event, but by a gradual process of evolution which may still be ongoing undetected on the island. These resistant strains could undermine malaria local control efforts, and constitute a global threat.
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- 2019
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75. The number of SNPs required for distinguishing Japanese from other East Asians
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Kunihiko Kurosaki, Fuzuki Mizuno, Izumi Naka, Shintaroh Ueda, and Jun Ohashi
- Subjects
Forensic Genetics ,Male ,Principal Component Analysis ,Asia, Eastern ,Single-nucleotide polymorphism ,Computational biology ,Biology ,Polymorphism, Single Nucleotide ,DNA sequencing ,Pathology and Forensic Medicine ,Hierarchical clustering ,Issues, ethics and legal aspects ,Genetics, Population ,Asian People ,Japan ,Databases, Genetic ,Human Genome Project ,Genotype ,Principal component analysis ,Cluster Analysis ,Humans ,SNP ,Computer Simulation ,Female - Abstract
In some cases, it is necessary to estimate the national origin of an unknown subject in forensic medicine. The use of single nucleotide polymorphism (SNP) markers appears to be very effective for this purpose, since genome-wide SNP genotype data of many human populations are publicly available. In this study, we examined the number of SNPs that could objectively and accurately distinguish Japanese subjects (1KG-JPT) from the other East Asians (1KG-CDX, -CHB, -CHS, and -KHV) using the combination of principal component analysis and hierarchical cluster analysis. A computer simulation showed that approximately 3000 randomly selected SNPs were enough for the discrimination. Our results suggest that at least a 0.024% coverage is needed in the next generation sequencing experiment to objectively determine whether an unknown person is Japanese or not if the amount of DNA sample from him/her is insufficient or the quality is low.
- Published
- 2021
76. Elucidating the origin of HLA-B*73 allelic lineage: Did modern humans benefit by archaic introgression?
- Author
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Jun Ohashi and Yoshiki Yasukochi
- Subjects
0301 basic medicine ,Neanderthal ,Lineage (genetic) ,Pan troglodytes ,Introgression ,Short Communication ,Immunology ,Population ,Black People ,Single-nucleotide polymorphism ,Archaic humans ,Evolution, Molecular ,03 medical and health sciences ,Asian People ,biology.animal ,Genetics ,Animals ,Humans ,Denisovan ,Allele ,education ,Alleles ,Phylogeny ,Neanderthals ,education.field_of_study ,biology ,Genome, Human ,Haplotype ,Hominidae ,biology.organism_classification ,Europe ,HLA ,030104 developmental biology ,Haplotypes ,HLA-B Antigens ,Evolutionary biology ,Allelic divergence ,HLA-B*73 - Abstract
A previous study reported that some of the human leukocyte antigen (HLA) alleles and haplotypes in present-day humans were acquired by admixture with archaic humans; specifically, an exceptionally diverged HLA-B*73 allele was proposed to be transmitted from Denisovans, although the DNA sequence of HLA-B*73 has not been detected in the Denisovan genome. Here, we argue against the hypothesis that HLA-B*73 introgressed from Denisovans into early modern humans. A phylogenetic analysis revealed that HLA-B*73:01 formed a monophyletic group with a chimpanzee MHC-B allele, strongly suggesting that the HLA-B*73 allelic lineage has been maintained in humans as well as in chimpanzees since the divergence of humans and chimpanzees. The global distribution of HLA-B*73 allele showed that the population frequency of HLA-B*73 in west Asia (0.24 %)—a possible site of admixture with Denisovans—is lower than that in Europe (0.72 %) and in south Asia (0.69 %). Furthermore, HLA-B*73 is not observed in Melanesia even though the Melanesian genome contains the highest proportion of Denisovan ancestry in present-day human populations. Single nucleotide polymorphisms in HLA-A*11-HLA-C*12:02 or HLA-A*11-C*15 haplotypes, one of which was assumed to be transmitted together with HLA-B*73 from Denisovans by the study of Abi-Rached and colleagues, were not differentiated from those in other HLA-A-C haplotypes in modern humans. These results do not support the introgression hypothesis. Thus, we conclude that it is highly likely that HLA-B*73 allelic lineage has been maintained in the direct ancestors of modern humans. Electronic supplementary material The online version of this article (doi:10.1007/s00251-016-0952-8) contains supplementary material, which is available to authorized users.
- Published
- 2016
77. Identification of two unique naturally occurring Vpr sequence polymorphisms associated with clinical parameters in HIV-1 chronic infection
- Author
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Takamasa Ueno, Shinichi Oka, Doreen Kamori, Ai Kawana-Tachikawa, Zafrul Hasan, Jun Ohashi, and Hiroyuki Gatanaga
- Subjects
0301 basic medicine ,Genetics ,viruses ,Human immunodeficiency virus (HIV) ,Human leukocyte antigen ,Biology ,medicine.disease_cause ,Virology ,Plasma viral load ,03 medical and health sciences ,Chronic infection ,030104 developmental biology ,Infectious Diseases ,Viral replication ,In vivo ,Genotype ,medicine ,Sequence (medicine) - Abstract
HIV-1 viral protein R (Vpr) plays important roles in HIV-1 replication. Despite the identification of a number of HLA class I-associated immune escape mutations; it is yet known whether immune-driven Vpr polymorphisms are associated with disease outcome. Hereby, we comprehensively analyzed Vpr sequence polymorphisms and their association with disease outcome and host HLA genotypes, by using plasma viral RNA isolated from 444 HLA-typed, treatment-naive, chronically HIV-1 infected individuals. Vpr amino acid residues at positions 13, 37, 45, 55, 63, 77, 84, 85, 86, and 93 were significantly associated with patients' plasma viral load and/or CD4 count. Further analysis revealed Ala at position 55 was significantly associated with lower plasma viral load; and Thr at position 63 was significantly associated with lower plasma viral load and higher CD4 count. Also, the number of amino acid residues at the two positions, located in a functionally important α-helical domain, correlated inversely with plasma viral load and positively with CD4 count. Moreover, a phylogenetically corrected method revealed residues at positions 55 and 63 are associated with patients' HLA genotypes. Taken together, our results suggest that Vpr polymorphisms at functionally important and immune-reactive sites may contribute, at least in part, to viral replication and disease outcome in vivo. J. Med. Virol. 89:123-129, 2017. © 2016 Wiley Periodicals, Inc.
- Published
- 2016
78. Endoplasmic reticulum stress induced by tunicamycin increases resistin messenger ribonucleic acid through the pancreatic endoplasmic reticulum eukaryotic initiation factor 2α kinase–activating transcription factor 4–CAAT/enhancer binding protein‐α homologous protein pathway in THP‐1 human monocytes
- Author
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Hiroki Hirai, Ryoichi Kawamura, Haruhiko Osawa, Wataru Nishida, Eiichi Ishii, Koji Takemoto, Hiroshi Onuma, Akiko Miyoshi, Yasunori Takata, Jun Ohashi, Yuko Kadota, Seiichi Hashida, Junpei Hamada, Fumihiro Ochi, and Manami Matsushita
- Subjects
0301 basic medicine ,Adult ,Male ,Basic Science and Research ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Gene Expression ,Biology ,Monocytes ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,eIF-2 Kinase ,Gene expression ,Internal Medicine ,Humans ,Resistin ,RNA, Messenger ,Transcription Factor CHOP ,Messenger RNA ,Gene knockdown ,Endoplasmic reticulum ,Tunicamycin ,nutritional and metabolic diseases ,General Medicine ,Articles ,respiratory system ,Endoplasmic Reticulum Stress ,Molecular biology ,Activating Transcription Factor 4 ,030104 developmental biology ,chemistry ,Human monocytes ,Unfolded protein response ,Original Article ,Female ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction - Abstract
Aims/Introduction Resistin, secreted from adipocytes, causes insulin resistance in mice. In humans, the resistin gene is mainly expressed in monocytes and macrophages. Tunicamycin is known to induce endoplasmic reticulum (ER) stress, and reduce resistin gene expression in 3T3-L1 mouse adipocytes. The aim of the present study was to examine whether ER stress affects resistin gene expression in human monocytes. Materials and Methods The relationship between resistin messenger ribonucleic acid (mRNA) and ER stress markers mRNA was analyzed by reverse transcription polymerase chain reaction in isolated monocytes of 30 healthy volunteers. The effect of endotoxin/lipopolysaccharides or tunicamycin on resistin gene expression was analyzed in THP-1 human monocytes. Signaling pathways leading to resistin mRNA were assessed by the knockdown using small interfering RNA or overexpression of key molecules involved in unfolded protein response. Results Resistin mRNA was positively associated with immunoglobulin heavy chain-binding protein (BiP) or CAAT/enhancer binding protein-α homologous protein (CHOP) mRNA in human isolated monocytes. In THP-1 cells, lipopolysaccharides increased mRNA of BiP, pancreatic endoplasmic reticulum eukaryotic initiation factor 2α kinase (PERK) and CHOP, as well as resistin. Tunicamycin also increased resistin mRNA. This induction appeared to be dose- and time-dependent. Tunicamycin-induced resistin mRNA was inhibited by chemical chaperone, 4-phenylbutyric acid. The knockdown of either PERK, activating transcription factor 4 (ATF4) or CHOP reduced tunicamycin-induced resistin mRNA. Conversely, overexpression of ATF4 or CHOP increased resistin mRNA. Conclusions Endoplasmic reticulum stress induced by tunicamycin increased resistin mRNA through the PERK–ATF4–CHOP pathway in THP-1 human monocytes. ER stress could lead to insulin resistance through enhanced resistin gene expression in human monocytes.
- Published
- 2015
79. Admixture and natural selection shaped genomes of an Austronesian-speaking population in the Solomon Islands
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Minato Nakazawa, Takafumi Ishida, Takuro Furusawa, Ryutaro Ohtsuka, Kazumi Natsuhara, Mariko Isshiki, Jun Ohashi, Yusuke Watanabe, Nao Nishida, Izumi Naka, Ryosuke Kimura, Taro Yamauchi, and Ricky Eddie
- Subjects
0106 biological sciences ,0301 basic medicine ,Native Hawaiian or Other Pacific Islander ,Evolution ,Remote Oceania ,Population ,lcsh:Medicine ,010603 evolutionary biology ,01 natural sciences ,Genome ,Article ,Southeast asia ,Papua New Guinea ,03 medical and health sciences ,parasitic diseases ,Genetics ,Humans ,Computer Simulation ,Melanesians ,Selection, Genetic ,lcsh:Science ,education ,Phylogeny ,Principal Component Analysis ,education.field_of_study ,Multidisciplinary ,Natural selection ,Genome, Human ,lcsh:R ,Immunity ,Gene Pool ,030104 developmental biology ,Geography ,Evolutionary biology ,Chromosomes, Human, Pair 6 ,lcsh:Q ,Melanesia ,Gene pool ,Near Oceania - Abstract
People in the Solomon Islands today are considered to have derived from Asian- and Papuan-related ancestors. Papuan-related ancestors colonized Near Oceania about 47,000 years ago, and Asian-related ancestors were Austronesian (AN)-speaking population, called Lapita, who migrated from Southeast Asia about 3,500 years ago. These two ancestral populations admixed in Near Oceania before the expansion of Lapita people into Remote Oceania. To understand the impact of the admixture on the adaptation of AN-speaking Melanesians in Near Oceania, we performed the genome-wide single nucleotide polymorphism (SNP) analysis of 21 individuals from Munda, the main town of the New Georgia Islands in the western Solomon Islands. Population samples from Munda were genetically similar to other Solomon Island population samples. The analysis of genetic contribution from the two different ancestries to the Munda genome revealed significantly higher proportions of Asian- and Papuan-related ancestries in the region containing the annexin A1 (ANXA1) gene (Asian component > 82.6%) and in the human leukocyte antigen (HLA) class II region (Papuan component > 85.4%), respectively. These regions were suspected to have undergone natural selection since the time of admixture. Our results suggest that admixture had affected adaptation of AN-speaking Melanesians in the Solomon Islands., 論文
- Published
- 2020
80. Association study of CREBRF missense variant (rs373863828:G A; p.Arg457Gln) with levels of serum lipid profile in the Pacific populations
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Ryutaro Ohtsuka, Yasuhiro Matsumura, Kazumi Natsuhara, Taro Yamauchi, Jun Ohashi, Minato Nakazawa, Tsukasa Inaoka, Takuro Furusawa, Izumi Naka, Ryosuke Kimura, and Takafumi Ishida
- Subjects
0301 basic medicine ,Adult ,Male ,Aging ,medicine.medical_specialty ,Physiology ,Epidemiology ,Mutation, Missense ,Biology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,Genetics ,medicine ,Missense mutation ,Humans ,Triglycerides ,Aged ,medicine.diagnostic_test ,Tumor Suppressor Proteins ,Cholesterol, HDL ,Tonga ,Public Health, Environmental and Occupational Health ,CREBRF gene ,Cholesterol, LDL ,Middle Aged ,030104 developmental biology ,Endocrinology ,Female ,Melanesia ,Lipid profile ,Body mass index ,030217 neurology & neurosurgery - Abstract
A missense variant (rs373863828:G A; p.Arg457Gln) of the CREBRF gene is strongly associated with a higher body mass index (BMI; kg/mThe aim of this study is to examine the association of rs373863828:G A with levels of serum lipids in four Pacific populations.A total of 613 adult subjects were recruited from Tonga (Polynesians) and the Solomon Islands (Melanesians and Micronesians). Multiple regression analyses adjusted for age and sex were performed to examine the association of rs373863828 with levels of serum lipids in each population.A significant association of rs373863828:G A with lower level of HDL-cholesterol was detected in the Tonga population (β = -3.32 and p-value = 0.030). The expected change in HDL-cholesterol with respect to a single copy of the rs373863828-A allele was 3.32 mg/dL. However, the association between rs373863828-A and lower levels of HDL-cholesterol was not significant after further adjustment for BMI in the Tonga population (β = -2.32 and p-value = 0.13).The rs373863828-A allele may not directly affect the level of serum HDL-cholesterol independent of BMI. To confirm the present findings, association studies with large sample sizes and functional analyses are required.
- Published
- 2018
81. Rapid selection of sulphadoxine-resistant Plasmodium falciparum and its effect on within-population genetic diversity in Papua New Guinea
- Author
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Masato Yamauchi, Akira Kaneko, Francis Hombhanje, Toshihiro Mita, Hiroyoshi Endo, Jun Ohashi, Makoto Sekihara, Nobuyuki Takahashi, and Takahiro Tsukahara
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0301 basic medicine ,Time Factors ,Plasmodium falciparum ,030231 tropical medicine ,Population ,Drug Resistance ,lcsh:Medicine ,Zoology ,Outcrossing ,Genetic analysis ,Article ,Evolution, Molecular ,Papua New Guinea ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Molecular evolution ,Sulfadoxine ,Genetic variation ,Humans ,Selection, Genetic ,lcsh:Science ,education ,Genetic diversity ,education.field_of_study ,Multidisciplinary ,biology ,lcsh:R ,Genetic Variation ,biology.organism_classification ,Antiparasitic agent ,030104 developmental biology ,lcsh:Q ,Microsatellite Repeats - Abstract
The ability of the human malarial parasite Plasmodium falciparum to adapt to environmental changes depends considerably on its ability to maintain within-population genetic variation. Strong selection, consequent to widespread antimalarial drug usage, occasionally elicits a rapid expansion of drug-resistant isolates, which can act as founders. To investigate whether this phenomenon induces a loss of within-population genetic variation, we performed a population genetic analysis on 302 P. falciparum cases detected during two cross-sectional surveys in 2002/2003, just after the official introduction of sulphadoxine/pyrimethamine as a first-line treatment, and again in 2010/2011, in highly endemic areas in Papua New Guinea. We found that a single-origin sulphadoxine-resistant parasite isolate rapidly increased from 0% in 2002/2003 to 54% in 2010 and 84% in 2011. However, a considerable number of pairs exhibited random associations among 10 neutral microsatellite markers located in various chromosomes, suggesting that outcrossing effectively reduced non-random associations, albeit at a low average multiplicity of infection (1.35–1.52). Within-population genetic diversity was maintained throughout the study period. This indicates that the parasites maintained within-population variation, even after a clonal expansion of drug-resistant parasites. Outcrossing played a role in the preservation of within-population genetic diversity despite low levels of multiplicity of infection.
- Published
- 2018
82. Sequence variation in Plasmodium falciparum merozoite surface protein-2 is associated with virulence causing severe and cerebral malaria
- Author
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Pornlada Nuchnoi, Jun Ohashi, Suwanna Chaorattanakawee, Uranan Tumkosit, Izumi Naka, Jintana Patarapotikul, Hathairad Hananantachai, and David L. Saunders
- Subjects
0301 basic medicine ,Plasmodium ,Heredity ,lcsh:Medicine ,Disease ,Database and Informatics Methods ,0302 clinical medicine ,Multiplicity of infection ,Medicine and Health Sciences ,Merozoite surface protein ,lcsh:Science ,Protozoans ,Multidisciplinary ,Malarial Parasites ,Eukaryota ,Genetic Mapping ,Cerebral Malaria ,Sequence Analysis ,Research Article ,Bioinformatics ,030231 tropical medicine ,Virulence ,macromolecular substances ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Parasite Groups ,parasitic diseases ,medicine ,Parasitic Diseases ,Genetics ,Allele ,Alleles ,lcsh:R ,Organisms ,Biology and Life Sciences ,Plasmodium falciparum ,biology.organism_classification ,medicine.disease ,Tropical Diseases ,Parasitic Protozoans ,Malaria ,030104 developmental biology ,Haplotypes ,Genetic Loci ,Immunology ,Parasitology ,lcsh:Q ,Apicomplexa ,Sequence Alignment - Abstract
Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease. The association of msp2 variations with disease severity was examined. We found that the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly associated with severe disease without cerebral complications (odds ratio = 2.73, P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data suggests possible roles for the associated alleles on parasite invasion processes and immune-mediated pathogenicity. Multiplicity of infection was found to associate with severe disease without cerebral complications, but not cerebral malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear to be parasite virulence markers, and may be useful in determining the likelihood for severe and cerebral malaria. Their interactions with potential host factors for severe diseases should also be explored.
- Published
- 2018
83. Human Biology of Japan
- Author
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Jun Ohashi, Noel Cameron, and Taro Yamauchi
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Aging ,History ,Anthropometry ,Physiology ,Epidemiology ,Public Health, Environmental and Occupational Health ,MEDLINE ,Library science ,Growth ,Phenotype ,Annals ,Japan ,Human biology ,Genetics ,Humans ,Introductory Journal Article - Abstract
This special issue of the Annals of Human Biology features articles under the general title of ‘The Human Biology of Japan’. Japan is the world's 4th largest island country made up of more than 6,8...
- Published
- 2019
84. Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals
- Author
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Eiji Tanaka, Osamu Yokosuka, Akinobu Taketomi, Takayo Tsuchiura, Masashi Mizokami, Katsushi Tokunaga, Masaya Sugiyama, Masayuki Kurosaki, Masao Honda, Naoya Sakamoto, Yuichiro Eguchi, Namiki Izumi, Jun Ohashi, Nao Nishida, Kazuhiko Koike, Hiroshi Yatsuhashi, Takehiko Sasazuki, Keisuke Hino, Shuichi Kaneko, and Ken Yamamoto
- Subjects
Hepatitis ,Hepatitis B virus ,education.field_of_study ,Immunology ,Population ,General Medicine ,Human leukocyte antigen ,Biology ,medicine.disease ,Compound heterozygosity ,medicine.disease_cause ,Biochemistry ,Virology ,Antigen ,Genotype ,Genetics ,medicine ,Immunology and Allergy ,Allele ,education - Abstract
Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1(*) 05:01 and (*) 09:01, and three protective alleles, DPB1(*) 02:01, (*) 04:01, and (*) 04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.
- Published
- 2015
85. Cell-surface MHC density profiling reveals instability of autoimmunity-associated HLA
- Author
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Hiroko Miyadera, Toshio Kitamura, Åke Lernmark, Katsushi Tokunaga, and Jun Ohashi
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Human leukocyte antigen ,Endocrinology and Diabetes ,Major histocompatibility complex ,medicine.disease_cause ,Autoimmunity ,Evolution, Molecular ,Mice ,Gene Frequency ,HLA-DQ Antigens ,Genetic variation ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Allele ,Gene ,Genetics ,Polymorphism, Genetic ,HLA-DQ Antigen ,biology ,Protein Stability ,Cell Membrane ,Haplotype ,General Medicine ,Diabetes Mellitus, Type 1 ,Amino Acid Substitution ,Case-Control Studies ,NIH 3T3 Cells ,biology.protein ,geographic locations ,Research Article - Abstract
UTokyo Research掲載「免疫タンパク質の不安定さが、自己免疫疾患のかかりやすさに関係」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/autoimmunity-associated-genes-encode-exceptionally-unstable-proteins/, UTokyo Research "Autoimmunity associated genes encode exceptionally unstable proteins" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/autoimmunity-associated-genes-encode-exceptionally-unstable-proteins/
- Published
- 2014
86. Mitochondrial DNA variations in Austronesian-speaking populations living in the New Georgia Islands, the Western Province of the Solomon Islands
- Author
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Jun Ohashi, Ryutaro Ohtsuka, Ryosuke Kimura, Minato Nakazawa, Kazumi Natsuhara, Takuro Furusawa, Mariko Issiki, Izumi Naka, Takafumi Ishida, and Taro Yamauchi
- Subjects
0106 biological sciences ,0301 basic medicine ,Male ,Mitochondrial DNA ,common ,Population ,010603 evolutionary biology ,01 natural sciences ,DNA, Mitochondrial ,Haplogroup ,Gene flow ,03 medical and health sciences ,Polynesians ,Genetic variation ,Genetics ,Humans ,Melanesians ,education ,Genetics (clinical) ,education.field_of_study ,Ecology ,Genetic Variation ,030104 developmental biology ,Geography ,common.group ,Micronesian ,Female ,Melanesia - Abstract
Modern Austronesian (AN)-speaking Melanesians are considered to be derived from the admixture of indigenous non-Austronesian (NAN)-speaking people and AN-speaking people from Southeast Asia. In this study, we analyzed mitochondrial DNA (mtDNA) variations in the D-loop region for two AN-speaking Melanesian populations (Munda and Kusaghe) and an AN-speaking Micronesian population (Rawaki) in the New Georgia Islands, the Western Province of the Solomon Islands to examine their genetic similarities to AN-speaking Polynesians in Tonga and NAN-speaking Melanesians, Gidra, in Papua New Guinea. The ‘Polynesian motif’, which is well-characterized mtDNA marker for Polynesians, was frequently observed in Munda and Kusaghe. Of particular interest, haplogroup E1a2 + 16261, which has been rarely observed in the Solomon Islands, accounted for 12.8% in Kusaghe. It has been reported that the haplogroup E1a2 arose in Island Southeast Asia (ISEA) 9400 ± 2850 years ago. Phylogenetic and principle component analyses for 24 Oceanian populations revealed that Munda and Kusaghe populations were genetically close to Tongan population, but not to Gidra. Rawaki population showed no apparent genetic similarities to populations of Tonga and Gidra. Our results suggest that considerable gene flow from AN-speaking populations originated from Southeast Asia to indigenous Melanesians occurred in the New Georgia Islands.
- Published
- 2017
87. Evidence for Very Recent Positive Selection in Mongolians
- Author
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Sadahiko Iwamoto, Jun Ohashi, Kazuhisa Watanabe, Lkagvasuren Munkhtulga, and Kazuhiro Nakayama
- Subjects
0106 biological sciences ,0301 basic medicine ,Lineage (genetic) ,Genotype ,Single-nucleotide polymorphism ,Biology ,010603 evolutionary biology ,01 natural sciences ,Polymorphism, Single Nucleotide ,Evolution, Molecular ,03 medical and health sciences ,Asian People ,Gene Frequency ,Genetics ,Ethnicity ,Humans ,Allele ,Selection, Genetic ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Alleles ,Genetic association ,Adiposity ,Genome, Human ,Mongolia ,Adaptation, Physiological ,030104 developmental biology ,Genetics, Population ,Phenotype ,Haplotypes ,Homo sapiens ,Evolutionary biology ,Chromosomal region ,Approximate Bayesian computation ,Adaptation ,Cell Adhesion Molecules ,Genome-Wide Association Study ,Transcription Factors - Abstract
Mongols, the founders of the largest continental empire in history, successfully adapted to the harsh environments of Inner Asia through nomadic pastoralism. Considerable interest exists in ascertaining whether genetic adaptation also contributed to the Mongols' success, and dissecting the genome diversity of present-day populations in Mongolia can help address this question. To this end, we determined the genotypes of nearly 2.4 million single nucleotide polymorphisms (SNPs) of 96 unrelated Mongolian individuals in Ulaanbaatar city, and performed genome-wide scans for population-specific positive selection. We discovered signatures of Mongolian-specific positive selection at the chromosomal region 3p12.1, in which hits in genome-wide association studies were reported for medical and biological traits related to energy metabolism and reproduction. The top SNP, rs117799927, showed a distinctive geographic distribution: the frequency of the derived allele, rs117799927 G, was extremely low among worldwide populations (0.005) but exceptionally high in Mongolians (0.247). Approximate Bayesian computation-based age estimation showed that the rs117799927 G allele emerged or positive selection began to operate 50 generations before the present, near the age of the climate anomaly named Late Antique Little Ice Age. Furthermore, rs117799927 showed significant associations with multiple adiposity-related traits in Mongolians and allelic difference in enhancer activity in cells of adipocyte lineage, suggesting that positive selection at 3p12.1 might be related to adaptation in the energy metabolism system. These findings provide novel evidence for a very recent positive-selection event in Homo sapiens and offer insights into the roles of genes in 3p12.1 in the adaptive evolution of our species.
- Published
- 2017
88. A missense variant, rs373863828-A (p.Arg457Gln), of CREBRF and body mass index in Oceanic populations
- Author
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Yuji Ataka, Yasuhiro Matsumura, Ryutaro Ohtsuka, Tsukasa Inaoka, Ryosuke Kimura, Kazumi Natsuhara, Jun Ohashi, Taro Yamauchi, Takafumi Ishida, Minato Nakazawa, Takuro Furusawa, and Izumi Naka
- Subjects
0301 basic medicine ,Male ,Native Hawaiian or Other Pacific Islander ,Genotype ,common ,Oceania ,Mutation, Missense ,030209 endocrinology & metabolism ,Biology ,Polymorphism, Single Nucleotide ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Polynesians ,Quantitative Trait, Heritable ,Gene Frequency ,Genetics ,medicine ,Missense mutation ,Humans ,Melanesians ,Obesity ,Allele ,Allele frequency ,Genetics (clinical) ,Alleles ,Geography ,Tumor Suppressor Proteins ,medicine.disease ,030104 developmental biology ,Genetics, Population ,Amino Acid Substitution ,common.group ,Female ,Body mass index - Abstract
It has been suggested that a ‘thrifty’ genotype hypothesis can account for high prevalence of obesity in the island populations of Oceania. A recent genome-wide association study revealed that a missense variant, rs373863828-A (p.Arg457Gln), of the CREBRF gene (encoding CREB3 regulatory factor) was associated with an excessive increase in body mass index (BMI) in Samoans. In the present study, the association of rs373863828-A with an increase in BMI was examined in four Austronesian (AN)-speaking populations in Oceania. We found that rs373863828-A was frequently observed (frequency of 0.15) in Tongans (Polynesians), and was strongly associated with higher BMI (P=6.1 × 10−4). A single copy of the rs373863828-A allele increased BMI by 3.09 kg m−2 after adjustment of age and sex. No significant association was detected in the other three AN-speaking populations (Melanesians and Micronesians) living in Solomon Islands. This was probably due to the low allele frequency (0.02–0.06) of rs373863828-A as well as small sample size. The rs373863828-A allele was not found in both AN-speaking and non-AN-speaking Melanesians living in Papua New Guinea. Our results suggest that rs373863828-A of CREBRF, a promising thrifty variant, arose in recent ancestors of AN-speaking Polynesians.
- Published
- 2017
89. (Im)politeness and Relationality
- Author
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Jun Ohashi and Wei-Lin Melody Chang
- Subjects
060201 languages & linguistics ,Politeness ,media_common.quotation_subject ,Italian language ,05 social sciences ,06 humanities and the arts ,Interpersonal communication ,Pragmatics ,050105 experimental psychology ,Reciprocity (social psychology) ,0602 languages and literature ,Mediation ,Emic and etic ,0501 psychology and cognitive sciences ,Obligation ,Psychology ,Social psychology ,media_common - Abstract
The chapter illuminates some of the under-explored relational aspects of (Im)politeness in interpersonal pragmatics. It consists of two case studies explicating how conversational participants manifest and interpret relationships in interaction. Specifically, case study 1 illustrates how reciprocity (balancing obligations) as a social norm can be used in interpreting relationality in terms of (Im)politeness. Case study 2 demonstrates how relationality is manifested in mediation interactions, where the participants evoke their interrelated relational ties and relational entitlements in order to achieve their interactional goals. The two case studies in both Japanese and Chinese, in particular, highlight the significance of studying emic concepts of relationality and related concepts, including the ‘balance sheet of obligation’ in Japanese contexts, and ‘relational ties’ and ‘relational entitlements’ in Taiwanese interactions.
- Published
- 2017
90. Generation of Rodent Malaria Parasites with a High Mutation Rate by Destructing Proofreading Activity of DNA Polymerase δ
- Author
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Satoru Kawai, Hiroyoshi Endo, Makoto Hirai, Shin-ichiro Kawazu, Mitsuru Furusawa, Toshihiro Horii, Shota Nakamura, Toshihiro Mita, Kazuyuki Tanabe, Hajime Honma, Nirianne Marie Q. Palacpac, Jun Ohashi, Hiroyuki Matsuoka, Hassan Hakimi, Teruo Yasunaga, and Hajime Hisaeda
- Subjects
Plasmodium ,Mutation rate ,Sex Differentiation ,Plasmodium berghei ,DNA polymerase ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Mutation Rate ,parasitic diseases ,Genetics ,medicine ,Gametocyte ,Animals ,Molecular Biology ,DNA Polymerase III ,030304 developmental biology ,0303 health sciences ,biology ,mutator ,Plasmodium falciparum ,DNA polymerase δ ,General Medicine ,Full Papers ,biology.organism_classification ,medicine.disease ,Virology ,Malaria ,3. Good health ,genome sequencing ,biology.protein ,Proofreading ,Female ,030217 neurology & neurosurgery - Abstract
Plasmodium falciparum malaria imposes a serious public health concern throughout the tropics. Although genetic tools are principally important to fully investigate malaria parasites, currently available forward and reverse tools are fairly limited. It is expected that parasites with a high mutation rate can readily acquire novel phenotypes/traits; however, they remain an untapped tool for malaria biology. Here, we generated a mutator malaria parasite (hereinafter called a 'malaria mutator'), using site-directed mutagenesis and gene transfection techniques. A mutator Plasmodium berghei line with a defective proofreading 3' → 5' exonuclease activity in DNA polymerase δ (referred to as PbMut) and a control P. berghei line with wild-type DNA polymerase δ (referred to as PbCtl) were maintained by weekly passage in ddY mice for 122 weeks. High-throughput genome sequencing analysis revealed that two PbMut lines had 175-178 mutations and a 86- to 90-fold higher mutation rate than that of a PbCtl line. PbMut, PbCtl, and their parent strain, PbWT, showed similar course of infection. Interestingly, PbMut lost the ability to form gametocytes during serial passages. We believe that the malaria mutator system could provide a novel and useful tool to investigate malaria biology.
- Published
- 2014
91. Association of IL1B -31C/T and IL1RA Variable Number of an 86-bp Tandem Repeat With Dengue Shock Syndrome in Thailand
- Author
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Surapee Anantapreecha, Jintana Patarapotikul, Izumi Naka, Pathom Sawanpanyalert, Jun Ohashi, and Areerat Sa-ngasang
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Genotype ,Interleukin-1beta ,Logistic regression ,Gastroenterology ,Dengue fever ,Polymorphism (computer science) ,Internal medicine ,medicine ,Humans ,Point Mutation ,Immunology and Allergy ,Genetic Predisposition to Disease ,Severe Dengue ,Child ,Genetic Association Studies ,Polymorphism, Genetic ,business.industry ,Infant ,Interleukin ,Odds ratio ,Thailand ,medicine.disease ,Virology ,digestive system diseases ,Confidence interval ,Interleukin 1 Receptor Antagonist Protein ,stomatognathic diseases ,Infectious Diseases ,Interleukin 1 receptor antagonist ,Tandem Repeat Sequences ,Child, Preschool ,Female ,business - Abstract
Background Dengue patients present a range of symptoms: dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It is not clear whether this variability is due to their genetic background. Here we tested polymorphisms of interleukin 1 beta (IL1B) and interleukin 1 receptor antagonist (IL1RA) genes for association with DSS in the Thai population. Methods Polymorphisms of IL1B -31C/T (rs1143627) and IL1RA 86-base-pair tandem repeat were analyzed in 871 patients (DF = 384, DHF = 413, and DSS = 74). Results IL1B -31C and IL1RA 2/4 genotype were associated with DSS (IL1B -31C: DSS vs DHF: P = .0061, odds ratio [OR, 95% confidence interval {CI}], 3.49 [1.36-8.95]; DSS vs DF: P = .027, OR [95% CI], 2.81 [1.12-7.06]; IL1RA 2/4: DSS vs DHF: P = .017, OR [95% CI], 1.94 [1.12-3.40]; DSS vs DF: P = .024, OR [95% CI], 1.90 [1.07-3.4]). No difference was found between DF and DHF. Logistic regression analysis revealed that IL1B -31C and IL1RA 2/4 genotypes were each independently associated with DSS. Conclusions Patients with IL1B -31C carrier, or IL1RA 2/4 genotype carry a risk for DSS, implying that IL1B may play a role in pathogenesis of DSS.
- Published
- 2014
92. Analysis of whole Y-chromosome sequences reveals the Japanese population history in the Jomon period
- Author
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Yusuke Watanabe, Katsushi Tokunaga, Seik-Soon Khor, Izumi Naka, Hiromi Sawai, Jun Ohashi, and Yuki Hitomi
- Subjects
Male ,0301 basic medicine ,Population genetics ,Climate ,Population Dynamics ,Population ,lcsh:Medicine ,Zoology ,Y chromosome ,Article ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Japan ,Humans ,East Asia ,lcsh:Science ,education ,Clade ,History, Ancient ,Phylogeny ,education.field_of_study ,Chromosomes, Human, Y ,Multidisciplinary ,Population size ,lcsh:R ,High-Throughput Nucleotide Sequencing ,Agriculture ,Bayes Theorem ,Oryza ,Before Present ,030104 developmental biology ,Geography ,Anthropology ,Diet, Paleolithic ,Period (geology) ,lcsh:Q ,Female ,Mainland ,Monte Carlo Method ,030217 neurology & neurosurgery - Abstract
The Jomon and the Yayoi are considered to be the two major ancestral populations of the modern mainland Japanese. The Jomon people, who inhabited mainland Japan, admixed with Yayoi immigrants from the Asian continent. To investigate the population history in the Jomon period (14,500–2,300 years before present [YBP]), we analyzed whole Y-chromosome sequences of 345 Japanese males living in mainland Japan. A phylogenetic analysis of East Asian Y chromosomes identified a major clade (35.4% of mainland Japanese) consisting of only Japanese Y chromosomes, which seem to have originated from indigenous Jomon people. A Monte Carlo simulation indicated that ~70% of Jomon males had Y chromosomes in this clade. The Bayesian skyline plots of 122 Japanese Y chromosomes in the clade detected a marked decrease followed by a subsequent increase in the male population size from around the end of the Jomon period to the beginning of the Yayoi period (2,300 YBP). The colder climate in the Late to Final Jomon period may have resulted in critical shortages of food for the Jomon people, who were hunter-gatherers, and the rice farming introduced by Yayoi immigrants may have helped the population size of the Jomon people to recover.
- Published
- 2019
93. microRNA-27a and microRNA-146a SNP in cerebral malaria
- Author
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Hathairad Hananantachai, Pornlada Nuchnoi, Izumi Naka, Saw Thu Wah, Jintana Patarapotikul, and Jun Ohashi
- Subjects
0301 basic medicine ,Malaria, Cerebral ,Single-nucleotide polymorphism ,030105 genetics & heredity ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,03 medical and health sciences ,Gene Frequency ,parasitic diseases ,Genotype ,microRNA ,Genetics ,medicine ,Humans ,SNP ,Molecular Biology ,Genotyping ,Allele frequency ,Genetics (clinical) ,rs2910164 ,Original Articles ,Thailand ,medicine.disease ,MicroRNAs ,030104 developmental biology ,Cerebral Malaria ,Immunology ,Original Article ,cerebral malaria ,rs895819 ,Thai ,microRNA SNP ,rs57095329 ,Malaria - Abstract
Background During Plasmodium falciparum infection, microRNA expression alters in brain tissue of mice with cerebral malaria compared to noninfected controls. MicroRNA regulates gene expression post‐transcriptionally to influence biological processes. Cerebral malaria pathology caused mainly by the immunological disorder. We hypothesize that single‐nucleotide polymorphism in a microRNA influences microRNA biogenesis or target gene recognition and altering susceptibility to cerebral malaria. Methods We performed a literature search based on immunological mechanism and applied microRNA‐related single‐nucleotide polymorphisms database to examine candidate microRNA SNPs possibly responsible for cerebral malaria. MicroRNA‐27a and microRNA‐146a are supposed to involve in cerebral malaria pathology. To assess the relationship of microRNA SNP to cerebral malaria outcome, we performed TaqMan Genotyping Assays in 110 cerebral malaria and 207 uncomplicated malaria cases for three candidate microRNA SNPs (rs895819 of microRNA‐27a, rs57095329 and rs2910164 of microRNA‐146a). Results Our study detected no significant difference in genotype and allele frequency of individual microRNA SNPs as well as in haplotypes of microRNA‐146a between these two groups of malaria patients in Thailand. Hardy–Weinberg disequilibrium of rs57095329 in the cerebral malaria group showed a heterozygous excess which might be due to natural selection. Conclusion Our data supported that the candidate microRNA SNPs have no major role to develop cerebral malaria.
- Published
- 2019
94. Effects of carbohydrate counting on glycemic control and quality of life in patients with type 1 diabetes: a pilot study
- Author
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Kazue Ochi, Sanshiro Shiraishi, Jun Ohashi, Haruhiko Osawa, Satoshi Miyao, Ryoichi Kawamura, Eiko Sato, Hideichi Makino, and Nozomi Kikuchi
- Subjects
medicine.medical_specialty ,Type 1 diabetes ,medicine.diagnostic_test ,business.industry ,Diet therapy ,Endocrinology, Diabetes and Metabolism ,medicine.disease ,Carbohydrate counting ,Endocrinology ,Quality of life ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Medicine ,business ,Lipid profile ,Body mass index ,Glycemic - Abstract
We investigated the effects of carbohydrate counting (CC) on glycemic control and the quality of life in Japanese patients with adult-onset type 1 diabetes as a pilot study. Seven patients with type 1 diabetes (3 males and 4 females) aged 62.0 ± 11.9 years were instructed in CC with subsequent insulin dose adjustments. We measured the HbA1c, glycated albumin, body mass index (BMI) and lipid profile, recorded daily energy intake and insulin dose, and administered the Diabetes Satisfaction Questionnaire (DTSQ) and the shortened version of the Diabetes Diet-Related Quality-of-Life (sDDRQOL) scale questionnaire at baseline, 3 or 6 months, and 12 months. Glycated albumin but not HbA1c was significantly reduced at 6 months (P = 0.021), and both HbA1c and glycated albumin were significantly reduced at 12 months (P = 0.004 and P = 0.003, respectively) compared with those at baseline. The total satisfaction score of the DTSQ and burden of diet therapy score of the sDDRQOL scale were significantly improved at 3 and 12 months compared with those at baseline (P = 0.047 and P = 0.034 in the former and P = 0.049 and P = 0.044 in the latter). BMI, lipid profile, daily energy intake and insulin dose at 12 months were not different compared with those at baseline. This study suggests that CC may improve glycemic control as well as the quality of life without worsening lipid profiles or increasing the BMI in patients with type 1 diabetes.
- Published
- 2013
95. Hypertension-susceptibility gene prevalence in the Pacific Islands and associations with hypertension in Melanesia
- Author
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Minato Nakazawa, Takuro Furusawa, Ricky Eddie, Jun Ohashi, Ryosuke Kimura, Tsukasa Inaoka, Yuji Ataka, Kazumi Natsuhara, Takafumi Ishida, Ryutaro Ohtsuka, Izumi Naka, Taro Yamauchi, and Yasuhiro Matsumura
- Subjects
Adult ,Male ,Linkage disequilibrium ,Adolescent ,Human Migration ,Angiotensinogen ,Single-nucleotide polymorphism ,Biology ,Pacific Islands ,Essential hypertension ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Young Adult ,Gene Frequency ,Risk Factors ,parasitic diseases ,Genotype ,Prevalence ,Genetics ,medicine ,Cytochrome P-450 CYP3A ,Humans ,Genetic Predisposition to Disease ,Allele frequency ,Genotyping ,Alleles ,Genetic Association Studies ,Genetics (clinical) ,Aged ,Middle Aged ,medicine.disease ,Heterotrimeric GTP-Binding Proteins ,Genetics, Population ,Hypertension ,Pacific islanders ,Female ,Melanesia ,GNB3 - Abstract
Human essential hypertension is partly caused by genetic factors. Angiotensinogen (AGT), G-protein β3-subunit (GNB3) and cytochrome P450 3A5 (CYP3A5) are candidate hypertension susceptibility genes and risk alleles at these loci have been thought to arise owing to human adaptation to climatic changes following the migration out-of-Africa. This study aimed to reveal the frequencies of hypertension-susceptibility genotypes in Pacific Island populations and associations of these single-nucleotide polymorphisms (SNPs) to hypertension. Genotyping was conducted for 804 individuals from Melanesian, Micronesian and Polynesian populations at SNPs in the genes encoding AGT (rs699, rs5049 and rs5051), GNB3 (rs5443) and CYP3A5*1/*3 (rs776746). Associations between these SNPs and hypertension were tested for 383 Melanesian Solomon Islanders. We found that the A/A genotype at rs5049 was a risk factor for hypertension (P=0.025) in the Melanesian Solomon Islanders; three SNPs for AGT were in linkage disequilibrium. The ancestral alleles of rs699, rs5051 and rs776746, and the derived allele of rs5443 were as frequent in the populations surveyed here as in other equatorial populations. Although other polymorphisms associated with hypertension and additional populations remain to be studied, these findings suggest that the Pacific Islanders' susceptibility to hypertension arose because of human migration and adaptation.
- Published
- 2013
96. Plasma Resistin Is Associated With Single Nucleotide Polymorphisms of a Possible Resistin Receptor, the Decorin Gene, in the General Japanese Population
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Katsuhiko Kohara, Haruhiko Osawa, Tatsuya Nishimiya, Jun Ohashi, Yasunori Takata, Yasuharu Tabara, Tetsuro Miki, Masaaki Ochi, Hiroshi Onuma, Wataru Nishida, Ryuichi Kawamoto, and Ryoichi Kawamura
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Male ,medicine.medical_specialty ,Linkage disequilibrium ,endocrine system diseases ,Decorin ,Endocrinology, Diabetes and Metabolism ,Adipokine ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Body Mass Index ,Asian People ,Japan ,Polymorphism (computer science) ,Internal medicine ,Internal Medicine ,medicine ,Humans ,SNP ,Resistin ,Receptor ,Original Research ,Aged ,nutritional and metabolic diseases ,Genetics/Genomes/Proteomics/Metabolomics ,Middle Aged ,respiratory system ,Cross-Sectional Studies ,Endocrinology ,Female ,Insulin Resistance ,hormones, hormone substitutes, and hormone antagonists - Abstract
Resistin is an adipokine secreted from adipocytes in mice. We previously reported that a single nucleotide polymorphism (SNP) –420 (rs1862513) in the human resistin gene (RETN), is correlated with plasma resistin. Decorin is a multifunctional proteoglycan, and its isoform, lacking 14 amino acids from the N terminal region of mature core decorin, recently was identified as a resistin receptor in mice. To examine whether SNPs in the vicinity of the human decorin gene (DCN) are associated with plasma resistin, we cross-sectionally analyzed six tag SNPs selected around DCN in the same linkage disequilibrium block in 2,078 community-dwelling Japanese subjects. Plasma resistin was associated with the rs7139228, rs7956537, rs516115, and rs3138167 genotypes in DCN. A multiple regression analysis revealed that the genotype of rs7308752 (G/G) or rs516115 (C/C) was associated with decreased plasma resistin after adjusted for age, sex, BMI, and the RETN SNP rs1862513. The effect of rs7139228 and rs1862513 seemed to be additive without synergistic interaction. Therefore, plasma resistin was associated with some tag SNPs around DCN in the general Japanese population. The possibility that human decorin is a human resistin receptor should be pursued.
- Published
- 2013
97. A functional SNP upstream of the beta-2 adrenergic receptor gene (ADRB2) is associated with obesity in Oceanic populations
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Tsukasa Inaoka, Taro Yamauchi, Nao Nishida, Ryutaro Ohtsuka, Izumi Naka, Ryosuke Kimura, Yuji Ataka, Kazuhiro Nakayama, Yasuhiro Matsumura, Koki Hikami, Kazumi Natsuhara, Minori Koga, Sadahiko Iwamoto, Jun Ohashi, Minato Nakazawa, Takuro Furusawa, Takafumi Ishida, and Naoyuki Tsuchiya
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Adult ,Male ,obesity ,Linkage disequilibrium ,Native Hawaiian or Other Pacific Islander ,Genotype ,Adrenergic receptor ,Endocrinology, Diabetes and Metabolism ,Population ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Medicine (miscellaneous) ,Adrenergic ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,beta-2 adrenergic receptor gene (ADRB2) ,Body Mass Index ,polymorphism ,Prevalence ,Humans ,body mass index (BMI) ,SNP ,Genetic Predisposition to Disease ,education ,Receptor ,Gene ,Genetics ,education.field_of_study ,Nutrition and Dietetics ,Tonga ,fungi ,Proteins ,Oceanic population ,Middle Aged ,Phenotype ,Body Composition ,Beta-2 adrenergic receptor ,Female ,Original Article ,Melanesia ,Receptors, Adrenergic, beta-2 - Abstract
OBJECTIVE:Obesity is a growing health concern in the Oceanic populations. To investigate the genetic factors associated with adult obesity in the Oceanic populations, the association of single nucleotide polymorphisms (SNPs) of the beta-2 adrenergic receptor (ADRB2) gene with obesity was examined in 694 adults living in Tonga and Solomon Islands.\nRESULTS:A screening for variation in 16 Oceanic subjects detected 17 SNPs in the entire region of ADRB2, of which nine SNPs including two non-synonymous ones, rs1042713 (Arg16Gly) and rs1042714 (Gln27Glu), were further genotyped for all subjects. The rs34623097-A allele, at a SNP located upstream of ADRB2, showed the strongest association with risk for obesity in a logistic regression analysis adjusted for age, sex, and population (P=5.6 × 10^, odds ratio [OR]=2.5, 95% confidence interval [CI]=1.5–4.2). The 27Glu was also significantly associated with obesity in the single-point association analysis (P=0.013, OR=2.0, 95%CI=1.2–3.4); however, this association was no longer significant after adjustment for rs34623097 since these SNPs were in linkage disequilibrium with each other. A copy of the obesity-risk allele, rs34623097-A, led to a 1.6 kg/m^2 increase in body mass index (BMI; defined as weight in kilograms divided by height in meters squared) (P=0.0019). A luciferase reporter assay indicated that rs34623097-A reduced the transcriptional activity of the luciferase reporter gene by approximately 10% compared with rs34623097-G. An electrophoretic mobility shift assay demonstrated that rs34623097 modulated the binding affinity with nuclear factors. An evolutionary analysis implies that a G>A mutation at rs34623097 occurred in the Neandertal genome and then the rs34623097-A allele flowed into the ancestors of present-day humans.\nCONCLUSION:The present results suggest that rs34623097-A, which would lead to lower expression of ADRB2, contributes to the onset of obesity in the Oceanic populations., 論文
- Published
- 2012
98. The history of human populations in the Japanese Archipelago inferred from genome-wide SNP data with a special reference to the Ainu and the Ryukyuan populations
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Toshimichi Yamamoto, Yumiko Suto, Momoki Hirai, Hiroki Oota, Kumiko Yanagi, Keiichi Omoto, Nao Nishida, Shuhei Mano, Atsushi Tajima, Hideyuki Tanabe, Tadashi Kaname, Katsushi Tokunaga, Naruya Saitou, Timothy A. Jinam, Shoji Kawamura, Norio Niikawa, Kazuo Umetsu, Jun Ohashi, Kenji Naritomi, and Ryosuke Kimura
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Mainland China ,Population ,DNA, Mitochondrial ,Polymorphism, Single Nucleotide ,Genome ,Asian People ,Phylogenetics ,Genetics ,Chromosomes, Human ,Humans ,Structured model ,education ,Ecosystem ,History, Ancient ,Phylogeny ,Genetics (clinical) ,Snp data ,education.field_of_study ,geography.geographical_feature_category ,Phylogenetic tree ,Genome, Human ,Genetics, Population ,Geography ,Evolutionary biology ,Archipelago ,Genome-Wide Association Study - Abstract
The Japanese Archipelago stretches over 4000 km from north to south, and is the homeland of the three human populations; the Ainu, the Mainland Japanese and the Ryukyuan. The archeological evidence of human residence on this Archipelago goes back to >30 000 years, and various migration routes and root populations have been proposed. Here, we determined close to one million single-nucleotide polymorphisms (SNPs) for the Ainu and the Ryukyuan, and compared these with existing data sets. This is the first report of these genome-wide SNP data. Major findings are: (1) Recent admixture with the Mainland Japanese was observed for more than one third of the Ainu individuals from principal component analysis and frappe analyses; (2) The Ainu population seems to have experienced admixture with another population, and a combination of two types of admixtures is the unique characteristics of this population; (3) The Ainu and the Ryukyuan are tightly clustered with 100% bootstrap probability followed by the Mainland Japanese in the phylogenetic trees of East Eurasian populations. These results clearly support the dual structure model on the Japanese Archipelago populations, though the origins of the Jomon and the Yayoi people still remain to be solved.
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- 2012
99. MxA transcripts with distinct first exons and modulation of gene expression levels by single-nucleotide polymorphisms in human bronchial epithelial cells
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Naoto Keicho, Ikumi Matsushita, Hideyuki Ito, Satoshi Noguchi, Jun Ohashi, Minako Hijikata, Takahide Nagase, and Emi Hamano
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Myxovirus Resistance Proteins ,Genotype ,Transcription, Genetic ,Immunology ,Response element ,Single-nucleotide polymorphism ,Bronchi ,Myxovirus resistance A ,Respiratory Mucosa ,Biology ,Polymorphism, Single Nucleotide ,Exon ,Transcript variants ,Transcription (biology) ,Interferon ,GTP-Binding Proteins ,Gene expression ,Genetics ,medicine ,Humans ,Cells, Cultured ,Original Paper ,Gene Expression Profiling ,Epithelial Cells ,Exons ,Virology ,Molecular biology ,Gene expression profiling ,Reverse transcription polymerase chain reaction ,Gene Expression Regulation ,Interferon Type I ,5' Untranslated Regions ,Human bronchial epithelial cells ,medicine.drug - Abstract
Myxovirus resistance A (MxA) is a major interferon (IFN)-inducible antiviral protein. Promoter single-nucleotide polymorphisms (SNPs) of MxA near the IFN-stimulated response element (ISRE) have been frequently associated with various viral diseases, including emerging respiratory infections. We investigated the expression profile of MxA transcripts with distinct first exons in human bronchial epithelial cells. For primary culture, the bronchial epithelium was isolated from lung tissues with different genotypes, and total RNA was subjected to real-time reverse transcription polymerase chain reaction. The previously reported MxA transcript (T1) and a recently registered transcript with a distinct 5′ first exon (T0) were identified. IFN-β and polyinosinic–polycytidylic acid induced approximately 100-fold higher expression of the T1 transcript than that of the T0 transcript, which also had a potential ISRE motif near its transcription start site. Even without inducers, the T1 transcript accounted for approximately two thirds of the total expression of MxA, levels of which were significantly associated with its promoter and exon 1 SNPs (rs17000900, rs2071430, and rs464138). Our results suggest that MxA observed in respiratory viral infections is possibly dominated by the T1 transcript and partly influenced by relevant 5′ SNPs. Electronic supplementary material The online version of this article (doi:10.1007/s00251-012-0663-8) contains supplementary material, which is available to authorized users.
- Published
- 2012
100. Identification of candidate genes involved in the etiology of sporadic Tourette syndrome by exome sequencing
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Naoto Aoki, Kayoko Kato, Shoji Tsuji, Tsukasa Sasaki, Kiyoto Kasai, Mamoru Tochigi, Jun Yoshimura, Chihiro Kakiuchi, Jun Mitsui, Hiroyuki Ishiura, Tadashi Umekage, Aya Inai, Takafumi Shimada, Masaomi Furukawa, Koichiro Doi, Hitoshi Kuwabara, Jun Ohashi, Shinichi Morishita, Yukiko KanoMD, Yosuke Eriguchi, Fumichika Nishimura, and Yuki Kawakubo
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0301 basic medicine ,Proband ,Adult ,Genetic Markers ,Male ,Candidate gene ,Adolescent ,Population ,Mutation, Missense ,Locus (genetics) ,Biology ,Transcriptome ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Young Adult ,0302 clinical medicine ,Missense mutation ,Humans ,Exome ,Family ,Genetic Predisposition to Disease ,education ,Child ,Genetics (clinical) ,Exome sequencing ,Genetics ,education.field_of_study ,Sequence Analysis, DNA ,Middle Aged ,Prognosis ,Psychiatry and Mental health ,030104 developmental biology ,Rapamycin-Insensitive Companion of mTOR Protein ,Female ,030217 neurology & neurosurgery ,Follow-Up Studies ,Tourette Syndrome - Abstract
Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Although there is a large genetic contribution, the genetic architecture of TS remains unclear. Exome sequencing has successfully revealed the contribution of de novo mutations in sporadic cases with neuropsychiatric disorders such as autism and schizophrenia. Here, using exome sequencing, we investigated de novo mutations in individuals with sporadic TS to identify novel risk loci and elucidate the genetic background of TS. Exome analysis was conducted for sporadic TS cases: nine trio families and one quartet family with concordant twins were investigated. Missense mutations were evaluated using functional prediction algorithms, and their population frequencies were calculated based on three public databases. Gene expression patterns in the brain were analyzed using the BrainSpan Developmental Transcriptome. Thirty de novo mutations, including four synonymous and four missense mutations, were identified. Among the missense mutations, one in the rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR)-coding gene (rs140964083: G > A, found in one proband) was predicted to be hazardous. In the three public databases analyzed, variants in the same SNP locus were absent, and variants in the same gene were either absent or present at an extremely low frequency (3/5,008), indicating the rarity of hazardous RICTOR mutations in the general population. The de novo variant of RICTOR may be implicated in the development of sporadic TS, and RICTOR is a novel candidate factor for TS etiology.
- Published
- 2016
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