Polymorphisms of Genes in Neurotransmitter Systems Were Associated with Alcohol Use Disorders in a Tibetan Population

Studies of linkage and association in various ethnic populations have revealed many predisposing genes of multiple neurotransmitter systems for alcohol use disorders (AUD). However, evidence often is contradictory regarding the contribution of most candidate genes to the susceptibility of AUD. We, therefore, performed a case-control study to investigate the possible associations of genes selected from multiple neurotransmitter systems with AUD in a homogeneous Tibetan community population in China. AUD cases (N = 281) with an alcohol use disorder identification test (AUDIT) score ≥10, as well as healthy controls (N = 277) with an AUDIT score ≤5, were recruited. All participants were genotyped for 366 single nucleotide polymorphisms (SNPs) of 34 genes selected from those involved in neurotransmitter systems. Association analyses were performed using PLINK version 1.07 software. Allelic analyses before adjustment for multiple tests showed that 15 polymorphisms within seven genes were associated with AUD (p<0.05). After adjustment for the number of SNPs genotyped within each gene, only the association of a single marker (rs10044881) in HTR4 remained statistically significant. Haplotype analysis for two SNPs in HTR4 (rs17777298 and rs10044881) showed that the haplotype AG was significantly associated with the protective effect for AUD. In conclusion, the present study discovered that the HTR4 gene may play a marked role in the pathogenesis of AUD. In addition, this Tibetan population sample marginally replicated previous evidence regarding the associations of six genes in AUD.     

Molecular Variant Estimation of SLC11A1 Related Microsatellites in Chinese Indigenous Goats

Russian Journal of Genetics - The aim of this study was to investigate the polymorphism of the SLC11A1 gene in Chinese indigenous goats. A total of 215 individuals from nine goat breeds were...     

Evolutionary significance of selected EDAR variants in Tibetan high-altitude adaptations

Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude adaptations.However, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation (SaO_2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO_2 and platelet count, respectively) were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations.     

Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas

Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Both behavioral and biological adaptations have contributed to their success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at >3,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan-specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations.     

HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans

Hypoxia inducible factors, including HIF1A and HIF2A, play central roles in response to high-altitude hypoxia and genetic variants of HIF1A or HIF2A were associated with high-altitude sickness or adaptation. However, it remains to determine whether they are associated with tolerance to different levels of high-altitude selection pressure among native Tibetans. We recruited 189 Tibetan subjects living at 2,700 meters (Low level of high altitude, LHA), 197 at 3,200 meters (Middle level of high altitude of high altitude, MHA), 249 at 3,700 meters (High level of high altitude, HHA) and 269 at 4,700 meters (Very high level of high altitude, VHA) and performed association analysis of twelve tSNPs (tagging SNPs) in HIF1A and HIF2A with high-altitude. We found (1) a increasing trend of HIF2A rs5621780-C(18.4%, 15.9%, 32.8% and 31.1%, respectively, in LHA, MHA, HHA and VHA)(P = 3.56E-9); (2) increasing trends of HIF2A rs6756667-A(68.7%, 73.4%, 79.9% and 89.6%), rs7589621- G(74.6%, 77.9%, 83.7%, and 92.1%) and rs1868092-A(64.1%, 67.3%, 75.1% and 84.4%) (P = 3.56E-9, 4.68E-16, 1.17E-13 and 7.09E-14, respectively); (3) a increasing trend of haplotype AG (68.7%, 73.1%, 79.9% and 89.6%) (P = 2.22E-7) which was constructed by rs6756667 and rs7589621; (4) a strong linear correlation between major alleles of rs6756667-A (R ² = 0.997, P = 0.002), rs7589621-G (R ² = 0.994, P = 0.003), rs1868092-A (R ² = 0.985, P = 0.008) and altitude by linear correlation test. The associations between HIF2A variants and different level of high altitude support that extremely high-altitude hypoxia challenge imposes selective effects on HIF2A variants among native Tibetans.     

西藏拉鲁湿地夏季土壤线虫群落特征

2010年6–7月,对拉鲁湿地5个样点的土壤动物进行了调查,共捕获土壤线虫10183条,隶属于2纲6目8科14属,其中真矛线属(Eudorylaimus)、似绕线属(Anaplectus)、地单宫属(Geomonhystera)为优势类群,占土壤线虫总个体数的62.23%。营养类群有食细菌线虫和捕食-杂食线虫。不同样点中,土壤线虫的类群数和个体数垂直分布差异显著(P<0.05),大小顺序为0–5 cm>5–15 cm。5个样点的土壤线虫Shannon-Weiner多样性指数(H′)依次为3#>5#>4#>1#>2#。5个样点间土壤线虫群落的相似程度为极不相似到中等不相似(S值在0.154–0.667)。     

西藏三种苔藓栖生纤毛虫的形态和系统发育分析

本研究利用活体观察和蛋白银染色方法对采自西藏日喀则和那曲的3种苔藓栖生纤毛虫,鬃异源棘尾虫(Tetmemena pustulata)、棘毛虫未定种(Sterkiella sp.)和殖口虫未定种(Gonostomum sp.)进行了形态学研究,描述了活体、核器以及纤毛图式等形态学特征.同时,测定了这3种纤毛虫的SSU r...     

西藏年楚河流域种子植物组成及区系特征

通过野外数据采集和资料整理分析,以年楚河流域种子植物为研究对象,对区域种子植物科、属组成、区系特征和资源型进行分析。年楚河流域共记录到种子植物58科179属339种;生活型以多年生草本为主;资源类型中药用植物最多。科内种水平上大型科为优势科,有菊科(Asteraceae)、禾本科(Poaceae)、豆科(Fabaceae);科内属的数量水平上,大型科、较大型科和小型科是植物科组成的主要成分。科的分布区类型中除世界广布型外,以温带性质为主导,热带性质次之。属的组成以单种属和小型属为主,其分布区类型表现出明显的温带性质;科、属的特有性不高。与邻近区域的植物区系R/T值比较中,本研究区与拉萨河流域、佩枯错地区植物区系的性质较接近;比较这两个区域与研究区域植物属、种的相似性系数,发现拉萨河流域与研究区域植物属、种的相似性均高于佩枯错,本研究区植物区系与拉萨河流域的亲缘关系更为亲近。     

Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin

Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in either TSC1 or TSC2 tumor suppressor gene. TSC1 and TSC2 products, Harmatin and Tuberin, form the functional complex to serve as the negative regulator for insulin-induced phosphorylation of S6 kinase and elF4E-binding protein 1. High-risk human papillomavirus (HPV) infection is the necessary cause for cervical cancer. E6 oncoprotein encoded by HPV plays a pivotal role in carcinogenesis by interference with the host intracellular protein functions. In this study, we show that HPV16 E6 interacts with tumor suppressor gene TSC2 product, Tuberin, and results in the phosphorylation of S6 kinase and S6 even in the absence of insulin. The overexpression of Tuberin overcomes the effect of E6 on S6 kinase phosphorylation. Binding with HPV16 E6 causes the proteasome-mediated degradation of Tuberin. A DILG motif and an ELVG motif located in the carboxyl-terminal of Tuberin are required for E6 binding. In addition, the Tuberin interaction region in E6 has been mapped in the amino-terminal portion of HPV16 E6, which is different from the binding domain with p53. These results provide a possible link between E6-induced oncogenesis and the insulin-stimulated cell proliferation signaling pathway.