GENOMICS AND MOLECULAR GENETICS

Research in the field of epigenetics challenges the assumption on which the molecular genetics of the past 50 years has been based, namely, genetic determinism. This paper reviews the social science literature that considers the social effects of the application of molecular genetics and genetic testing in connection with Mendelian conditions. It is argued that anthropologists must now go farther and respond to the challenge posed by current moves toward the implementation of genetic profiling and testing for susceptibility genes. Following a discussion of ontological problems associated with molecular genetics raised by philosophers and biologists who subscribe to epigenetics, current knowledge about molecular and population genetics of lateonset Alzheimers disease and crosscultural findings about the epidemiology of this disease are introduced. These findings illustrate the provisional nature of these bodies of knowledge and the complexity associated with susceptibility genes, which makes estimations of probabilities of individual risk unrealistic. A controlled clinical trial is discussed in which firstdegree relatives of Alzheimers disease patients are genotyped for risk for lateonset Alzheimers disease. In conclusion, the social implications of testing for susceptibility genes are discussed, with comments about the role that anthropologists might play in future research.

INFORMED DISCUSSION of the ethical aspects of the application of discoveries in molecular genetics to human society requires a reasonably detailed understanding of the current and future technical possibilities. Yet, understandable descriptions of the technical possibilities are frequently difficult to come by, especially in an area which is changing as fast as molecular genetics. While newspaper reports of the latest scientific break-throughs are common, they are not always accompanied by sufficient information to enable the reader to put this latest revolutionary development in perspective. This paper is an attempt to describe in simplified terms some recent developments in the areas of molecular and human genetics, with special emphasis on developments which are already finding medical application, or which seem to me to be likely to do so in the near future. In order to focus this paper specifically on recent developments in genetics, I have not described work in other important areas such as in vitro fertilization and cloning. A review of recent developments in these areas, as well as an ethical critique of the experiments, can be found in the recent paper by Kass. While I have attempted to sketch the realm of the currently possible, and to extrapolate current trends a little into the future, nothing could be more deceptive than to assume that this is anything more than a highly selective snapshot as of early 1972. The pace of discoveries in the area of molecular genetics and the rate of development of our ability to synthesize, alter, and manipulate genetic elements in vitro is currently very rapid, and problems which looked like barriers to further development of genetic technology are rapidly disappearing.

The phosphotransferase system (PTS) controls preferential use of sugars in bacteria. It comprises of two general proteins, enzyme I (EI) and HPr, and various sugar-specific permeases. Using fluorescence microscopy, we show here that EI and HPr localize near the Escherichia coli cell poles. Polar localization of each protein occurs independently, but HPr is released from the poles in an EI- and sugar-dependent manner. Conversely, the β-glucoside-specific permease, BglF, localizes to the cell membrane. EI, HPr and BglF control the β-glucoside utilization (bgl) operon by modulating the activity of the BglG transcription factor; BglF inactivates BglG by membrane sequestration and phosphorylation, whereas EI and HPr activate it by an unknown mechanism in response to β-glucosides availability. Using biochemical, genetic and imaging methodologies, we show that EI and HPr interact with BglG and affect its subcellular localization in a phosphorylation-independent manner. Upon sugar stimulation, BglG migrates from the cell periphery to the cytoplasm through the poles. Hence, the PTS components appear to control bgl operon expression by ushering BglG between the cellular compartments. Our results reinforce the notion that signal transduction in bacteria involves dynamic localization of proteins.

We have converted a bacterial tRNA precursor containing a 205 nt self-splicing group I intron into a RNA enzyme that catalyzes polymerization of an external RNA substrate. The reaction involves transesterification steps analogous to both the forward and reverse exon ligation steps of group I splicing; as such it depends entirely on 3' splice site reactions. The RNA substrate is a 20 nt analogue of the ligated exons (E1.E2), whose 3' end resembles the 3' terminus of the intron RNA enzyme (IVS). The splice junction of the substrate is attacked by the 3' end of the intron, then the molecule displaces the original 3' terminal guanosine so that the new 3' terminus is brought into the active site and used as the attacking nucleophile in the next reaction. Polymerization occurs via a series of covalent enzyme-linked intermediates of the structure IVS.(E2)n, where n = 1 to > or = 18. The 5' exon accumulates during the course of the reaction and can attack the covalent intermediates to produce elongation products of structure E1.(E2)n, regenerating the intron RNA enzyme in unchanged form. In this manner, the enzyme converts 20 nt oligoribonucleotides into polyribonucleotides up to at least 180 nt by 10 nt increments. These results have significant implications for the evolution of RNA-based self-replicating systems.

No field of medicine is better able to translate the revolutionary advances in molecular biology and genetics into the care of patients than the field of molecular nuclear medicine. The human genome project has been a stimulus to the development of what might be called “genetic sciences,” i.e., molecular genetics, human genetics, molecular nuclear medicine, and pharmacology.

Research on taxonomic and genetic diversity of cultivated plants provides valuable data that help to clarify how the flora of cultivated plants was formed in a particular region. Paleogenetics, a discipline that developed at the intersection of molecular biology, archeology and genetics, helps to explore plant origin and changes in plant genotype during evolution. By the 12th century, the economy of medieval Northern Russia was based on a developed farming culture. Tracing the origin of its constituent agricultural traditions is an important fundamental task. The objective of this work was to study and identify the species affiliation of carbonized fossil remains of plants that grew in the Russian Northwest in the 12th century using morphological and molecular genetic methods. The results of the morphological analysis of grain fossils showed that most of the unearthed plant material was barley. Other cereals, such as wheat, rye and oat, were also observed. Molecular genetic studies helped to clarify the species affiliation of partially destroyed grains and reconstruct their lifetime morphology.

Reviewed by: Heredity under the Microscope: Chromosomes and the Study of the Human Genome by Soraya de Chadarevian Miguel García-Sancho Soraya de Chadarevian. Heredity under the Microscope: Chromosomes and the Study of the Human Genome. Chicago: University of Chicago Press, 2020. 272 pp. Ill. $37.50 (978-0-226-68511-3). In Heredity under the Microscope, Soraya de Chadarevian complements the picture of post-World War II biomedicine that she uncovered in her previous book, Designs for Life: Molecular Biology after World War II.1 Unlike in her earlier monograph, here she focuses on chromosomes as spaces of convergence of several lines of inquiry. This focus on research objects rather than disciplinary developments leads her to investigate a variety of practices that life scientists deployed to visualize and [End Page 466] interpret human chromosomes. The diversity of disciplinary backgrounds of these scientists and the multiplicity of uses to which their chromosome practices were put enable the author to expand the historiographical boundaries of both molecular biology and genetics research. Firstly, de Chadarevian disentangles “the study of postwar human heredity from the predominant concern about continuities with eugenic practices” (p. 5). The book does not limit itself to documenting the invention of karyotyping techniques to represent and detect anomalies in human chromosomes; it follows their standardization and spread, including their use as evidence of safe levels of radiation in the workplace (chapter 1) or sex assignment in the Olympic games (chapter 3). The emphasis on these uses, departed as they were from scientific theories about population improvement, displaces eugenics as the dominant interpretative framework of the history of human genetics. Secondly, the book presents chromosomes as showing “historical commonalities” (p. 177) between two approaches that have been traditionally considered as separate: molecular genetics and microscope-assisted chromosome observations. De Chadarevian stresses how these two approaches emerged as a consequence of the key role that nuclear research had played during World War II and the search of peacetime applications. Radioactive isotopes decisively fostered molecular biology, while the investigation of the effects of radiation was a crucial concern of human and medical geneticists using chromosome observations (chapter 1). Both molecular biologists and chromosome researchers also attempted to apply computers to their investigations, the former as an aid to the structural study of proteins and DNA, and the latter to automate the interpretation of karyotype images (chapter 4). However, whereas molecular biologists focused on simpler organisms, chromosome researchers engaged with both human populations and patients in the clinic. Radiation-induced leukemia was their first focus for then rapidly shifting to other conditions (especially those affecting mental abilities and sex identity) and larger-scale epidemiological studies (chapters 2 and 4). The 1960s, a decade that historians have dubbed the golden age of molecular biology,2 was also a time of expansion of chromosome observations. From the mid-1970s onward, molecular biologists turned to human subjects in order to realize the medical promise of the new recombinant DNA techniques. It is at this point when the intersection with chromosome research becomes more visible and de Chadarevian wonders “whose turn” this represents in history, a molecularization of human genetics or a humanization of molecular biology (pp. 171–76). Although subsequent success stories have put the emphasis on molecular biology, chapter 5 shows the importance of chromosome research as a key tool for gene mapping and the emergence of the human genome as an object of study. Even in the so-called post-genomic era, chromosome observations are [End Page 467] essential to clinically interpret the molecular sequence data derived from the Human Genome Project. Overall, the book offers a most welcomed framework to address the coexistence of chromosome observations and molecular biology, and their importance in genomics research. Understanding this is a pressing historiographical problem, given the dominance of molecular biologists in existing narratives and the apparent revival of chromosome research. There is yet still work to do in exploring specific overlaps between the visual and molecular approaches to the genome. A potential candidate is Victor McKusick, a main actor in de Chadarevian’s account and a co-author of the article in which Celera Genomics presented one of the draft sequences of the human...

Pushing the boundaries of organ identity: Homology of the grass lemma

The study of the evolution of development (evo‐devo) has advanced dramatically in the last two decades. Although there had been a strong interest in evo‐devo for nearly a century, it was only with the advent of molecular developmental genetics that provided a strong basis for a conceptual and methodological integration of developmental studies with evolutionary biology. The study of plant evolution of development has also progressed in the last two decades beginning with the study of the molecular basis for floral diversification in the angiosperms. The confluence of studies in development, molecular genetics, phylogenetics, paleobotany, population genetics, and molecular evolution in the study of plant form is now a robust discipline, with various opportunities to further our understanding of plant morphological evolution at all levels of biological organization.

Two approaches are applied to studies of the phylogeny of the plague microbe Yersinia pestis, i.e., the reconstruction of its history: Molecular genetic (MG) and ecological (ECO). The MG approach dominates. Phylogenies created with MG and ECO methods are not congruent. MG conclusions contradict the known facts and patterns of ecology, biogeography, paleontology, etc. We discuss some obvious contradictions and inconsistencies and suggest that real phylogenies of the plague microbe can be constructed only on the basis of the integration of MG and ECO approaches.

The Evolution of Gene Regulation Underlies a Morphological Difference between Two Drosophila Sister Species

Annals of the New York Academy of SciencesVolume 894, Issue 1 p. 189-198 Where Have All My Pumpkins Gone?: The Vulnerability of Insect Pollinatorsa BARRY H. THOMPSON, Corresponding Author BARRY H. THOMPSON Center for Medical and Molecular Genetics, Armed Forces Institute of Pathology, Rockville, Maryland 20850–3125, USAAddress correspondence to: Barry H. Thompson, Colonel, USAF, MC, Center for Medical and Molecular Genetics, 1413 Research Boulevard, Rockville, Maryland 20850–3125; Telephone: 301–319–0200 and Fax: 301–295–9507.Search for more papers by this author BARRY H. THOMPSON, Corresponding Author BARRY H. THOMPSON Center for Medical and Molecular Genetics, Armed Forces Institute of Pathology, Rockville, Maryland 20850–3125, USAAddress correspondence to: Barry H. Thompson, Colonel, USAF, MC, Center for Medical and Molecular Genetics, 1413 Research Boulevard, Rockville, Maryland 20850–3125; Telephone: 301–319–0200 and Fax: 301–295–9507.Search for more papers by this author First published: 06 February 2006 https://doi.org/10.1111/j.1749-6632.1999.tb08064.x a The opinions expressed herein are those of the author and are not be interpreted as representing those of the Armed Forces Institute of Pathology, the United States Army or the Department Defense. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume894, Issue1FOOD AND AGRICULTURAL SECURITY: GUARDING AGAINST NATURAL THREATS AND TERRORIST ATTACKS AFFECTING HEALTH, NATIONAL FOOD SUPPLIES, AND AGRICULTURAL ECONOMICSDecember 1999Pages 189-198 RelatedInformation

Clinical chemistry is going through an identity crisis, squeezed between automation (de-skilling) on the service side and molecular genetics in research. Automated routine estimations are now carried out and interpreted by machines; the skilled staff members required are more likely to have degrees in electronics than medicine or biochemistry. The role of molecular genetics is more ambiguous; it is inherently reductionist, in that it attempts to explain most clinical phenomena in terms of DNA sequence alone. This has been remarkably successful for single-gene defects (such as those causing Duchenne muscular dystrophy, hemoglobinopathies, cystic fibrosis, and ataxias) and may well prove equally so for Alzheimer's disease, cancer, heart disease, and schizophrenia. DNA diagnosis is not yet routine, but because of technical advances such as gene amplification ("PCR") and high-sensitivity gene-detection assays, it may soon become so, not only in major centers but also in local pathology laboratories and general practice. Clinical chemists must decide whether they wish to respond to this new and stimulating challenge by retooling and retraining. Should anyone be permitted into clinical chemistry during the 1990s without knowledge of both electronics and molecular genetics? Will there be a clinical chemistry in the twenty-first century other than through molecular genetics? This article is a personal response to these questions.

To review the role of molecular genetics in the diagnosis of malignant lymphomas. Primary research studies and reviews published in the English literature that focus on molecular genetics and malignant lymphoma, in particular, clonality, chromosomal translocations, tumor suppressor genes, and Hodgkin disease. Molecular genetics has an important role in the assessment of malignant lymphomas. Clonality, detected by Southern blot analysis or the polymerase chain reaction, is helpful for establishing the diagnosis of lymphoma in lesions with ambiguous morphologic and immunophenotypic findings. Southern blot analysis is the "gold standard" for clonality assessment, but the process is labor-intensive and time-consuming. Polymerase chain reaction analysis is more convenient, but a potentially significant false-negative rate exists in the analysis of some antigen receptor genes as a result of using consensus primers and the process of somatic hypermutation. Chromosomal translocations, which result in oncogene activation, occur in many types of B- and T-cell lymphomas, and their detection is helpful in classification as well as in establishing a diagnosis of malignancy. Gene rearrangements and chromosomal translocations also can be used to monitor minimal residual disease. Tumor suppressor genes, although their analysis is relatively less useful for diagnosis, are involved in both pathogenesis and tumor progression and will be more important diagnostically as this field continues to expand. Molecular genetic analysis has played a major role in improving our understanding of Hodgkin disease. Molecular genetic tests are currently important ancillary tools for the diagnosis and classification of malignant lymphomas, and their role is likely to increase in the future.

Journal of the European Academy of Dermatology and VenereologyVolume 29, Issue 12 p. 2489-2490 Letter to the Editor Pachydermoperiostosis genetic screening in Lebanese families uncovers a novel SLCO2A1mutation D. Saadeh, D. Saadeh Department of Dermatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorM. Kurban, M. Kurban Department of Dermatology, American University of Beirut, Beirut, Lebanon Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon Department of Dermatology, Columbia University, New york, USASearch for more papers by this authorS. Ghosn, S. Ghosn Department of Dermatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorW. Btadini, W. Btadini Department of Dermatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorG. Nemer, G. Nemer Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, LebanonSearch for more papers by this authorT. Arayssi, T. Arayssi Department of Rheumatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorI. Uthman, I. Uthman Department of Rheumatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorR. Badra, R. Badra Department of Pathology and Laboratory Medicine, Medical Genetics Unit, American University of Beirut, Beirut, LebanonSearch for more papers by this authorC. Farra, Corresponding Author C. Farra Department of Pathology and Laboratory Medicine, Medical Genetics Unit, American University of Beirut, Beirut, LebanonCorrespondence: C. Farra. E-mail: [email protected]Search for more papers by this author D. Saadeh, D. Saadeh Department of Dermatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorM. Kurban, M. Kurban Department of Dermatology, American University of Beirut, Beirut, Lebanon Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon Department of Dermatology, Columbia University, New york, USASearch for more papers by this authorS. Ghosn, S. Ghosn Department of Dermatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorW. Btadini, W. Btadini Department of Dermatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorG. Nemer, G. Nemer Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, LebanonSearch for more papers by this authorT. Arayssi, T. Arayssi Department of Rheumatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorI. Uthman, I. Uthman Department of Rheumatology, American University of Beirut, Beirut, LebanonSearch for more papers by this authorR. Badra, R. Badra Department of Pathology and Laboratory Medicine, Medical Genetics Unit, American University of Beirut, Beirut, LebanonSearch for more papers by this authorC. Farra, Corresponding Author C. Farra Department of Pathology and Laboratory Medicine, Medical Genetics Unit, American University of Beirut, Beirut, LebanonCorrespondence: C. Farra. E-mail: [email protected]Search for more papers by this author First published: 25 July 2014 https://doi.org/10.1111/jdv.12584Citations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume29, Issue12December 2015Pages 2489-2490 RelatedInformation