Chunjie Xiao

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.

Y-Chromosome Evidence of Southern Origin of the East Asian–Specific Haplogroup O3-M122

The prehistoric peopling of East Asia by modern humans remains controversial with respect to early population migrations. Here, we present a systematic sampling and genetic screening of an East Asian-specific Y-chromosome haplogroup (O3-M122) in 2,332 individuals from diverse East Asian populations. Our results indicate that the O3-M122 lineage is dominant in East Asian populations, with an average frequency of 44.3%. The microsatellite data show that the O3-M122 haplotypes in southern East Asia are more diverse than those in northern East Asia, suggesting a southern origin of the O3-M122 mutation. It was estimated that the early northward migration of the O3-M122 lineages in East Asia occurred approximately 25,000-30,000 years ago, consistent with the fossil records of modern humans in East Asia.

Analyses of genetic structure of Tibeto-Burman populations reveals sex-biased admixture in southern Tibeto-Burmans

An unequal contribution of male and female lineages from parental populations to admixed ones is not uncommon in the American continents, as a consequence of directional gene flow from European men into African and Hispanic Americans in the past several centuries. However, little is known about sex-biased admixture in East Asia, where substantial migrations are recorded. Tibeto-Burman (TB) populations were historically derived from ancient tribes of northwestern China and subsequently moved to the south, where they admixed with the southern natives during the past 2600 years. They are currently extensively distributed in China and Southeast Asia. In this study, we analyze the variations of 965 Y chromosomes and 754 mtDNAs in >20 TB populations from China. By examining the haplotype group distributions of Y-chromosome and mtDNA markers and their principal components, we show that the genetic structure of the extant southern Tibeto-Burman (STB) populations were primarily formed by two parental groups: northern immigrants and native southerners. Furthermore, the admixture has a bias between male and female lineages, with a stronger influence of northern immigrants on the male lineages (approximately 62%) and with the southern natives contributing more extensively to the female lineages (approximately 56%) in the extant STBs. This is the first genetic evidence revealing sex-biased admixture in STB populations, which has genetic, historical, and anthropological implications.

Resveratrol Inhibits Inflammatory Responses via the Mammalian Target of Rapamycin Signaling Pathway in Cultured LPS-Stimulated Microglial Cells

Background Resveratrol have been known to possess many pharmacological properties including antioxidant, cardioprotective and anticancer effects. Although current studies indicate that resveratrol produces neuroprotection against neurological disorders, the precise mechanisms for its beneficial effects are still not fully understood. We investigate the effect of anti-inflammatory and mechamisms of resveratrol by using lipopolysaccharide (LPS)-stimulated murine microglial BV-2 cells. Methodology/Principal Findings BV-2 cells were treated with resveratrol (25, 50, and 100 µM) and/or LPS (1 µg/ml). Nitric oxide (NO) and prostaglandin E2 (PGE2) were measured by Griess reagent and ELISA. The mRNA and protein levels of proinflammatory proteins and cytokines were analysed by RT-PCR and double immunofluorescence labeling, respectively. Phosphorylation levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10), Akt, mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) cascades, inhibitor κB-α (IκB-α) and cyclic AMP-responsive element-binding protein (CREB) were measured by western blot. Resveratrol significantly attenuated the LPS-induced expression of NO, PGE2, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and nuclear factor-κB (NF-κB) in BV-2 cells. Resveratrol increased PTEN, Akt and mTOR phosphorylation in a dose-dependent manner or a time-dependent manner. Rapamycin (10 nM), a specific mTOR inhibitor, blocked the effects of resveratrol on LPS-induced microglial activation. In addition, mTOR inhibition partially abolished the inhibitory effect of resveratrol on the phosphorylation of IκB-α, CREB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK). Conclusion and Implications This study indicates that resveratrol inhibited LPS-induced proinflammatory enzymes and proinflammatory cytokines via down-regulation phosphorylation of NF-κB, CREB and MAPKs family in a mTOR-dependent manner. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of resveratrol.

Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations

BackgroundThe phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000–30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario.ResultsIn this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations.ConclusionWe proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.

Global distribution of Y-chromosome haplogroup C reveals the prehistoric migration routes of African exodus and early settlement in East Asia

The regional distribution of an ancient Y-chromosome haplogroup C-M130 (Hg C) in Asia provides an ideal tool of dissecting prehistoric migration events. We identified 465 Hg C individuals out of 4284 males from 140 East and Southeast Asian populations. We genotyped these Hg C individuals using 12 Y-chromosome biallelic markers and 8 commonly used Y-short tandem repeats (Y-STRs), and performed phylogeographic analysis in combination with the published data. The results show that most of the Hg C subhaplogroups have distinct geographical distribution and have undergone long-time isolation, although Hg C individuals are distributed widely across Eurasia. Furthermore, a general south-to-north and east-to-west cline of Y-STR diversity is observed with the highest diversity in Southeast Asia. The phylogeographic distribution pattern of Hg C supports a single coastal ‘Out-of-Africa’ route by way of the Indian subcontinent, which eventually led to the early settlement of modern humans in mainland Southeast Asia. The northward expansion of Hg C in East Asia started ∼40 thousand of years ago (KYA) along the coastline of mainland China and reached Siberia ∼15 KYA and finally made its way to the Americas.

Winter temperature and UV are tightly linked to genetic changes in the p53 tumor suppressor pathway in Eastern Asia.

The tumor suppressor p53 is a master sensor of stress. Two human-specific polymorphisms, p53 codon 72 and MDM2 SNP309, influence the activities of p53. There is a tight association between cold winter temperature and p53 Arg72 and between low UV intensity and MDM2 SNP309 G/G in a cohort of 4029 individuals across Eastern Asia that suggests causative selection. Moreover, the two polymorphisms are not coselected. Haplotype-based selection analysis further suggests that this is a striking example of two functional polymorphisms being strongly selected for in human populations in response to environmental stresses.

The ADH1B Arg47His polymorphism in East Asian populations and expansion of rice domestication in history

BackgroundThe emergence of agriculture about 10,000 years ago marks a dramatic change in human evolutionary history. The diet shift in agriculture societies might have a great impact on the genetic makeup of Neolithic human populations. The regionally restricted enrichment of the class I alcohol dehydrogenase sequence polymorphism (ADH1BArg47His) in southern China and the adjacent areas suggests Darwinian positive selection on this genetic locus during Neolithic time though the driving force is yet to be disclosed.ResultsWe studied a total of 38 populations (2,275 individuals) including Han Chinese, Tibetan and other ethnic populations across China. The geographic distribution of the ADH1B*47His allele in these populations indicates a clear east-to-west cline, and it is dominant in south-eastern populations but rare in Tibetan populations. The molecular dating suggests that the emergence of the ADH1B*47His allele occurred about 10,000~7,000 years ago.ConclusionWe present genetic evidence of selection on the ADH1BArg47His polymorphism caused by the emergence and expansion of rice domestication in East Asia. The geographic distribution of the ADH1B*47His allele in East Asia is consistent with the unearthed culture relic sites of rice domestication in China. The estimated origin time of ADH1B*47His allele in those populations coincides with the time of origin and expansion of Neolithic agriculture in southern China.

Association of the beta2-adrenergic receptor gene with essential hypertension in the non-Han Chinese Yi minority human population.

Objective The human β2-adrenergic receptor (ADRB2) gene is a candidate for contributing to the pathophysiology of essential hypertension. The aims of the present study were to investigate the associations of differing single nucleotide polymorphisms (SNPs) and haplotypes of the ADRB2 gene promoter and coding regions with essential hypertension in genetically homogeneous Hani and Yi minority groups that are non-Han Chinese. Methods Four SNPs in the regulatory and seven SNPs in the coding region were genotyped in 271 essential hypertension individuals and 267 controls, and eight haplotypes in the regulatory and five haplotypes in the coding region were determined and tested for association using the likelihood test statistic. Results There were significant associations of essential hypertension with separate SNPs located in both the regulatory and coding regions in the Yi minority group. In contrast, no associations of essential hypertension were detected with any of single SNPs in the Hani minority group. There is a significant difference in haplotype frequency distributions between the hypertensive participants and the controls in two groups (P < 10−3). Conclusion The results indicate that variants at the ADRB2 locus may play a role in the pathophysiology of hypertension specifically in the Yi minority group.

Relationship between the CAG Repeat Polymorphism in the Androgen Receptor Gene and Acne in the Han Ethnic Group

Background: The modulatory domain of the human androgen receptor (AR) gene contains a polymorphic CAG repeat coding for a polyglutamine tract which is inversely correlated with transcriptional activity of the AR. Androgens acting through the AR play a crucial role in the pathogenesis of acne vulgaris. We therefore investigated the relationship between CAG repeat polymorphism in the AR gene and acne susceptibility. Methods: 206 acne patients and 200 controls participated in the study. Genomic DNA was extracted from peripheral blood lymphocytes of individual patients, and the CAG repeat region was amplified by polymerase chain reaction (PCR) using fluorescence-labeled primers. Samples were then run on an ABI 377 gene scan analysis gel with an internal molecular-weight marker. Ten male samples were chosen randomly for sequencing to confirm the number of CAG repeats. The 2-sample independent t test was used to analyze the data. Results: The mean number of the CAG repeat in the AR was 22.07 (14–28) in the controls and 20.61 (13–26) in the male acne group. There was a significant correlation between the CAG repeat length and male acne. No significant difference was observed between female patients and their controls. Conclusion: The results suggest that the AR gene CAG repeat polymorphism may be one of the candidate genetic markers for male acne susceptibility in the Han population.