全基因组关联研究的深度分析策略

2005年至今,全基因组关联研究(Genome-wide association study,GWAS)发现了大量复杂疾病/性状相关变异。近来,科学家们关注的焦点又集中在了如何利用GWAS数据进行深入分析,期待发现更多复杂疾病/性状的易感基因。一些新的策略和方法已经被尝试应用到复杂疾病/性状GWAS的后续研究中,例如深入分析GWAS数据;鉴定新的复杂疾病/性状易感基因/位点;国际合作和Meta分析;易感区域精细定位及测序;多种疾病共同易感基因研究;以及基因型填补,基于通路的关联分析,基因-基因、基因-环境交互作用和上位研究等。这些策略和方法的应用弥补了经典GWAS的一些不足之处,进一步推动了人类对复杂疾病/性状遗传机制的认识。文章对上述研究的策略、方法以及所面临的问题和挑战进行了综述,为读者描绘了GWAS后期工作的一个简要框架。     

大蜡螟幼虫的体色遗传规律

对大蜡螟Galleria mellonella幼虫不同颜色品系的普通遗传学分析表明,大蜡螟幼虫的体色遗传是常染色体遗传且符合复等位基因遗传规律。深黄色基因（AA）对灰黑色基因(BB)和灰色基因(CC)为显性,深黄色基因(AA)对白黄色基因(DD)、灰黑色基因(BB)对白黄色基因(DD)和灰色基因(CC)、灰色基因(CC)对白黄色基因(DD)为不完全显性。基因型为AD、BD、CD的个体,其表现型均为黄色;基因型为AA、BC的个体,其表现型均为深黄色。     

多个典范选择性状的综合优化研究

利用综合优化方法,研究了在育种目标约束下,选择性状表现型向量与目标性状基因型向量的典范相关,提出了综合典范性状对的数学模型。综合典范性状对是Ｓ个间撞遗传系数较在的典范选择－目标性状对,在育种目标约束下间接遗传系数极大化的线性组合。综合典范选择性状,作为间接选择的指标,有较好地满足多目标育种的要求。     

汉族和藏族的皮肤反射系数分析

人类的肤色是在遗传和环境因素的共同作用下形成的。最近在人类复杂性状基因定位中,统计学和遗传学研究方法的发展,使得肤色相关基因有可能利用这些方法来甄别。而且,有了Photovolt ColorWalk色度计等便携的新式光谱反射系数测量工具,研究者可以方便准确地测量大量人群的皮肤反射系数作为遗传学研究用的人类表型性状。我们衣物Photovolt ColorWark测试了372人的一个汉族群体和274人的一个藏族群体的上臂内侧不受阳光照射的皮肤反射系数,以建立反射系数测量的基准数据。我们调查了年龄、性别、居住地纬度、种族等不同因素对皮肤反射系数的影响,也调查了皮肤反射系数的正态分布。在这些研究结果的基础上我们设计了皮肤反射系数遗传学研究的策略。     

作物数量性状基因研究进展

分子生物技术的发展对作物数量性状基因（QTL）研究提供了条件,不同的定位群体各有其特点,相继出现的QTL定位也逐步完善。大量的研究揭示了QTL的基本特征,剖析了重要农艺4性状的遗传基础,给作物遗传改良带来了新的策略,不断深入的研究已经完成了特定的QTL的精细定位和克隆。本从QTL的定位群体,定位方法,研究现状,精细定位与克隆,以及QTL利用等方面对作物数量性状基因的研究进行了综述。     

家养动物多样性研究要素和成就

家养动物多样性的研究多年来侧重于经济性状和生态多样性及品种多样性。近几年来在遗传多样性方面取得重大进展 ,在品种聚类、系统保种、遗传多样性与经济性状和生态多态性的相关研究都取得了重要结果 ,有的已经做到数量性状基因定位、转基因和克隆动物检测等。家养动物与其野生近缘种的基因分析和利用野生种血液的育种也取得一定的效果。利用多样性鉴别技术已确认许多地方品种为中国特有种 ,引起了国际广泛关注     

冠心病易感基因的筛选

作为一种多基因疾病 ,冠心病是由遗传和环境因素共同作用的结果 ,在许多国家是主要的死因之一。由于目前冠心病的发病机制尚不十分清楚 ,阻碍了其易感基因的定位分离研究。冠心病遗传因素的确定 ,显然将有助于其易感基因定位分离研究。迄今除发现了个别的相关基因外 ,绝大部分的遗传易感性相关基因尚未被发现 ,其研究仍然存在许多问题。为此 ,本文就其易感基因可能的研究策略和方法作一综述。这些方法同样也适用于诸如中风、外周血管阻塞、高血压、心力衰竭等心血管疾病以及其它多基因疾病     

水稻产量相关QTL研究现状

产量是最为复杂的数量性状,对它的遗传机理了解甚微。近15年来,许多学者利用随机分离群体定位了许多影响水稻产量及其组分的QTL,即以QTL定位的方法对产量潜力进行遗传剖析。试验证明上位性效应对产量及其组分性状遗传变异起着重要作用,但目前大多数QTL研究仍侧重于发掘和克隆单个主效QTL,然而对单一基因／QTL的深入了解还不足以诠释复杂性状遗传基础的全貌,还没有为育种家提供足够的可应用于分子标记辅助育种的遗传信息并用于提高水稻产量。笔者认为今后的数量性状研究尚需加强复杂性状QTL遗传网络的发掘,在改良水稻品种性状的同时发展并完善QTL研究。     

革螨染色体及同工酶的研究进展

<正> 革螨染色体的研究,对革螨的分类、生态、生殖、进化、性决定机理等研究,以及对害螨的遗传防治和益螨的遗传改良都有重要的现实意义。 同工酶是由基因决定的,故其研究是从基因产物认识基因的存在及表达,由生化表现型反映基因型,将宏观的遗传现象结合到微观的分子水平,联系基因、酶、性状与结构、功能、调控的关系,对分子遗传学和分子分类学具有极其重要的意义。     

同源四倍体水稻糯性基因的遗传分析

许多学者研究了二倍体水稻糯性胚乳的遗传。他们指出糯性胚乳是单基因隐性遗传的。二倍体杂种Wx。的自交后代有3种基因型,显隐性比例为3:1。同源四倍体糯稻在。二位点上有4个等位基因,它与非糯稻的杂种后代的基因型种类和表现型比例要比二倍体复杂得多。以双显性WxWxwxwx为例,它的自交后代有,种基因型,其显隐性比例将依染色体、染色单体随机分离和完全均衡分离分别表现为35：1, 20.8:1和19.3:1,而3显性Wxwxwx.wx和单显性Wxwxw二,x杂合体也会依3种分离方式而产生相应的表现型比例。虽然过去对同源四倍体水稻的形态学和细胞学有过一些研究,但同源四倍体水稻单基因遗传的报道尚未见过。为了探索同源四倍体水稻的性状遗传规律,我们先从质量性状人手,对糯性胚乳进行了初步研究,现将观察分析结果报道如下。     

自然保护区生态旅游对野生动物的影响

目前中国的很多自然保护区开展了生态旅游,但这类活动对野生动物的影响研究却十分薄弱,因此十分有必要在介绍欧美、澳洲学者的研究进展基础上,针对我国的研究现状,提出该领域的研究方向、监测和管理策略.自然保护区的生态旅游活动主要有野生动物观赏、徒步行走、摄影、野外宿营、山地车或雪地车、电动或机动艇游湖、溪涧漂流、环境教育、社区访问等,旅游活动类型、范围、强度、时空分布等是影响对野生动物干扰大小的主要因素.生态旅游对野生动物的影响包括直接影响(个体的行为反应和生理指标改变、繁殖力降低、种群分布和物种组成的改变等)和间接影响(生境破坏、外来种散布和环境污染等).国外生态旅游对鸟类的影响研究较多,主要集中鸟类的惊飞反应、取食、能量消耗、繁殖等方面;对兽类影响的研究主要集中在行为、生理指标改变、种群数量等方面.我国未来的研究应注重收集基础性研究数据和深入探讨一些理论与应用问题,要运用多种技术手段对自然保护区野生动物的行为、生理、种群动态、物种多样性、生境质量、游客的时空分布、态度和行为等进行长期监测,而后将其结果应用到野生动物、生境以及游客的管理决策中去.另外,研究中应重视自然科学和社会科学的多学科交叉融合.     

Expert thinking and environmental institutions

The paper explores environmental institutions that facilitate the trial and error search for sustainable development. The argumentation refers to four case studies of environmental management in the US, Europe, and China. To diagnose the institutional constraints of environmental management, the studies focus on the mental models with which experts understand environmental problems and justify their efforts to fix the problems. As such, the mental models also reflect the institutional rules that constrain expert actions. Design principles for novel environmental institutions are developed on the basis of institutional theory and case study findings. In conclusion, implications of the proposed institutional arrangements for the public role of experts are discussed.     

Autistic Disorders and Schizophrenia: Related or Remote? An Anatomical Likelihood Estimation

Shared genetic and environmental risk factors have been identified for autistic spectrum disorders (ASD) and schizophrenia. Social interaction, communication, emotion processing, sensorimotor gating and executive function are disrupted in both, stimulating debate about whether these are related conditions. Brain imaging studies constitute an informative and expanding resource to determine whether brain structural phenotype of these disorders is distinct or overlapping. We aimed to synthesize existing datasets characterizing ASD and schizophrenia within a common framework, to quantify their structural similarities. In a novel modification of Anatomical Likelihood Estimation (ALE), 313 foci were extracted from 25 voxel-based studies comprising 660 participants (308 ASD, 352 first-episode schizophrenia) and 801 controls. The results revealed that, compared to controls, lower grey matter volumes within limbic-striato-thalamic circuitry were common to ASD and schizophrenia. Unique features of each disorder included lower grey matter volume in amygdala, caudate, frontal and medial gyrus for schizophrenia and putamen for autism. Thus, in terms of brain volumetrics, ASD and schizophrenia have a clear degree of overlap that may reflect shared etiological mechanisms. However, the distinctive neuroanatomy also mapped in each condition raises the question about how this is arrived in the context of common etiological pressures.     

Comparisons of case-selection approaches based on allele sharing and/or disease severity index: application to the GAW14 simulated data

For mapping complex disease traits, linkage studies are often followed by a case-control association strategy in order to identify disease-associated genes/single-nucleotide polymorphisms (SNPs). Substantial efforts are required in selecting the most informative cases from a large collection of affected individuals in order to maximize the power of the study, while taking into consideration study cost. In this article, we applied and extended three case-selection strategies that use allele-sharing information method for families with multiple affected offspring to select most informative cases using additional information on disease severity. Our results revealed that most significant associations, as measured by the lowest p-values, were obtained from a strategy that selected a case with the most allele sharing with other affected sibs from linked families ("linked-best"), despite reduction in sample size resulting from discarding unlinked families. Moreover, information on disease severity appears to be useful to improve the ability to detect associations between markers and disease loci.     

Informativeness of genetic markers for inference of ancestry

Inference of individual ancestry is useful in various applications, such as admixture mapping and structured-association mapping. Using information-theoretic principles, we introduce a general measure, the informativeness for assignment (I(n)), applicable to any number of potential source populations, for determining the amount of information that multiallelic markers provide about individual ancestry. In a worldwide human microsatellite data set, we identify markers of highest informativeness for inference of regional ancestry and for inference of population ancestry within regions; these markers, which are listed in online-only tables in our article, can be useful both in testing for and in controlling the influence of ancestry on case-control genetic association studies. Markers that are informative in one collection of source populations are generally informative in others. Informativeness of random dinucleotides, the most informative class of microsatellites, is five to eight times that of random single-nucleotide polymorphisms (SNPs), but 2%-12% of SNPs have higher informativeness than the median for dinucleotides. Our results can aid in decisions about the type, quantity, and specific choice of markers for use in studies of ancestry.     

Genetic investigation of quantitative traits related to autism: use of multivariate polygenic models with ascertainment adjustment

Autism is a severe developmental disorder of unknown etiology but with evidence for genetic influences. Here, we provide evidence for a genetic basis of several quantitative traits that are related to autism. These traits, from the Broader Phenotype Autism Symptom Scale (BPASS), were measured in nuclear families, each ascertained through two probands affected by autism spectrum disorder. The BPASS traits capture the continuum of severity of impairments and may be more informative for genetic studies than are the discrete diagnoses of autism that have been used by others. Using a sample of 201 nuclear families consisting of a total of 694 individuals, we implemented multivariate polygenic models with ascertainment adjustment to estimate heritabilities and genetic and environmental correlations between these traits. Our ascertainment adjustment uses conditioning on the phenotypes of probands, requires no modeling of the ascertainment process, and is applicable to multiplex ascertainment and multivariate traits. This appears to be the first such implementation for multivariate quantitative traits. The marked difference between heritability estimates of the trait for language onset with and without an ascertainment adjustment (0.08 and 0.22, respectively) shows that conclusions are sensitive to whether or not an ascertainment adjustment is used. Among the five BPASS traits that were analyzed, the traits for social motivation and range of interest/flexibility show the highest heritability (0.19 and 0.16, respectively) and also have the highest genetic correlation (0.92). This finding suggests a shared genetic basis of these two traits and that they may be most promising for future gene mapping and for extending pedigrees by phenotyping additional relatives.     

Hybridization,introgression, and linkage evolution

Genetic mapping methods provide a unique opportunity to study the interactions of differentiated genes and genomes in a hybrid genetic background. After a brief discussion of theoretical and analytical concerns, we review the application of these methods to a wide range of evolutionary issues. Map-based studies of experimental hybrids indicate that most postzygotic reproductive barriers in plants are polygenic and that the expression of extreme or novel traits in segregating hybrids (transgressive segregation) results from the complementary action of divergent parental alleles. However, genetic studies of hybrid vigor do not concur in their interpretations of the relative roles of dominance, overdominance, and epistasis. Map-based studies of natural hybrids are much rarer, but the few existing studies confirm the polygenic basis of postzygotic barriers and demonstrate the utility of genetic linkage for detecting cryptic introgression. In addition, studies of experimental and natural hybrid lineages provide compelling evidence that homoploid hybrid speciation has occurred in nature, and that it represents a rapid and repeatable mode of speciation. Data further indicate that this mode is facilitated by strong fertility selection and high chromosomal mutation rates. We recommend that future studies of hybrid genomes focus on natural hybrids, not only because of the paucity of data in this area, but also because of the availability of highly recombinant hybrid genotypes in hybrid zones. Of particular value will be studies of long-lived or difficult-to-propagate organisms, which previously have not been amenable to genetic study.     

A theoretical quantitative genetic study of negative ecological interactions and extinction times in changing environments

Background  

Rapid human-induced changes in the environment at local, regional and global scales appear to be contributing to population declines and extinctions, resulting in an unprecedented biodiversity crisis. Although in the short term populations can respond ecologically to environmental alterations, in the face of persistent change populations must evolve or become extinct. Existing models of evolution and extinction in changing environments focus only on single species, even though the dynamics of extinction almost certainly depend upon the nature of species interactions.     

Information requirements and regulatory approaches for heritable genetic risk assessment and risk communication

With the evolution of genetic toxicology as a scientific discipline and the formation of the Environmental Mutagen Society (EMS), much thought was given to the study of chemicals in the human environment for their mutagenic effects. The Society's goal was to promote scientific investigation and dissemination of information related to genetic toxicology. Subsequently, the concern for chemically induced genetic damage in human germ cells and its potential impact on genetic diseases was detailed in the Committee 17 Report (1975). With new information on the involvement of genetic alterations in disease and on the ramifications of possible effects of exposures to environmental mutagens, it is becoming increasingly necessary to again focus our attention on the assessment of heritable genetic effects. Clearly, strategies for communication of genetic hazard/risk assessments to exposed individuals and to those charged with regulating environmental agents need to be developed.     

QTL mapping and the genetic basis of adaptation: recent developments

Quantitative trait loci (QTL) mapping has been used in a number of evolutionary studies to study the genetic basis of adaptation by mapping individual QTL that explain the differences between differentiated populations and also estimating their effects and interaction in the mapping population. This analysis can provide clues about the evolutionary history of populations and causes of the population differentiation. QTL mapping analysis methods and associated computer programs provide us tools for such an inference on the genetic basis and architecture of quantitative trait variation in a mapping population. Current methods have the capability to separate and localize multiple QTL and estimate their effects and interaction on a quantitative trait. More recent methods have been targeted to provide a comprehensive inference on the overall genetic architecture of multiple traits in a number of environments. This development is important for evolutionary studies on the genetic basis of multiple trait variation, genotype by environment interaction, host–parasite interaction, and also microarray gene expression QTL analysis.