基于高密度SNP数据的东亚人群遗传结构研究

目的 东亚疆域辽阔,民族众多,有着广泛多样的语言。中国34个省级行政区可划分为7个地理分区,人群主要分属世界七大语系。已有研究主要集中在东亚人群的起源、迁徙、融合等遗传历史。本文基于5 147份世界人群个体的高密度单核苷酸多态性（SNP）数据,从地域及语言两个角度研究东亚人群尤其是中国人群与世界其他人群的遗传关系,研究中国人群的遗传关系和遗传结构。方法 收集了5 147份世界人群个体的高密度SNP数据,并对其进行质控、合并。通过频率差异分析方法对最终获得的32 789个SNP进行统计学检验,并进一步使用主成分分析、系统发育树、祖先成分分析和D检验统计等方法,对东亚人群与世界其他人群的遗传关系,以及中国人群的遗传关系和遗传结构进行研究。结果 研究发现东亚人群与非洲、美洲和欧洲人群存在显著差异。中国人群可分为7个亚群,不同人群间的遗传聚类与其地理分布、语系语族和族源历史有很强的相关性。结论 本文研究了中国人群与世界人群的遗传关系和差异,并系统研究了中国人群的遗传亚结构。这将丰富东亚人群的群体遗传学、法医遗传学等研究基础,为个体化医疗等工作提供数据支撑。     

Civil Liability and Compensation for Damage in Connection With the Carriage of Hazardous and Noxious Substances: Chinese Perspective

Abstract

The International Convention on Liability and Compensation for Damage in Connection with the Carriage of Hazardous and Noxious Substances by Sea (the HNS Convention) has not entered into force. In China, a two-tier compensation regime has been established for vessel-source oil pollution damage, but this regime does not address damage in connection with the carriage of HNS by sea. This article examines the Chinese law approach to civil liability and compensation for damage in this respect, and discusses whether there is an adequate framework in place to address issues that may arise.     

Genetic influences on acquisition of tolerance to alcohol

Abstract

This paper provides a general review of the nature of tolerance to alcohol and describes specific studies designed to evaluate genetic influences on the acquisition of tolerance. Both environmental and genetic factors are involved in acquisition of either acute or chronic tolerance. Studies showing inbred strain differences in rates of acquisition of tolerance in mice are prima facie evidence for genetic influences, but the possible interactions between genes and environmental factors have not been investigated. Potential relationship between acutely and chronically acquired tolerance to alcohol is discussed.     

Civil liability for oil‐pollution damage on the Norwegian continental shelf

Abstract

This paper will survey the legal framework which controls civil liability for oil‐pollution damage emanating from the extraction and transportation of petroleum on the North Sea. This framework largely comprises two Intergovernmental Maritime Consulative Organization conventions dealing with vessel‐source pollution damage and a newly created convention among the northwest European states concerning pollution damage caused by offshore drilling operations. The major purpose of this paper is to familiarize the reader with these conventions as they apply to a party seeking recovery under Norwegian law. In addition, preceding domestic legislation and case‐law doctrines which may still be relevant will be discussed.     

Examination of the Relationship between Oral Health and Arterial Sclerosis without Genetic Confounding through the Study of Older Japanese Twins

ObjectiveAlthough researchers have recently demonstrated a relationship between oral health and arterial sclerosis, the genetic contribution to this relationship has been ignored even though genetic factors are expected to have some effect on various diseases. The aim of this study was to evaluate oral health as a significant risk factor related to arterial sclerosis after eliminating genetic confounding through study of older Japanese twins.ResultsWe examined 91 monozygotic and 15 dizygotic twin pairs (males: 42, females: 64) with a mean (± standard deviation) age of 67.4 ± 10.0 years. Out of all of the oral health-related measurements collected, only the number of teeth was significantly related to arterial sclerosis (odds ratio: 0.72, 95% confidence interval: 0.52-0.99 per five teeth). Regression analysis showed a significant association between the IMT-Cmax and the number of teeth as an environmental factor (p = 0.037).ConclusionsAnalysis of monozygotic twins older than 50 years of age showed that having fewer teeth could be a significant environmental factor related to arterial sclerosis, even after controlling for genetic and familial confounding.     

The genotype x environment-to-phenotype relationship

Summary Proceeding from the formal genotype x environment-to-phenotype functional relationship, a few common concepts essentially based upon this relationship have been reviewed and redefined. Particular attention was given to forming unambiguous representations. In summary, these concepts were: the reaction norm and phenotypic range of a genotype, the genetic control of traits, the general representation of genotypic and environmental contributions to a phenotype and the related problem of genotype x environment interaction, the fitness function, selective neutrality and superiority. The role of joint frequency distributions of genotypes and environmental situations for detecting and describing certain properties of the underlying genotype x environment-to-phenotype functional relationship has been demonstrated by means of models for genotype x environment interaction and the fitness function.     

沙门氏菌CRISPR位点的结构特征比较

成簇规律间隔的短回文重复序列(Clustered regularly interspaced short palindromic repeats,CRISPR),是存在于多数细菌和古菌中的遗传结构,能够有效防御外源DNA的入侵(质粒、噬菌体等),进而防御外源基因的水平转移。【目的】本研究以沙门氏菌属中常见的鸡伤寒沙门氏菌(Salmonella gallinarum)、鼠伤寒沙门氏菌(Salmonella typhimurium)、猪霍乱沙门氏菌(Salmonella choleraesuis)以及肠炎沙门氏菌(salmonella enteritidis)等30个菌株为研究对象。探索CRISPR位点在不同沙门氏菌种中的结构差异。【方法】通过生物信息学的方法比较间隔序列与插入序列的同源性以及CRISPR位点与质粒数量关系。【结果】30株沙门氏菌中均存在CRISPR结构,包括CRISPR位点61个以及可疑位点12个。重复序列和cas1基因均不能作为这4类细菌的分类依据。【结论】虽然我们发现CRISPR位点数量与间隔区数量和质粒数量之间均不存在统计学关系,但间隔序列整合子、耐药基因等移动遗传原件具有一定的同源性,说明沙门氏菌在进化过程中不断受外源基因的侵袭。     

Copy number variation-based gene set analysis reveals cytokine signalling pathways associated with psychiatric comorbidity in patients with inflammatory bowel disease

BackgroundRecent studies discovered many genetic variants associated with both psychiatric and inflammatory disorders, but the role of genetic factors in the development of psychiatric comorbidity (PC) in inflammatory bowel disease (IBD) is underexplored. Particularly, it has been shown that some of the genetic variants have been linked to the concentrations of circulating cytokines and symptoms of the inflammatory cytokine-associated depression. We analysed genomic features of individuals with IBD by comparing IBD patients with PC with those who have IBD but without PC. We hypothesized that cytokine related signalling pathways may be significantly associated with the psychiatric comorbidity in patients with IBD.MethodsIndividuals enrolled in the Manitoba IBD Cohort Study were separated to two groups accordingly to the presence of PC. A sample set comprising 97 IBD individuals with PC (IBD + PC) and 146 IBD individuals without PC (IBD) was first used to identify copy number variations (CNVs) from genome-wide genetic data using three different detection algorithms. IBD + PC and IBD groups were compared by the number of CNVs overlapping each gene; deletions and duplications were analysed separately. Gene set overrepresentation analysis was then conducted using CNV-overlapped genes and the candidate gene sets of neurological and immunological relevance.ResultsMedium-sized CNV (size between 100 and 500 kilobase pairs)-burden is significantly higher in IBD + PC than IBD groups. Gene-based CNV association analysis did not show significant differences between the two IBD groups. Gene set overrepresentation analysis demonstrated the significant enrichment of gene sets related to cytokine signalling pathways by the genes overlapped by deletions in the IBD individuals with PC.ConclusionOur results confirm the role of cytokine signalling pathways in the development of PC in IBD. Additionally, our results warrant further study with a larger sample size focusing on cytokine SNPs to further understand the relationship between inflammatory and psychiatric disorders.     

Ecophysiology and genetic diversity in species of the bamboo Chusquea in the high Andes,Venezuela

ABSTRACT

Background: Woody bamboos of the genus Chusquea grow along a broad range of elevations in the Venezuelan Andes. Their growth-form and density vary along the cloud forest – páramo gradient. In this article, we related ecophysiological traits and population genetic diversity information to explain the distribution of growth-form patterns of Chusquea in the Merida Andes, Venezuela.

Aims: We quantified differences in the ecophysiological response and genetic diversity of scandent cloud forest and shrub-like páramo bamboos of the genus Chusquea, taking in account the differences in their flowering patterns, growth-form and habitat.

Methods: We related low temperature resistance, water relations and leaf gas exchange variables to the growth-form, habitat, flowering patterns and genetic diversity in species of Chusquea. The genetic diversity study was based on Inter Sequence Simple Repeats and Random Amplified Polymorphic DNA markers analysis of cloud forest and páramo populations.

Results: Scandent cloud forest and shrub-like páramo species of Chusquea had a very similar ecophysiological response for all the variables analysed during wet and dry seasons and were capable of enduring freezing temperatures through moderate supercooling. Species associated with the cloud forest – páramo gradient maintained low stomatal conductance and transpiration rates that favoured high leaf water potentials, without limiting photosynthetic rates. Shrub-like bamboos growing above the continuous forest line had a small decline in net photosynthesis rates, associated with an increase in water use efficiency. Both scandent and shrub-like bamboos had a remarkably high genetic diversity, comparable to non-clonal species.

Conclusions: Species of Chusquea in the Venezuelan Andes are a physiologically relatively homogeneous group across a broad elevation gradient. Population genetic diversity appears to be more related with their flowering pattern and habitat conditions than with their growth form.     

临床医生在基因检测咨询中面对伦理两难问题态度与选择 ——基于情景案例分析

目的 通过情景案例分析,聚焦基因检测咨询中的伦理两难事件,探究临床医生的伦理道德抉择及可能的影响因素。 方法 采用分层随机抽样方法,对624名临床医生进行了匿名问卷调查。 结果 对于XY染色体女性案件,88%的应答者选择告知敏感性信息;对于父系信息的披露,近60%的应答者选择单独告诉母亲;对于是否告知患儿其他亲属相关遗传病信息的案件,应答者的意见则相对分散。 结论 针对三个典型的基因检测咨询中的伦理两难问题,应结合国际相关指南的要求,进一步加大相关的法律与伦理理念、知识的教育与普及。     

基于多位点序列分型对新疆伊宁学龄儿童肠道两歧双歧杆菌(Bifidobacterium bifidum)群体遗传差异解析

【背景】两歧双歧杆菌(Bifidobacterium bifidum)是专性代谢人体母乳寡糖(human milk oligosaccharides, HMOs)和宿主肠道黏膜上皮黏蛋白聚糖的肠道共栖益生菌,对生命早期健康和发育至关重要,目前对其不同人群来源的群体遗传报道较少。【目的】探究在有限地域内遗传、饮食相近人群来源的B. bifidum菌株集的遗传结构是否具有族群特异的规律性,为开发个性化的益生菌株提供理论基础。【方法】对来自新疆伊宁两个族群(维吾尔族和哈萨克族)学龄儿童队列的肠道两歧双歧杆菌进行分离和鉴定,共获得115个菌株,对基于细菌基因组重复序列PCR (repetitive sequence-PCR, rep-PCR)方法筛选的53株代表菌株采用多位点序列分型(multilocus sequence typing, MLST)进行群体遗传差异分析。【结果】53株代表菌株共分为37个序列型(sequence type, ST),具有很高的遗传多样性;其中26株源自维吾尔族儿童的菌株有17个ST,而20个ST来自27株哈萨克族儿童的菌株,两个族群来源的菌株之间检测到较少的同源基因重组事件。goeBURST分析显示,来自同一族群的B. bifidum分离株比来自另一族群的菌株更有可能被归入特定的系统发育分支或克隆复合体(clonal complexes, CC)。【结论】不同族群来源的B. bifidum分离株显示出较高的遗传多样性,群体遗传结构一定程度上呈现出民族族群来源的特异性,需要更大规模的取样证实。这为进一步开展体内外实验并筛选针对区域族群的特色优良益生菌株提供了理论基础。     

23株不同地理来源嗜酸硫杆菌的系统发育及其遗传差异

【目的】研究不同地理来源嗜酸硫杆菌的系统发育及其遗传差异,以及基因指纹图谱技术聚类与嗜酸硫杆菌地理来源的相关性。【方法】采用16S-23S r RNA间隔区(ITS)序列建立系统发育树,并结合ERIC和BOXAIR两种引物进行rep-PCR,以及rus基因扩增,对不同地理来源嗜酸硫杆菌进行分析。【结果】分离自不同样点的23株嗜酸硫杆菌遗传差异显著,依据ITS序列系统发育树被划分为5个大类群,与rep-PCR指纹图谱的分类结果较为接近,其中Acidithiobacillus ferrooxidans在ITS系统发育和BOXAIR-PCR指纹聚类分析中被划分为2个类群,但在ERIC-PCR中归为1个类群,rus基因分组中,在系统发育和聚类分析中处于同一类群的菌株拥有不同类型的rus基因,说明嗜酸硫杆菌的亚铁氧化途径与系统发育类群无明显相关性;ITS基因拥有区分近缘种或亚种的能力,且BOXAIR-PCR的分辨能力较强,非常适于嗜酸硫杆菌的遗传差异分析。     

Assessment of the causal relevance of ECG parameters for risk of atrial fibrillation: A mendelian randomisation study

BackgroundAtrial electrical and structural remodelling in older individuals with cardiovascular risk factors has been associated with changes in surface electrocardiographic (ECG) parameters (e.g., prolongation of the PR interval) and higher risks of atrial fibrillation (AF). However, it has been difficult to establish whether altered ECG parameters are the cause or a consequence of the myocardial substrate leading to AF. This study aimed to examine the potential causal relevance of ECG parameters on risk of AF using mendelian randomisation (MR).Methods and findingsWeighted genetic scores explaining lifelong differences in P-wave duration, PR interval, and QT interval were constructed, and associations between these ECG scores and risk of AF were estimated among 278,792 UK Biobank participants (mean age: 57 years at recruitment; 19,132 AF cases). The independent genetic variants contributing to each of the separate ECG scores, and their corresponding weights, were based on published genome-wide association studies. In UK Biobank, genetic scores representing a 5 ms longer P-wave duration or PR interval were significantly associated with lower risks of AF (odds ratio [OR] 0.91; 95% confidence interval [CI]: 0.87–0.96, P = 2 × 10⁻⁴ and OR 0.94; 95% CI: 0.93–0.96, P = 2 × 10⁻¹⁹, respectively), while longer QT interval was not significantly associated with AF. These effects were independently replicated among a further 17,931 AF cases from the AFGen Consortium. Investigation of potential mechanistic pathways showed that differences in ECG parameters associated with specific ion channel genes had effects on risk of AF consistent with the overall scores, while the overall scores were not associated with changes in left atrial size. Limitations of the study included the inherent assumptions of MR, restriction to individuals of European ancestry, and possible restriction of results to the normal ECG ranges represented in UK Biobank.ConclusionsIn UK Biobank, we observed evidence suggesting a causal relationship between lifelong differences in ECG parameters (particularly PR interval) that reflect longer atrial conduction times and a lower risk of AF. These findings, which appear to be independent of atrial size and concomitant cardiovascular comorbidity, support the relevance of varying mechanisms underpinning AF and indicate that more individualised treatment strategies warrant consideration.

In a Mendelian randomization analysis, Parag Gajendragadkar and colleagues investigate associations between genetically-predicted EEG parameters and risk of atrial fibrillation among UK Biobank participants.     

Regulation of offspring and the Roman Catholic Church

Abstract

The 1976 enactment of the National Sickle Cell Anemia, Cooley's Anemia, Tay‐Sachs, and Genetic Disease Act may mark the emergence of a national policy on mass genetic screening. The law includes provisions intended to protect persons who are tested for genetic traits in screening programs operated with government funds. Two key features are (1) guaranteed access to competent genetic counseling and (2) strict confidentiality of test results. Because genetic screening will be conducted through state public health departments, I surveyed the states to determine how they were currently providing access to genetic counseling and protection of genetic data. The responses indicated that (1) there is an extreme heterogeneity of counseling services, and (2) that most states have not developed programs to safeguard genetic data.     

Compensation for Material and Moral Damage to Small Island States' Reputations and Economies due to an Incident during the Shipment of Radioactive Material

An incident in the course of the shipment of radioactive material could have serious consequences for affected states, whether or not a release of radiation actually resulted from the incident. In particular, small island states could potentially suffer serious damage to their reputations and to their economies. Pacific Island states are taking an initiative in response to their exposure to this risk. Assurances that they will not be left unsupported in such circumstances are being sought through a process of direct discussions presently taking place with source states and operators involved in the shipment of radioactive material through the Pacific.

This article examines the legal background to these discussions, investigating the legal uncertainties in the situation of states affected by an incident in the course of shipment of radioactive material that arise from limitations in the nuclear civil liability conventions and other aspects of applicable international law.     

Characterization of Chlamydomonas Ribulose-1,5-bisphosphate carboxylase/oxygenase variants mutated at residues that are post-translationally modified

BackgroundRibulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the chloroplast enzyme that fixes CO₂ in photosynthesis, but the enzyme also fixes O₂, which leads to the wasteful photorespiratory pathway. If we better understand the structure-function relationship of the enzyme, we might be able to engineer improvements. When the crystal structure of Chlamydomonas Rubisco was solved, four new posttranslational modifications were observed which are not present in other species. The modifications were 4-hydroxylation of the conserved Pro-104 and 151 residues, and S-methylation of the variable Cys-256 and 369 residues, which are Phe-256 and Val-369 in land plants. Because the modifications were only observed in Chlamydomonas Rubisco, they might account for the differences in kinetic properties between the algal and plant enzymes.MethodsSite-directed mutagenesis and chloroplast transformation have been used to test the essentiality of these modifications by replacing each of the residues with alanine (Ala). Biochemical analyses were done to determine the specificity factors and kinetic constants.ResultsReplacing the modified-residues in Chlamydomonas Rubisco affected the enzyme's catalytic activity. Substituting hydroxy-Pro-104 and methyl-Cys-256 with alanine influenced Rubisco catalysis.ConclusionThis is the first study on these posttranslationally-modified residues in Rubisco by genetic engineering. As these forms of modifications/regulation are not available in plants, the modified residues could be a means to modulate Rubisco activity.General significanceWith a better understanding of Rubisco structure-function, we can define targets for improving the enzyme.     

Gendered genetics in Iceland

The integration of Iceland's phenotype and genotype, by bringing together the medical records, genealogies and genetic data by the commercial firm deCODE has been one of the most studied and controversial cases of the new pharmacogenomics. This paper explores the differences between the concerns and conceptualizations of women and men in debating this biomedical innovation.     

The prediction of civil violence to the year 2001

Abstract

Annual predictions of global deaths from civil war to the year 2001 have been made based on an earlier two‐stage cyclical model. In stage one three cycles (8.6, 17.4, and 34 yr) predict to changes in the global political system, while four cycles (5.6, 9.4, 20.5, and 54 yr) predict to changes in the global economic system. In stage two, changes in the political and economic systems predict to changes in the level of civil violence. Fifteen regression equations, four tables, and six diagrams are included with the text     

Quantitative Trait Loci Identification by Estimating the Genetic Model based on the Extremal Samples

Background In genetic association studies with quantitative trait loci (QTL), the association between a candidate genetic marker and the trait of interest is commonly examined by the omnibus F test or by the t-test corresponding to a given genetic model or mode of inheritance. It is known that the t-test with a correct model specification is more powerful than the F test. However, since the underlying genetic model is rarely known in practice, the use of a model-specific t-test may incur substantial power loss. Robust-efficient tests, such as the Maximin Efficiency Robust Test (MERT) and MAX3 have been proposed in the literature.Methods In this paper, we propose a novel two-step robust-efficient approach, namely, the genetic model selection (GMS) method for quantitative trait analysis. GMS selects a genetic model by testing Hardy-Weinberg disequilibrium (HWD) with extremal samples of the population in the first step and then applies the corresponding genetic model-specific t-test in the second step.Results Simulations show that GMS is not only more efficient than MERT and MAX3, but also has comparable power to the optimal t-test when the genetic model is known.Conclusion Application to the data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort demonstrates that the proposed approach can identify meaningful biological SNPs on chromosome 19.