ABO血型综合实验基因分型技术简化及其群体遗传分析拓展

ABO血型是生活中最常见、运用最广泛的遗传性状之一。人类ABO血型由I ^A、I ^B和i 3个复等位基因决定,它们负责编码不同的糖基转移酶,进而决定3种血红细胞表面抗原。ABO血型涉及复等位基因、基因互作、单核苷酸多态(SNP)、基因演化等多个关键知识内容,是理想的遗传学教学案例。本文以ABO血型为研究对象,对遗传学实验进行了创新与整合。首先,在分子遗传学模块中建立了新颖的ABO血型基因分型方法：基于SNP位点设计特异性引物,通过实时定量PCR鉴定基因型; 其次,在群体遗传学模块中创新了基因演化的实验教学方法,开发群体遗传学软件,利用计算机模拟不同条件下ABO血型决定基因频率的演化趋势。这些教学改革举措旨在丰富遗传学实验内容,拓展教学手段,提高学习效率。     

本科遗传学教学中的遗传漂变概念探讨

遗传漂变是遗传学教学的难点之一,因其涉及随机性和概率,特别容易引起误解。定义中的“抽样误差”常被误解为遗传漂变是由于“抽样”这一研究方法干扰才导致基因频率的随机变化。本文首先对国内外《遗传学》教材中的遗传漂变定义进行了分析比较,发现“抽样误差”的定义为各教材普遍采用,但只有少数教材对“抽样误差”概念进行了正确的解释,多数未作进一步的说明。文章介绍了遗传漂变的研究历史,亦即Wright、 Fisher和Kimura等学者对遗传漂变研究的贡献。进而,特别介绍了近年来国外关于本科生遗传漂变教学的两篇代表性教学研究论文,指出本科生在学习过程中容易出现错误理解是难以避免的现象,对此也提供了初步的解决办法。作者最后结合自己的教学实践,提出本科生教学中遗传漂变仍然采用含有“抽样误差”概念的定义,只是需要对“抽样误差”做进一步的解释,指出“抽样误差”是等位基因世代传递过程中存在的、配子间的随机结合,“相当于”对整个参与交配的配子库中的配子进行的一次“随机抽样”,而与一般遗传学研究中的人为抽样行为无关。本文旨在为本科遗传学教学中关于遗传源变概念的讲解提供借鉴和参考。     

以人类血型为遗传学案例教学的思考与实践

血型是人类日常生活中非常常见的一种遗传表型, 拥有丰富的遗传学内涵。随着科技的发展, 其内涵不断得到新的揭示, 新的研究结果不断补充, 持续吸引着人们对血型遗传机制的探索。血型遗传案例除了与孟德尔遗传和连锁遗传、基因突变和染色体畸变四大内容关联外, 还涉及到其他多方面的遗传学知识点。在教学中, 依据遗传学的知识脉络, 贯穿以ABO血型作为经典案例, 结合拓展的白细胞血型, 孟买、Rh、MN等血型的遗传规律及其应用, 并且开展相关的实验教学, 理论联系实际, 增强了学生的兴趣, 提高了教学效果。在遗传学实验教学中, 有80%的学生选择ABO血型鉴定这个自选实验, 并表示出对这个实验的浓厚兴趣。在讲授相关知识点时, 用恰当的血型案例为引导, 设计相关的讨论主题, 开展PPT展示性讨论和辩论式讨论, 所有的学生都积极主动参与进来, 与现实生活相结合, 引导学生思考问题, 使学生的思维在辨析中得到操练, 提高分析问题和解决问题的能力, 深刻理解遗传学基本理论知识。     

金针菇单孢菌株菌丝生长速度QTL定位分析

本研究以已经完成基因组测序的单核菌株“6-3”与“6-21”为出发菌株,配对后获得有锁状联合的异核菌株并进行出菇,收集担孢子,单孢分离获得90个菌株构成作图群体,对作图群体的每个菌株进行二代测序并测定菌丝在PDA培养基的生长速度。分析“6-3”与“6-21”两单核菌株的SNP,获得68 914个高质量SNP标记用于遗传连锁群分析,构建了14个遗传连锁群,总长度744.32cM,平均长度为53.17cM,标记间平均遗传距离为1.88cM。QTL分析获得一个控制菌丝生长速度的基因座qMGRP1-LG7,该基因座包含134个基因,富集了与物质代谢有关的通路和基因。     

ABO血型的遗传平衡问题解析

人类控制ABO血型的基因座位上的等位基因频率的估计是相当棘手的问题.在遗传学著作、教材和教学中,群体遗传平衡相关估算中常出现"循环论证",这一问题需要深入分析.从根本上讲,ABO血型遗传平衡估算问题的困难来自2个等位基因对第3个的完全显性.在实际中.人类大群体中的ABO血型一般是平衡的,因此可用r=(-O)1/2、q=1-((-A) (-O))1/2和p=1-((-B) (-O))1/2近似地求基因频率.     

黔南布依族、苗族和水族人群ABO血型分布及基因频率

本文对黔南州布依族、苗族、水族人群ABO血型的表现型及基因型频率进行检测。结果显示:黔南布依族ABO血型分布为O>B>A>AB;苗族、水族为O>A>B>AB。3个民族ABO血型基因频率相接近;经吻合度检测,符合Hardy-Weinberg平衡定律。黔南与黔东南、黔西南布依族和苗族群体间以及黔南水族男女群体间ABO血型分布差异均具有显著性(P<0.05或P<0.01),结果提示ABO血型分布存在民族、地区和性别差异。     

氮磷肥配施对冬小麦灌浆期光合参数及产量的影响

在西北绿洲生态条件下, 实验设4个处理, 即165(N₁)和225 kg·hm^-2(N₂)2个氮素(纯氮)水平及105(P₁)和165 kg·hm^-2(P₂)2个磷素(P₂O₅)水平, 研究了氮磷肥配施对冬小麦(Triticum aestivum)品种临抗2号光合特性及产量的影响。结果表明, 低氮(165 kg·hm^-2)处理组的净光合速率(P_n)、气孔导度(G_s)及蒸腾速率(T_r)日变化均呈双峰曲线, 有光合“午休”现象; 高氮(225 kg·hm^-2)处理可减弱甚至使光合“午休”现象消失; 高磷(165 kg·hm^-2)和低磷(105 kg·hm^-2)处理对光合特性的影响差异不显著。N₂P₂具有最高的群体叶面积指数(LAI)、群体光合速率(CAP)、穗粒数、亩穗数、千粒重及产量, 且与N₁P₁和N₁P₂的差异均达显著水平, 与N₂P₁则无显著差异。但N₂P₂水分利用效率(WUE)低于N₂P₁, 显著高于N₁P₁和N₁P₂ (N₁P₁高于N₁P₂, 但无显著差异)。氮肥对光合“午休”的影响大于磷肥, 二者互作效应差异不显著。该实验条件下, 当N、P分别为225和105 kg·hm^-2时有利于提高冬小麦的光合速率及产量。     

“一带一路”与生物遗传资源获取和惠益分享: 关联、路径与策略

“一带一路”倡议的提出具有重要的时代意义和深远的历史影响。“一带一路”的持续推进和贯彻落实也使得其发展面向和具体内容日趋多元和丰富。生物遗传资源获取和惠益分享已成为全球生物多样性领域长期、持续关注的焦点领域和热门话题, 其在理念、目标、方式与主体等方面与“一带一路”高度契合。对于中国而言, 在“一带一路”背景下开展生物遗传资源获取和惠益分享应选择双边路径为主、多边路径为辅的方案。未来“一带一路”倡议下中国与沿线国家开展生物遗传资源获取和惠益分享可能的策略包括：提出地区或区域性生物遗传资源获取和惠益分享行动规划, 实施地区或区域性生物遗传资源获取和惠益分享行动倡议, 持续推动国内生物遗传资源获取管制法律和监管体制创设, 开展生物遗传资源获取和惠益分享能力建设项目。     

偏孟德尔分离的遗传学实验设计与探讨

本文将科研中发现的一个含调控杂种花粉不育基因座(S23)的水稻材料(DSSL)应用于教学,设计了一个基于SSR分子标记对比经典孟德尔分离和偏孟德尔分离的综合性实验。利用位于水稻两条染色体上的4个SSR标记对两亲本及其杂交构建的F_2代群体进行单株基因型检测,用显微图像观察与统计分析亲本及杂种F1的花粉育性,不仅从分子水平上验证了分离定律,更从基因型到表型的观察实验中完整展现了水稻的偏孟德尔分离现象及其原因,加深了学生对植物遗传规律、基因型与表型关系的理解,激发了学生对实验的兴趣与探究动机,增强了学生对实验学习的自觉性和积极性。并在此基础上构思一个科研成果转化至教学应用的可持续发展思路,以推动实验教学的改革与创新。     

ABO血型遗传习题一例

《日本中学生物课基础》一书中(第194页)有这样一道试题(本题有增改): 人类的ABO血型系统是遗传的。该血型系统决定于I~A、I~B和i三个基因。基因I~A、I~B对i是显性,基因型I~AI~A和I~Ai的个体为A型血;基因型I~BI~B和I~Bi的个体为B型血;基因型     

The Synthesis Paradigm in Genetics

Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics—and other fields of biology—are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous “-omics” data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time.MAJOR advances in the field of genetics have been developed on a foundation supported by three major pillars (i.e., paradigms, by which I mean a framework of basic assumptions, logical approaches, and methodologies), two of which are widely known and appreciated while the third is rarely even acknowledged. The first major paradigm is experimental genetics, especially in the context of model organisms. The work of Thomas H. Morgan and his colleagues at Cal Tech during the early 20th century is a classic example of this approach. A succession of elegant experimental studies by this research team led to the development of the Drosophila melanogaster model system, which Morgan et al. (1915) used to construct the first genomic map that included genes assigned to precise locations on all of an organism’s chromosomes. Their accumulated experimental results also contributed importantly to their book, The Mechanism of Mendelian Heredity (1915), which many consider to be the catalyst that launched the modern era of genetics.The second paradigm is mathematically explicit genetic theory. The succession of genetical theory papers published throughout the first half of the 20th century by Ronald A. Fisher is a classic example of this approach. Fisher’s work reconciled a fundamental rift in the early history of modern genetics—i.e., the genetic approaches of the Mendelians (advocated by William Bateson and Hugo de Vries) vs. the Galtonians (also known as the biometricians, represented in particular by Karl Pearson and Walter F. Weldon)—by showing that Mendelian particulate inheritance could be unified with the quantitative genetics used to analyze continuously varying traits such as height and weight (Fisher 1918). Although Darwin developed the basic framework of evolution, it was Fisher—and contemporary theoreticians Sewall Wright and J. B. S. Haldane—who integrated this qualitative idea into a quantitatively explicit genetic theory that led to the modern synthesis of evolution and launched the field of evolutionary genetics (also known as population genetics and summarized in Fisher’s now classic book, The Genetical Theory of Natural Selection, first published in 1930). Of course, some theory in genetics is not mathematically explicit, such as the “chromosomal theory of inheritance” or the “central dogma.” But this form of theory usually represents the culmination of studies using the experimental genetics paradigm rather than a unique approach to genetics.Most major advances in genetics have been achieved via one, the other, or a combination of these experimental and theoretical paradigms. But there is a well-known exception: Watson and Crick’s discovery of the structure of DNA (Watson and Crick 1953a,b, ∼11,000 combined citations—throughout, numbers of citations are taken from Google Scholar—, and arguably the pivotal publications that launched the modern field of molecular genetics). Watson and Crick used no mathematical genetic theory, nor did they do any critical experiments; instead, they integrated many threads of established information (some unpublished) to deduce the chemical structure of the hereditary material, i.e., the DNA double helix and how this structure could explain gene replication. Although later experiments, such as those of Meselson and Stahl (1958) on DNA replication, would ultimately confirm the deduced structure and replication of DNA that was proposed by Watson and Crick, the pivotal publications of these researchers used neither the experimental nor the theory paradigms of genetics. Their approach exemplifies what I will call the “synthesis paradigm.” Watson and Crick’s work demonstrates that there is actually a trichotomy of approaches—the experimental, theoretical-mathematical, and theoretical-synthetic approaches—that combine like interwoven, reinforcing strands in a cord of historical advances in genetics.In the next few sections I describe other instances in which the synthesis paradigm has been of critical importance in the field of genetics. This set of examples is meant to be illustrative and by no means exhaustive. Next I illustrate how the synthesis paradigm has been of critical importance in other fields of biology. Finally, I describe how a fuller appreciation of the synthesis paradigm can influence the training of the next cohort of geneticists and the career trajectory of current geneticists.     

Transposing from the Laboratory to the Classroom to Generate Authentic Research Experiences for Undergraduates

Large lecture classes and standardized laboratory exercises are characteristic of introductory biology courses. Previous research has found that these courses do not adequately convey the process of scientific research and the excitement of discovery. Here we propose a model that provides beginning biology students with an inquiry-based, active learning laboratory experience. The Dynamic Genome course replicates a modern research laboratory focused on eukaryotic transposable elements where beginning undergraduates learn key genetics concepts, experimental design, and molecular biological skills. Here we report on two key features of the course, a didactic module and the capstone original research project. The module is a modified version of a published experiment where students experience how virtual transposable elements from rice (Oryza sativa) are assayed for function in transgenic Arabidopsis thaliana. As part of the module, students analyze the phenotypes and genotypes of transgenic plants to determine the requirements for transposition. After mastering the skills and concepts, students participate in an authentic research project where they use computational analysis and PCR to detect transposable element insertion site polymorphism in a panel of diverse maize strains. As a consequence of their engagement in this course, students report large gains in their ability to understand the nature of research and demonstrate that they can apply that knowledge to independent research projects.     

运用多重PCR-直接测序法检测ABO基因型及其遗传多态性

根据ABO基因座第6和7外显子9个SNP位点设计引物, 复合扩增后直接测序, 根据测序结果判定不同物证检材ABO基因型及其在藏族群体中的多态性分布。成功地检测出经过不同方法处理的血痕、毛发、口腔拭子、骨骼、混合斑等101例腐败、降解及微量检材的ABO基因型, 结果与免疫血清学分型一致, 且该方法具有灵敏度高、特异性好、操作简单、结果准确、客观及能够发现新等位基因等优点。对80名青海藏族无关个体的调查表明, ABO基因型分布符合Hardy-Weinberg平衡, 杂合度H为0.675, 多态信息含量PIC为0.672, 个人识别力DP值为0.874, 非父排除率PE值为0.391, 偶合度I为0.126; 青海藏族ABO等位基因频率O>B>A, 且O等位基因频率高达0.6125。多重PCR-直接测序法检测ABO基因型适用于法医学不同来源的样本, 提高了ABO血型系统的个体识别能力; ABO基因型在青海藏族人群中的分布具有较高多态性, 可用于法医学个体识别及群体遗传学研究。     

Lack of impact of undergraduate genetic courses on the teaching of medical genetics.

The impact of undergraduate genetic courses on the academic performance of first-year medical students in the medical genetics course at the University of Pittsburgh School of Medicine was evaluated over a period of 9 years. Comparisons were made between medical students who had taken a formal undergraduate course in genetics and those who had not. Little if any differences were found in the academic performance in the medical genetics course between these two groups of students. Perhaps the design of undergraduate courses in genetics should be re-evaluated to give more depth to the medical student's preparation for appreciating the significance of genetics in normal and abnormal human variation.     

基于SSLP分子标记验证遗传学三大定律的教学实践探索与体会

文章对“水稻SSLP分子标记的遗传分析”作为遗传学实验教学案例的实施过程及其效果进行了探讨。利用位于水稻两条染色体上的3个SSLP标记,对两亲本及其杂交构建的F₂代群体进行单株SSLP标记基因型检测,利用检测所得到的基因型结果验证分离定律、独立分配定律及连锁交换定律等遗传学三大定律。实践证明这不仅有利于加深学生对遗传学三大定律的认识,而且在提高学生实验操作技能和综合分析能力的基础上,还有助于培养学生的科研兴趣和创新意识。同时,对该实验的适用范围以及尚需完善之处做了讨论。此综合性实验也是科研成果转化为本科实验教学的一个有益探索。     

Validation of a cost-efficient multi-purpose SNP panel for disease based research

Background

Here we present convergent methodologies using theoretical calculations, empirical assessment on in-house and publicly available datasets as well as in silico simulations, that validate a panel of SNPs for a variety of necessary tasks in human genetics disease research before resources are committed to larger-scale genotyping studies on those samples. While large-scale well-funded human genetic studies routinely have up to a million SNP genotypes, samples in a human genetics laboratory that are not yet part of such studies may be productively utilized in pilot projects or as part of targeted follow-up work though such smaller scale applications require at least some genome-wide genotype data for quality control purposes such as DNA “barcoding” to detect swaps or contamination issues, determining familial relationships between samples and correcting biases due to population effects such as population stratification in pilot studies.

Principal Findings

Empirical performance in classification of relative types for any two given DNA samples (e.g., full siblings, parental, etc) indicated that for outbred populations the panel performs sufficiently to classify relationship in extended families and therefore also for smaller structures such as trios and for twin zygosity testing. Additionally, familial relationships do not significantly diminish the (mean match) probability of sharing SNP genotypes in pedigrees, further indicating the uniqueness of the “barcode.” Simulation using these SNPs for an African American case-control disease association study demonstrated that population stratification, even in complex admixed samples, can be adequately corrected under a range of disease models using the SNP panel.

Conclusion

The panel has been validated for use in a variety of human disease genetics research tasks including sample barcoding, relationship verification, population substructure detection and statistical correction. Given the ease of genotyping our specific assay contained herein, this panel represents a useful and economical panel for human geneticists.     

化学在农业院校遗传学教学中的渗透与思考

农业院校多数专业的课程设置里面, 化学是一类重要的基础课程, 而遗传学是核心的专业基础课。怎样将先修的化学知识向遗传学教学进行渗透, 从而在逻辑上体现专业基础课对基础课的“承上”功能, 是遗传学教师值得探讨的新问题。作者认为, 在农业院校的本科遗传学教学中, 应充分利用先修课程特别是化学的知识原理, 采用“渗透式”教学, 分析学科间知识点的内在联系, 加深学生对遗传学知识的认知和理解, 构建完整的知识体系, 提高学生分析能力、综合能力和逻辑思维能力, 探索综合竞争力强的复合型人才培养的教学模式。     

WinPop 2.5: software for representing population genetics phenomena

The curriculum for genetics courses is shifting from a classical to a more molecular genetics focus, increasing the importance of subjects such as population genetics. Population genetics is a computational and statistical field that requires a good understanding of the nature of stochastic events. It is a difficult field for biology students with a limited mathematical background and there is a need for visualisation tools to facilitate understanding by the use of practical examples. WinPop provides students and researchers with a visual tool to allow the simulation and representation of population genetics phenomena. WinPop is a user-friendly software meant for use in population genetics courses and basic research. WinPop 2.5 contains six different modules that represent and simulate population genetics models. Genotype and allele frequencies are calculated under the different models: panmixia, genetic drift, assortative matings, selection, gene flow and mutation. The program's interface presents information in Cartesian graphics and isosceles triangular coordinate systems, allowing the user to save graphical and textual data output from the simulations. WinPop is developed in Visual Basic 6.0 and uses Windows 95 and higher. WinPop 2.5 can be downloaded from http://www.genedrift.org/winpop.php.