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

Abstract TP53 mutations are observed in about 40e70% 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 5e8 of the TP53 gene were analyzed by sequencing DNA of cancerous tissue and peripheral blood leukocyte samples from 55 nonesmall 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

<p>Abstract</p> <p>Background</p> <p>The 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.</p> <p>Results</p> <p>We 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.</p> <p>Conclusion</p> <p>Our 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.</p

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

Background: Ethnic 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 wife's 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. Results: Genetic 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. Conclusion: Overall, 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

Identification of Close Relatives in the HUGO Pan-Asian SNP Database

The HUGO Pan-Asian SNP Consortium has recently released a genome-wide dataset, which consists of 1,719 DNA samples collected from 71 Asian populations. For studies of human population genetics such as genetic structure and migration history, this provided the most comprehensive large-scale survey of genetic variation to date in East and Southeast Asia. However, although considered in the analysis, close relatives were not clearly reported in the original paper. Here we performed a systematic analysis of genetic relationships among individuals from the Pan-Asian SNP (PASNP) database and identified 3 pairs of monozygotic twins or duplicate samples, 100 pairs of first-degree and 161 second-degree of relationships. Three standardized subsets with different levels of unrelated individuals were suggested here for future applications of the samples in most types of population-genetics studies (denoted by PASNP1716, PASNP1640 and PASNP1583 respectively) based on the relationships inferred in this study. In addition, we provided gender information for PASNP samples, which were not included in the original dataset, based on analysis of X chromosome data

Population Genetic Structure of Peninsular Malaysia Malay Sub-Ethnic Groups

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia

South Asian maternal and paternal lineages in southern Thailand and the role of sex-biased admixture.

Previous genome-wide studies have reported South Asian (SA) ancestry in several Mainland Southeast Asian (MSEA) populations; however, additional details concerning population history, in particular the role of sex-specific aspects of the SA admixture in MSEA populations can be addressed with uniparental markers. Here, we generated ∼2.3 mB sequences of the male-specific portions of the Y chromosome (MSY) of a Tai-Kadai (TK)-speaking Southern Thai group (SouthernThai_TK), and complete mitochondrial (mtDNA) genomes of the SouthernThai_TK and an Austronesian (AN)-speaking Southern Thai (SouthernThai_AN) group. We identified new mtDNA haplogroups, e.g. Q3, E1a1a1, B4a1a and M7c1c3 that have not previously reported in Thai populations, but are frequent in Island Southeast Asia and Oceania, suggesting interactions between MSEA and these regions. SA prevalent mtDNA haplogroups were observed at frequencies of ~35-45% in the Southern Thai groups; both of them showed more genetic relatedness to Austroasiatic (AA) speaking Mon than to any other group. For MSY, SouthernThai_TK had ~35% SA prevalent haplogroups and exhibited closer genetic affinity to Central Thais. We also analyzed published data from other MSEA populations and observed SA ancestry in some additional MSEA populations that also reflects sex-biased admixture; in general, most AA- and AN-speaking groups in MSEA were closer to SA than to TK groups based on mtDNA, but the opposite pattern was observed for the MSY. Overall, our results of new genetic lineages and sex-biased admixture from SA to MSEA groups attest to the additional value that uniparental markers can add to studies of genome-wide variation

Antioxidative and neuroprotective activities of peanut sprout extracts against oxidative stress in SK-N-SH cells

Objective: To evaluate the protective effect of peanut sprout extract (PSE) against paraquat (PQ) induced SK-N-SH cells. Methods: Three groups of cells were used in the experiment, together with a fourth, control group. One group was treated with PQ, the second group was treated with PSE, and the third group was pre-treated with PSE. The control group was untreated. Cell viability and toxicity were detected by MTT assay, cellular reactive oxygen species (ROS) was detected by Muse Cell Analyzer, quantitative RT-PCR was applied to investigate the expression of SIRT1 and α-synuclein genes, and Aβ42 was detected by western blot. Results: The 50% effective concentration of PQ was 0.75 mmol/L. PSE had no significant cytotoxicity at a concentration of 1.5 mg/mL. In the group of cells pre-treated with PSE, cell death was significantly inhibited. In the PQ treated group, PQ was increased in the intracellular ROS in the cells. Intracellular ROS was significantly decreased in the cells treated with PSE and also those pre-treated with PSE. PSE significantly downregulated the expression of SIRT1 and α-syn genes, and it was found that PQ significantly increased β-amyloid 42 levels whereas this action was inhibited by PSE. Conclusions: PSE has neuroprotective activities against oxidative stress in SK-N-SH cells induced by PQ, suggesting that PSE is a highly promising agent in the prevention of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease