Evolving use of ancestry, ethnicity, and race in genetics research-A survey spanning seven decades.

To inform continuous and rigorous reflection about the description of human populations in genomics research, this study investigates the historical and contemporary use of the terms "ancestry," "ethnicity," "race," and other population labels in The American Journal of Human Genetics from 1949 to 2018. We characterize these terms' frequency of use and assess their odds of co-occurrence with a set of social and genetic topical terms. Throughout The Journal's 70-year history, "ancestry" and "ethnicity" have increased in use, appearing in 33% and 26% of articles in 2009-2018, while the use of "race" has decreased, occurring in 4% of articles in 2009-2018. Although its overall use has declined, the odds of "race" appearing in the presence of "ethnicity" has increased relative to the odds of occurring in its absence. Forms of population descriptors "Caucasian" and "Negro" have largely disappeared from The Journal (<1% of articles in 2009-2018). Conversely, the continental labels "African," "Asian," and "European" have increased in use and appear in 18%, 14%, and 42% of articles from 2009-2018, respectively. Decreasing uses of the terms "race," "Caucasian," and "Negro" are indicative of a transition away from the field's history of explicitly biological race science; at the same time, the increasing use of "ancestry," "ethnicity," and continental labels should serve to motivate ongoing reflection as the terminology used to describe genetic variation continues to evolve.

Narratives of contingency and practices of comparing in the emergence of German molecular genetics (1958-1968).

This article explores the emergence of molecular approaches in German genetic research during the 1958-1968 decade as a period of contingency and alternative possibilities. We introduce "Narratives of Contingency" as an analytical framework to examine how scientists construct a specific narrative - linking past experiences with expectations of future conditions - in order to outline and navigate pathway-decisions in the present. We apply this framework to Hans-Jörg Rheinberger's developmental model of molecular genetics and illustrate how the stages he identifies - the direction of the field, institutional developments, and epistemological demarcations - were already central themes in the comparative practices underlying narratives of contingency in this early period. Narratives of contingency can thus serve as a systematic framework for analyzing the processes through which new scientific fields, institutions, and epistemic horizons emerge, and possibly also for identifying historically plausible fork moments or alternative pathways not taken.

Human genetics in post-WWII Italy: blood, genes and platforms.

Italian Life sciences in post-WWII faced important challenges: the reconstruction of a scientific panorama suffering heavily after two decades of Fascism and the damages of war. Modernization was not only a matter of recreating a favorable environment for research, by modernizing Italian biomedical institutions and connecting the Italian scientists with the new ideas coming from abroad. The introduction of new genetics required a new array of concepts and instruments, but also, the ability to connect to international networks and to become active members of a broader scientific community. Because of the several socio-cultural issues involved (eugenics, racism, religion, politics), human genetics is a good case study in order to analyze how Italian life sciences managed the transition towards a new research system, and the influences Italian human geneticists received. The paper focuses primarily on the development of the early career of Luigi Luca Cavalli-Sforza, probably the most prominent scientist in post-WWII human genetics in Italy, and his friend and colleague Ruggero Ceppellini. In following their path, a healthy mix of local traditions and international stimuli emerges, allowing for the establishment-within and beyond national borders-of the discipline.

Anticipating the ethical, legal, and social implications of human genome research: An ongoing experiment.

Dr. Victor McKusick was a founding member of the joint NIH-DOE working group that designed the federal effort to address the ethical, legal, and social implications of the US Human Genome Project in 1989. A key feature of this effort was its commitment to anticipating genomics-driven questions before they became urgent practical dilemmas, by complementing the scientific effort to map and sequence the human genome with projects by a wide range of social scientists, humanities scholars, legal experts, and public educators designed to equip society with the foresight required to optimize the public welfare benefits of new genomic information. This article describes the origins of that experiment and the model of anticipatory science policy that it produced, as one piece of Dr. McKusick's extraordinary intellectual legacy.

Mendel and Darwin: untangling a persistent enigma.

Mendel and Darwin were contemporaries, with much overlap in their scientifically productive years. Available evidence shows that Mendel knew much about Darwin, whereas Darwin knew nothing of Mendel. Because of the fragmentary nature of this evidence, published inferences regarding Mendel's views on Darwinian evolution are contradictory and enigmatic, with claims ranging from enthusiastic acceptance to outright rejection. The objective of this review is to examine evidence from Mendel's published and private writings on evolution and Darwin, and the influence of the scientific environment in which he was immersed. Much of this evidence lies in Mendel's handwritten annotations in his copies of Darwin's books, which this review scrutinises in detail. Darwin's writings directly influenced Mendel's classic 1866 paper, and his letters to Nägeli. He commended and criticised Darwin on specific issues pertinent to his research, including the provisional hypothesis of pangenesis, the role of pollen in fertilisation, and the influence of "conditions of life" on heritable variation. In his final letter to Nägeli, Mendel proposed a Darwinian scenario for natural selection using the same German term for "struggle for existence" as in his copies of Darwin's books. His published and private scientific writings are entirely objective, devoid of polemics or religious allusions, and address evolutionary questions in a manner consistent with that of his scientific contemporaries. The image that emerges of Mendel is of a meticulous scientist who accepted the tenets of Darwinian evolution, while privately pinpointing aspects of Darwin's views of inheritance that were not supported by Mendel's own experiments.

Göte Turesson's research legacy to Hereditas: from the ecotype concept in plants to the analysis of landraces' diversity in crops.

Hereditas began with articles on plants since its first issue in May 1920 (six out of eight) and continued with more original articles (43% of the total of this journal) on plants (of which 72% of those in plants were on crops) until today. In December 1922, the 140-page article The Genotypical Response of the Plant Species to the Habitat by evolutionary botanist Göte Turesson (Institute of Genetics, Lund University, Åkarp, Sweden) became available. This publication shows that plant phenology has a genetic basis and may ensue from local adaptation. As a result of this research involving various plant species, Turesson elaborated further in this article his term ecotype "as an ecological sub-unit to cover the product arising as a result of the genotypical response of an ecospecies to a particular habitat." Although plant articles included in Hereditas involved from its beginning, trait inheritance, mutants, linkage analysis, cytology or cytogenetics, and more recently gene mapping and analysis of quantitative trait loci with the aid of DNA markers, among others, since the mid-1980s several publications refer to the population biology of plant landraces, which are locally grown cultivars that evolved over time by adapting to their natural and cultural environment (i.e., agriculture), and that may become isolated from other populations of the same crop. This article provides a briefing about research on plant science in the journal with emphasis on crops, summarizes the legacy to genetics of Göte Turesson, and highlights some landrace diversity research results and their potential for plant breeding.

[Retrospect and prospect of the genetic research on birth defects in China].

An important part of China's "Healthy China 2030" planning is to lower the rate of birth defects. Because genetic factors contribute solely or collaboratively to about 80% of the occurrence of birth defects, genetic studies on birth defects can provide precise molecular targets for clinical screening, diagnosis and treatment. Genetic research on birth defects in China has developed by leaps and bounds since 1960s. At the same time, as related research achievements keep accumulating, translation of these scientific discoveries to clinical applications, with genetic counseling and testing as the core practices, has been developed and optimized. A close collaboration between genetic researches and clinical applications would provide reliable technical support for giving birth to more "healthy children" in China. This article firstly reviews China's history of genetic research on birth defects, then introduces current situation and hot topics of the research area at home and abroad and finally discusses about future trend and related clinical applications. In summary, an overall view is provided here for the readers to understand the development route of genetic research on birth defects in China.

The historical role of species from the Solanaceae plant family in genetic research.

KEY MESSAGE: This article evaluates the main contributions of tomato, tobacco, petunia, potato, pepper and eggplant to classical and molecular plant genetics and genomics since the beginning of the twentieth century. Species from the Solanaceae family form integral parts of human civilizations as food sources and drugs since thousands of years, and, more recently, as ornamentals. Some Solanaceous species were subjects of classical and molecular genetic research over the last 100 years. The tomato was one of the principal models in twentieth century classical genetics and a pacemaker of genome analysis in plants including molecular linkage maps, positional cloning of disease resistance genes and quantitative trait loci (QTL). Besides that, tomato is the model for the genetics of fruit development and composition. Tobacco was the major model used to establish the principals and methods of plant somatic cell genetics including in vitro propagation of cells and tissues, totipotency of somatic cells, doubled haploid production and genetic transformation. Petunia was a model for elucidating the biochemical and genetic basis of flower color and development. The cultivated potato is the economically most important Solanaceous plant and ranks third after wheat and rice as one of the world's great food crops. Potato is the model for studying the genetic basis of tuber development. Molecular genetics and genomics of potato, in particular association genetics, made valuable contributions to the genetic dissection of complex agronomic traits and the development of diagnostic markers for breeding applications. Pepper and eggplant are horticultural crops of worldwide relevance. Genetic and genomic research in pepper and eggplant mostly followed the tomato model. Comparative genome analysis of tomato, potato, pepper and eggplant contributed to the understanding of plant genome evolution.

James L. German, a pioneer in early human genetic research turned 90.

In the early 1960s, J. German established the non-synchronous human DNA replication pattern in metaphases of cultured lymphocytes and fibroblasts. This could be used to distinguish several chromosomes of similar morphology. From 1965 on over the next 30 years, he and his coworkers systematically studied Bloom's syndrome in depth, cumulating in the identification in 1995 of the BLM gene as encoding a DNA helicase. © 2016 Wiley Periodicals, Inc.

Science beyond boundary: are premature discoveries things of the past?

Mendel's name more than of any other draws our attention to the personal side in terms of success and failure in science. Mendel lived 19 years after presenting his research findings and died without receiving any recognition for his work. Are premature discoveries things of the past, you may ask? I review the material basis of science in terms of science boundary and field accessibility and analyze the possibility of premature discoveries in different fields of science such as, for example, physics and biology. I conclude that science has reached a stage where progress is being made mostly by pushing the boundary of the known from inside than by leaping across boundaries. As more researchers become engaged in science, and as more publications become open access, on-line, and interactive, the probability of an important discovery remaining buried and going unrecognized would become exceedingly small. Of course, as examples from physics show, a new theory or an important idea can always lie low, unrecognized until it becomes re-discovered and popularized by other researchers. Thus, premature discoveries will become less likely but not forbidden.

Darwin and Mendel today: a comment on "Limits of imagination: the 150th Anniversary of Mendel's Laws, and why Mendel failed to see the importance of his discovery for Darwin's theory of evolution".

We comment on a recent paper by Rama Singh, who concludes that Mendel deserved to be called the father of genetics, and Darwin would not have understood the significance of Mendel's paper had he read it. We argue that Darwin should have been regarded as the father of genetics not only because he was the first to formulate a unifying theory of heredity, variation, and development -- Pangenesis, but also because he clearly described almost all genetical phenomena of fundamental importance, including what he called "prepotency" and what we now call "dominance" or "Mendelian inheritance". The word "gene" evolved from Darwin's imagined "gemmules", instead of Mendel's so-called "factors".

Limits of imagination: the 150th Anniversary of Mendel's Laws, and why Mendel failed to see the importance of his discovery for Darwin's theory of evolution.

Mendel is credited for discovering Laws of Heredity, but his work has come under criticism on three grounds: for possible falsification of data to fit his expectations, for getting undue credit for the laws of heredity without having ideas of segregation and independent assortment, and for being interested in the development of hybrids rather than in the laws of heredity. I present a brief review of these criticisms and conclude that Mendel deserved to be called the father of genetics even if he may not, and most likely did not, have clear ideas of segregation and particulate determiners as we know them now. I argue that neither Mendel understood the evolutionary significance of his findings for the problem of genetic variation, nor would Darwin have understood their significance had he read Mendel's paper. I argue that the limits to imagination, in both cases, came from their mental framework being shaped by existing paradigms-blending inheritance in the case of Darwin, hybrid development in the case of Mendel. Like Einstein, Darwin's natural selection was deterministic; like Niels Bohr, Mendel's Laws were probabilistic-based on random segregation of trait-determining "factors". Unlike Einstein who understood quantum mechanics, Darwin would have been at a loss with Mendel's paper with no guide to turn to. Geniuses in their imaginations are like heat-seeking missiles locked-in with their targets of deep interests and they generally see things in one dimension only. Imagination has limits; unaided imagination is like a bird without wings--it goes nowhere.

Heterochromatin and gene positioning: inside, outside, any side?

All cellular processes depend on the expression and repression of the right sets of genes at the right time. As each cell contains the same DNA, transcriptional and epigenetic factors have to maintain tight control over gene expression. Even a small divergence from the correct transcriptional program can lead to severe defects and even death. Having deciphered the complete linear genetic information, we need to clarify how this information is organized into the dynamic and highly heterogeneous three-dimensional space of the eukaryotic cell nucleus. Observations on the higher order organization of DNA into differentiated condensation levels date back to the early twentieth century, and potential implications of these structural features to gene expression were postulated shortly after. In particular, proximity of genes to condensed regions of heterochromatin was proposed to negatively influence their expression and, henceforward, the concept of heterochromatin as subnuclear silencing compartment emerged. Methodological advances fueled a flurry of recent studies, which only, in part, led support to this concept. In this review, we address how (hetero)chromatin structure and proximity might influence gene expression and discuss the challenges and means to unravel this fundamental biological question.

The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009.

The large mouse genetics program at the Oak Ridge National Laboratory (ORNL) is often remembered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-chromosome's importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a valuable source of mouse models for human genetic disorders.

What fruit flies can tell us about human birth defects.

Many times, when a human genetic disease is mapped to mutations in a specific gene, little is known about the biological functions of the affected gene. Development of new therapeutic methods is facilitated by understanding the gene's biological roles. Such information can often be obtained in animal models, such as the fruit fly. Here we describe how understanding a gene's function in fruit flies has illuminated the etiology of Cornelia de Lange syndrome.