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The origin of Minnan and Hakka, the so-called “Taiwanese”, inferred by HLA study

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Abstract

The Minnan and Hakka people groups, the so-called "Taiwanese", are the descendants of early settlers from the southeast coast of China during the last few centuries. Genetically they showed affinities to southern Asian populations, as determined by phylogenetic trees and correspondence analysis calculated from HLA allele frequencies. This corresponds historically with the fact that they are the descendants of the southeast coastal indigenous population (Yueh) of China and should therefore not be considered as descendants of "pure" northern Han Chinese. A33-B58-DRB1*03 (A33-Cw10-B58-DRB1*03-DQB1*02), the most common HLA haplotype among "Taiwanese", with a haplotype frequency of 6.3%, has also been found to be the most common haplotype among Thai-Chinese and Singapore Chinese, two other populations also originating from the southeast coast of China. These observations suggests that this haplotype is the most well-conserved ancient haplotype of the Yueh.

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... Historically Sai-Kirapa has had significant interaction with the northeastern Atayal tribe while the Sai-Maghahyobun has had more contacts with the Hakka who migrated there from East China in the last 400 years [2][3][4][5][6]. Similarly, Saisyat has two main dialects: the Taai Dialect in the North, and the Tungho Dialect in the south [7]. ...
... Although Atayal and Saisiyat have a genetic profile that distinguishes them from the southern TwMtA, the polymorphism is homogenously distributed through all the tribes. [2, 3,6,[21][22][23][24].In this study, we analyze the mitochondrial genetic polymorphism of the Saisiyat tribe and search genetic evidence of the speculated presence of Negritos in all Taiwan indigenous groups. The mitochondrial molecular clock is faster than the molecular clock of Non-Recombination Y-chromosome (NRY) haplogroups determined using Single Nucleotide Polymorphisms (SNPs) and slower for NRY haplotypes determined using Short Tandem Repeats (STRs) [25]. ...
... Papua New Guinea highlanders, Maoris of New Zealand, and Australian Aborigines is intriguing. These findings suggest that HLA A * 34:01 could be a genetic indicator of the pre-dispersal period of the Negrito throughout ISEA in the late Pleistocene era and should warrant further HLA analysis of the Philippines Negritos[3,6,40,41]. ...
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... Historically Sai-Kirapa has had significant interaction with the northeastern Atayal tribe while the Sai-Maghahyobun has had more contacts with the Hakka who migrated there from East China in the last 400 years [2][3][4][5][6]. Similarly, Saisyat has two main dialects: the Taai Dialect in the North, and the Tungho Dialect in the south [7]. ...
... Although Atayal and Saisiyat have a genetic profile that distinguishes them from the southern TwMtA, the polymorphism is homogenously distributed through all the tribes. [2, 3,6,[21][22][23][24].In this study, we analyze the mitochondrial genetic polymorphism of the Saisiyat tribe and search genetic evidence of the speculated presence of Negritos in all Taiwan indigenous groups. The mitochondrial molecular clock is faster than the molecular clock of Non-Recombination Y-chromosome (NRY) haplogroups determined using Single Nucleotide Polymorphisms (SNPs) and slower for NRY haplotypes determined using Short Tandem Repeats (STRs) [25]. ...
... Papua New Guinea highlanders, Maoris of New Zealand, and Australian Aborigines is intriguing. These findings suggest that HLA A * 34:01 could be a genetic indicator of the pre-dispersal period of the Negrito throughout ISEA in the late Pleistocene era and should warrant further HLA analysis of the Philippines Negritos[3,6,40,41]. ...
Article
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The genetic profile of Negritos of the Philippines differs from the non-Negrito groups with mitochondrial DNA haplogroups B4b1a2, B5, D6a, M, M52a, and N11b. Although Negritos are not seen in Taiwan, the strong genetic affinity between the Philippines and Taiwan Mountain Tribe Aborigines (TwMtA), and Folks tales of TwMtA, Saisiyat and Atayal recounting past contacts with Negritos, warrant the search for a Negrito signature in Taiwan. Material and Method: Discriminant Analysis of Principal Component (DAPC) was used to determine the genetic relationship between TwMtA, Filipino and non-TwMtA groups. Results: The deep coalescence of B4b1a2 in the Philippine Negritos, Saisiyat, Atayal, Island Southeast Asia, and SEA (Southeast Asia) suggested a deeply rooted common ancestry, but could not support a past Negrito presence in Taiwan. Conversely, the sharing of cultural components and mtDNA (mitochondrial DNA) haplogroup D6a2 in Saisiyat, Atayal and Philippine Negritos may characterize a Negrito signature in Taiwan. Although the molecular variation of D6a2 determines its presence in Taiwan back to middle Neolithic, other markers, Y-SNP haplogroups C-M146 and K-M9, warrant further analysis. Conclusion: Most likely, the physical characteristics, languages, and the genetic makeup of the Negritos in Taiwan have been diluted as the result of heavy migration from the mainland in the last 400 years.
... HLA characterized clear genetic differences between the Continental East Asian multilinguistic areas, such as Fujian, the non-aboriginal or mixed groups (Minnan, Hakka, and TwPp), and the Austronesian speaking TwrIP (Fig. 4). In brief, excluding HLA-DRB1*08:02 (1.67%) and DRB1*13:12 (1.67%) (Additional file 1: Table S1), all other Thao HLA-A, B, and DRB1 alleles were seen at various frequencies in most other Austronesian and non-Austronesian speaking groups of Taiwan and Southeast China [34][35][36]. Among these groups, the sole difference in this apparent homogeneity of distribution observable within the groups was most likely brought about by drift. ...
... Accordingly, we used the Expectation Maximum likelihood procedure in Arlequin 3.5.2.2 to infer HLA-A-B-DRB1 haplotypes and use them as indicators to retrace the events of past migrations and the dispersal history of all groups studied [37,38]. [34,36]. Here, using tri-loci haplotypes, only six (26%) of the 23 Thao triplet haplotypes ( Fig. 4 right, Additional file 1: Table S1, and S8) were shared between the Thao (k = 23 haplotypes) and Fujian (k = 82 haplotypes) out of 962 haplotypes in the complete data set. ...
... For the male counterpart, haplogroup O1a1*P203 in the Thao (87.5%) produced a unique Y-STR network showing no sharing of Y-STRs haplotypes with other Formosan groups, and having an age estimate of molecular variation of 1590 ± 690 YBP (Table 2, Fig. 2 and Additional file 1: Table S1). It is possible that this low age estimate is the consequence of a male bottleneck following bad health or the result of the very small number [27,31,34,36]. In each MDS plot, Thao is highlighted in yellow and colors characterizing other groups are described in the insert of "A". ...
Article
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Background Despite attempts in retracing the history of the Thao people in Taiwan using folktales, linguistics, physical anthropology, and ethnic studies, their history remains incomplete. The heritage of Thao has been associated with the Pazeh Western plains peoples and several other mountain peoples of Taiwan. In the last 400 years, their culture and genetic profile have been reshaped by East Asian migrants. They were displaced by the Japanese and the construction of a dam and almost faced extinction. In this paper, genetic information from mitochondrial DNA (mtDNA), Histoleucocyte antigens (HLA), and the non-recombining Y chromosome of 30 Thao individuals are compared to 836 other Taiwan Mountain and Plains Aborigines (TwrIP & TwPp), 384 Non-Aboriginal Taiwanese (non-TwA) and 149 Continental East Asians. Results The phylogeographic analyses of mtDNA haplogroups F4b and B4b1a2 indicated gene flow between Thao, Bunun, and Tsou, and suggested a common ancestry from 10,000 to 3000 years ago. A claim of close contact with the heavily Sinicized Pazeh of the plains was not rejected and suggests that the plains and mountain peoples most likely shared the same Austronesian agriculturist gene pool in the Neolithic. Conclusions Having been moving repeatedly since their arrival in Taiwan between 6000 and 4500 years ago, the Thao finally settled in the central mountain range. They represent the last plains people whose strong bonds with their original culture allowed them to preserve their genetic heritage, despite significant gene flow from the mainland of Asia. Representing a considerable contribution to the genealogical history of the Thao people, the findings of this study bear on ongoing anthropological and linguistic debates on their origin. Electronic supplementary material The online version of this article (10.1186/s12862-019-1389-0) contains supplementary material, which is available to authorized users.
... HLA-B* 4601/B46 displays higher frequencies in Southern Han (15.4%), Singaporean (15.1%) and Vietnamese (13.2%) than in Northern Han (2.8%) [9]. There were a few studies that have focused on the association between HLA markers and disease using Southern Han Chinese data. ...
... There were a few studies that have focused on the association between HLA markers and disease using Southern Han Chinese data. Most of the studies found them a homogeneous group [8][9][10][11]. ...
... The size difference in the optimal flanking region was even more dramatic for HLA-DQB1, which was ±40 kb for the Han Chinese and ±300 kb for the Caucasians. The comparisons of flanking region were based on Affy 5.0 chip ( [9] were different from ours (Affy 5.0) probably due to population stratification. From our chip data, the range of the highest D' for the HLA markers was between 0.47 and 0.83 without imputation. ...
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Genetic variation associated with human leukocyte antigen (HLA) genes has immunological functions and is associated with autoimmune diseases. To date, large-scale studies involving classical HLA genes have been limited by time-consuming and expensive HLA-typing technologies. To reduce these costs, single-nucleotide polymorphisms (SNPs) have been used to predict HLA-allele types. Although HLA allelic distributions differ among populations, most prediction model of HLA genes are based on Caucasian samples, with few reported studies involving non-Caucasians. Our sample consisted of 437 Han Chinese with Affymetrix 5.0 and Illumina 550 K SNPs, of whom 214 also had data on Affymetrix 6.0 SNPs. All individuals had HLA typings at a 4-digit resolution. Using these data, we have built prediction model of HLA genes that are specific for a Han Chinese population. To optimize our prediction model of HLA genes, we analyzed a number of critical parameters, including flanking-region size, genotyping platform, and imputation. Predictive accuracies generally increased both with sample size and SNP density. SNP data from the HapMap Project are about five times more dense than commercially available genotype chip data. Using chips to genotype our samples, however, only reduced the accuracy of our HLA predictions by only ~3%, while saving a great deal of time and expense. We demonstrated that classical HLA alleles can be predicted from SNP genotype data with a high level of accuracy (80.37% (HLA-B) ~95.79% (HLA-DQB1)) in a Han Chinese population. This finding offers new opportunities for researchers in obtaining HLA genotypes via prediction using their already existing chip datasets. Since the genetic variation structure (e.g. SNP, HLA, Linkage disequilibrium) is different between Han Chinese and Caucasians, and has strong impact in building prediction models for HLA genes, our findings emphasize the importance of building ethnic-specific models when analyzing human populations.
... In the past few decades, molecular geneticists have characterized the genetic diversity of most Asian populations by first analyzing the highly polymorphic autosomal HLA system 15 . These studies allowed scientists to use the polymorphism of East Asian populations to investigate a possible relationship between genetics and Austronesian language families in Southeast Asia 16 . ...
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Many studies have described the diversity of Austronesian-speaking Taiwanese people to shed more light on their origin and their connection with the “Out of Taiwan” migrations. However, the genetic relationship between the non-Austronesian-speaking groups of Taiwan and the populations of continental Asia is still unclear. Here, we studied the diversity of mtDNA in 767 non-Austronesian speakers from 16 locations in Taiwan using partial sequencing obtained from the hypervariable segment I (HVS-I) and coding regions 8,001-9,000 and 9.801–10,900 and 85 complete mtDNA genome sequences. Bayesian analysis of population structure was used to examine their relationship with over 3662 individuals representing indigenous groups of Taiwan, continental East Asia, Japan, and Island Southeast Asia. The whole analysis identified 278 haplotypes. Complete genomes revealed 62 novel subhaplogroups, of which 31 were exclusive to Taiwan. Estimates of coalescence times of all subhaplogroups showed peaks of diversification greater than 5.0 kya, likely characterizing gene flow from continental East Asian groups but not excluding in situ Taiwanese ancestry. Furthermore, a significant number of clades exclusive to non-Austronesian speakers of Taiwan (NAN_Tw) showed coalescence peaks between 1.0 and 2.6 kya, suggesting possible late Neolithic to early metal age settlements of NAN_Tw and local expansion in Taiwan.
... 54 Taiwan's reported NAFLD prevalence ranks as one of the highest among Asian countries, 55 but the population includes both indigenous people and other ethnic groups including Minnan and Hakka, as well as mainland Chinese. Minnan and Hakka have potential risk profiles similar to southern Asian populations, based on phylogenetic treesand analysis of HLA allele frequencies.55 These heterogenous populations will have different risk profiles with BMI cut-off levels predictive of health risks that vary between ethnic groups.28 ...
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Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) account for an increasing proportion of liver disease in the Asia-Pacific region. Many areas in the region are experiencing epidemics of metabolic syndrome among rapidly ageing populations. Aims: To estimate using modelling the growth in NAFLD populations, including cases with significant fibrosis that are most likely to experience advanced liver disease and related mortality. Methods: A disease progression model was used to summarise and project fibrosis progression among the NAFLD populations of Hong Kong, Singapore, South Korea and Taiwan. For each area, changes in the adult prevalence of obesity was used to extrapolate long-term trends in NAFLD incidence. Results: In the areas studied, prevalent NAFLD cases were projected to increase 6%-20% during 2019-2030, while prevalent NASH cases increase 20%-35%. Incident cases of hepatocellular carcinoma are projected to increase by 65%-85%, while incident decompensated cirrhosis cases increase 65%-100% by 2030. Likewise, NAFLD-related mortality is projected to increase between 65% and 100% from 2019 to 2030. NAFLD disease burden is expected to increase alongside rising trends in metabolic syndrome and obesity among populations in the region. This leads to more cases of advanced liver disease and associated mortality. Conclusions: Preventing the growth of diabetic and obese populations will be a key factor in reducing ongoing increases in NAFLD-related disease burden in the Asia-Pacific region.
... Minnan songs (also called Hokkien Song) are an important part of ancient Chinese music, the pronunciation, grammar and tone of Minnan songs are quite different from that of Mandarin songs. Minnan songs, which originated in the 1930s and formed in the 1950s and 1960s, are widely spread in Southern Fujian and Taiwan [1][2][3]. Minnan songs are popular among people in south Fujian and Taiwan, overseas Chinese and Chinese businessmen in southeast Asia [1,4,5]. The vivid rhythms and lyrics of Minnan songs contain rich cultural and spiritual treasures, and become the spiritual link connecting the Chinese in Southern Fujian [1]. ...
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Most of the existing research papers study the emotion recognition of Minnan songs from the perspectives of music analysis theory and music appreciation. However, these investigations do not explore any possibility of carrying out an automatic emotion recognition of Minnan songs. In this paper, we propose a model that consists of four main modules to classify the emotion of Minnan songs by using the bimodal data—song lyrics and audio. In the proposed model, an attention-based Long Short-Term Memory (LSTM) neural network is applied to extract lyrical features, and a Convolutional Neural Network (CNN) is used to extract the audio features from the spectrum. Then, two kinds of extracted features are concatenated by multimodal compact bilinear pooling, and finally, the concatenated features are input to the classifying module to determine the song emotion. We designed three experiment groups to investigate the classifying performance of combinations of the four main parts, the comparisons of proposed model with the current approaches and the influence of a few key parameters on the performance of emotion recognition. The results show that the proposed model exhibits better performance over all other experimental groups. The accuracy, precision and recall of the proposed model exceed 0.80 in a combination of appropriate parameters.
... Past genetic studies, using Histoleucocyte antigens (HLA), nonrecombining Y-chromosome (NRY), mitochondrial DNA (mtDNA), and complete Human genome using Affymetrix Human Origins SNP, have shown that non-TwA and TwA have clearly distinct genetic profiles, and the TwPlt are heavily mixed with non-TwA (approximately 75% to 90%) [6][7][8][9][10]. In addition, more than 85% of the maternal lineages in TwA are nested within mtDNA haplogroups B4a1, B5a, F1a1, F3b, E1a1, and M7 [9,[11][12][13][14]. ...
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Full-text available
There is a consensus that gene flow characterizing modern Mainland Chinese arrived in Taiwan during the last 400 years, mostly from East China. However, primary genetic studies of ancient human remains of the middle Neolithic era, revealing inconsistencies between the archaic genes profile and that of modern Mainland Chinese, raised debates about the time of arrival of modern Chinese in Taiwan. To resolve this problem, this study focuses on the analysis of 3000 years BP human remains excavated from the Neolithic east coast archeological Ling-Ding site II near Hualien in Taiwan. The mitochondrial DNA (mtDNA) recovered from five archeological human remains was analyzed to elucidate their genealogy, and to characterize their genetic relationship with the present-day aboriginal and non-aboriginal people of Taiwan. Five mtDNA haplogroups were characterized from the Ling-Ding site II skeletons, C4a2, N9a1, B4c1b2a, Z, and B4b. Except for mtDNA haplogroups B4c1b2a, commonly seen among the present-day central Taiwan Aborigines and scarce in the heavily sinicised Taiwan western plain tribes, all other haplogroups were common to urban Taiwanese and modern Mainland Chinese. It is proposed that a middle Neolithic gene flow, characterizing Modern Mainland East Asians, was introduced to Taiwan by settlers who reached the East coast of Taiwan in Hualien (Ling- Ding site II) and co-habited with Taiwan Mountain tribe Aborigines. The findings of this study may be relevant for the understanding of the middle Neolithic peopling of Taiwan by non-Austronesian speakers.
... Past genetic studies, using Histoleucocyte antigens (HLA), non- recombining Y-chromosome (NRY), mitochondrial DNA (mtDNA), and complete Human genome using Affymetrix Human Origins SNP, have shown that non-TwA and TwA have clearly distinct genetic profiles, and the TwPlt are heavily mixed with non-TwA (approximately 75% to 90%) [6][7][8][9][10]. In addition, more than 85% of the maternal lineages in TwA are nested within mtDNA haplogroups B4a1, B5a, F1a1, F3b, E1a1, and M7 [9,[11][12][13][14]. ...
Article
There is a consensus that gene flow characterizing modern Mainland Chinese arrived in Taiwan during the last 400 years, mostly from East China. However, primary genetic studies of ancient human remains of the middle Neolithic era, revealing inconsistencies between the archaic genes profile and that of modern Mainland Chinese, raised debates about the time of arrival of modern Chinese in Taiwan. To resolve this problem, this study focuses on the analysis of 3000 years BP human remains excavated from the Neolithic east coast archeological Ling-Ding site II near Hualien in Taiwan. The mitochondrial DNA (mtDNA) recovered from five archeological human remains was analyzed to elucidate their genealogy, and to characterize their genetic relationship with the present-day aboriginal and non-aboriginal people of Taiwan. Five mtDNA haplogroups were characterized from the Ling-Ding site II skeletons, C4a2, N9a1, B4c1b2a, Z, and B4b. Except for mtDNA haplogroups B4c1b2a, commonly seen among the present-day central Taiwan Aborigines and scarce in the heavily sinicised Taiwan western plain tribes, all other haplogroups were common to urban Taiwanese and modern Mainland Chinese. It is proposed that a middle Neolithic gene flow, characterizing Modern Mainland East Asians, was introduced to Taiwan by settlers who reached the East coast of Taiwan in Hualien (Ling- Ding site II) and co-habited with Taiwan Mountain tribe Aborigines. The findings of this study may be relevant for the understanding of the middle Neolithic peopling of Taiwan by non-Austronesian speakers.
... Specifically, Marie Lin of Mackay Memorial Hospital in Taipei County and her colleagues have conducted human leukocyte antigen (HLA) analyses that suggest that Taiwanese (defined in their study as Minnan/Hoklo and Hakka) are descendants of an ancient Yueh people who were indigenous to southeastern coastal mainland China. They suggest that the Yueh are also ancestors to "Singapore Chinese" and "Thai-Chinese" (Lin et al. 2001). In this way, they represent Taiwanese as genetically distinct from northern Han Chinese and closer to their contemporary southeastern Asian neighbors. ...
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... The TNNI3 (p.Glu124Gln) mutation was originally reported in Taiwanese patients with familial HCM (29). The Taiwanese are the descendants of early settlers from the southeast coast of China during the last few centuries (31). The present study showed its second appearance in Chinese HCM patient. ...
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Hypertrophic cardiomyopathy (HCM), one of the most common forms of myocardial diseases, is the major cause of sudden cardiac death in young adults and competitive athletes. Analyses of gene mutations associated with HCM are valuable for its molecular diagnosis, genetic counseling, and management of familial HCM. To dissect the relationship between the clinical presentation and gene mutations of HCM, the genetic characterizations of 19 HCM-related genes in 18 patients (8 cases from 6 pedigrees with familial HCM and 10 cases without familial HCM) were detected using next-generation sequencing (NGS). As a result, 12 disease-related mutations were identified in the 18 subjects, including 6 single mutations and 3 double mutations [MYBPC3 (p.Gln998Glu) plus TNNI3 (p.Arg145Gly), PRKAG2 (p.Gly100Ser) plus MYBPC3 (p.Lys1209Serfs*28) and TNNI3 (p.Glu124Gln) plus GLA (p.Trp47*)]. The 3 heterozygous double mutations were discovered for the first time in the malignant familial HCM patients. Of the 6 single mutations, a novel mutation was found in tafazzin (TAZ, p.Ile208Val), and a mutation in β-myosin heavy chain gene (MYH7, p.Arg54Gln), which was reported as rare in the general population, was firstly found in one HCM patient. Identification of novel and rare mutations in HCM patients have added new data to the spectrum of gene mutations associated with this disease. These findings provide an essential basis for the molecular diagnosis and better management of family members at risk of familial HCM.
... each other; this would show that bridging studies were necessary and that a single bridging study for all East Asians would be adequate. Such a study appeared when Chern read in a local newspaper about a controversial scientific paper (Lin et al. 2001). This paper addressed the sensitive matter of the ethnic origin of the Minnan (Holonese) and Hakka ethnic groups (both together comprise the so-called "Taiwanese") 35 , an issue made even more delicate by Taiwan's political status. ...
Article
This paper analyzes Taiwan's engagement with the standardization of pharmaceutical clinical trials at the turn of this century. Unlike approaches that treat local encounters with globalization as either reluctant acceptance or lasting resistance, this study calls attention to a complicated process of negotiation, the conceptual gap between the illusion of a unified world and the reality of persistently divided nation-states. To address this gap, an ethnographic investigation is required. Two concepts, “bridging” and “voicing” (fasheng), are introduced in order to capture Taiwan's unstable status, what I term “the voice on the bridge,” in this process. Bridging emerged as a technical concept for evaluating pharmaceutical drugs' possible differential ethnic effects. But it also reflects the ambiguous reality of a world in which each state is an islet connected to others by imaginary bridges. Fasheng (“voicing”) has to do with Taiwan's long-held desire for world recognition as a state. This paper is an ethnography of globalization and the state that traces how Taiwan created a regulatory resolution through the idea of bridging and how this “voice” was articulated through various social strategies. It explores not only the complexity of interactions in the technical field of regulatory science, but also argues that looking at such entanglements of science and society makes it possible to move beyond simple interpretations of globalization.
... Overpopulation in the southeastern coastal provinces of Fujian and Guangdong in China and the close proximity of these provinces to Taiwan led the ancestors of the Min-Nan and Hakka to move to Taiwan during the past few centuries (2). The two populations have been reported to share similar genetic backgrounds, as they are descendants of an admixture of Han Chinese and the southeast coastal indigenous population (Yueh) of China (3). All other Han Chinese are referred to as Mainlanders, and most moved from mainland China to Taiwan after World War II and registered themselves as originating from other provinces of China (1). ...
Article
The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history, and long-term health outcomes of 300,000 residents of Taiwan. We describe here an investigation of the population structure of Han Chinese on this Pacific island using genotype data of 591,048 SNPs in an initial freeze of 10,801 unrelated TWB participants. In addition to the North-South cline reported in other Han Chinese populations, we find the Taiwanese Han Chinese clustered into three cline groups: 5% were of northern Han Chinese ancestry, 79.9% were of southern Han Chinese ancestry, and 14.5% belonged to a third (T) group. We also find that this T group is genetically distinct from neighboring Southeast Asians and Austronesian tribes but similar to other southern Han Chinese. Interestingly, high degree of LD between HLA haplotype A*33:03-B*58:01, a MHC allele being of pathological relevance, and SNPs across the MHC region was observed in subjects with T origin, but not in other Han Chinese. This suggested the T group individuals may have experienced evolutionary events independent from other southern Han Chinese. Based on the newly-discovered population structure, we detect different loci susceptible to type II diabetes in individuals with southern and northern Han Chinese ancestries. Finally, as one of the largest dataset currently available for the Chinese population, genome-wide statistics for the 10,810 subjects are made publicly accessible through Taiwan View (https://taiwanview.twbiobank.org.tw/index) to encourage future genetic research and collaborations with the island Taiwan.
... CTL epitopes are peptides presented by the human leukocyte antigen (HLA) class I molecules and recognized by CTLs. In the present study, the HLA-A * 1101 allele was selected for investigation as it is the most common HLA-I allele within the Chinese population (18,19). The present study identified five potential EPS8 peptides, which bind with high affinity to HLA-A * 1101. ...
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Epidermal growth factor receptor pathway substrate 8 (EPS8) is critical in the proliferation, progression and metastasis of solid and hematological types of cancer, and thus constitutes an ideal target for cancer immunotherapy. The present study aimed to identify human leukocyte antigen (HLA)‑A*1101‑restricted cytotoxic T lymphocyte (CTL) epitopes from EPS8 and characterize their immunotherapeutic efficacy in vitro. Two computer‑based algorithms were used to predict native EPS8 epitopes with potential high binding affinity to the HLA‑A*1101 molecule, which is the HLA‑A allele with the highest frequency in the Chinese population. The peptide‑induced cytokine production from the CTLs was examined using enzyme‑linked immunosorbent spot analysis. The cytotoxic effects on cancer cells by CTLs primed with the identified peptides were examined using flow cytometry. A total of five peptides, designated as P380, P70, P82, P30 and P529, presented with high affinity towards the HLA‑A*1101 molecule. In response to stimulation by these five peptides, enhanced secretion of interferon‑γ from the CTLs and increased cytolytic capabilities of the CTLs toward cancer cells were noted, with the most potent effects observed from the P380 peptide. Taken together, the present study identified five potential CTL epitopes from EPS8. Among these, P380 presented with the highest therapeutic efficacy in vitro. These peptides may benefit the development of EPS8‑based immunotherapy for the treatment of HLA‑A*1101‑positive hematological malignancies.
... Three of our selected loci from Taiwan are included in the VNTR-9 loci reported by Luo et al. 26 Our results suggest that seven selected loci could achieve nearly the same resolution as VNTR-9 (all strains: 0.9882; Beijing strains: 0.9674; EAI strains: 0.9509). Moreover, the combination of seven selected loci and spoligotyping was able to achieve resolution comparable with the VNTR-9 loci used by Luo et al 26 28 used ODEN software and allele frequencies of HLA-A, -B, and -C to construct a neighborjoining tree that also revealed that Minnan and Hakka merge together and cluster with Thai Chinese and Singapore Chinese. Taiwan is a major trading partner of Cambodia. ...
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Background: The Beijing lineage of Mycobacterium tuberculosis (MTB) is the most predominant MTB strain in Asian countries and is spreading worldwide, but the East African-Indian (EAI) lineage is also particularly prevalent in many tropical Asian countries. The evolutionary relationships among MTB EAI isolates from Taiwan and those of tropical Asian countries remain unknown. Methods: The EAI strains collected from patients in Taiwan by using spoligotyping and MIRU-VNTR typing were compared to published profiles from Cambodia and Singapore to investigate potential epidemiological linkages. Results: Among the three countries, the EAI lineage was most prevalent in Cambodia (60%; Singapore, 25.62%; and Taiwan, 21.85%), having also the highest rates of multi-drug resistance (MDR) and lowest rates of clustering of MTB isolates. Also, we describe a convenient method using 7 selected MIRU-VNTR loci for first-line typing to discriminate Beijing and EAI lineages. A potential epidemiological linkage in these tropical Asian countries is also discussed based on a minimum-spanning tree (MST) constructed using 24 MIRU-VNTR loci of MTB EAI strains. Conclusion: This study identified evolutionary relationships among MTB EAI isolates from Taiwan and those of two other tropical Asian countries, Cambodia and Singapore.
... All patient and control individuals were Taiwanese, descendant of early Minnan or Hakka Chinese from the Fukien and Kwangton provinces on the south-east-coast of China who settle in Taiwan in the last 400 years. Other studies have shown that, although Minnan and Hakka speak different Chinese dialects, they have a similar HLA profile [18,19]. Allele frequencies of Minnan and Hakka in our previous study have been deposited in a worldwide database (http://www.allelefrequencies.net/). ...
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Background: End stage renal disease (ESRD) is prevalent in Taiwan. Human leukocyte antigens (HLA) have been found to be associated with the pathogenesis of autoimmune diseases, allergies and inflammatory bowel diseases, and there are emerging evidences of correlations between HLA genotypes and renal diseases such as diabetic nephropathy, IgA nephropathy, and glomerulonephritis. The aim of this study is to investigate detailed HLA subtypes in a case-control study of Taiwanese individuals. Methods: The polymorphisms of HLA class I and II antigens in ESRD patients and a healthy control group were retrospectively analyzed. The information of 141 ESRD patients was obtained from the medical record of the Keelung branch of Chang Gung Memorial Hospital and was compared to the HLA type of a control group comprized of 190 healthy unrelated Taiwanese from one of our previous studies. In order to standardize the HLA designation of prior low-resolution typings with the more advanced DNA based typings, all HLA-A, -B and -DR were analyzed using a low resolution serologic equivalent. Results: The current work suggests that HLA-DR3 (odds ratio = 1.91, 95 % CI = 1.098-3.324, P = 0.024, Pc = 0.312) and HLA-DR11 (odds ratio = 2.06, 95 % CI = 1.133-3.761, P = 0.021, Pc = 0.273) may represent susceptibility risk factors for the development of ESRD in Taiwanese individuals. On the other hand, HLA-DR8 (odds ratio = 0.47, 95 % CI = 0.236-0.920, p = 0.027. Pc = 0.351) may be a protective factor. HLA-A and -B antigens did not show any contribution of progression to ESRD. However, we note that the significance of all these findings is lost when the results are corrected for multiple comparisons according to Bonferroni. Further investigation with a larger group of patients and control is needed to resolve this issue. Conclusions: HLA typing might be a useful clinical method for screening patients with high risk of progression to ESRD.
... However, the feasibility and utilization of this method for identifying familial HTG is not well known [18][19][20] . Accordingly, the aims of this study were: 1) to test the hypothesis that WES can be used to identify the causative gene in patients with clinical manifestations of the familial form of HTG and 2) to use these findings to explore the prevalence of adults with very high TG levels among Taiwanese 21) . ...
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Whole exome sequencing (WES) is a recently developed method for discovering rare mutations associated with hereditary disorders. However, the feasibility and utilization of this method in identifying familial hypertriglyceridemia is not well known. The purpose of the study was to identify the genetic locus that causes hypertriglyceridemia and assess its prevalence in Taiwanese subjects with hypertriglyceridemia. We performed WES among two individuals with hypertriglyceridemia and one control subject in an index family (22 members). Based on the WES findings, we extended the study to genotype 65 unrelated adult index patients with a fasting serum triglyceride level of >500 mg/dL and 125 normal controls using polymerase chain reaction. Using WES alignment, variant calling and annotation, 15 presumptive causal variants were initially identified, including 13 cases by the autosomal dominant model and two cases by the autosomal recessive model. Only APOA5 c.553 G>T (rs2075291), resulting in the amino acid mutation Gly185Cys, co-segregated well with hypertriglyceridemia in terms of autosomal recessive inheritance (homozygote TT: mean triglyceride level: 1,071 mg/dL vs non TT (GT and GG): mean triglyceride level: 118 mg/dL; p<0.001) in the index family. In the unrelated cohorts, the frequency of the TT genotype of rs2075291 was 12.3% in the hypertriglyceridemic group; however, no TT genotype was found in the control group. Our results demonstrate that WES is feasible for identifying the genetic locus that causes hypertriglyceridemia. The TT genotype of APOA5 c.553G>T acts as an important indicator of hypertriglyceridemia in patients in Taiwan.
... It is important to understand the genetic makeup of Asians, specifically Chinese, which represent more than half of the Asian population. Taiwanese are the descendants of mainland China and also show genetic affinities to southern Asian populations (8), so Taiwanese people are representative ethnic group for investigating PG variabilities in Asians and Chinese. ...
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To understand the genetic makeup and impact on pharmacokinetics (PK) in the Taiwanese population, we analyzed the pharmacogenetic (PG) profile and demonstrated its effects on enzyme metabolism using indapamide as an example. A multiplex mass spectrometry method was used to examine the single nucleotide polymorphism (SNP) profile of eight major phases I and II metabolic enzymes in 1,038 Taiwanese subjects. A PG/PK study was conducted in 24 healthy subjects to investigate the possible effects of 28 SNPs on drug biotransformation. Among the genetic profile analyzed, eight SNPs from CYP2A6, CYP2C19, CYP2D6, CYP2E1, CYP3A5, and UGT2B7 showed higher variant frequencies than those previously reported in Caucasians or Africans. For instance, we observed 14.7% frequency of the SNP rs5031016 (I471T) from CYP2A6 in Taiwanese, whereas 0% variation was reported in Caucasians and Africans. The PG/PK study of indapamide demonstrated that the polymorphic SNPs CYP2C9 rs4918758 and CYP2C19 rs4244285 appeared to confer lowered enzyme activity, as indicated by increased C max (25% ∼ 64%), increased area under the plasma level-time curves (30∼76%), increased area under the time infinity (43% ∼ 80%), and lower apparent clearance values than PK for wild-type indapamide. Our results reinforce the biochemical support of CYP2C19 in indapamide metabolism and identify a possible new participating enzyme CYP2C9. The PG/PK approach contributed toward understanding the genetic makeup of different ethnic groups and associations of enzymes in drug metabolism. It could be used to identify two genetic markers that enable to differentiate subjects with varied PK outcomes of indapamide.
... Previous studies of CTL epitopes from HBV-associated proteins have mostly focused on the HLA- A*0201 allele (Penna et al., 1991; Bertoletti et al., 1993; Nayersina et al., 1993; Loirat et al., 2000 ). However, HLA- A*1101, rather than HLA-A*0201, is the most common HLA class I allele in Asian countries, and in China in particular (Lee et al., 1988; Lin et al., 2001). However, compared with a considerable number of HLA-A*0201- restricted HBV-derived epitopes, less than 10 % of HBV epitopes currently described fall within the HLA-A*1101 context (Desmond et al., 2008). ...
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Hepatitis B virus (HBV) infection is a worldwide public health problem. HBV-specific CD8+ cytotoxic T lymphocytes (CTL) are vital for viral clearance. Identification of immunodominant CTL epitopes from HBV-associated antigens is necessary for therapeutic vaccine development. We showed that HLA-A*1101 allele is one of the most common alleles in both healthy individuals and chronic hepatitis B (CHB) patients in the Chongqing area, China. However, less than 10% of epitopes of HBV-associated antigens have been identified in an HLA-A*1101 context. Here, we described an immunodominant CD8+ T cell response targeting a hepatitis B surface antigen determinant (HBs295-304) restricted by HLA-A*1101 in both healthy individuals and CHB patients. Moreover, HBs295-304 is more immunogenic for CTL induction than a known naturally HLA-A*1101-processed epitope from hepatitis B core antigen (HBc88-96). Therefore, the newly identified epitope, HBs295-304, will benefit the development of immunotherapeutic approaches for HBV infection.
... each other; this would show that bridging studies were necessary and that a single bridging study for all East Asians would be adequate. Such a study appeared when Chern read in a local newspaper about a controversial scientific paper (Lin et al. 2001). This paper addressed the sensitive matter of the ethnic origin of the Minnan (Holonese) and Hakka ethnic groups (both together comprise the so-called "Taiwanese") 35 , an issue made even more delicate by Taiwan's political status. ...
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This paper analyzes Taiwan’s engagement with the standardization of pharmaceutical clinical trials at the turn of this century. Unlike approaches that treat local encounters with globalization as either reluctant acceptance or lasting resistance, this study calls attention to a complicated process of negotiation, the conceptual gap between the illusion of a unified world and the reality of persistently divided nation-states. To address this gap, an ethnographic investigation is required. Two concepts, “bridging” and “voicing” (fasheng), are introduced in order to capture Taiwan’s unstable status, what I term “the voice on the bridge,” in this process. Bridging emerged as a technical concept for evaluating pharmaceutical drugs’ possible differential ethnic effects. But it also reflects the ambiguous reality of a world in which each state is an islet connected to others by imaginary bridges. Fasheng (“voicing”) has to do with Taiwan’s long-held desire for world recognition as a state. This paper is an ethnography of globalization and the state that traces how Taiwan created a regulatory resolution through the idea of bridging and how this “voice” was articulated through various social strategies. It explores not only the complexity of interactions in the technical field of regulatory science, but also argues that looking at such entanglements of science and society makes it possible to move beyond simple interpretations of globalization.
... Further studies on mitochondrial DNA (mtDNA) (Trejaut et al. 2005), on autosomal Human Leukocyte Antigen (HLA) (Lin et al. 2001), and 58 of paternal non recombining Y SNP (NRY ) of hundred NTwA (Trejaut and Lin in preparation), showed strong genetic affinity between NTwA and CSEA, and showed that about half of the NTwA shared their genetic origin with TwA or with ISEA. Also, it was shown about 85% of NTwA could carry at least one gene (either HLA, NRY or mtDNA) of TwA or ISEA origin . ...
... The deviance may also be caused by genetic diversities within the population since Taiwan is home to a heterogeneous mix of ethnic groups (Trejaut et al., 2005). The unexpected genotype frequencies in the population may be caused by intermarriage between Taiwanese Han and various aborigines since a report showed that 13% of Taiwanese have HLAlinked genetic traits originating from aborigines (Lin et al., 2001). ...
Article
STUDY QUESTION Do gene polymorphisms of two members of the human innate immune sensor nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing proteins (NLRP) family, NLRP2 and NLRP7, confer susceptibility to idiopathic recurrent miscarriage (RM)?
... This finding is similar to previous reports from Taiwan and Hong Kong (Hsieh et al. 2008;Lin et al. 2002;Shu et al. 2003;Tang et al. 2000). Since around 91 % of the population in Taiwan is descended from people who came to the island from southeastern China a few hundred years ago (Lin et al. 2001), IVS10-2A>C is likely a founder mutation in the Southern Chinese population. For GA-I, the most well-known GCDH founder mutation is c.1296C>T (p.A421V), which is found among the Lancaster Amish (Strauss et al. 2003). ...
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Glutaric aciduria type I (GA-I) is an inborn error of lysine and tryptophan metabolism. Clinical manifestations of GA-I include dystonic or dyskinetic cerebral palsy, but when the symptoms occur, treatment is not effective. In Taiwan, newborn screening for GA-I started in 2001; we wish to evaluate the outcomes of patients detected through newborn screening. Newborns diagnosed with GA-I by abnormal dried blood spot glutarylcarnitine (C5DC) levels followed in our hospital were included in this study. They were treated with special diets, carnitine supplements, and immediate stress avoidance. Six patients were included in this study. All patients were treated prior to reaching 1 month of age. They were followed up with for 4 to 9 years. One patient had encephalopathic crisis episodes prior to turning 1 year old that caused pallidal lesions. Another patient had a chronic progressive disease during infancy that caused bilateral putamen lesions. These two patients had delayed development, but their brain lesions were resolved. The other four patients ran uneventful courses. They had normal intelligenece, ranged between average to low average level and their brain magnetic resonance imaging showed only high intensity over deep white matter. Patients with GA-I diagnosed by newborn screening have promising outcomes, though the risks of disease progression prior to 1 year of age remain significant.
... This may be related to the founder effect, a bias of a small sample size, the influence of admixture between the Taiwanese ancestral population and the local South Polynesian population, or spontaneous TGFBI mutations. Phylogenetic trees and correspondence analysis calculated from human leukocyte antigens allele frequencies have shown that Taiwanese have a more affinity to southern Asian population than northern Han Chinese or Japanese [41]. Our results of TGFBI mutations in Taiwanese were correspondence to these findings. ...
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To determine the phenotype-genotype correlations in patients with corneal dystrophies associated with human transforming growth factor-β-induced (TGFBI) mutations at the National Taiwan University Hospital. Twenty-five affected patients from 15 families with corneal dystrophies were recruited. They underwent slit-lamp biomicroscopy and visual acuity examinations. Genomic DNA was extracted from their peripheral blood, and the exons amplified from TGFBI were sequenced. Eleven patients from 9 families with granular corneal dystrophy (GCD) presented with a wide spectrum of dot or fleck opacities and shared some similar clinical features. Genetic studies revealed an R124H mutation in 5 families and an R555W mutation in 4 families. A patient with GCD type 2 and an R124H mutation showed a marked increase in opacities in the laser-assisted in situ keratomileusis (LASIK) flap interface. Six patients from 3 families with superficial honeycomb opacities had an R555Q mutation. Of the 4 patients from 3 families with variant lattice line opacities, 3 from 2 families had an R124C mutation, whereas 1 from the third family had an A546D mutation. Spontaneous mutations were detected in 2 families: an R124C mutation in 1 family with lattice corneal dystrophy (LCD) type I and an A546D mutation in the other with atypical LCD. In most cases, TGFBI-linked corneal dystrophies had good phenotype-genotype correlations; however, some phenotypic variation was present. The most common mutations in Taiwan were R124H in GCD type 2 and R555W in GCD type 1. The R555Q mutation in Thiel-Behnke corneal dystrophy is not as rare in Taiwan as it is in other Asian countries. Sequencing of TGFBI can aid in the precise classification of these corneal dystrophies.
... The frequencies of DR 1, 2, 5, 6, 10 were lower than 1% in both groups and were excluded in further analysis. There was no significant difference in DRB1 general patterns (P = 0.83) between our controls and the Min Nan population, the predominant Han Chinese in Taiwan (Lin et al., 2001). The case-control association analysis revealed that the pattern of DRB1 alleles was significantly different between patients with autism and the controls (w 2 = 19.15, ...
Article
Evidence suggests an association between autism and immune dysfunction. The associations between human lymphocyte antigen (HLA)-A2, B44, DRβ1*04 (DR4), C4B, and haplotype B44-SC30-DR4 and autism have been reported in western countries but there is a lack of such information in Asian population. This study aimed to assess the association between HLA-DRB1 allele frequencies and the clinical phenomenology of autism. The sample included 141 participants (male, 87.2%), who were diagnosed with autistic disorder based on clinical assessments and structured interviews using the Chinese version of the Autism Diagnostic Interview-Revised, and 156 healthy controls (male, 38.6%). The HLA-DRB1 alleles were determined by sequencing-based typing method. A subsample of patients (n=39) were assessed for intelligence and neuropsychological functions. The results showed that the pattern of DRB1 allele frequencies was significantly different between patients with autism and the controls (P=0.047). After adjusting for sex by haplotype regression, the frequencies of DR4, DR11, and DR14 were significantly different between patients with autism and healthy controls. In addition, patients with autism and DR4, DR11, or DR14 had different performance on intelligence and neuropsychology tests. Despite a relatively small sample size and a case-control association design, the findings suggest HLA-DRB1 gene might be associated with autism in Han Chinese. The true functional variants associated with autism in our samples remain to be further clarified. It warrants a replication study of a larger family sample and to validate the HLA genetic association with autism and its influence on neuropsychological function.
... Chaoshanese, Minnanese, Taiwanese , Malaysia Chinese, and Singapore Chinese, though geographically far apart, clustered together more closely among the Southern Han populations (Figs. 1, 4). These five ethnic groups speak the Min dialect, one of the 10 major dialects within the Han family (Gan et al. 2008), and share common ancestors (Huang 2002;Tang 2002;Lin and Qiu 2005;Zhang 2006;Hu et al. 2007;Xu et al. 2009). Our results indicate that the paternal genetic relationships among Chinese populations correlated more strongly with linguistic rather than geographic relationships, in agreement with prior observations in worldwide populations that linguistic distances present a higher correlation with Y chromosome than with mtDNA markers (Cavalli-Sforza et al. 1992;Chen et al. 1995;Poloni et al. 1997). ...
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We investigated the Y chromosome of various Chinese populations to determine the patrilineal origin of the Chaoshanese population. Admixture analysis of six specific Y short tandem repeat (STR) loci in 6,292 individual samples taken from 51 populations, including Chaoshanese and Minnanese of our earlier studies, showed that over 85% of the Chaoshanese Y chromosomes were derived from the Central China Han (M RH: 0.8614; M BE: 1.1868 ± 0.2054), and a very small portion were from the southern aborigines. These results support a Central China Han origin of the Chaoshanese and additionally reveal that males from the Central China Han were the predominant contributor to the patrilineal genetics of the Chaoshanese. A phylogenetic tree and analysis of molecular variance signified a strong association between Y chromosomes of Chinese populations and their linguistic affiliations, revealing a coevolution of Y chromosome diversity and languages in East Asia.
... NPC has been observed among Taiwanese Han and Taiwan aborigines (TwA), among island Southeast Asia (ISEA) islanders and Polynesians. Except for the Han who moved to Taiwan 400 years before present (YBP) and finally contributed to 98% of the Taiwan population[2], TwA and most other populations of ISEA are speakers of Austronesian languages and are believed to share a common ancestry with the Bai Yue of south China[3]. It has been genetically demonstrated [4]–[7] that islanders from ISEA and TwA had separated from mainland Southeast Asia (MSEA) more than 15 000 YBP. ...
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Mitochondrial DNA (mtDNA) and non-recombining Y chromosome (NRY) are inherited uni-parentally from mother to daughter or from father to son respectively. Their polymorphism has initially been studied throughout populations of the world to demonstrate the "Out of Africa" hypothesis. Here, to correlate the distribution of nasopharyngeal carcinoma (NPC) in different populations of insular Asia, we analyze the mtDNA information (lineages) obtained from genotyping of the hyper variable region (HVS I & II) among 1400 individuals from island Southeast Asia (ISEA), Taiwan and Fujian and supplemented with the analysis of relevant coding region polymorphisms. Lineages that best represented a clade (a branch of the genetic tree) in the phylogeny were further analyzed using complete genomic mtDNA sequencing. Finally, these complete mtDNA sequences were used to construct a most parsimonious tree which now constitutes the most up-to-date mtDNA dataset available on ISEA and Taiwan. This analysis has exposed new insights of the evolutionary history of insular Asia and has strong implications in assessing possible correlations with linguistic, archaeology, demography and the NPC distribution in populations within these regions. To obtain a more objective and balanced genetic point of view, slowly evolving biallelic Y single nucleotide polymorphism (Y-SNP) was also analyzed. As in the first step above, the technique was first applied to determine affinities (macro analysis) between populations of insular Asia. Secondly, sixteen Y short tandem repeats (Y-STR) were used as they allow deeper insight (micro analysis) into the relationship between individuals of a same region. Together, mtDNA and NRY allowed a better definition of the relational, demographic, cultural and genetic components that constitute the make up of the present day peoples of ISEA. Outstanding findings were obtained on the routes of migration that occurred along with the spread of NPC during the settlement of insular Asia. The results of this analysis will be discussed using a conceptual approach.
... Roti et al. (26) studied the reactions of CD4 þ T cells collected from healthy individuals to H5N1 influenza viruses, but focused on DR0101, DR0404, DR0701, and DR1101 HLA alleles, which are more prevalent in Caucasian populations. Since our focus was on Minnan populations, we focused on the DR1501 allele (20). Our ICS assay data indicate the potential presence of HLA DR1501-restricted T-cell epitopes of H5 HA1 proteins in six peptides: 22 (H5HA 148-162 ), 23 (H5HA 155-169 ), 37 (H5HA 253-267 ), 38 (H5HA 260-274 ), 39 (H5HA 267-281 ), and 45 (H5HA 309-323 ). ...
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Highly pathogenic avian influenza H5N1 viruses are capable of causing poultry epidemics and human mortality. Vaccines that induce protective neutralizing antibodies can prevent outbreaks and decrease the potential for influenza A pandemics. Identifying unique H5N1 virus-specific HLA class II-restricted epitopes is essential for monitoring cellular strain-specific immunity. Our results indicate that 80% of the 30 study participants who were inoculated with an H5N1 vaccine produced neutralizing antibodies. We used intracellular cytokine staining (ICS) to screen and identify six DR1501-restricted H5N1 virus epitopes: H5HA(148-162), H5HA(155-169), H5HA(253-267), H5HA(260-274), H5HA(267-281) and H5HA(309-323.) Tetramer staining results confirmed that two immunodominant epitopes were DR1501-restricted: H5HA(155-169) and H5HA(267-281). Both are located at the HA surface and are highly conserved in currently circulating H5N1 clades. These results suggest that a combination of ICS and tetramer staining can be used as a T-cell epitope-mapping platform, and the identified epitopes may serve as markers for monitoring vaccine efficacy.
Article
Background: The World Health Organization (WHO) set out to eliminate hepatitis C virus (HCV) infection by 2030, a goal Taiwan might achieve before 2025. Using effective direct antiviral agents (DAAs) against chronic hepatitis C (CHC) in Taiwan, the treatment of CHC has been initiated in rural areas. Here, we aimed to elucidate the clinical and virological characteristics of HCV infection, and the treatment efficacy of DAAs in patients from Pingtung county in southern Taiwan. Methods: A total of 152 chronic hepatitis patients treated with DAAs were consecutively enrolled. Baseline characteristics and therapeutic efficacy were evaluated. Results: HCV genotype 2 was the most common viral genotype (39.5 %), followed by 1b (36.8%), 6 (10.5%), and 1a (9.2%). The sustained virological response (SVR) rate was 98.7%. Hakka patients accounted for 22.4 % of the study cohort, of which 14.7% had HCV genotype 6. There were no differences in clinical characteristics between Hakka and non-Hakka patients. Patients with HCV genotype 6 were younger in age (OR/CI: 0.95/0.91-1.00, p = 0.04) and comprised of more people who inject drugs (PWID) (OR/CI: 17.6/3.6-85.5, p <0.001), when compared to other patients. Conclusion: We demonstrated that DAA therapy can achieve a 98.7% SVR rate among CHC patients in Pingtung county of southern Taiwan, with a relative higher prevalence of genotype 6. The most important factor attributed to genotype 6 infection was PWID.
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Background: The frequency of the RhD negative (D-) phenotype among the population of Taiwan is only 0·34% and so anti-D is a relatively rare antibody. Routine pretransfusion D typing of patients at Mackay Memorial Hospital (MMH) was discontinued in 1988, and this report is a look back and retrospective evaluation over 30-years (1988-2017). Study design and methods: The incidence of anti-D among patients at MMH during the periods 1984-1988 (when D typing was performed) and 1988-2017 (when D typing was not performed) was reviewed. Also, the incidence of anti-D among both MMH patients and voluntary blood donors at the Taiwan Blood Foundation was compared. The importance of anti-'Mia ' in Taiwan is also discussed. Results: The incidence of anti-D relative to other Rh antibodies among MMH patients when D typing was performed and D typing not performed has remained relatively unchanged (5%). The frequencies of anti-D and anti-'Mia ' among 38 537 patients who were transfused at MMH during 2008-2017 were found to be 0·06% and 2·6%, respectively. During the same period, among 3 510 131 blood donors at Taiwan Blood Foundation, the frequencies of anti-D and anti-'Mia ' were 0·004% and 0·2%, respectively. Conclusion: The elimination of D typing of patients at MMH has proven to have been a correct and logical decision. D- patients, if they do not carry anti-D, can thus be safely transfused with D+ red cells.
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We read with interest the article by Zhou et al.,(1) who studied the epidemiological characteristics of nonalcoholic fatty liver disease (NAFLD) in China. The study was ambitious, aiming to clarify the status of this common liver disorder in a large country. It provided a big piece of the puzzles across different variables, including time period, age, gender, body mass index, ethnicity, geographical region, and income. However, two points should be taken into consideration.
Objective: To describe the psychological stress and quality of life experienced by women who underwent fertility treatment in Taiwan. Design: Cross-sectional, correlational study. Setting: Recruitment was conducted and questionnaires administered at a reproductive medicine center in Chiayi City, Taiwan. Participants: Informed consent to participate was obtained from 126 women who sought fertility treatment at the center. Methods: The Chinese Fertility Problem Inventory and Fertility Quality of Life scale were used to measure participants' levels of fertility-related stress and fertility-related quality of life. Descriptive statistics, correlation, and regression analysis were used. Results: Overall, participants reported low levels of fertility-related stress and fertility-related quality of life; however, they had relatively high levels of stress related to need for parenthood. Women who were older, had greater body mass indexes, and consumed coffee regularly had lower fertility-related quality of life. Social and relationship concerns and stress related to need for parenthood were significant predictors of low fertility-related quality of life. Conclusion: In a culture in which childbearing is generally an expectation and an important part of family life, women who experience infertility are at risk to experience fertility-related stress. Social support and family consultation might be offered to improve women's fertility-related quality of life.
Article
Objective(s) The population in Iran is a genetic admixture of the ancestral Aryan and other populations neighboring Iran. Different ethnic groups in Iran show wide regional distributions for many human leukocyte antigen (HLA) alleles. Therefore, it is necessary and sensible to study the differences in HLA allele distribution in different area. We studied the HLA class I and II allele frequencies in a large unrelated healthy Iranian population from Mashhad in the Northeast region. Materials and Methods Five hundred unrelated healthy adult individuals borne and living in Mashhad, Northeast of Iran, were genotyped for HLA-A, B and HLA-DRB1 alleles using PCR with low resolution sequence specific primers (SSP-PCR) technique. Results A total of 14 HLA-A, 24 HLA-B and 10 HLA-DRB1 alleles were spread throughout the studied population with distinct allele frequencies. At the HLA-A locus, HLA-A*02 was found to be the most frequent allele, with a frequency of 20.9%. The most common HLA-B alleles was B*35 (16.4%). The two most common observed alleles in HLA class II alleles were DRB1*15 (20.0%) followed by DRB1*13 (16.2%). Conclusion This study is the first on the HLA class I and II allele frequencies in Northeastern Iranian population living in Mashhad. Distribution of HLA-A and B loci showed some similarities with those of other Iranians. Some difference in HLA-DRB1 polymorphisms however was observed. Considering the highly mixed population of Mashhad, the finding was not unexpected.
Article
Background Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder associated with sudden death, heart failure, and stroke. The aim of the present study was to evaluate the prevalence and types of mutations in symptomatic patients with HCM in Taiwan. Methods Thirty-eight HCM index patients (mean age 60 ± 16 years) underwent systematic mutation screening of eight sarcomeric genes: β-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2), troponin I (TNNI3), myosin ventricular regulatory light chain 2 (MYL2), myosin ventricular essential light chain 1 (MYL3), α-tropomyosin (TPM1), and cardiac α-actin (ACTC), using direct DNA sequencing. In silico programs predicted damaging amino acids. In the positive families, genotype–phenotype correlation studies were done. Results Overall, 13 mutations were identified in 13 index patients (34.2%). The three most frequently mutated genes were MYH7, MYBPC3, and TNNT2. One patient carried double mutations. Five mutations (MYH7 R147S; MYBPC3 R597Q; MYBPC3 W1007R; TNNI3 E124Q; MYL3 R63C) were novel; all were missense mutations. Analysis using in silico tools showed near consensus to classify these five novel mutations as pathological. Family pedigree analysis showed the presence of cosegregation in at least two affected members in each proband family, but incomplete penetrance in young family members with a positive genotype. Conclusions We identified 13 HCM pedigrees, including 5 carrying novel mutations and 1 with a double mutation. The three most commonly mutated genes were MYH7, MYBPC3, and TNNT2. These results, together with genetic counseling, could lead to earlier diagnosis and better management of family members at risk of HCM.
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In 2004 I put together three unpublished bibliographic volumes concerning correspondence analysis. These papers provide an extensive overview of more than 1300 articles that explore the diversity of mathematical and practical issues of correspondence analysis. I conceed that, with the increasing availability of online databases, more extensive bibliographies are now available. This bibliography has the references listed by publication.
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Phenylalanine hydroxylase (PAH) deficiency is responsible for most cases of phenylketonuria (PKU). In this study of the PAH mutation spectrum in the Taiwanese population, 139 alleles were identified including 34 different mutations. The V190G, Q267R and F392I mutations are first reported in this study. The most common mutations, R241C, R408Q and Ex6-96A>G, account for 23.2%, 12.0% and 9.2%, of the mutant alleles, respectively. Haplotype analysis shows that R241C and Ex6-96A>G are exclusively associated with haplotype 4.3 to suggest founder effects. On the other hand, R408Q is found on two distinct haplotypes suggesting recurrent mutations. The spectrum of PAH mutations in Taiwan shows various links to those of other Asian regions, yet remarkable differences exist. Notably, R408Q, E286K and -4173_-407del, accounting for 21% of all mutant alleles in Taiwan, are very rare or are undetected among PKU cohorts of other Asian regions to suggest local founder effects. Moreover, the low homozygosity value of 0.092 hints at a high degree of ethnic heterogeneity within the Taiwanese population. Our study of PAH mutation spectrum and the associated haplotypes is useful for subsequent study on the origin and migration pattern via Taiwan, an island at the historical crossroad of migration of ancient populations.Journal of Human Genetics advance online publication, 9 January 2014; doi:10.1038/jhg.2013.136.
Article
In 2001, the Bridging Study Evaluation (BSE) review process based on the ICH E5 guideline was introduced in Taiwan. The purpose of BSE is to assess the impact of ethnic factors on a drug's safety and efficacy and to determine whether pharmaceutical sponsors should conduct regional bridging studies in Taiwan. In this report, we provide the background and experience of BSE implementation in Taiwan and its influence on the global drug development process. Our BSE review process, allowing bridging studies to be waived, has successfully prevented conducting clinical trials with meaningless results. The trend of Investigational New Drug Application submission after New Drug Application (post-NDA) in other countries has also been shifted to the pre-NDA stage. The implementation of BSE in new regions has encouraged the pharmaceutical industry to consider the impact of ethnic factors in the early phase of clinical studies.
Article
In the past 10 years since the implementation of the E5 guideline, bridging studies have been one of the most controversial ICH concepts for East Asian states. This article reveals the dynamics of bridging studies by comprehensively reviewing their evolution and policy impacts in Japan and Taiwan from a comparative perspective.This article addresses the following. First, the concept of bridging studies has proved to be a diplomatic resolution rather than a scientific consensus. Although it facilitated the making of the E5 guideline, it left the problem of putting it into practice. Second, Japan did not wholeheartedly welcome bridging studies; it believed that a transition to spontaneous global trials would soon follow and exhausted its regulatory means to pursue it. Third, Taiwan captured this controversial concept as an ICH outsider, and showed the ICH the feasibility of bridging studies. It further attempted to extend their feasibility to create a multistate trial scheme, thereby keeping its visibility to the ICH.In addition, based on these findings, this article provides a regulatory outlook on pan-Asian clinical trial schemes.
Article
In recent years, global collaboration has led to a new strategy for drug development. However, clinical outcomes may be influenced by geographic variations in efficacy and safety; significant ethnic differences seem to exist in the enzymatic activity of several drug metabolizing enzymes and a patient’s response to therapeutics may vary from one racial/ethnic group to another. In 1998, the International Conference on Harmonisation (ICH) issued the E5 guideline on ‘Ethnic Factors in the Acceptability of Foreign Clinical Data’ to determine if clinical data generated from the original region are acceptable in a new region. The purpose of this guideline is not only to permit adequate evaluation of the influence of ethnic factors on clinical efficacy and safety, but also to minimize duplication of clinical studies and, consequently, to not delay the availability of the drug in the new region. More specifically, the ICH E5 guideline suggests that a bridging study be conducted in the new region to generate additional information to bridge the foreign clinical data when the foreign clinical data contained in the Complete Clinical Data Package (CCDP) cannot provide sufficient bridging evidence.
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Notions of identity in Taiwan are configured in relation to numbers. I examine the polyvalent capacities of enumerative technologies in both the production of ethnic identities and claims to political representation and justice. By critically historicizing the manner in which Aborigines in Taiwan have been, and continue to be, constructed as objects and subjects of scientific knowledge production through technologies of measuring, I examine the genetic claim made by some Taiwanese to be "fractionally" Aboriginal. Numbers and techniques of measuring are used ostensibly to know the Aborigines, but they are also used to construct a genetically unique Taiwanese identity and to incorporate the Aborigines within projects of democratic governance. Technologies of enumeration thus serve within multiple, and sometimes contradictory, projects of representation and knowledge production.
Article
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. This study investigated FH patients carrying common mutations in Taiwan and compared them to FH southeastern Asians. Causal FH mutations were identified by exon-by-exon sequencing with/without multiplex ligation-dependent probe amplification among 208 Taiwanese with clinically diagnosed FH. Haplotype analyses among probands and family members were undertaken using TaqMan® Assays. Totally, LDLR mutations were found in 118 probands, consisting of 61 different loci, and APOB 10579C>T mutations in 12 probands. Three mutations (64delG, 1661C>T, and 2099A>G) were novel. LDLR 986G>A (13.1%), 1747C>T (10.8%), and APOB 10579C>T (9.2%) were common mutations with no differences in phenotypes. LDLR 1747C>T associated with one haplotype (CAAGCCCCATGG/(dTA)n-112nt); LDLR 986G>A with two. APOB 10579C>T associated with the same LDLR binding-domain pattern in Taiwanese and southeastern Asians. We concluded that LDLR 986G>A, 1747C>T and APOB 10579C>T are common mutations, with combined frequency of approximately 33%. The presence of different haplotypes associated with FH common mutations in Taiwan indicates multiple historical migrations, probable multiple recurrent origins from southern China, and haplotype homologies reflect the presence of common ancestors in southern China.
Article
HLA-Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA-Cw*06. To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated. We conducted a case-control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA-B and HLA-C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high-need patients with moderate to severe psoriasis) and B (general patients with psoriasis). The frequencies of HLA-B*60, HLA-B*75, HLA-Cw*06 and HLA-Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA-Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc=0·04). HLA-B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA-Cw*01/HLA-B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA-Cw*01+ and HLA-Cw*01- individuals in the alefacept treatment group, and between HLA-B*37+ and HLA-B*37-, and HLA-B*58+ and HLA-B*58- individuals in the efalizumab treatment group. In addition to HLA-Cw*06, the HLA-Cw*01/HLA-B*46 haplotype was also increased in Chinese patients with psoriasis. High-need patients with psoriasis had a lower frequency of HLA-Cw*06 but a higher prevalence of HLA-B*46 compared with general patients with psoriasis in our population.
Article
The diagnosis of aromatic L-amino acid decarboxylase (AADC) deficiency, one of the pediatric neurotransmitter disorders, is classically made with plasma enzyme level or cerebrospinal fluid (CSF) neurotransmitter profile, while both are technically demanding and the latter requires the invasive lumbar puncture. So far less than 100 cases have been reported worldwide with 20% from Taiwan. It was postulated that the condition might have been under-diagnosed among Chinese populations and a non-invasive screening tool should be developed in areas with high prevalence. Urine metabolic profiles performed by gas chromatography-mass spectrometry (GC-MS) in a 31-month period were retrospectively reviewed: those with vanilmandelic acid concentration lower than one percentile plus the presence of 3-o-methyldopa were defined as positive and the patients were further evaluated. Among 1046 metabolic profiles (from 845 patients) reviewed, 3 profiles from 2 patients were screened positive: both cases had compatible CSF neurotransmitter profiles and the diagnosis was further confirmed by genetic analysis of DDC gene. 13 negative urinary metabolic profiles from 7 patients who had CSF neurotransmitters analyzed were identified as controls: all 7 CSF neurotransmitter profiles were not compatible for AADC deficiency. The GC-MS-based urine metabolic profiling was shown to be a satisfactory screening tool for AADC deficiency. Further confirmation can be performed by mutation analysis in the DDC gene, thus avoiding risks of lumbar puncture. We advocate all ethnic Chinese patients presenting with dystonia have their urine organic acids analyzed before proceeding to CSF neurotransmitters analysis.
Article
We report here an HLA-A allele, A*11:90, found in a Taiwanese cord blood sample using DNA sequence-based typing (SBT) protocol after observing an anomalous reaction pattern in a sequence-specific oligonucleotide (SSO) typing exercise. The sequence of A*11:90 is identical to A*11:01:01, the most predominant A*11 variant in Taiwanese, in exon 2 but differs from A*11:01:01 in exon 3 by two nucleotide substitutions at codon 163 (c.487C>G and c.488G>A), resulting R163E. In comparison with the sequence of A*11:02:01, the second most predominant subtype of A*11 in Taiwanese A*11:90 has one nucleotide difference at codon 19 (c.55A>G) in exon 2 resulting K19E and two nucleotides variations at codon 163 (c.487C>G and c.488G>A) in exon 3 resulting R163E. HLA-A*11:90-B*40:02-DRB1*11:01 is the deduced probable HLA haplotype in association with A*11:90. The generation of A*11:90 is thought to involve a DNA recombination event between alleles A*11:01:01 and A*80:01 where A*80:01 donated a fragment of the DNA sequence (from n.t. 487 to n.t. 497) to the recipient sequence of A*11:01:01.
Article
In recent years, global collaboration has become a conventional strategy for new drug development. To accelerate the development process and to shorten approval time, the design of multi-regional trials incorporates subjects from many countries around the world under the same protocol. After showing the overall efficacy of a drug in all global regions, one can also simultaneously evaluate the possibility of applying the overall trial results to all regions and subsequently support drug registration in each of them. Recently, the trend for simultaneous clinical development in Asian countries being undertaken simultaneously with clinical trials conducted in Europe and the United States has been rapidly rising. In this paper, proposals of statistical consideration to multi-regional trials are provided. More specifically, three aspects are addressed: the definition of the 'Asian region,' the consistency criterion between the 'Asian region' and the overall regions, and the sample size determination for the multi-regional trial.
Article
Familial hypercholesterolemia (FH) is commonly caused by mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B, and proprotein convertase subtilisin/kexin type 9 genes. The study aim was to investigate patients with FH in Taiwan, using molecular diagnostic methods, and compare the abnormalities in the small mutation and large DNA rearrangement subgroups. In total, 102 unrelated probands with FH were tested for mutations by exon-by-exon sequence analysis (EBESA) and multiple ligation-dependent probe amplification (MLPA). EBESA identified gene apolipoprotein B R3500W in 8 probands and 25 mis-sense, 5 nonsense, and 6 frameshift LDLR mutations in 52 probands; 11 were novel mutations. Of the 42 probands with mutations undetected by EBESA, 8 had abnormal MLPA patterns, including 2 with exon 6 to 18 deletions, 2 with exon 9 deletion, 1 with exon 6 to 8 deletions, 1 with exon 11 deletion, 1 with exon 3 to 5 duplications, and 1 with exon 7 to 12 duplications. Pedigree analysis showed mutation cosegregation with hypercholesterolemia in affected family members. Mean lipid profiles and rate of failure to lower LDL cholesterol <100 mg/dl in response to rosuvastatin/ezetimibe treatment were similar in groups with abnormal MLPA patterns and groups carrying nonsense or frameshift mutations. In conclusion, frequency of large LDLR rearrangement was approximately 8% in Taiwanese patients with FH. The response to statin drugs differed between probands with abnormal MLPA patterns and probands carrying mis-sense or undetected mutations.
Article
Human leukocyte antigens (HLAs) are useful markers for anthropological investigations because the allele and haplotype distributions at these loci vary widely among ethnic groups. HLA frequencies in Koreans, however, have not previously been analyzed on a phylogenetic basis. We determined the allele frequencies of four HLA class II (HLA-DRB1, -DQA1, -DQB1, and -DPB1) loci in 149 unrelated Korean individuals using a sequence-based typing method. A total of 29 HLA-DRB1, 17 HLA-DQA1, 16 HLA-DQB1, and 15 HLA-DPB1 alleles were identified. The most common allele at each locus was DRB1*0901, DQA1*0102, DQB1*0301, and DPB1*0501, respectively. Four-locus allelic association analysis showed the existence of 25 DRB1-DQA1-DQB1-DPB1 haplotypes with a frequency greater than 0.010. A dataset comprising ethnicity-specific information from published literature and the dbMHC database, as well as the allele frequencies determined in this study, was subjected to phylogenetic analysis. The analysis showed that Koreans are most closely related to Japanese and Han Chinese from Shandong province. Correspondence analyses showed that the current Korean population is located in a position intermediate between the northern and southern East Asian groups, supporting the theory of a bi- and/or multidirectional route of migration of early Korean settlers. This report can be used for anthropological studies, and may also be of use in the International Hematopoietic Stem Cell Sharing program.
Article
Full-text available
Despite the fact that the continuity of morphology of fossil specimens of modern humans found in China has repeatedly challenged the Out-of-Africa hypothesis, Chinese populations are underrepresented in genetic studies. Genetic profiles of 28 populations sampled in China supported the distinction between southern and northern populations, while the latter are biphyletic. Linguistic boundaries are often transgressed across language families studied, reflecting substantial gene flow between populations. Nevertheless, genetic evidence does not support an independent origin of Homo sapiens in China. The phylogeny also suggested that it is more likely that ancestors of the populations currently residing in East Asia entered from Southeast Asia.
Book
Spectacular progress has been made recently in the study of evolution at the molecular level, primarily due to new biochemical techniques such as gene cloning and DNA sequencing. In this book, the author summarizes new developments and seeks to unify studies of evolutionary histories of organisms and the mechanisms of evolution into a single science - molecular evolutionary genetics.
Article
Since the discovery in 1966 of the Gm ab3st gene, which characterizes Mongoloid populations, the distribution of allotypes of immunoglobulins (Gm) among Mongoloid populations scattered from Southeast Asia through East Asia to South America has been investigated, and the following conclusions can be drawn: 1. Mongoloid populations can be characterized by four Gm haplotypes, Gm ag, axg, ab3st, and afb1b3, and can be divided into two groups based on the analysis of genetic distances utilizing Gm haplotype frequency distributions: the first is a southern group characterized by a remarkably high frequency of Gm afb1b3 and a low frequency of Gm ag, and the second, a northern group characterized by a high frequency of both Gm ag and Gm ab3st but an extremely low frequency of Gm afb1b3. 2. Populations in China, mainly Han but including minority nationalities, show remarkable heterogeneity of Gm allotypes from north to south and contrast sharply to Korean and Japanese populations, which are considerably more homogenous with respect to these genetic markers. The center of dispersion of the Gm afb1b3 gene characterizing southern Mongoloids has been identified as the Guangxi and Yunnan area in the southwest of China. 3. The Gm ab3st gene, which is found with its the highest incidence among the northern Baikal Buriats, flows in all directions. However, this gene shows a precipitous drop from mainland China to Taiwan and Southeast Asia and from North to South America, although it is still found in high frequency among Eskimos, Koryaks, Yakuts, Tibetans, Olunchuns, Tungus, Koreans, Japanese, and Ainus. On the other hand, the gene was introduced into Huis, Uyghurs, Indians, Iranians, and spread as far as to include Hungarians and Sardinians in Italy. On the basis of these results, it is concluded that the Japanese race belongs to northern Mongoloids and that the origin of the Japanese race was in Siberia, and most likely in the Baikal area of the Soviet Union.
Article
Remarkable differences were observed in antigen frequencies (AF), gene frequencies (GF) and haplotype frequencies (HF) when 2441 healthy Chinese individuals representing nine different ethnic groups and living in 14 different geographic locations were examined for the genetic distribution of the various HLA Class I and II markers. A sizable number of individuals of each ethnic group within each of the three major categories of the Chinese population, namely, Hans, Mongols, and Southern minorities, have been studied here, providing useful population statistics for applications such as determination of probabilities of paternity, comparisons for HLA and disease associations, and anthropologic studies.
Article
A new method called the neighbor-joining method is proposed for reconstructing phylogenetic trees from evolutionary distance data. The principle of this method is to find pairs of operational taxonomic units (OTUs [= neighbors]) that minimize the total branch length at each stage of clustering of OTUs starting with a starlike tree. The branch lengths as well as the topology of a parsimonious tree can quickly be obtained by using this method. Using computer simulation, we studied the efficiency of this method in obtaining the correct unrooted tree in comparison with that of five other tree-making methods: the unweighted pair group method of analysis, Farris's method, Sattath and Tversky's method, Li's method, and Tateno et al.'s modified Farris method. The new, neighbor-joining method and Sattath and Tversky's method are shown to be generally better than the other methods.
Article
The accuracies and efficiencies of three different methods of making phylogenetic trees from gene frequency data were examined by using computer simulation. The methods examined are UPGMA, Farris' (1972) method, and Tateno et al.'s (1982) modified Farris method. In the computer simulation eight species (or populations) were assumed to evolve according to a given model tree, and the evolutionary changes of allele frequencies were followed by using the infinite-allele model. At the end of the simulated evolution five genetic distance measures (Nei's standard and minimum distances, Rogers' distance, Cavalli-Sforza's f theta, and the modified Cavalli-Sforza distance) were computed for all pairs of species, and the distance matrix obtained for each distance measure was used for reconstructing a phylogenetic tree. The phylogenetic tree obtained was then compared with the model tree. The results obtained indicate that in all tree-making methods examined the accuracies of both the topology and branch lengths of a reconstructed tree (rooted tree) are very low when the number of loci used is less than 20 but gradually increase with increasing number of loci. When the expected number of gene substitutions (M) for the shortest branch is 0.1 or more per locus and 30 or more loci are used, the topological error as measured by the distortion index (dT) is not great, but the probability of obtaining the correct topology (P) is less than 0.5 even with 60 loci. When M is as small as 0.004, P is substantially lower. In obtaining a good topology (small dT and high P) UPGMA and the modified Farris method generally show a better performance than the Farris method. The poor performance of the Farris method is observed even when Rogers' distance which obeys the triangle inequality is used. The main reason for this seems to be that the Farris method often gives overestimates of branch lengths. For estimating the expected branch lengths of the true tree UPGMA shows the best performance. For this purpose Nei's standard distance gives a better result than the others because of its linear relationship with the number of gene substitutions. Rogers' or Cavalli-Sforza's distance gives a phylogenetic tree in which the parts near the root are condensed and the other parts are elongated. It is recommended that more than 30 loci, including both polymorphic and monomorphic loci, be used for making phylogenetic trees. The conclusions from this study seem to apply also to data on nucleotide differences obtained by the restriction enzyme techniques.
Article
There are major differences in the distribution of blood group antigens and antibodies between the different population groups of Taiwan and whites. As a result, standard Western pretransfusion testing procedures have been modified for use in Taiwan, resulting in great reductions in cost and labor. These differences, in addition to their influence on the clinical practise of transfusion medicine in Taiwan, are also important anthropologically, and it is hoped that more population groups in Asia can be investigated in the near future. Further DNA studies on the B3 phenotype, the MiIII phenotype, and the Lewis phenotypes among our different population groups are in progress and further interesting findings are awaited.
Article
There are marked differences in the distribution of HLA haplotypes among different populations, and multilocus HLA haplotypes can best be studied by family analysis. In the present study, 107 Korean families were analyzed for HLA-A, B, C, DR, and DQ antigens and haplotypes. Allele frequencies of more than 10% for class I antigens were A2, A24, A33, B44, B62, Cwl, Cw7, Cw9, Cw10, and C blank (CBL) and those for class II antigens were DR4, DR8, DR13, DR15, DQ1, DQ3, DQ4 and DQ7. In the analysis of HLA haplotypes, 18 kinds of A-B-DR and 11 kinds of A-C-B-DR-DQ haplotypes occurred at frequencies of more than 1%, comprising 34% and 24% of the total theoretical haplotypes, respectively. The five most common A-B-DR haplotypes were exclusively related with the five most common A-C-B-DR-DQ haplotypes (frequency>2%). These remarkably conserved five-locus haplotypes in Koreans were A33-CBL-B44-DR13-DQ1 (5.4%), A24-Cw7-B7-DR1-DQ1 (3.5%), A33-Cw7-B44-DR7-DQ2 (3.0%), A33-Cw10-B58-DR13-DQ1 (2.3%), and A30-Cw6-B13-DR7-DQ2 (2.3%). Comparison of the distribution of A-B-DR haplotypes among East Asian populations revealed that Koreans are closest to Japanese, but show a higher degree of polymorphism in the distribution of HLA haplotypes compared to Japanese. The results obtained in this study will be useful as basic data on Koreans for anthropology and organ transplantation.
Article
A total of 8,497 blood samples were typed for HLA-A, B, DR and DQ. Of these, 7,137 Min-nan, 714 Hakka, 535 Mainland Chinese (152 from North China, 211 from Middle China, and 172 from South China) and 111 Aborigines were randomly selected from Tzu Chi Taiwan Marrow Donor Registry (TCTMDR). Differences in HLA gene and antigen frequencies have been observed between various ethnic groups of the Chinese population in Taiwan. The phylogenic tree shows Taiwan Aborigines and Javanese cluster together; Min-nan shares a common cluster with Hakka, Southern Hans and Thai; and Northern Hans shares a cluster with Middle Hans. The separation between Northern/Middle and Southern Chinese Hans support the idea that Northern and Southern Chinese have different genetic background. Aborigines appeared to be quite distinct in the distribution of a majority of the class I and class II antigens. High frequency of HLA-A24 (60.4%) and relatively restricted HLA polymorphisms are noted in Aborigines. The HLA haplotypes with high frequency in Aborigines included A24-B60-DRB1*04, A24-B60-DRB1*14, A24-B48-DRB1*04, and A24-B48-DRB1*14, which are different from the other ethnic groups. Although the phylogenic tree separates Aborigines and Han Chinese populations, 4 out of 20 most common HLA-A, -B, and -DR haplotypes presented in both Aborigines and Han Chinese may reflect an ancient common origin or intermixture between early settlers of Han Chinese and Taiwan Aborigines. The results in this study are essentially a summary of the observed gene/haplotype frequencies and differences among various ethnic groups in Taiwan.
Article
The distribution of HLA-B17 alleles and their association with HLA-A, -C and -DRB1 alleles were investigated in seven East Asian populations Japanese, South Korean, Chinese-Korean, Man, Northern Han, Mongolian and Buryat populations). The B17 alleles were identified from genomic DNA using group-specific polymerase chain reaction (PCR) followed by hybridization with sequence-specific oligonucleotide probes (SSOP). In all of these East Asian populations, except Japanese and Chinese-Koreans, B*5701 was detected and strongly associated with A*0101, Cw*0602 and DRB1*0701. In contrast, B*5801 was detected in all the seven populations and strongly associated with A*3303, Cw*0302, DRB1*0301 and DRB1*1302. The A*3303-Cw*0302-B*5801-DRB1*1302 haplotype was observed in South Korean, Chinese-Korean, Buryat and Japanese populations, while A*3303-Cw*0302-B*5801-DRB1*0301 was predominantly observed in the Mongolian population. A similar haplotype, A*0101-Cw*0302-B*5801-DRB1*1302, was observed in the Buryat population. A novel Cw6 allele, Cw*0604, was identified in the Man population. This Cw allele was observed on the haplotype A*0101-B*5701-DRB1*0701. Thus, we confirmed, at the sequence level, that the common haplotypes carrying B*5701 and B*5801 have been conserved and shared in East Asian populations.
Article
Taiwan's 9 indigenous tribes (Tsou, Bunun, Paiwan, Rukai, Atayal, Saisiat, Ami, Puyuma, Yami) are highly homogeneous within each tribe, but diversified among the different tribes due to long-term isolation, most probably since Taiwan became an island about 12,000 years ago. Homogeneity of each tribe is evidenced by many HLA-A,B,C alleles having the world's highest ever reported frequencies, e.g. A24 (86.3%), A26 (18.8%), Cw10 (36.8%), Cw7 (66%), Cw8 (32.1%), B13 (27.9%), B62 (37.4%), B75 (18%), B39 (53.5%), B60 (33.3%), and B48 (24%). Also, all of these tribes have HLA class I haplotype frequencies greater than 10%, with A24-Cw7-B39 in Saisiat (44.5%) being the highest, suggesting Taiwan's indigenous tribes are probably the most homogeneous ( the "purest") population in the world. A24-Cw8-B48, A24-Cw10-B60 and A24-Cw9-B61 found common to many Taiwan indigenous tribes, have also been observed in Maori, Papua New Guinea Highlanders, Orochons, Mongolians, Inuit, Japanese, Man, Buryat, Yakut, Tlingit, Tibetans and Thais. These findings suggest Taiwan's indigenous groups are more or less genetically related to both northern and southern Asians. Principal component analysis and the phylogenetic tree (using the neighbor-joining method) showed close relationship between the indigenous groups and Oceanians. This relationship supports the hypothesis that Taiwan was probably on the route of prehistoric Mongoloid dispersals that most likely took place along the coastal lowland of the Asian continent (which is under the sea today). Cultural anthropology also suggests a relationship between Taiwan's indigenous tribes and southern Asians and to a lesser extent, northern Asians. However, the indigenous groups show little genetic relationship to current southern and northern Han Chinese.
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