Asia Institute - Research Publications
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ItemThe Fragmented Self: Cross-cultural Difference, Conflict and the Lessons of Ethnographic Experience(Frobenius Institute, 2006)
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ItemArriving in the Future: The Utopia of Here and Now in the Work of Modern-Day Mystics From Eric Fromm to Eckhart Tolle(MONASH UNIV, CENTRE COMPARATIVE LITERATURE & CULTURAL STUDIES, 2009-12-01)
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ItemNo Preview AvailableACE1 polymorphism and progression of SARS.(Elsevier BV, 2004-10-22)We have hypothesized that genetic predisposition influences the progression of SARS. Angiotensin converting enzyme (ACE1) insertion/deletion (I/D) polymorphism was previously reported to show association with the adult respiratory distress syndrome, which is also thought to play a key role in damaging the lung tissues in SARS cases. This time, the polymorphism was genotyped in 44 Vietnamese SARS cases, with 103 healthy controls who had had a contact with the SARS patients and 50 controls without any contact history. SARS cases were divided into either non-hypoxemic or hypoxemic groups. Despite the small sample size, the frequency of the D allele was significantly higher in the hypoxemic group than in the non-hypoxemic group (p=0.013), whereas there was no significant difference between the SARS cases and controls, irrespective of a contact history. ACE1 might be one of the candidate genes that influence the progression of pneumonia in SARS.
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ItemNo Preview AvailablePolymorphisms of human leucocyte antigen genes in Maonan people in China.(Wiley, 2007-02)We examined human leucocyte antigen (HLA) gene polymorphisms in the Maonan people from southern China. HLA-A, -B and -DRB1 alleles were determined in 108 healthy unrelated Maonan individuals by the polymerase chain reaction-Luminex method, and haplotype frequencies for HLA-A, -B and -DRB1 loci were estimated. The most frequent HLA-A alleles were A*1101 (35.2%), A*0203 (17.6%), A*0207 (13.4%) and A*2402 (13.4%); HLA-B alleles were B*1301(19.9%), B*1502 (14.8%), B*4601 (13.4%) and B*4001 (13.4%); HLA-DRB1 alleles were DRB1*1202 (17.1%), DRB1*1602 (13.0%) and DRB1*1401 (10.7%). The most common haplotypes were A*0207-B*4601 (10.6%), A*1101-B*1301 (10.0%), A*1101-B*4001 (8.4%), B*1502-DRB1*1202 (12.0%), B*4601-DRB1*1401 (5.8%), A*1101-B*1502-DRB1*1202 (7.1%) and A*0207-B*4601-DRB1*1401 (5.3%), profiles that are also found in populations from the southern region of East Asia. Phylogenetic and principal component analyses revealed that the Maonan people belong to the southeastern Asian group and are most closely related to the Buyi people.
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ItemA replication study of the association between the IL12B promoter allele CTCTAA and susceptibility to cerebral malaria in Thai population.(Springer Science and Business Media LLC, 2009-12-11)BACKGROUND: Interleukin-12 (IL-12), a heterodimeric cytokine composed of p35 and p40 subunits, has been thought to play an important role in the pathogenesis of malaria. The IL-12p40 subunit is encoded by the IL12B gene. An IL12B promoter allele, CTCTAA, at rs17860508 has been reported to be associated with susceptibility to cerebral malaria in African populations. However, this association has not so far been replicated in non-African populations. METHODS: To examine whether the CTCTAA allele is associated with susceptibility to cerebral malaria in Asian populations, 303 Thai patients with Plasmodium falciparum malaria (109 cerebral malaria and 194 mild malaria patients) were genotyped for rs17860508 by PCR-direct sequencing. RESULTS: The CTCTAA allele showed a significant association with susceptibility to cerebral malaria in the Thai population (allelic OR = 1.37; one sided P-value = 0.030). CONCLUSIONS: The existence of a significant association between the CTCTAA allele and susceptibility to cerebral malaria was confirmed in Southeast Asian population, which was previously reported in African populations.
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ItemIdentification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria.(Springer Science and Business Media LLC, 2009-10-19)BACKGROUND: It has been previously demonstrated that a single nucleotide polymorphism (SNP) in the IL13 promoter region, IL13 -1055T>C (rs1800925), was associated with susceptibility to severe malaria in Thais. In the present study, fine association mapping for a cytokine gene cluster including IL4, IL5, and IL13 on chromosome 5q31 was conducted using the same malaria subjects to refine the region containing a primary variant or a haplotype susceptible to severe malaria. METHODS: A total of 82 SNPs spanning 522 kb of the 5q31 region were analysed in 368 patients with Plasmodium falciparum malaria (203 mild malaria and 165 severe malaria patients). RESULTS: Only rs1881457 located in the promoter region of IL13, which is in linkage disequilibrium with rs1800925 (r2 = 0.73), showed a significant association with severe malaria after adjusting for multiple testing (P = 0.046 by permutation test). This SNP was in a haplotype block spanning 97 kb (from rs2069812 to rs2240032). The detected haplotype block contained the RAD50 gene and the promoter of IL13, but not the other genes. CONCLUSION: A haplotype block in which a primary polymorphism associated with severe malaria is likely to be encoded was identified in Thai malaria patients.
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ItemPopulation diversity and antibody selective pressure to Plasmodium falciparum MSP1 block2 locus in an African malaria-endemic setting.(Springer Science and Business Media LLC, 2009-10-15)BACKGROUND: Genetic evidence for diversifying selection identified the Merozoite Surface Protein1 block2 (PfMSP1 block2) as a putative target of protective immunity against Plasmodium falciparum. The locus displays three family types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and arrangement variation of three amino acid repeats. The family-specific antibody responses observed in endemic settings support immune selection operating at the family level. However, the factors contributing to the large intra-family allelic diversity remain unclear. To address this question, population allelic polymorphism and sequence variant-specific antibody responses were studied in a single Senegalese rural community where malaria transmission is intense and perennial. RESULTS: Family distribution showed no significant temporal fluctuation over the 10 y period surveyed. Sequencing of 358 PCR fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. The parasite population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. Population diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic sequence diversity and all families combined. Seroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was moderate and increased with age. Reactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences shared by numerous allelic forms within a family type. Seroreactivity to K1-, Mad20- and R033 families correlated with the relative family genotype distribution within the village. Antibody specificity remained unchanged with cumulated exposure to an increasingly large number of alleles. CONCLUSION: The Pfmsp1 block2 locus presents a very large population sequence diversity. The lack of stable acquisition of novel antibody specificities despite exposure to novel allelic forms is reminiscent of clonal imprinting. The locus appears under antibody-mediated diversifying selection in a variable environment that maintains a balance between the various family types without selecting for sequence variant allelic forms. There is no evidence of positive selection for intra-family sequence diversity, consistent with the observed characteristics of the antibody response.
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ItemRole of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region.(Springer Science and Business Media LLC, 2008)INTRODUCTION: Recent studies identified STAT4 (signal transducers and activators of transcription-4) as a susceptibility gene for systemic lupus erythematosus (SLE). STAT1 is encoded adjacently to STAT4 on 2q32.2-q32.3, upregulated in peripheral blood mononuclear cells from SLE patients, and functionally relevant to SLE. This study was conducted to test whether STAT4 is associated with SLE in a Japanese population also, to identify the risk haplotype, and to examine the potential genetic contribution of STAT1. To accomplish these aims, we carried out a comprehensive association analysis of 52 tag single nucleotide polymorphisms (SNPs) encompassing the STAT1-STAT4 region. METHODS: In the first screening, 52 tag SNPs were selected based on HapMap Phase II JPT (Japanese in Tokyo, Japan) data, and case-control association analysis was carried out on 105 Japanese female patients with SLE and 102 female controls. For associated SNPs, additional cases and controls were genotyped and association was analyzed using 308 SLE patients and 306 controls. Estimation of haplotype frequencies and an association study using the permutation test were performed with Haploview version 4.0 software. Population attributable risk percentage was estimated to compare the epidemiological significance of the risk genotype among populations. RESULTS: In the first screening, rs7574865, rs11889341, and rs10168266 in STAT4 were most significantly associated (P < 0.01). Significant association was not observed for STAT1. Subsequent association studies of the three SNPs using 308 SLE patients and 306 controls confirmed a strong association of the rs7574865T allele (SLE patients: 46.3%, controls: 33.5%, P = 4.9 x 10(-6), odds ratio 1.71) as well as TTT haplotype (rs10168266/rs11889341/rs7574865) (P = 1.5 x 10(-6)). The association was stronger in subgroups of SLE with nephritis and anti-double-stranded DNA antibodies. Population attributable risk percentage was estimated to be higher in the Japanese population (40.2%) than in Americans of European descent (19.5%). CONCLUSIONS: The same STAT4 risk allele is associated with SLE in Caucasian and Japanese populations. Evidence for a role of STAT1 in genetic susceptibility to SLE was not detected. The contribution of STAT4 for the genetic background of SLE may be greater in the Japanese population than in Americans of European descent.
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ItemA practical genome scan for population-specific strong selective sweeps that have reached fixation.(Public Library of Science (PLoS), 2007-03-14)Phenotypic divergences between modern human populations have developed as a result of genetic adaptation to local environments over the past 100,000 years. To identify genes involved in population-specific phenotypes, it is necessary to detect signatures of recent positive selection in the human genome. Although detection of elongated linkage disequilibrium (LD) has been a powerful tool in the field of evolutionary genetics, current LD-based approaches are not applicable to already fixed loci. Here, we report a method of scanning for population-specific strong selective sweeps that have reached fixation. In this method, genome-wide SNP data is used to analyze differences in the haplotype frequency, nucleotide diversity, and LD between populations, using the ratio of haplotype homozygosity between populations. To estimate the detection power of the statistics used in this study, we performed computer simulations and found that these tests are relatively robust against the density of typed SNPs and demographic parameters if the advantageous allele has reached fixation. Therefore, we could determine the threshold for maintaining high detection power, regardless of SNP density and demographic history. When this method was applied to the HapMap data, it was able to identify the candidates of population-specific strong selective sweeps more efficiently than the outlier approach that depends on the empirical distribution. This study, confirming strong positive selection on genes previously reported to be associated with specific phenotypes, also identifies other candidates that are likely to contribute to phenotypic differences between human populations.
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ItemPacific: Japan, Australia, New Zealand(Harvard University Press, 2007)