Going the distance: human population genetics in a clinal world

Global human genetic variation is greatly influenced by geography, with genetic differentiation between populations increasing with geographic distance and within-population diversity decreasing with distance from Africa. In fact, these 'clines' can explain most of the variation in human populations. Despite this, population genetics inferences often rely on models that do not take geography into account, which could result in misleading conclusions when working at global geographic scales. Geographically explicit approaches have great potential for the study of human population genetics. Here, we discuss the most promising avenues of research in the context of human settlement history and the detection of genomic elements under natural selection. We also review recent technical advances and address the challenges of integrating geography and genetics.     

Zeitgeschichte der Humangenetik in Deutschland

Together with the German Society for Human Genetics (Deutsche Gesellschaft für Humangenetik, GfH) a team of researchers from the Department for the History, Philosophy, and Ethics of Medicine of Heinrich Heine University Düsseldorf in cooperation with the Department for History of Medicine and Science Studies of the University of Lübeck has begun a research project on the history of human genetics in Germany since the 1970s. We employ the method of oral history to add to printed secondary and primary sources. In this contribution we present the project, its research questions and situate it in the historiography of human genetics in Germany. Approaches to writing contemporary history of medicine and challenges of conducting and analyzing expert interviews are discussed.     

Inferring number of populations and changes in connectivity under the n-island model

Inferring the demographic history of species is one of the greatest challenges in populations genetics. This history is often represented as a history of size changes, ignoring population structure. Alternatively, when structure is assumed, it is defined a priori as a population tree and not inferred. Here we propose a framework based on the IICR (Inverse Instantaneous Coalescence Rate). The IICR can be estimated for a single diploid individual using the PSMC method of Li and Durbin (2011). For an isolated panmictic population, the IICR matches the population size history, and this is how the PSMC outputs are generally interpreted. However, it is increasingly acknowledged that the IICR is a function of the demographic model and sampling scheme with limited connection to population size changes. Our method fits observed IICR curves of diploid individuals with IICR curves obtained under piecewise stationary symmetrical island models. In our models we assume a fixed number of time periods during which gene flow is constant, but gene flow is allowed to change between time periods. We infer the number of islands, their sizes, the periods at which connectivity changes and the corresponding rates of connectivity. Validation with simulated data showed that the method can accurately recover most of the scenario parameters. Our application to a set of five human PSMCs yielded demographic histories that are in agreement with previous studies using similar methods and with recent research suggesting ancient human structure. They are in contrast with the view of human evolution consisting of one ancestral population branching into three large continental and panmictic populations with varying degrees of connectivity and no population structure within each continent.Subject terms: Population genetics, Biological models, Population genetics     

Welsh I am

With developments in genetics, researchers are increasingly able to address historical issues surrounding human migration and provenance by studying present populations. Nigel Williams reports on one of the latest studies looking at a crucial period of British history.     

Quantitative trait loci and the study of plant domestication

Plant domestication ranks as one of the most important developments in human history, giving human populations the potential to harness unprecedented quantities of the earths resources. But domestication has also played a more subtle historical role as the foundation of the modern study of evolution and adaptation. Until recently, however, researchers interested in domestication were limited to studying phenotypic changes or the genetics of simple Mendelian traits, when often the characters of most interest – fruit size, yield, height, flowering time, etc. – are quantitative in nature. The goals of this paper are to review some of the recent work on the quantitative genetics of plant domestication, identify some of the common trends found in this literature, and offer some novel interpretations of the data that is currently available.     

I3:A Self-organising Learning Workflow for Intuitive Integrative Interpretation of Complex Genetic Data

We propose a computational workflow(I3) for intuitive integrative interpretation of complex genetic data mainly building on the self-organising principle.We illustrate the use in interpreting genetics of gene expression and understanding genetic regulators of protein phenotypes,particularly in conjunction with information from human population genetics and/or evolutionary history of human genes.We reveal that loss-of-function intolerant genes tend to be depleted of tissue-sharing genetics of gene expression in brains,and if highly expressed,have broad effects on the protein phenotypes studied.We suggest that this workflow presents a general solution to the challenge of complex genetic data interpretation.I3 is available at http://suprahex.r-forge.r-project.org/I3.html.     

遗传学史在遗传学教学中的作用

科学史的研究和发展状况能反映一个国家的科学技术水平,遗传学史是生命科学发展史的一个重要分支,21世纪是生命科学的世纪,在遗传学教学中加强遗传学发展史的介绍,不仅具有教育功能,使学生了解遗传学的产生和发展,而且可以培养学生的思维能力和科学素质。本文就遗传学史的教育功能及在教学中的作用进行论述。     

Sixty Years of Modern Human Origins in the American Anthropological Association

We present a review of the history of scientific inquiry into modern human origins, focusing on the role of the American Anthropologist . We begin during the mid–20th century, at the time when the problem of modern human origins was first presented in the American Anthropologist and could first be distinguished from more general questions about human and hominid origins. Next, we discuss the effects of the modern evolutionary synthesis on biological anthropology and paleoanthropology in particular, and its role in the origin of anthropological genetics. The rise of human genetics is discussed along two tracks, which have taken starkly different approaches to the historical interpretation of recent human diversity. We cover varying paleoanthropological interpretations, including paleoanthropologists' reactions to genetic interpretations. We hope to identify some of the crucial inflection points in which the debate went astray, to rectify some of the points of misunderstanding among current scientists, and to clarify the likely path ahead. [Keywords: multiregional evolution, recent African origin, bottleneck, polygenism, race]     

Mouse Forward Genetics in the Study of the Peripheral Nervous System and Human Peripheral Neuropathy

Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. Special issue article in honor of Dr. George DeVries.     

The multifactor pelvis: An alternative to the adaptationist approach of the obstetrical dilemma

The obstetrical dilemma describes the competing demands that a bipedally adapted pelvis and a large-brained neonate place on human childbirth and is the predominant model within which hypotheses about the evolution of the pelvis are framed. I argue the obstetrical dilemma follows the adaptationist program outlined by Gould and Lewontin in 1979 and should be replaced with a new model, the multifactor pelvis. This change will allow thorough consideration of nonadaptive explanations for the evolution of the human pelvis and avoid negative social impacts from considering human childbirth inherently dangerous. First, the atomization of the pelvis into discrete traits is discussed, after which current evidence for both adaptive and nonadaptive hypotheses is evaluated, including childbirth, locomotion, shared genetics with other traits under selection, evolutionary history, genetic drift, and environmental and epigenetic influences on the pelvis.     

ASHG activities relative to education: Human genetics as a component of medical school curricula: A report to the American society of human genetics

In recent years, there has been a remarkable increase in both the rate of acquiring new information about human genetics and the importance of human genetics for modern health care. As a result, human genetics educators have queried whether the teaching of human genetics in North-American medical schools has kept pace with these increases. To address this question, a survey of these medical schools was undertaken to assess how human geneticists perceive the teaching of human genetics in their respective institutions. The results of the survey, begun and completed in 1985, indicate the following: (1) the teaching of human genetics in medical schools is extremely variable from one institution to another, with some schools having no identifiable human genetics teaching at all; (2) the relevance of human genetics to other basic science and clinical disciplines apparently leads to noncategorical or fragmented teaching of human genetics, which may also contribute to the absence of a specific medical school course in the subject; and (3) there is a need for closer collaboration between human genetics educators and their respective medical school administrators and curriculum committees.     

《遗传学》教学中若干问题的数学解析Ⅱ

遗传学教学过程中会发现一系列启发性的问题,涉及孟德尔遗传、数量遗传、群体遗传和人类遗传等领域,这些问题对许多学生来讲有趣且有一定难度。收集了若干启发性问题,包括自交后代各种表型可能出现的频率、多次回交的目的、显性性状是否在群体中占有更大的比例、为什么母亲的年龄与子女的正常与否有很大的关系、遗传力的估算方法等,并用数学方法一一进行剖析,以供相关同学和同行借鉴和思考。     

植物分子群体遗传学研究动态

分子群体遗传学是当代进化生物学研究的支柱学科, 也是遗传育种和关于遗传关联作图和连锁分析的基础理论学科。分子群体遗传学是在经典群体遗传的基础上发展起来的, 它利用大分子主要是DNA序列的变异式样来研究群体的遗传结构及引起群体遗传变化的因素与群体遗传结构的关系, 从而使得遗传学家能够从数量上精确地推知群体的进化演变, 不仅克服了经典的群体遗传学通常只能研究群体遗传结构短期变化的局限性, 而且可检验以往关于长期进化或遗传系统稳定性推论的可靠程度。同时, 对群体中分子序列变异式样的研究也使人们开始重新审视达尔文的以“自然选择”为核心的进化学说。到目前为止, 分子群体遗传学已经取得长足的发展, 阐明了许多重要的科学问题, 如一些重要农作物的DNA多态性式样、连锁不平衡水平及其影响因素、种群的变迁历史、基因进化的遗传学动力等, 更为重要的是, 在分子群体遗传学基础上建立起来的新兴的学科如分子系统地理学等也得到了迅速的发展。文中综述了植物分子群体遗传研究的内容及最新成果。     

Eugenics: past, present, and the future.

During the past 20 years there has been a resurgence of interest in the history of the eugenics movements, particularly those of the United States and Germany. Unfortunately, most of these accounts have been published in nonmedical and nongenetic journals, so they are not readily available to geneticists or physicians. The authors of this article are concerned about the lack of information that geneticists, physicians, and students have concerning the origin and progress of these movements. This article provides a short history of the American and German eugenics programs and concludes with a review of their possible relations to our current practices. It is hoped that this will encourage institutions to include, in master's Ph.D., and M.D. programs in human genetics, lectures, seminars, and journal clubs on the topic of eugenics.     

Mutational Dynamics of Microsatellites

Microsatellites are a ubiquitous class of simple repetitive DNA sequences, which are widespread in both eukaryotic and prokaryotic genomes. The use of microsatellites as polymorphic DNA markers has considerably increased both in the number of studies and in the number of organisms, primarily for genetic mapping, studying genomic instability in cancer, population genetics, forensics, conservation biology, molecular anthropology and in the studies of human evolutionary history. Although simple sequence repeats have been extensively used in studies encompassing varied areas of genetics, the mutation dynamics of these genome regions is still not well understood. The present review focuses on the mutational dynamics of microsatellite DNA with special reference to mutational mechanisms and their role in microsatellite evolution.     

动物生活史进化理论研究进展

综述了生活史性状、生活史对策、权衡、适合度及进化种群统计学等动物生活史进化领域的进展。权衡是生活史性状之间相互联系的纽带,分为生理权衡与进化权衡。适合度是相对的,与个体所处的特定环境条件有关,性状进化与适合度之间关系紧密。适合度是生活史进化理论研究的焦点。探讨动物生活史对策的理论很多,影响最大的是MacArthur和Wilson提出的r对策及K对策理论。随年龄的增长,动物存活率及繁殖率逐步下降的过程,称为衰老;解释衰老的进化理论主要有突变-选择平衡假设和多效对抗假设。进化种群统计学将种群统计学应用于生活史进化研究,为探讨表型适合度的进化提供了有效的手段。将进化种群统计学、数量遗传学及特定种系效应理论进行整合,建立完整的动物生活史进化综合理论体系,是当代此领域的最大挑战。     

Invasion genetics of a human commensal rodent: the black rat Rattus rattus in Madagascar

Studies focusing on geographical genetic patterns of commensal species and on human history complement each other and provide proxies to trace common colonization events. On Madagascar, the unintentional introduction and spread of the commensal species Rattus rattus by people may have left a living clue of human colonization patterns and history. In this study, we addressed this question by characterizing the genetic structure of natural populations of R. rattus using both microsatellites and mitochondrial sequences, on an extensive sampling across the island. Such data sets were analysed by a combination of methods using population genetics, phylogeography and approximate Bayesian computation. Our results indicated two introduction events to Madagascar from the same ancestral source of R. rattus, one in the extreme north of the island and the other further south. The latter was the source of a large spatial expansion, which may have initially started from an original point located on the southern coast. The inferred timing of introduction events—several centuries ago—is temporally congruent with the Arabian trade network in the Indian Ocean, which was flourishing from the middle of the first millennium.     

Human behavioural genetics of cognitive abilities and disabilities

Although neither the genome nor the environment can be manipulated in research on human behaviour, some of the new tools of molecular genetics can be brought to bear on human behavioural disorders (e.g. cognitive disabilities) and quantitative traits (e.g. cognitive abilities). The inability to manipulate the human genome experimentally has had the positive effect of focusing attention on naturally occuring genetic variation responsible for behavioural differences among individuals in all their complex multifactorial splendour. Genes in such complex multiple-gene systems are called quantitative trait loci (QTLs), which merge the two worlds of genetic research, quantitative genetics and molecular genetics. Although most genetic research on complex human behaviour has focused on severe mental disorders, cognitive abilities and disabilities may be even more immediately relevant to neuroscience. For example, verbal ability and spatial ability are two of the most heritable cognitive abilities, and reading disability is the first behavioural disability for which replicated QTL linkage has been found. The purpose of this essay is to provide an overview of the genetics of cognitive abilities and disabilities as an example of the impending merger of quantitative genetics and molecular genetics in QTL analysis of complex traits.     

Zukunft der Zytogenetik

This issue of the journal “Medizinische Genetik” emphasizes the current development of cytogenetic technologies. Changes in classical banding analysis, which has been a cornerstone of routine human genetics diagnostics for decades, are illustrated by means of quality assurance measures. Several contributions in this issue describe molecular cytogenetic technologies, which are based on fluorescence in situ hybridization (FISH). The introduction of comparative genomic hybridization, especially on various array platforms, revolutionized cytogenetics even further and now allows researchers to address entirely new questions and problems in human genetics. An especial stronghold of cytogenetics that distinguishes it from other molecular technologies is the option to perform analyses on a single-cell level. In this issue, possible future developments in cytogenetics are also discussed.