Daoroong Kangwanpong

Mapping Human Genetic Diversity in Asia

Patterns of Early Migration In order to gain insight into various migrations that must have happened during movement of early humans into Asia and the subsequent populating of the largest continent on Earth, the HUGO Pan-Asian SNP Consortium (p. 1541) analyzed genetic variation in almost 2000 individuals representing 73 Asian and two non-Asian populations. The results suggest that there may have been a single major migration of people into Asia and a subsequent south-to-north migration across the continent. While most populations from the same linguistic group tend to cluster together in terms of relatedness, several do not, clustering instead with their geographic neighbors, suggesting either substantial recent mixing among the populations or language replacement. Furthermore, data from indigenous Taiwanese populations appear to be inconsistent with the idea of a Taiwan homeland for Austronesian populations. Genetic analyses of Asian peoples suggest that the continent was populated through a single migration event. Asia harbors substantial cultural and linguistic diversity, but the geographic structure of genetic variation across the continent remains enigmatic. Here we report a large-scale survey of autosomal variation from a broad geographic sample of Asian human populations. Our results show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography. Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene flow among populations. More than 90% of East Asian (EA) haplotypes could be found in either Southeast Asian (SEA) or Central-South Asian (CSA) populations and show clinal structure with haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic source of EA populations.

Y chromosome haplotypes reveal prehistorical migrations to the Himalayas

By using 19 Y chromosome biallelic markers and 3 Y chromosome microsatellite markers, we analyzed the genetic structure of 31 indigenous Sino-Tibetan speaking populations (607 individuals) currently residing in East, Southeast, and South Asia. Our results showed that a T to C mutation at locus M122 is highly prevalent in almost all of the Sino-Tibetan populations, implying a strong genetic affinity among populations in the same language family. Furthermore, the extremely high frequency of H8, a haplotype derived from M122C, in the Sino-Tibetan speaking populations in the Himalayas including Tibet and northeast India indicated a strong bottleneck effect that occurred during a westward and then southward migration of the founding population of Tibeto-Burmans. We, therefore, postulate that the ancient people, who lived in the upper-middle Yellow River basin about 10,000 years ago and developed one of the earliest Neolithic cultures in East Asia, were the ancestors of modern Sino-Tibetan populations.

Genetic variation in Northern Thailand Hill Tribes: origins and relationships with social structure and linguistic differences

BackgroundEthnic minorities in Northern Thailand, often referred to as Hill Tribes, are considered an ideal model to study the different genetic impact of sex-specific migration rates expected in matrilocal (women remain in their natal villages after the marriage and men move to their wifes village) and patrilocal societies (the opposite is true). Previous studies identified such differences, but little is known about the possible interaction with another cultural factor that may potentially affect genetic diversity, i.e. linguistic differences. In addition, Hill Tribes started to migrate to Thailand in the last centuries from different Northern areas, but the history of these migrations, the level of genetic legacy with their places of origin, and the possible confounding effects related to this migration history in the patterns of genetic diversity, have not been analysed yet. Using both original and published data on the Hill Tribes and several other Asian populations, we focused on all these aspects.ResultsGenetic variation within population at mtDNA is lower in matrilocal, compared to patrilocal, tribes. The opposite is true for Y-chromosome microsatellites within the Sino-Tibetan linguistic family, but Hmong-Mien speaking patrilocal groups have a genetic diversity very similar to the matrilocal samples. Population divergence ranges between 5% and 14% at mtDNA sequences, and between 5% and 36% at Y- chromosomes STRs, and follows the sex-specific differences expected in patrilocal and matrilocal tribes. On the average, about 2 men and 14 women, and 4 men and 4 women, are exchanged in patrilocal and matrilocal tribes every generation, respectively. Most of the Hill Tribes in Thailand seem to preserve a genetic legacy with their likely geographic origin, with children adoption probably affecting this pattern in one tribe.ConclusionOverall, the sex specific genetic signature of different postmarital habits of residence in the Hill Tribes is robust. However, specific perturbations related to linguistic differences, population specific traits, and the complex migratory history of these groups, can be identified. Additional studies in different populations are needed, especially to obtain more precise estimates of the migration parameters.

Genetic structure of the Mon-Khmer speaking groups and their affinity to the neighbouring Tai populations in Northern Thailand

BackgroundThe Mon-Khmer speaking peoples inhabited northern Thailand before the arrival of the Tai speaking people from southern China in the thirteenth century A.D. Historical and anthropological evidence suggests a close relationship between the Mon-Khmer groups and the present day majority northern Thai groups. In this study, mitochondrial and Y-chromosomal DNA polymorphisms in more than 800 volunteers from eight Mon-Khmer and ten Tai speaking populations were investigated to estimate the degree of genetic divergence between these major linguistic groups and their internal structure.ResultsA large fraction of genetic variation is observed within populations (about 80% and 90% for mtDNA and the Y-chromosome, respectively). The genetic divergence between populations is much higher in Mon-Khmer than in Tai speaking groups, especially at the paternally inherited markers. The two major linguistic groups are genetically distinct, but only for a marginal fraction (1 to 2%) of the total genetic variation. Genetic distances between populations correlate with their linguistic differences, whereas the geographic distance does not explain the genetic divergence pattern.ConclusionsThe Mon-Khmer speaking populations in northern Thailand exhibited the genetic divergence among each other and also when compared to Tai speaking peoples. The different drift effects and the post-marital residence patterns between the two linguistic groups are the explanation for a small but significant fraction of the genetic variation pattern within and between them.

TP53 gene mutations of lung cancer patients in upper northern Thailand and environmental risk factors.

TP53 mutations are observed in about 40-70% of lung cancer tissues, and the hot spot codon mutations are in exons 5 through 8. Previous studies revealed that the distinct TP53 mutational pattern between population groups may be due to different racial or exogenous factors. This research aims to identify risk factors that influence TP53 gene mutation in lung cancer patients residing areas with high lung cancer incidence, in the upper northern part of Thailand. Germline TP53 mutational analyses were also performed to determine the inherited cancer predisposition. Exons 5-8 of the TP53 gene were analyzed by sequencing DNA of cancerous tissue and peripheral blood leukocyte samples from 55 non-small lung cell cancer patients. The results showed that the TP53 germline mutation was not found in all patients, indicating that the TP53 germline mutations were not exclusively responsible for cancer predisposition in this group of lung cancer patients. A total of 19 somatic mutations were found in 18 patients. Mutations were predominantly found in exons, with only 10.53% observed at the splice sites of intron 7. No characteristic hot spot codons were observed. The data suggest that TP53 mutations in this study group are induced by exposure to substances other than tobacco smoke. Pesticide exposure or habitation in poorly ventilated houses may instead be related to the tumorigenesis of lung cancer via TP53 mutations.

Genetic evidence supports linguistic affinity of Mlabri - a hunter-gatherer group in Thailand

BackgroundThe Mlabri are a group of nomadic hunter-gatherers inhabiting the rural highlands of Thailand. Little is known about the origins of the Mlabri and linguistic evidence suggests that the present-day Mlabri language most likely arose from Tin, a Khmuic language in the Austro-Asiatic language family. This study aims to examine whether the genetic affinity of the Mlabri is consistent with this linguistic relationship, and to further explore the origins of this enigmatic population.ResultsWe conducted a genome-wide analysis of genetic variation using more than fifty thousand single nucleotide polymorphisms (SNPs) typed in thirteen population samples from Thailand, including the Mlabri, Htin and neighboring populations of the Northern Highlands, speaking Austro-Asiatic, Tai-Kadai and Hmong-Mien languages. The Mlabri population showed higher LD and lower haplotype diversity when compared with its neighboring populations. Both model-free and Bayesian model-based clustering analyses indicated a close genetic relationship between the Mlabri and the Htin, a group speaking a Tin language.ConclusionOur results strongly suggested that the Mlabri share more recent common ancestry with the Htin. We thus provided, to our knowledge, the first genetic evidence that supports the linguistic affinity of Mlabri, and this association between linguistic and genetic classifications could reflect the same past population processes.

Genetic affinity and admixture of northern Thai people along their migration route in northern Thailand: evidence from autosomal STR loci.

The Khon Mueang (KM) are the largest group of northern Thai people. Our previous mtDNA studies have suggested an admixture process among the KM with the earlier Mon-Khmer-speaking inhabitants of this region. In this study, we evaluate genetic affinities and admixture among 10 KM populations in northern Thailand lying along the historical Yuan migration route, and 10 neighboring populations belonging to 7 additional ethnic groups: Lawa, Mon (Mon-Khmer-speaking groups), Shan, Yuan, Lue, Khuen and Yong (Tai-speaking groups) by analyzing 15 hypervariable autosomal short tandem repeat loci. The KM exhibited close relationships with neighboring populations, especially the Tai-speaking groups, reflecting an admixed origin of the KM. Admixture proportions were observed in all KM populations, which had a higher contribution from the parental Tai than the Mon-Khmer groups. Different admixture patterns of the KM along the migration route might indicate high heterogeneity among the KM. These patterns were not directly associated with geographical proximity, suggesting other factors, like variation in the timing of admixture with the existing populations may have had an important role. More genetic data from different marker systems solely transmitted through the male or female lineages are needed to complete the description of genetic admixture and population history of the KM.

A Biological Evaluation of DNA Damage Detected by Comet Assay in Healthy Populations Residing in Areas that Differ in Lung Cancer Incidence

The comet assay was performed to evaluate the effect of environmental exposure between human populations residing in two areas that differ in lung cancer incidence, Saraphi (n = 91) and Chom Thong (n = 94). Three parameters, the tail length, tail intensity, and tail moment, were used to detect DNA damage in peripheral blood and stimulated lymphocytes with and without the DNA repair inhibitor, aphidicolin. Internal standards, cryopreserved isolated lymphocytes, and isolated lymphocytes irradiated with 2 Gy gamma rays, were used to correct the interexperimental variability. Results revealed a significant difference between two populations only when the tail length was used to measure DNA damage. The evaluation of various potential confounding factors, such as gender, pesticide exposure, smoking, alcohol drinking, and fermented tea leaf or betel nut chewing, indicated no significant influence in DNA damage. In conclusion, significant difference in DNA damage, detected only by tail length between the two populations residing in the areas with different incidence of lung cancer, may reflect a nonhazardous level of exposure to toxic substances. The authors thank all of the blood donors for their samples, time, and interest in this project. We are grateful to Prof. Dr. Günter Speit, Department of Human Genetics, Faculty of Medicine, University of Ulm, Federal Republic of Germany, for providing the laboratory and analysis facilities and his valuable comment on the articles. The present work was supported by grants PHD/069/2543 and BGJ/40/2543 from the Royal Golden Jubilee PhD Program, Thailand Research Fund, and grant A/02/09887 from the Deutscher Akademischer Austauschdienst, Bonn, Federal Republic of Germany.

Hemoglobin E Prevalence among Ethnic Groups Residing in Malaria-Endemic Areas of Northern Thailand and Its Lack of Association with Plasmodium falciparum Invasion In Vitro

Hemoglobin E (HbE) is one of the most common hemoglobin variants caused by a mutation in the β-globin gene, and found at high frequencies in various Southeast Asian groups. We surveyed HbE prevalence among 8 ethnic groups residing in 5 villages selected for their high period malaria endemicity, and 5 for low endemicity in northern Thailand, in order to uncover factors which may affect genetic persistence of HbE in these groups. We found the overall HbE prevalence 6.7%, with differing frequencies from 0% in the Pwo Karen, the Lawa, and the Skaw Karen to 24% in the Mon. All HbE genes were heterozygous (AE). Differences in HbE prevalence among the studied ethnic groups indirectly documents that ancestries and evolutionary forces, such as drift and admixture, are the important factors in the persistence of HbE distribution in northern Thailand. Furthermore, the presence of HbE in groups of northern Thailand had no effect on the in vitro infectivity and proliferation of Plasmodium falciparum, nor the production of hemozoin, a heme crystal produced by malaria parasites, when compared to normal red-blood-cell controls. Our data may contribute to a better understanding on the persistence of HbE among ethnic groups and its association with malaria.

Geography has more influence than language on maternal genetic structure of various northeastern Thai ethnicities.

Several literatures have shown the influence of geographic and linguistic factors in shaping genetic variation patterns, but their relative impact, if any, in the very heterogeneous northeastern region of Thailand has not yet been studied. This area, called Isan, is geographically structured in two wide basins, the Sakon Nakorn Basin and the Korat Basin, serving today as home to diverse ethnicities encompassing two different linguistic families, that is, the Austro-Asiatic; Suay (Kui), Mon, Chaobon (Nyahkur), So and Khmer, and the Tai-Kadai; Saek, Nyaw, Phu Tai, Kaleung and Lao Isan. In this study, we evaluated the relative role of geographic distance and barriers as well as linguistic differences as possible causes affecting the maternal genetic distances among northeastern Thai ethnicities. A 596-bp segment of the hypervariable region I mitochondrial DNA was utilized to elucidate the genetic structure and biological affinity from 433 individuals. Different statistical analyses agreed in suggesting that most ethnic groups in the Sakon Nakorn Basin are closely related. Mantel test revealed that genetic distances were highly associated to geographic (r=0.445, P<0.01) but not to linguistic (r=0.001, P>0.01) distances. Three evolutionary models were compared by Approximate Bayesian Computation. The posterior probability of the scenario, which assumed an initial population divergence possibly related to reduced gene flow among basins, was equal or higher than 0.87. All analyses exhibited concordant results supporting that geography was the most relevant factor in determining the maternal genetic structure of northeastern Thai populations.