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Sample records for human genetics research

  1. Mixture distributions in human genetics research.

    PubMed

    Schork, N J; Allison, D B; Thiel, B

    1996-06-01

    The use of mixture distributions in genetics research dates back to at least the late 1800s when Karl Pearson applied them in an analysis of crab morphometry. Pearson's use of normal mixture distributions to model the mixing of different species of crab (or 'families' of crab as he referred to them) within a defined geographic area motivated further use of mixture distributions in genetics research settings, and ultimately led to their development and recognition as intuitive modelling devices for the effects of underlying genes on quantitative phenotypic (i.e. trait) expression. In addition, mixture distributions are now used routinely to model or accommodate the genetic heterogeneity thought to underlie many human diseases. Specific applications of mixture distribution models in contemporary human genetics research are, in fact, too numerous to count. Despite this long, consistent and arguably illustrious history of use, little mention of mixture distributions in genetics research is made in many recent reviews on mixture models. This review attempts to rectify this by providing insight into the role that mixture distributions play in contemporary human genetics research. Tables providing examples from the literature that describe applications of mixture models in human genetics research are offered as a way of acquainting the interested reader with relevant studies. In addition, some of the more problematic aspects of the use of mixture models in genetics research are outlined and addressed. PMID:8817796

  2. Caries: Review of Human Genetics Research

    PubMed Central

    Vieira, Alexandre R.; Modesto, Adriana; Marazita, Mary L.

    2014-01-01

    The NIH Consensus Development Program released a statement in 2001 (NIH Consensus Statement, 2001) and listed six major clinical caries research directions. One of these directions was the need for genetic studies to identify genes and genetic markers of diagnostic, prognostic, and therapeutic value. This last decade has seen a steep increase in studies investigating the presence of genetic factors influencing individual susceptibility to caries. This review revisits recent caries human genetic studies and provides a perspective for future studies in order to fulfill their promise of revolutionizing our understanding of and the standard of care for the most prevalent bacteria-mediated non-contagious disease in the world. PMID:24853115

  3. Research strategies in human behaviour genetics.

    PubMed Central

    Vogel, F

    1987-01-01

    Genetic variation influencing normal and abnormal human behaviour has been studied since Francis Galton's work in the second half of the 19th century. However, most of these studies have consisted of biometric analysis of complex phenotypes; the genotype has been treated as a 'black box'. The concepts and analytical tools of modern genetics have rarely been used. In this lecture, some examples are given of approaches combining tools from genetics, cytogenetics, and various fields of neurobiology which might help in the analysis of genetic mechanisms leading, in interaction with the environment, to individual differences in behaviour, mental performance, and susceptibility to mental diseases. PMID:2883319

  4. Genetic Testing and Its Implications: Human Genetics Researchers Grapple with Ethical Issues.

    ERIC Educational Resources Information Center

    Rabino, Isaac

    2003-01-01

    Contributes systematic data on the attitudes of scientific experts who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. Finds that they are highly supportive of voluntary testing and the right to know one's genetic heritage. Calls for greater genetic literacy. (Contains 87 references.) (Author/NB)

  5. Different differences: The use of ‘genetic ancestry’ versus race in biomedical human genetic research

    PubMed Central

    Fujimura, Joan H.; Rajagopalan, Ramya

    2011-01-01

    This article presents findings from our ethnographic research on biomedical scientists’ studies of human genetic variation and common complex disease. We examine the socio-material work involved in genome-wide association studies (GWAS) and discuss whether, how, and when notions of race and ethnicity are or are not used. We analyze how researchers produce simultaneously different kinds of populations and population differences. Although many geneticists use race in their analyses, we find some who have invented a statistical genetics method and associated software that they use specifically to avoid using categories of race in their genetics analysis. Their method allows them to operationalize their concept of ‘genetic ancestry’ without resorting to notions of race and ethnicity. We focus on the construction and implementation of the software’s algorithms, and discuss the consequences and implications of the software technology for debates and policies around the use of race in genetics research. We also demonstrate that the production and use of their method involves a dynamic and fluid assemblage of actors in various disciplines responding to disciplinary and sociopolitical contexts and concerns. This assemblage also includes particular discourses on human history and geography as they become entangled with research on genetic markers and disease. We introduce the concept of ‘genome geography’, to analyze how some researchers studying human genetic variation ‘locate’ stretches of DNA in different places and times. The concept of genetic ancestry and the practice of genome geography rely on old discourses, but they also incorporate new technologies, infrastructures, and political and scientific commitments. Some of these new technologies provide opportunities to change some of our institutional and cultural forms and frames around notions of difference and similarity. Neverthless, we also highlight the slipperiness of genome geography and the

  6. Robotics for recombinant DNA and human genetics research

    SciTech Connect

    Beugelsdijk, T.J.

    1990-01-01

    In October of 1989, molecular biologists throughout the world formally embarked on ultimately determining the set of genetic instructions for a human being. Called by some the Manhattan Project'' a molecular biology, pursuit of this goal is projected to require approximately 3000 man years of effort over a 15-year period. The Humane Genome Initiative is a worldwide research effort that has the goal of analyzing the structure of human deoxyribonucleic acid (DNA) and determining the location of all human genes. The Department of Energy (DOE) has designated three of its national laboratories as centers for the Human Genome Project. These are Los Alamos National Laboratory (LANL), Lawrence Livermore National Laboratory (LLNL), and Lawrence Berkeley Laboratory (LBL). These laboratories are currently working on different, but complementary technology development areas in support of the Human Genome Project. The robotics group at LANL is currently working at developing the technologies that address the problems associated with physical mapping. This article describes some of these problems and discusses some of the robotics approaches and engineering tolls applicable to their solution. 7 refs., 8 figs., 1 tab.

  7. Human molecular genetics research at the International Centre for Genetic Engineering and Biotechnology.

    PubMed

    Falaschi, P A

    1997-01-01

    The ICGEB started its activity in 1987 as a special project of UNIDO (United Nations Industrial Development Organization) and operates now as a fully autonomous International Organization, of which 40 countries are members at present. The mandate of ICGEB is to become a Centre of excellence for research and training in modern biology addressed to the needs of the developing world. The ICGEB consists of two main laboratories, one in Trieste (where the direction of the Centre is also located) and one in New Delhi, plus a network of 30 Affiliated Centres. The Centre operates through: 1) specific research programs of hish scientific content at the Trieste and New Delhi laboratories; 2) long term training through post-doctoral and pre-doctoral fellowships; 3) short term training; 4) collaborative research program, through which the Centre finances research projects of major impact to the need of the Member States; 5) scientific services, namely consultation for scientific programs, distribution of reagents and a bioinformatics network particularly geared to the human genome research. The research on human molecular genetics in particularly active in the Trieste Component and concerns the study at the molecular level of several genes important for human health: control of DNA replication, response to infectious diseases, cardiocirculatory diseases, cystic fibrosis and cancer. The methodologies for developing new diagnostic methods and for developing gene therapy protocols are actively pursued. Through these programs, the member countries have access to state-of-the-art technologies anf know-how essential for the development of the molecular approaches to medicine brought forward by the study of the human genome. PMID:9561632

  8. Research on human genetics in Iceland. Progress report

    SciTech Connect

    1980-10-31

    Records of the Icelandic Population are being used to investigate the possible inheritance of disabilities and diseases as well as other characters and the effect of environment on man. The progress report of research covers the period 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.

  9. Progress report on research on human genetics in Iceland

    SciTech Connect

    1980-10-31

    Records of the Icelandic population are being used to investigate the possible inheritance of disabilities and diseases as well as other characteristics and the effect of environment on man. The progress report of research covers the period from 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.

  10. Human genetics

    SciTech Connect

    Carlson, E.A.

    1984-01-01

    This text provides full and balanced coverage of the concepts requisite for a thorough understanding of human genetics. Applications to both the individual and society are integrated throughout the lively and personal narrative, and the essential principles of heredity are clearly presented to prepare students for informed participation in public controversies. High-interest, controversial topics, including recombinant DNA technology, oncogenes, embryo transfer, environmental mutagens and carcinogens, IQ testing, and eugenics encourage understanding of important social issues.

  11. The New Human Genetics: A Cell Bank Helps Researchers Fight Inherited Disease.

    ERIC Educational Resources Information Center

    Pines, Maya

    Research in human genetics is now expanding rapidly, leading to increasingly precise ways of preventing or treating some of the 2,000 or more inherited disorders that afflict human beings. At the same time, it has produced a wealth of new ideas and techniques which are laying the groundwork for new medical science for the 21st century. Recent work…

  12. Attitudes toward Genetic Research Review: Results from a National Survey of Professionals involved in Human Subjects Protection

    PubMed Central

    Lemke, Amy A.; Trinidad, Susan B.; Edwards, Karen L.; Starks, Helene; Wiesner, Georgia L.

    2010-01-01

    The recent expansion of human genetics research has raised complex ethical and regulatory issues. However, few published reports describe the views of professionals involved in human subjects protection (HSP) regarding the risks and benefits of genetic research. This anonymous, web-based study elicited the opinions of 208 HSP professionals about review of genetic research. The majority of respondents felt that different guidance is needed for various aspects of genetic protocol review compared with other types of human subjects research. Importantly, opinions were divided on specific genetic research issues such as what constitutes human subjects research, when to re-consent, and the likelihood and risks of research participant identification. Findings from this study illustrate the need for a collaborative approach to ethics oversight in the conduct and review of genetic research. PMID:20235866

  13. American Society of Human Genetics

    MedlinePlus

    ... Research Awards August 9, 2016 Media Advisory: American Society of Human Genetics 2016 Annual Meeting July 26, ... McKusick Leadership Award June 30, 2016 The American Society of Human Genetics, Incorporated 9650 Rockville Pike • Bethesda, ...

  14. Building capacity for human genetics and genomics research in Trinidad and Tobago.

    PubMed

    Roach, Allana; Warner, Wayne A; Llanos, Adana A M

    2015-11-01

    Advances in human genetics and genomic sciences and the corresponding explosion of biomedical technologies have deepened current understanding of human health and revolutionized medicine. In developed nations, this has led to marked improvements in disease risk stratification and diagnosis. These advances have also led to targeted intervention strategies aimed at promoting disease prevention, prolonging disease onset, and mitigating symptoms, as in the well-known case of breast cancer and the BRCA1 gene. In contrast, in the developing nation of Trinidad and Tobago, this scientific revolution has not translated into the development and application of effective genomics-based interventions for improving public health. While the reasons for this are multifactorial, the underlying basis may be rooted in the lack of pertinence of internationally driven genomics research to the local public health needs in the country, as well as a lack of relevance of internationally conducted genetics research to the genetic and environmental contexts of the population. Indeed, if Trinidad and Tobago is able to harness substantial public health benefit from genetics/genomics research, then there is a dire need, in the near future, to build local capacity for the conduct and translation of such research. Specifically, it is essential to establish a national human genetics/genomics research agenda in order to build sustainable human capacity through education and knowledge transfer and to generate public policies that will provide the basis for the creation of a mutually beneficial framework (including partnerships with more developed nations) that is informed by public health needs and contextual realities of the nation. PMID:26837529

  15. The role of community review in evaluating the risks of human genetic variation research.

    PubMed

    Foster, M W; Sharp, R R; Freeman, W L; Chino, M; Bernsten, D; Carter, T H

    1999-06-01

    The practicality and moral value of community review of human genetic research has become a focus of debate. Examples from two Native American communities are used to address four aspects of that debate: (1) the value of community review in larger, geographically dispersed populations; (2) the identification of culturally specific risks; (3) the potential conflict between individual and group assessments of research-related risks; and (4) the confusion of social categories with biological categories. Our experiences working with these two communities suggest that: (1) successful community review may require the involvement of private social units (e.g., families); (2) culturally specific implications of genetic research may be identifiable only by community members and are of valid concern in their moral universes; (3) community concerns can be incorporated into existing review mechanisms without necessarily giving communities the power to veto research proposals; and (4) the conflation of social and biological categories presents recruitment problems for genetic studies. These conclusions argue for the use of community review to identify and minimize research-related risks posed by genetic studies. Community review also can assist in facilitating participant recruitment and retention, as well as in developing partnerships between researchers and communities. PMID:10330360

  16. The New Human Genetics. How Gene Splicing Helps Researchers Fight Inherited Disease.

    ERIC Educational Resources Information Center

    Pines, Maya

    The science of genetics is perceived to offer hope that a large number of the 3,000 inherited diseases which afflict human beings may be prevented or controlled. This document addresses some of the advances that have been made in this field. It includes an introduction and sections on: "The Beginning of Human Genetics"; "Unlocking the Secrets of…

  17. Scientific rationality, uncertainty and the governance of human genetics: an interview study with researchers at deCODE genetics.

    PubMed

    Hjörleifsson, Stefán; Schei, Edvin

    2006-07-01

    Technology development in human genetics is fraught with uncertainty, controversy and unresolved moral issues, and industry scientists are sometimes accused of neglecting the implications of their work. The present study was carried out to elicit industry scientists' reflections on the relationship between commercial, scientific and ethical dimensions of present day genetics and the resources needed for robust governance of new technologies. Interviewing scientists of the company deCODE genetics in Iceland, we found that in spite of optimism, the informants revealed ambiguity and uncertainty concerning the use of human genetic technologies for the prevention of common diseases. They concurred that uncritical marketing of scientific success might cause exaggerated public expectations of health benefits from genetics, with the risk of backfiring and causing resistance to genetics in the population. On the other hand, the scientists did not address dilemmas arising from the commercial nature of their own employer. Although the scientists tended to describe public fear as irrational, they identified issues where scepticism might be well founded and explored examples where they, despite expert knowledge, held ambiguous or tentative personal views on the use of predictive genetic technologies. The rationality of science was not seen as sufficient to ensure beneficial governance of new technologies. The reflexivity and suspension of judgement demonstrated in the interviews exemplify productive features of moral deliberation in complex situations. Scientists should take part in dialogues concerning the governance of genetic technologies, acknowledge any vested interests, and use their expertise to highlight, not conceal the technical and moral complexity involved. PMID:16622446

  18. I'll be a monkey's uncle: a moral challenge to human genetic enhancement research.

    PubMed

    Rosoff, Philip M

    2011-10-01

    The potential for genetic engineering of enhancements to complex human traits has been the subject of vigorous debate for a number of years. Most of the discussion has centered on the possible moral consequences of pursuing enhancements, especially those that might affect complex behaviours and components of personality. Little has been written on the actual process of implementing this technology. This paper presents a 'thought experiment' about the likely form of final preclinical testing for a technology to enhance intelligence as a prototypical multiplex trait. The significance and the potential dangers of implementing enhancements in humans, especially to highly valued traits such as intelligence, would mandate a thorough programme of testing in animals, including non-human primates such as chimpanzees. The implications this would have for researchers, society and, most importantly, the animals themselves are discussed, and the paper concludes with a suggestion for a morally justifiable approach to resolve the tragic question of what to do with research animals who have a cognitive capacity that is close to that of humans. PMID:21515875

  19. Latest Research: Genetic Links

    MedlinePlus

    ... Current Issue Past Issues Feature: Vision Latest Research: Genetic Links Past Issues / Summer 2008 Table of Contents ... laboratories is one way the NEI is expanding genetic testing of eye diseases. Photo courtesy of National ...

  20. Human genetic research, race, ethnicity and the labeling of populations: recommendations based on an interdisciplinary workshop in Japan

    PubMed Central

    2014-01-01

    Background A challenge in human genome research is how to describe the populations being studied. The use of improper and/or imprecise terms has the potential to both generate and reinforce prejudices and to diminish the clinical value of the research. The issue of population descriptors has not attracted enough academic attention outside North America and Europe. In January 2012, we held a two-day workshop, the first of its kind in Japan, to engage in interdisciplinary dialogue between scholars in the humanities, social sciences, medical sciences, and genetics to begin an ongoing discussion of the social and ethical issues associated with population descriptors. Discussion Through the interdisciplinary dialogue, we confirmed that the issue of race, ethnicity and genetic research has not been extensively discussed in certain Asian communities and other regions. We have found, for example, the continued use of the problematic term, “Mongoloid” or continental terms such as “European,” “African,” and “Asian,” as population descriptors in genetic studies. We, therefore, introduce guidelines for reporting human genetic studies aimed at scientists and researchers in these regions. Conclusion We need to anticipate the various potential social and ethical problems entailed in population descriptors. Scientists have a social responsibility to convey their research findings outside of their communities as accurately as possible, and to consider how the public may perceive and respond to the descriptors that appear in research papers and media articles. PMID:24758583

  1. [Human genetics and ethics].

    PubMed

    Zergollern, L

    1990-01-01

    Many new problems and dilemmas have occurred in the practice of medical geneticists with the development of human genetics and its subdisciplines--molecular genetics, ethic genetics and juridical genetics. Devoid of the possibility to get adequate education, genetic informer or better to say, counsellor, although a scientist and a professional who has already formed his ethic attitudes, often finds himself in a dilemma when he has to decide whether a procedure made possible by progress of science is ethical or not. Thus, due to different attitudes, same decision is ethical for some, while for the others it is not. Ethic committees are groups of moral and good people trying to find an objective approach to certain genetic and ethic problems. There are more and more ethically unanswered questions in modern human genetics, and particularly in medical genetics. Medical geneticist-ethicist still encounters numerous problems in his work. These are, for example, experiments with human gametes and embryos, possibilities of hybridization of human gametes with animal gametes, in vitro fertilization, detection of heterozygotes and homozygotes for monogene diseases. early detection of chromosomopathies, substitute mothers, homo and hetero insemination, transplantation of fetal and cadeveric organs, uncontrolled consumption of alcohol and drugs, environmental pollution, etc. It is almost impossible to create a single attitude which shall be shared by all those engaged in human health protection. Therefore, it is best to have a neutral eugenetic attitude which allows free ethical choice of each individual, in any case, for the well-being of man. PMID:2366624

  2. Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment

    PubMed Central

    Sugiura, Saiko; Ueda, Hiromi; Nakashima, Tsutomu

    2014-01-01

    Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed. PMID:25140308

  3. Genetic studies in alcohol research

    SciTech Connect

    Karp, R.W.

    1994-12-15

    The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research to elucidate the specific genetic factors, now largely unknown, which underlie susceptibility to alcoholism and its medical complications (including fetal alcohol syndrome). Because of the genetic complexity and heterogeneity of alcoholism, identification of the multiple underlying factors will require the development of new study designs and methods of analysis of data from human families. While techniques of genetic analysis of animal behavioral traits (e.g., targeted gene disruption, quantitative trait locus (QTL) mapping) are more powerful that those applicable to humans (e.g., linkage and allelic association studies), the validation of animal behaviors as models of aspects of human alcoholism has been problematic. Newly developed methods for mapping QTL influencing animal behavioral traits can not only permit analyses of human family data to be directly informed by the results of animal studies, but can also serve as a novel means of validating animal models of aspects of alcoholism. 55 refs.

  4. Genetic Research and Native American Cultural Issues

    NASA Astrophysics Data System (ADS)

    Romero, Francine; Bemis, Lynne T.; Burhansstipanov, Linda; Dignan, Mark

    Cultural issues relevant to genetic education and research arc the focus of a new and innovative curriculum being developed for Native American college students and health professionals. Genetic Education for Native Americans (GENA) is funded by the National Human Genome Research Institute of the National Institutes of Health. The goal of the GENA project is to provide a balance of scientific and cultural information about genetic research, genetic testing, and careers in genetics for Native American students. This article describes issues related to the implementation of GENA and provides an example of an innovative approach to teaching about genetic research among Native American populations.

  5. High Points of Human Genetics

    ERIC Educational Resources Information Center

    Stern, Curt

    1975-01-01

    Discusses such high points of human genetics as the study of chromosomes, somatic cell hybrids, the population formula: the Hardy-Weinberg Law, biochemical genetics, the single-active X Theory, behavioral genetics and finally how genetics can serve humanity. (BR)

  6. Genetics for the Human Race

    SciTech Connect

    Myles Axton; Francis Collins; Charles Rotimi; Charmaine Royal; David Goldstein, Daniel Drell; Georgia Dunston; Rick Kittles; Lynn Jorde; Mildred Cho; Joanna Mountain; Ari Patrinos; Neil Risch; Shomarka Keita; Kenneth Kidd; Mark Shriver; Sarah Tishkoff

    2004-11-01

    This supplement has its origins on May 15, 2003, when the National Human Genome Center at Howard University held a small but important workshop in Washington DC. The workshop, Human Genome Variation and 'Race', and this special issue of Nature Genetics were proposed by scientists at Howard University and financially supported by the Genome Programs of the US Department of Energy, through its Office of Science; the Irving Harris Foundation; the National Institutes of Health, through the National Human Genome Research Institute; and Howard University. As summarized by Francis Collins, director of the National Human Genome Research Institute, the workshop focused on several key questions: ''What does the current body of scientific information say about the connections among race, ethnicity, genetics and health? What remains unknown? What additional research is needed? How can this information be applied to benefit human health? How might this information be applied in nonmedical settings? How can we adopt policies that will achieve beneficial societal outcomes?'' This supplement, supported by the Department of Energy through a grant to Howard University, contains articles based on the presentations at this workshop.

  7. Advances in human genetics

    SciTech Connect

    Harris, H.; Hirschhorn, K.

    1993-01-01

    This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention, to its organ system involvement and molecular biology.

  8. Genetics of Human and Canine Dilated Cardiomyopathy

    PubMed Central

    Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F. N.; Cobb, Malcolm; Mongan, Nigel P.; Rutland, Catrin S.

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed. PMID:26266250

  9. [Bioethical principles concerning human genetic data].

    PubMed

    Cruz-Coke, Ricardo

    2003-01-01

    UNESCO'S Universal declaration on the human genome and human rights (1997) has been accepted by the international scientific community. To apply these laws, it is necessary to get more specific rules about data regulation, human genetic samples and its derived information in biomedic research. Indeed, genetic material recollection, processing, use and storing, has potential risks over human rights' protection and exercise. The author, member of UNESCO'S intergovernmental Bioethics Committee which approved the final draft in June 2003, has taken part in the writing of the final text of an international declaration about human genetic data, whose abbreviate text is described and commented in this communication. PMID:15032097

  10. Human Heredity: Genetic Mechanisms in Humans.

    ERIC Educational Resources Information Center

    Blank, C. E.

    1988-01-01

    Discussed are some of the uncertainties in human genetic mechanisms that are often presented as dogma in Biology textbooks. Presented is a brief historical background and illustrations involving chromosome abnormality in humans and linkage studies in humans. (CW)

  11. Thoughts on Human Genetics Education.

    ERIC Educational Resources Information Center

    Epstein, Charles J.

    1980-01-01

    The director of the Birth Defects Center at the University of California at San Francisco addresses the reasons for developing good ways of teaching human genetics. Genetic counseling is discussed within the context of several case histories. (SA)

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

    PubMed

    Passarge, Eberhard

    2016-06-01

    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. PMID:27016306

  13. Genetic Mapping in Human Disease

    PubMed Central

    Altshuler, David; Daly, Mark J.; Lander, Eric S.

    2009-01-01

    Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead. PMID:18988837

  14. Genetic research in space

    NASA Technical Reports Server (NTRS)

    Delone, N. L.; Antipov, V. V.; Ilyin, Ye. A.

    1988-01-01

    The role of the genetic apparatus in the adaptation of the organism to conditions of weightlessness is studied. The investigation includes studies at the gene, chromosome, cell, tissue, and organism levels, as well as studies at the population level.

  15. Genetic Research on Biospecimens Poses Minimal Risk

    PubMed Central

    Wendler, David S.; Rid, Annette

    2014-01-01

    Genetic research on human biospecimens is increasingly common. Yet, debate continues over the level of risk that this research poses to sample donors. Some argue that genetic research on biospecimens poses minimal risk; others argue that it poses greater than minimal risk and therefore needs additional requirements and limitations. This debate raises concern that some donors are not receiving appropriate protection or, conversely, that valuable research is being subject to unnecessary requirements and limitations. The present paper attempts to address this concern using the widely-endorsed ‘risks of daily life’ standard. The three extant versions of this standard all suggest that, with proper measures in place to protect donor confidentiality, most genetic research on human biospecimens poses minimal risk to donors. PMID:25530152

  16. Genetic research on biospecimens poses minimal risk.

    PubMed

    Wendler, David S; Rid, Annette

    2015-01-01

    Genetic research on human biospecimens is increasingly common. However, debate continues over the level of risk that this research poses to sample donors. Some argue that genetic research on biospecimens poses minimal risk; others argue that it poses greater than minimal risk and therefore needs additional requirements and limitations. This debate raises concern that some donors are not receiving appropriate protection or, conversely, that valuable research is being subject to unnecessary requirements and limitations. The present paper attempts to resolve this debate using the widely-endorsed 'risks of daily life' standard. The three extant versions of this standard all suggest that, with proper measures in place to protect confidentiality, most genetic research on human biospecimens poses minimal risk to donors. PMID:25530152

  17. Basic Genetics: A Human Approach.

    ERIC Educational Resources Information Center

    Biological Sciences Curriculum Study, Colorado Springs, CO. Center for Education in Human and Medical Genetics.

    This document (which has the form of a magazine) provides a variety of articles, stories, editorials, letters, interviews, and other types of magazine features (such as book reviews) which focus on human genetics. In addition to providing information about the principles of genetics, nearly all of the sections in the "magazine" address moral,…

  18. Blending Genetics and Sociocultural Historical Inquiry: Ethics, Culture, and Human Subjects Protection in International Cross Cultural Research

    PubMed Central

    Sampson, Deborah A.; Caldwell, Dennis; Taylor, Andre D.; Taylor, Jacquelyn Y.

    2013-01-01

    In this paper, we examine the implementation and difficulties when conducting genetics research in a rural, traditional West African culture within the frame of the United States’ grounded research ethics. Research challenges are highlighted by Western researchers following U.S. Institutional Review Board (IRB) guidelines and practices in a non-Western country. IRB concepts are culture bound in Western ideals that may not have synchronicity and compatibility with non-Western cultures. Differences in sociocultural norms, traditions, language, and geography were influencing factors that can affect application of IRB principles. Suggestions for change are offered, which will potentially aid researchers considering application of IRB requirements when conducting research in non-Westernized, non-industrialized countries. PMID:23482512

  19. Human genetic databases and liberty.

    PubMed

    Adalsteinsson, Ragnar

    2004-01-01

    This paper examines an act of the Icelandic Parliament on health-sector databases. Both the legislation itself and the manner in which it was presented by the Government to the Parliament and the general public raise various questions about democratic parliamentary procedures, community consultation, autonomy, privacy, professional confidence, control of health data in hospitals and business relationships between medical doctors and biotechnology corporations. A major question to be asked is: In whose interest is it that such sensitive data are handed over to for-profit corporations? Furthermore, is it within the authority of the legislature to authorize politically appointed boards of health institutes to transfer such data without the direct informed consent of the patient and without the relevant physicians' having a say? Does experience teach us to entrust private companies with sensitive personal data? Should the Government be involved in the research policy-making of the biotechnology companies that have been given access to the genetic data of a population, or should the profit motive be the sole deciding influence? That is, should the interest of the shareholders of the companies prevail over the interest of underprivileged groups who are most in need of new methods or medicine to alleviate their situation due to incurable diseases? Or is the invisible hand of the market the only competent decision-maker? Finally, will the proliferation of databases containing sensitive personal data, such as human genetic data, limit our personal liberty? PMID:16755701

  20. Contemporary Genetics for Gender Researchers: Not Your Grandma's Genetics Anymore

    ERIC Educational Resources Information Center

    Salk, Rachel H.; Hyde, Janet S.

    2012-01-01

    Over the past century, much of genetics was deterministic, and feminist researchers framed justified criticisms of genetics research. However, over the past two decades, genetics research has evolved remarkably and has moved far from earlier deterministic approaches. Our article provides a brief primer on modern genetics, emphasizing contemporary…

  1. Genetic aspects of human congenital diaphragmatic hernia

    PubMed Central

    Pober, BR

    2010-01-01

    Congenital diaphragmatic hernia (CDH) is a common major malformation affecting 1/3000–1/4000 births, which continues to be associated with significant perinatal mortality. Much current research is focused on elucidating the genetics and pathophysiology contributing to CDH to develop more effective therapies. The latest data suggest that many cases of CDH are genetically determined and also indicate that CDH is etiologically heterogeneous. The present review will provide a brief summary of diaphragm development and model organism work most relevant to human CDH and will primarily describe important human phenotypes associated with CDH and also provide recommendations for diagnostic evaluation of a fetus or infant with CDH. PMID:18510546

  2. The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data.

    PubMed

    Van Otterloo, Eric; Williams, Trevor; Artinger, Kristin Bruk

    2016-07-15

    The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting "animal to man" approaches; that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight "man to animal" approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike. PMID:26808208

  3. Human genetic variability and HIV treatment response.

    PubMed

    Haas, David W

    2006-07-01

    Access to potent antiretroviral medications greatly reduces morbidity and mortality due to HIV/AIDS, but drug toxicity limits treatment success in many individuals. The field of pharmacogenomics strives to understand the influence of human genetic variants in response to medications. Investigators have begun to identify associations among human genetic variants, predisposition to HIV drug toxicities, and likelihood of virologic response. These include associations among abacavir hypersensitivity reactions, HLA type, and hsp70-hom genotypes, and among CYP2B6 polymorphisms, efavirenz pharmacokinetics, and central nervous system symptoms. Pharmacogenomics also holds great promise to suggest novel targets for drug development. The discovery that a naturally occurring, nonfunctional variant of the HIV receptor gene CCR5 protected against HIV infection encouraged the development of CCR5 antagonists. Through continued translational and applied research, pharmacogenomics will ultimately benefit persons living with HIV worldwide by identifying new therapeutic targets and through individualized drug prescribing that is informed by human genetic testing. PMID:16608660

  4. HGDBMS: a human genetics database management system.

    PubMed

    Seuchter, S A; Skolnick, M H

    1988-10-01

    Human genetics research involves a large number of complex data sets naturally organized in hierarchical structures. Data collection is performed on different levels, e.g., the project level, pedigree level, individual level, and sample level. Different aspects of a study utilize different views of the data, requiring a flexible database management system (DBMS) which satisfies these different needs for data collection and retrieval. We describe HGDBMS, a comprehensive relational DBMS, implemented as an application of the GENISYS I DBMS, which allows embedding the hierarchical structure of pedigrees in a relational structure. The system's file structure is described in detail. Currently our Melanoma and Chromosome 17 map studies are managed with HGDBMS. Our initial experience demonstrates the value of a flexible system which supports the needs for data entry, update, storage, reporting, and analysis required during different phases of genetic research. Further developments will focus on the integration of HGDBMS with a human genetics expert system shell and analysis programs. PMID:3180747

  5. Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

    PubMed

    Harper, Joyce C; Geraedts, Joep; Borry, Pascal; Cornel, Martina C; Dondorp, Wybo; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather; Soini, Sirpa; Spits, Claudia; Veiga, Anna; Vermeesch, Joris Robert; Viville, Stéphane; de Wert, Guido; Macek, Milan

    2013-11-01

    In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide

  6. Genetic variation and human longevity.

    PubMed

    Soerensen, Mette

    2012-05-01

    The overall aim of the PhD project was to elucidate the association of human longevity with genetic variation in major candidate genes and pathways of longevity. Based on a thorough literature and database search we chose to apply a pathway approach; to explore variation in genes composing the DNA damage signaling, DNA repair, GH/IGF-1/insulin signaling and pro-/antioxidant pathways. In addition, 16 genes which did not belong to the core of either pathway, however recurrently regarded as candidate genes of longevity (e.g. APOE), were included. In this way a total of 168 genes were selected for investigation. We decided to explore the genetic variation in the form of single nucleotide polymorphisms (SNPs), a highly investigated type of genetic variation. SNPs having potential functional impact (e.g. affecting binding of transcription factors) were identified, so were specific SNPs in the candidate genes previously published to be associated with human longevity. To cover the majority of the common genetic variation in the 168 gene regions (encoding regions plus 5,000 bp upstream and 1,000 downstream) we applied the tagging SNP approach via the HapMap Consortium. Consequently 1,536 SNPs were selected. The majority of the previous publications on genetic variation and human longevity had employed a case-control study design, e.g. comparing centenarians to middle-aged controls. This type of study design is somehow prone to bias introduced by for instance cohort effects, i.e. differences in characteristics of cases and controls, a kind of bias which is avoided when a prospective cohort is under study. Therefore, we chose to investigate 1,200 individuals of the Danish 1905 birth cohort, which have been followed since 1998 when the members were 92-93 years old. The genetic contribution to human longevity has been estimated to be most profound during the late part of life, thus these oldest-old individuals are excellent for investigating such effect. The follow-up survival

  7. Human Research Roadmap

    NASA Video Gallery

    Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) investigates and mitigates the highest risks to human health and per...

  8. [Ethical challenges of genetic manipulation and research with animals].

    PubMed

    Rodríguez Yunta, Eduardo

    2012-01-01

    Research with animals presents ethical questions both for being used as models of human diseases and for being a prerequisite for trials in humans, as in the introduction of genetic modifications. Some of these questions refer to the fact that, as models, they do not fully represent the human condition; that conducting toxicity tests causes great harm to animals; that their nature is altered by genetic modifications and that introducing genetically modified organisms is a risk. The use of animals in research for the benefit of humans imposes the moral responsibility to respect them, not making them suffer unnecessarily, since they are living beings capable of feeling. PMID:23338641

  9. PATENTS IN GENOMICS AND HUMAN GENETICS

    PubMed Central

    Cook-Deegan, Robert; Heaney, Christopher

    2010-01-01

    Genomics and human genetics are scientifically fundamental and commercially valuable. These fields grew to prominence in an era of growth in government and nonprofit research funding, and of even greater growth of privately funded research and development in biotechnology and pharmaceuticals. Patents on DNA technologies are a central feature of this story, illustrating how patent law adapts---and sometimes fails to adapt---to emerging genomic technologies. In instrumentation and for therapeutic proteins, patents have largely played their traditional role of inducing investment in engineering and product development, including expensive postdiscovery clinical research to prove safety and efficacy. Patents on methods and DNA sequences relevant to clinical genetic testing show less evidence of benefits and more evidence of problems and impediments, largely attributable to university exclusive licensing practices. Whole-genome sequencing will confront uncertainty about infringing granted patents but jurisprudence trends away from upholding the broadest and potentially most troublesome patent claims. PMID:20590431

  10. Gordon Research Conference on Genetic Toxicology

    SciTech Connect

    Project Director Penelope Jeggo

    2003-02-15

    Genetic toxicology represents a study of the genetic damage that a cell can incur, the agents that induce such damage, the damage response mechanisms available to cells and organisms, and the potential consequences of such damage. Genotoxic agents are abundant in the environment and are also induced endogenously. The consequences of such damage can include carcinogenesis and teratogenesis. An understanding of genetic toxicology is essential to carry out risk evaluations of the impact of genotoxic agents and to assess how individual genetic differences influence the response to genotoxic damage. In recent years, the importance of maintaining genomic stability has become increasingly recognized, in part by the realization that failure of the damage response mechanisms underlies many, if not all, cancer incidence. The importance of these mechanisms is also underscored by their remarkable conservation between species, allowing the study of simple organisms to provide significant input into our understanding of the underlying mechanisms. It has also become clear that the damage response mechanisms interface closely with other aspects of cellular metabolism including replication, transcription and cell cycle regulation. Moreover, defects in many of these mechanisms, as observed for example in ataxia telangiectasia patients, confer disorders with associated developmental abnormalities demonstrating their essential roles during growth and development. In short, while a decade ago, a study of the impact of DNA damage was seen as a compartmentalized area of cellular research, it is now appreciated to lie at the centre of an array of cellular responses of crucial importance to human health. Consequently, this has become a dynamic and rapidly advancing area of research. The Genetic Toxicology Gordon Research Conference is biannual with an evolving change in the emphasis of the meetings. From evaluating the nature of genotoxic chemicals, which lay at the centre of the early

  11. Pharmacogenetics and human genetic polymorphisms.

    PubMed

    Daly, Ann K

    2010-08-01

    The term pharmacogenetics was first used in the late 1950s and can be defined as the study of genetic factors affecting drug response. Prior to formal use of this term, there was already clinical data available in relation to variable patient responses to the drugs isoniazid, primaquine and succinylcholine. The subject area developed rapidly, particularly with regard to genetic factors affecting drug disposition. There is now comprehensive understanding of the molecular basis for variable drug metabolism by the cytochromes P450 and also for variable glucuronidation, acetylation and methylation of certain drugs. Some of this knowledge has already been translated to the clinic. The molecular basis of variation in drug targets, such as receptors and enzymes, is generally less well understood, although there is consistent evidence that polymorphisms in the genes encoding the beta-adrenergic receptors and the enzyme vitamin K epoxide reductase is of clinical importance. The genetic basis of rare idiosyncratic adverse drug reactions had also been examined. Susceptibility to reactions affecting skin and liver appears to be determined in part by the HLA (human leucocyte antigen) genotype, whereas reactions affecting the heart and muscle may be determined by polymorphisms in genes encoding ion channels and transporters respectively. Genome-wide association studies are increasingly being used to study drug response and susceptibility to adverse drug reactions, resulting in identification of some novel pharmacogenetic associations. PMID:20626352

  12. Human research subjects as human research workers.

    PubMed

    Lynch, Holly Fernandez

    2014-01-01

    Biomedical research involving human subjects has traditionally been treated as a unique endeavor, presenting special risks and demanding special protections. But in several ways, the regulatory scheme governing human subjects research is counter-intuitively less protective than the labor and employment laws applicable to many workers. This Article relies on analogical and legal reasoning to demonstrate that this should not be the case; in a number of ways, human research subjects ought to be fundamentally recast as human research workers. Like other workers protected under worklaw, biomedical research subjects often have interests that diverge from those in positions of control but little bargaining power for change. Bearing these important similarities in mind, the question becomes whether there is any good reason to treat subjects and protected workers differently as a matter of law. With regard to unrestricted payment, eligibility for a minimum wage, compensation for injury, and rights to engage in concerted activity, the answer is no and human subjects regulations ought to be revised accordingly. PMID:25051653

  13. Xenopus Research: Metamorphosed by Genetics and Genomics

    PubMed Central

    Harland, Richard M.; Grainger, Robert M.

    2011-01-01

    Research using Xenopus takes advantage of large, abundant eggs, and readily manipulated embryos in addition to conserved cellular, developmental and genomic organization with mammals. Research on Xenopus has defined key principles of gene regulation and signal transduction, embryonic induction, morphogenesis and patterning as well as cell cycle regulation. Genomic and genetic advances in this system, including development of Xenopus tropicalis as a genetically tractable complement to the widely used Xenopus laevis, capitalize on the classical strengths and wealth of achievements. These attributes provide the tools to tackle the complex biological problems of the new century, including cellular reprogramming, organogenesis, regeneration, gene regulatory networks and protein interactions controlling growth and development, all of which provide insights into a multitude of human diseases and their potential treatments. PMID:21963197

  14. [HIV infection and human genetics].

    PubMed

    Bobkova, M R

    2009-01-01

    The review summarizes data of recent studies on the impact of human gene polymorphisms on the possibility of HIV infection, as well as the specific features of its pathogenesis, the efficiency of HIV infection treatment and the likelihood of its complication. Main information on the mechanisms responsible for viral penetration into the sensitive cells, for immune response development and involvement of HLA and KIR molecules in this process are briefly outlined. Idea on major cell proteins affecting drug metabolism and excretion and encoding for their genes are generalized. There are many examples that show how different human gene alleles and their combinations affect the nature of the pathogenetic process and the occurrence and degree of adverse reactions. The first example of successfully using the prognostic genetic analysis (HLA-B*5701) registered in 2008 to upgrade the quality of HIV infection treatment is described in detail. Basic requirements for further genetic tests to use the optimal antiretroviral therapy schemes and to reduce its hazardous effects are formulated. PMID:20481056

  15. The Human as an Experimental System in Molecular Genetics.

    ERIC Educational Resources Information Center

    White, Ray; Caskey, C. Thomas

    1988-01-01

    Discusses insights discovered from research into human biology that are raising possibilities for therapy, prevention of disease, and challenges to society in the form of ethical decisions about the appropriate application of genetic information. (Author/RT)

  16. Human Research Program Opportunities

    NASA Technical Reports Server (NTRS)

    Kundrot, Craig E.

    2014-01-01

    The goal of HRP is to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. The Human Research Program was designed to meet the needs of human space exploration, and understand and reduce the risk to crew health and performance in exploration missions.

  17. Reverse Genetics in Ecological Research

    PubMed Central

    Schwachtje, Jens; Kutschbach, Susan; Baldwin, Ian T.

    2008-01-01

    By precisely manipulating the expression of individual genetic elements thought to be important for ecological performance, reverse genetics has the potential to revolutionize plant ecology. However, untested concerns about possible side-effects of the transformation technique, caused by Agrobacterium infection and tissue culture, on plant performance have stymied research by requiring onerous sample sizes. We compare 5 independently transformed Nicotiana attenuata lines harboring empty vector control (EVC) T-DNA lacking silencing information with isogenic wild types (WT), and measured a battery of ecologically relevant traits, known to be important in plant-herbivore interactions: phytohormones, secondary metabolites, growth and fitness parameters under stringent competitive conditions, and transcriptional regulation with microarrays. As a positive control, we included a line silenced in trypsin proteinase inhibitor gene (TPI) expression, a potent anti-herbivore defense known to exact fitness costs in its expression, in the analysis. The experiment was conducted twice, with 10 and 20 biological replicates per genotype. For all parameters, we detected no difference between any EVC and WT lines, but could readily detect a fitness benefit of silencing TPI production. A statistical power analyses revealed that the minimum sample sizes required for detecting significant fitness differences between EVC and WT was 2–3 orders of magnitude larger than the 10 replicates required to detect a fitness effect of TPI silencing. We conclude that possible side-effects of transformation are far too low to obfuscate the study of ecologically relevant phenotypes. PMID:18253491

  18. Personalized medicine and human genetic diversity.

    PubMed

    Lu, Yi-Fan; Goldstein, David B; Angrist, Misha; Cavalleri, Gianpiero

    2014-09-01

    Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In this article, we review historical and contemporary views of human genetic diversity, the rare and common mutations implicated in human disease susceptibility, and the relevance of genetic diversity to personalized medicine. First, we describe the development of thought about diversity through the 20th century and through more modern studies including genome-wide association studies (GWAS) and next-generation sequencing. We introduce several examples, such as sickle cell anemia and Tay-Sachs disease that are caused by rare mutations and are more frequent in certain geographical populations, and common treatment responses that are caused by common variants, such as hepatitis C infection. We conclude with comments about the continued relevance of human genetic diversity in medical genetics and personalized medicine more generally. PMID:25059740

  19. Personalized Medicine and Human Genetic Diversity

    PubMed Central

    Lu, Yi-Fan; Goldstein, David B.; Angrist, Misha; Cavalleri, Gianpiero

    2014-01-01

    Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In this article, we review historical and contemporary views of human genetic diversity, the rare and common mutations implicated in human disease susceptibility, and the relevance of genetic diversity to personalized medicine. First, we describe the development of thought about diversity through the 20th century and through more modern studies including genome-wide association studies (GWAS) and next-generation sequencing. We introduce several examples, such as sickle cell anemia and Tay–Sachs disease that are caused by rare mutations and are more frequent in certain geographical populations, and common treatment responses that are caused by common variants, such as hepatitis C infection. We conclude with comments about the continued relevance of human genetic diversity in medical genetics and personalized medicine more generally. PMID:25059740

  20. Variance components for statistical genetics: applications in medical research to characteristics related to human diseases and health.

    PubMed

    Hopper, J L

    1993-01-01

    RA Fisher introduced variance components in 1918. He synthesized Mendelian inheritance with Darwin's theory of evolution by showing that the genetic variance of a continuous trait could be decomposed into additive and non-additive components. The model can be extended to include environmental factors, interactions, covariation, and non-random mating. Identifiability depends critically on design. Methods of analysis include modelling the mean squares from a fixed effects analysis of variance, and covariance structure modelling, which can be extended to multivariate traits and has been used to study ordinal traits by reference to postulated, unmeasured, latent 'liabilities'. These methods operate on dependent observations within independent groups of the same size and structure, and therefore require balanced designs ('regular' pedigrees). A multivariate normal model handles data in its generic form, utilizes data efficiently from all members of pedigrees of unequal size or varying structure, accommodates individuals missing at random, and allows flexible modelling with tests of distributional assumptions and fit. Most analytical methods use least squares or maximum likelihood under normal theory. Robust methods, scale transformation, ascertainment, path diagrams and correlational path models (popular in behavioural genetics through addressing nonrandom mating and social interactions), 'heritability', and the contribution and limitations of statistical modelling to the 'nature-nurture' debate, are discussed. PMID:8261258

  1. Genetic & epigenetic approach to human obesity.

    PubMed

    Rao, K Rajender; Lal, Nirupama; Giridharan, N V

    2014-11-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed. PMID:25579139

  2. Genetic & epigenetic approach to human obesity

    PubMed Central

    Rao, K. Rajender; Lal, Nirupama; Giridharan, N.V.

    2014-01-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed. PMID:25579139

  3. Recollections of J.B.S. Haldane, with special reference to Human Genetics in India

    PubMed Central

    Dronamraju, Krishna R.

    2012-01-01

    This paper is a brief account of the scientific work of J.B.S. Haldane (1892–1964), with special reference to early research in Human Genetics. Brief descriptions of Haldane's background, his important contributions to the foundations of human genetics, his move to India from Great Britain and the research carried out in Human Genetics in India under his direction are outlined. Population genetic research on Y-linkage in man, inbreeding, color blindness and other aspects are described. PMID:22754215

  4. Recollections of J.B.S. Haldane, with special reference to Human Genetics in India.

    PubMed

    Dronamraju, Krishna R

    2012-01-01

    This paper is a brief account of the scientific work of J.B.S. Haldane (1892-1964), with special reference to early research in Human Genetics. Brief descriptions of Haldane's background, his important contributions to the foundations of human genetics, his move to India from Great Britain and the research carried out in Human Genetics in India under his direction are outlined. Population genetic research on Y-linkage in man, inbreeding, color blindness and other aspects are described. PMID:22754215

  5. Summary of research needs for sunflower genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic research of the sunflower research unit, USDA-ARS, in Fargo, ND, was discussed in a presentation to a group of producers, industry representatives, and scientists. The need for sunflower genetic research is ever increasing with more insect and disease problems nationwide. Combined with a ren...

  6. Genetic and environmental influences on human behavioral differences.

    PubMed

    McGue, M; Bouchard, T J

    1998-01-01

    Human behavioral genetic research aimed at characterizing the existence and nature of genetic and environmental influences on individual differences in cognitive ability, personality and interests, and psychopathology is reviewed. Twin and adoption studies indicate that most behavioral characteristics are heritable. Nonetheless, efforts to identify the genes influencing behavior have produced a limited number of confirmed linkages or associations. Behavioral genetic research also documents the importance of environmental factors, but contrary to the expectations of many behavioral scientists, the relevant environmental factors appear to be those that are not shared by reared together relatives. The observation of genotype-environment correlational processes and the hypothesized existence of genotype-environment interaction effects serve to distinguish behavioral traits from the medical and physiological phenotypes studied by human geneticists. Behavioral genetic research supports the heritability, not the genetic determination, of behavior. PMID:9530489

  7. Office for Human Research Protections

    MedlinePlus

    ... Office for Human Research Protections The Office for Human Research Protections (OHRP) provides leadership in the protection of the rights, welfare, and wellbeing of human subjects involved in ...

  8. Genetics of human iris colour and patterns.

    PubMed

    Sturm, Richard A; Larsson, Mats

    2009-10-01

    The presence of melanin pigment within the iris is responsible for the visual impression of human eye colouration with complex patterns also evident in this tissue, including Fuchs' crypts, nevi, Wolfflin nodules and contraction furrows. The genetic basis underlying the determination and inheritance of these traits has been the subject of debate and research from the very beginning of quantitative trait studies in humans. Although segregation of blue-brown eye colour has been described using a simple Mendelian dominant-recessive gene model this is too simplistic, and a new molecular genetic perspective is needed to fully understand the biological complexities of this process as a polygenic trait. Nevertheless, it has been estimated that 74% of the variance in human eye colour can be explained by one interval on chromosome 15 that contains the OCA2 gene. Fine mapping of this region has identified a single base change rs12913832 T/C within intron 86 of the upstream HERC2 locus that explains almost all of this association with blue-brown eye colour. A model is presented whereby this SNP, serving as a target site for the SWI/SNF family member HLTF, acts as part of a highly evolutionary conserved regulatory element required for OCA2 gene activation through chromatin remodelling. Major candidate genes possibly effecting iris patterns are also discussed, including MITF and PAX6. PMID:19619260

  9. Plasmodium falciparum genetic crosses in a humanized mouse model

    PubMed Central

    Vaughan, Ashley M.; Pinapati, Richard S.; Cheeseman, Ian H.; Camargo, Nelly; Fishbaugher, Matthew; Checkley, Lisa A.; Nair, Shalini; Hutyra, Carolyn A.; Nosten, François H.; Anderson, Timothy J. C.; Ferdig, Michael T.; Kappe, Stefan H. I.

    2015-01-01

    Genetic crosses of phenotypically distinct strains of the human malaria parasite Plasmodium falciparum are a powerful tool for identifying genes controlling drug resistance and other key phenotypes. Previous studies relied on the isolation of recombinant parasites from splenectomized chimpanzees, a research avenue that is no longer available. Here, we demonstrate that human-liver chimeric mice support recovery of recombinant progeny for the identification of genetic determinants of parasite traits and adaptations. PMID:26030447

  10. National Human Genome Research Institute

    MedlinePlus

    ... for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for Teachers ... Education Kit Online Genetics Education Resources Smithsonian NHGRI Genome Exhibition Talking Glossary: English Talking Glossary: Español Issues ...

  11. Mouse genetic and phenotypic resources for human genetics

    PubMed Central

    Schofield, Paul N.; Hoehndorf, Robert; Gkoutos, Georgios V.

    2012-01-01

    The use of model organisms to provide information on gene function has proved to be a powerful approach to our understanding of both human disease and fundamental mammalian biology. Large-scale community projects using mice, based on forward and reverse genetics, and now the pan-genomic phenotyping efforts of the International Mouse Phenotyping Consortium (IMPC), are generating resources on an unprecedented scale which will be extremely valuable to human genetics and medicine. We discuss the nature and availability of data, mice and ES cells from these large-scale programmes, the use of these resources to help prioritise and validate candidate genes in human genetic association studies, and how they can improve our understanding of the underlying pathobiology of human disease. PMID:22422677

  12. Human genetics in Johannesburg, South Africa: past, present and future.

    PubMed

    Kromberg, Jennifer G R; Krause, Amanda

    2013-12-01

    Genetic services were set up in Johannesburg, South Africa, in the late 1960s, but only became widespread and formalised after the first Professor of Human Genetics, Trefor Jenkins, was installed at the University of the Witwatersrand in 1974. The first services involved chromosome studies, and these developed into genetic counselling services. Prenatal diagnosis began to be offered, particularly for older women at risk for chromosome abnormalities in the fetus, and those at risk for neural tube defects. Genetic screening was then initiated for the Jewish community because of their high carrier rate for Tay-Sachs disease. Educational courses in human genetics were offered at Wits Medical School, and medical as well as other health professionals began to be trained. Research, supported by national and international bodies, was integral in the activities of the Department (now Division) of Human Genetics and focused on genetic conditions affecting the generally understudied black community. In the late 1980s the first training programme for genetic counsellors was started at MSc level, and postgraduate scientists at MSc and PhD levels studied in and qualified through the Department. At the same time molecular genetic laboratories were set up. In the late 1990s training for medical geneticists was initiated. Extensive high-quality genetic services developed over the four decades were comparable to those of most other departments in developed countries.  PMID:24300637

  13. The Sonoda–Tajima Cell Collection: A Human Genetics Research Resource with Emphasis on South American Indigenous Populations

    PubMed Central

    Danjoh, Inaho; Saijo, Kaoru; Hiroyama, Takashi

    2011-01-01

    The Sonoda–Tajima Cell Collection includes cell samples obtained from a range of ethnic minority groups across the world but in particular from South America. The collection is made all the more valuable by the fact that some of these ethnic populations have since died out, and thus it will be impossible to prepare a similar cell collection again. The collection was donated to our institute, a public cell bank in Japan, by Drs Sonoda and Tajima to make it available to researchers throughout the world. The original cell collection was composed of cryopreserved peripheral blood samples that would obviously have been rapidly exhausted if used directly. We, therefore, immortalized some samples with the Epstein–Barr virus and established B-lymphoblastoid cell lines (B-LCLs). As there is continuing controversy over whether the B-LCL genome is stably maintained, we performed an array comparative genomic hybridization (CGH) analysis to confirm the genomic stability of the cell lines. The array CGH analysis of the B-LCL lines and their parental B cells demonstrated that genomic stability was maintained in the long-term cell cultures. The B-LCLs of the Sonoda–Tajima Collection will therefore be made available to interested scientists around the world. At present, 512 B-LCLs have been developed, and we are willing to increase the number if there is sufficient demand. PMID:21383383

  14. CRISPR: a versatile tool for both forward and reverse genetics research.

    PubMed

    Gurumurthy, Channabasavaiah B; Grati, M'hamed; Ohtsuka, Masato; Schilit, Samantha L P; Quadros, Rolen M; Liu, Xue Zhong

    2016-09-01

    Human genetics research employs the two opposing approaches of forward and reverse genetics. While forward genetics identifies and links a mutation to an observed disease etiology, reverse genetics induces mutations in model organisms to study their role in disease. In most cases, causality for mutations identified by forward genetics is confirmed by reverse genetics through the development of genetically engineered animal models and an assessment of whether the model can recapitulate the disease. While many technological advances have helped improve these approaches, some gaps still remain. CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated), which has emerged as a revolutionary genetic engineering tool, holds great promise for closing such gaps. By combining the benefits of forward and reverse genetics, it has dramatically expedited human genetics research. We provide a perspective on the power of CRISPR-based forward and reverse genetics tools in human genetics and discuss its applications using some disease examples. PMID:27384229

  15. Mapping genetic influences on human brain structure.

    PubMed

    Thompson, Paul; Cannon, Tyrone D; Toga, Arthur W

    2002-01-01

    Recent advances in brain imaging and genetics have empowered the mapping of genetic and environmental influences on the human brain. These techniques shed light on the 'nature/nurture' debate, revealing how genes determine individual differences in intelligence quotient (IQ) or risk for disease. They visualize which aspects of brain structure and function are heritable, and to what degree, linking these features with behavioral or cognitive traits or disease phenotypes. In genetically transmitted disorders such as schizophrenia, patterns of brain structure can be associated with increased disease liability, and sites can be mapped where non-genetic triggers may initiate disease. We recently developed a large-scale computational brain atlas, including data components from the Finnish Twin registry, to store information on individual variations in brain structure and their heritability. Algorithms from random field theory, anatomical modeling, and population genetics were combined to detect a genetic continuum in which brain structure is heavily genetically determined in some areas but not others. These algorithmic advances motivate studies of disease in which the normative atlas acts as a quantitative reference for the heritability of structural differences and deficits in patient populations. The resulting genetic brain maps isolate biological markers for inherited traits and disease susceptibility, which may serve as targets for genetic linkage and association studies. Computational methods from brain imaging and genetics can be fruitfully merged, to shed light on the inheritance of personality differences and behavioral traits, and the genetic transmission of diseases that affect the human brain. PMID:12553492

  16. Counseling Implications of Genetic Research: A Dialogue with Thomas Bouchard.

    ERIC Educational Resources Information Center

    Skovholt, Thomas M.

    1990-01-01

    Presents interview with Thomas Bouchard, a leading researcher of identical twins reared apart. Describes major themes in the Minnesota twin research. Claims, although genetic influence is central, Bouchard pleas for the impact of environmental factors in optimal human development. Includes Bouchard's surprising experiences, current focus, and…

  17. GENETICS OF HUMAN AGE RELATED DISORDERS.

    PubMed

    Srivastava, I; Thukral, N; Hasija, Y

    2015-01-01

    Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID:26856084

  18. Human embryonic stem cells carrying mutations for severe genetic disorders.

    PubMed

    Frumkin, Tsvia; Malcov, Mira; Telias, Michael; Gold, Veronica; Schwartz, Tamar; Azem, Foad; Amit, Ami; Yaron, Yuval; Ben-Yosef, Dalit

    2010-04-01

    Human embryonic stem cells (HESCs) carrying specific mutations potentially provide a valuable tool for studying genetic disorders in humans. One preferable approach for obtaining these cell lines is by deriving them from affected preimplantation genetically diagnosed embryos. These unique cells are especially important for modeling human genetic disorders for which there are no adequate research models. They can be further used to gain new insights into developmentally regulated events that occur during human embryo development and that are responsible for the manifestation of genetically inherited disorders. They also have great value for the exploration of new therapeutic protocols, including gene-therapy-based treatments and disease-oriented drug screening and discovery. Here, we report the establishment of 15 different mutant human embryonic stem cell lines derived from genetically affected embryos, all donated by couples undergoing preimplantation genetic diagnosis in our in vitro fertilization unit. For further information regarding access to HESC lines from our repository, for research purposes, please email dalitb@tasmc.health.gov.il. PMID:20186514

  19. Molecular genetics of human myopia: an update.

    PubMed

    Young, Terri L

    2009-01-01

    Myopia, or nearsightedness, is the most common human eye disorder in the world, and is a significant global public health concern. Along with cataract, macular degeneration, infectious disease, and vitamin A deficiency, myopia is one of the most important causes of visual impairment worldwide. Severe or high-grade myopia is a leading cause of blindness because of its associated ocular morbidities of retinal detachment, macular choroidal degeneration, premature cataract, and glaucoma. Ample evidence documents the heritability of the non-syndromic forms of this condition, especially for high-grade myopia, commonly referred to as myopic spherical refractive power of 5 to 6 diopters or higher. Multiple high-grade myopia genetic loci have been identified, and confirmatory studies identifying high-grade and moderate myopia loci have also occurred. In general, myopia susceptibility genes are unknown with few association studies performed, and without confirmation in other research laboratories or testing of separate patient cohorts. PMID:19104467

  20. The genetics of neuroticism and human values

    PubMed Central

    Lancaster, Thomas M.; Maio, Gregory R.; Linden, David E. J.

    2016-01-01

    Human values and personality have been shown to share genetic variance in twin studies. However, there is a lack of evidence about the genetic components of this association. This study examined the interplay between genes, values and personality in the case of neuroticism, because polygenic scores were available for this personality trait. First, we replicated prior evidence of a positive association between the polygenic neuroticism score (PNS) and neuroticism. Second, we found that the PNS was significantly associated with the whole human value space in a sinusoidal waveform that was consistent with Schwartz's circular model of human values. These results suggest that it is useful to consider human values in the analyses of genetic contributions to personality traits. They also pave the way for an investigation of the biological mechanisms contributing to human value orientations. PMID:26915771

  1. Behavioral genetics '97: ASHG statement. Recent developments in human behavioral genetics: past accomplishments and future directions.

    PubMed Central

    Sherman, S L; DeFries, J C; Gottesman, I I; Loehlin, J C; Meyer, J M; Pelias, M Z; Rice, J; Waldman, I

    1997-01-01

    The field of behavioral genetics has enormous potential to uncover both genetic and environmental influences on normal and deviant behavior. Behavioral-genetic methods are based on a solid foundation of theories and methods that successfully have delineated components of complex traits in plants and animals. New resources are now available to dissect the genetic component of these complex traits. As specific genes are identified, we can begin to explore how these interact with environmental factors in development. How we interpret such findings, how we ask new questions, how we celebrate the knowledge, and how we use or misuse this knowledge are all important considerations. These issues are pervasive in all areas of human research, and they are especially salient in human behavioral genetics. PMID:9199545

  2. Genetically Engineered Pig Models for Human Diseases

    PubMed Central

    Prather, Randall S.; Lorson, Monique; Ross, Jason W.; Whyte, Jeffrey J.; Walters, Eric

    2015-01-01

    Although pigs are used widely as models of human disease, their utility as models has been enhanced by genetic engineering. Initially, transgenes were added randomly to the genome, but with the application of homologous recombination, zinc finger nucleases, and transcription activator-like effector nuclease (TALEN) technologies, now most any genetic change that can be envisioned can be completed. To date these genetic modifications have resulted in animals that have the potential to provide new insights into human diseases for which a good animal model did not exist previously. These new animal models should provide the preclinical data for treatments that are developed for diseases such as Alzheimer's disease, cystic fibrosis, retinitis pigmentosa, spinal muscular atrophy, diabetes, and organ failure. These new models will help to uncover aspects and treatments of these diseases that were otherwise unattainable. The focus of this review is to describe genetically engineered pigs that have resulted in models of human diseases. PMID:25387017

  3. Genetic Diversity and Human Equality.

    ERIC Educational Resources Information Center

    Dobzhansky, Theodosius

    The idea of equality often, if not frequently, bogs down in confusion and apparent contradictions; equality is confused with identity, and diversity with inequality. It would seem that the easiest way to discredit the idea of equality is to show that people are innately, genetically, and, therefore, irremediably diverse and unlike. The snare is,…

  4. Genetic variability in human immunodeficiency viruses.

    PubMed

    Alizon, M; Montagnier, L

    1987-01-01

    The genetic polymorphism of the human immunodeficiency virus (HIV) has been established. In addition to the nucleic acid variations responsible for the restriction map polymorphism, isolates of HIV differ significantly at the protein level, especially in the envelope, in terms of amino acid substitutions and reciprocal insertions-deletions. In this investigation, molecular cloning and nucleotide sequencing of the genomes of 2 HIV isolates obtained from patients in Zaire were carried out. The 1st isolate was recovered in 1983 from a 24-year-old woman with acquired immunodeficiency syndrome (AIDS); the 2nd was isolated in 1985 from a 7-year-old boy with AIDS-related complex (ARC). The genetic organization of these isolates was identical to that found in other HIV isolates from the US and Europe, particularly in terms of the conservation of the central region located between the pol and env genes composed of a series of overlapping open reading frames. There were, however, substantial differences in the primary structure of the viral proteins, with env being more variable than the gag and pol genes. Alignment of the envelopes revealed hypervariable domains with a great number of mutations and reciprocal insertions and deletions. Overall, this analysis suggests that the African and American HIV infections have a common origin given their identical genetic organization. The sequence variability reflects a divergent evolutionary process, and the fact that the 2 Zairian isolates were more divergent than American isolates studied by others indicates a longer evolution of HIV in Africa. An essential research goal is to identify the HIV envelope domains responsible for the virus-cellular surface antigen interaction since an immune response against these epitopes could elicit neutralizing antibodies for use in a vaccine. PMID:3439717

  5. Glenn Research Center Human Research Program: Overview

    NASA Technical Reports Server (NTRS)

    Nall, Marsha M.; Myers, Jerry G.

    2013-01-01

    The NASA-Glenn Research Centers Human Research Program office supports a wide range of technology development efforts aimed at enabling extended human presence in space. This presentation provides a brief overview of the historical successes, current 2013 activities and future projects of NASA-GRCs Human Research Program.

  6. Understanding of research, genetics and genetic research in a rapid ethical assessment in north west Cameroon

    PubMed Central

    Kengne-Ouafo, Jonas A.; Millard, James D.; Nji, Theobald M.; Tantoh, William F.; Nyoh, Doris N.; Tendongfor, Nicholas; Enyong, Peter A.; Newport, Melanie J.; Davey, Gail; Wanji, Samuel

    2016-01-01

    Background There is limited assessment of whether research participants in low-income settings are afforded a full understanding of the meaning of medical research. There may also be particular issues with the understanding of genetic research. We used a rapid ethical assessment methodology to explore perceptions surrounding the meaning of research, genetics and genetic research in north west Cameroon. Methods Eleven focus group discussions (including 107 adults) and 72 in-depth interviews were conducted with various stakeholders in two health districts in north west Cameroon between February and April 2012. Results Most participants appreciated the role of research in generating knowledge and identified a difference between research and healthcare but gave varied explanations as to this difference. Most participants' understanding of genetics was limited to concepts of hereditary, with potential benefits limited to the level of the individual or family. Explanations based on supernatural beliefs were identified as a special issue but participants tended not to identify any other special risks with genetic research. Conclusion We demonstrated a variable level of understanding of research, genetics and genetic research, with implications for those carrying out genetic research in this and other low resource settings. Our study highlights the utility of rapid ethical assessment prior to complex or sensitive research. PMID:25969503

  7. Sports genetics moving forward: lessons learned from medical research.

    PubMed

    Mattsson, C Mikael; Wheeler, Matthew T; Waggott, Daryl; Caleshu, Colleen; Ashley, Euan A

    2016-03-01

    Sports genetics can take advantage of lessons learned from human disease genetics. By righting past mistakes and increasing scientific rigor, we can magnify the breadth and depth of knowledge in the field. We present an outline of challenges facing sports genetics in the light of experiences from medical research. Sports performance is complex, resulting from a combination of a wide variety of different traits and attributes. Improving sports genetics will foremost require analyses based on detailed phenotyping. To find widely valid, reproducible common variants associated with athletic phenotypes, study sample sizes must be dramatically increased. One paradox is that in order to confirm relevance, replications in specific populations must be undertaken. Family studies of athletes may facilitate the discovery of rare variants with large effects on athletic phenotypes. The complexity of the human genome, combined with the complexity of athletic phenotypes, will require additional metadata and biological validation to identify a comprehensive set of genes involved. Analysis of personal genetic and multiomic profiles contribute to our conceptualization of precision medicine; the same will be the case in precision sports science. In the refinement of sports genetics it is essential to evaluate similarities and differences between sexes and among ethnicities. Sports genetics to date have been hampered by small sample sizes and biased methodology, which can lead to erroneous associations and overestimation of effect sizes. Consequently, currently available genetic tests based on these inherently limited data cannot predict athletic performance with any accuracy. PMID:26757801

  8. Inauguration of the cameroonian society of human genetics.

    PubMed

    Wonkam, Ambroise; Kenfack, Marcel Azabji; Bigoga, Jude; Nkegoum, Blaise; Muna, Wali

    2009-01-01

    The conjunction of "hard genetics" research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual meeting of the African Society of Human Genetics (AfSHG, 13th-15th March 2009) was an excellent opportunity to get together in synergy the entire Cameroonian "DNA/RNA scientists" . This laid to the foundation of the Cameroonian Society of Human Genetics (CSHG) that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health". The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an understanding of the state-of-knowledge of Human Origin and Genetic Diversity. Overall one opening ceremony eight session, five keynote and guest speakers, 18 invited oral communications, 13 free oral communications, 43 posters and two social events could summarize the meeting. This year's conference was graced by the presence of one Nobel Prize winner Dr Richard Roberts (Physiology and Medicine 1993). The meeting registered up to ten contributions of Cameroonian scientists from the Diaspora (currently in USA, Belgium, Gambia, Sudan and Zimbabwe). Such Diaspora participation is an opportunity to generate collaborations with home country scientists and ultimately turn the "brain drain" to "brain circulation" that could reduce the impact of the migration of health professional from Africa. Interestingly, the personal implication of the Cameroonian Ministry of Public Heath who opened the meeting in the presence of the Secretary General of the Ministry of Higher Education and a representative of the Ministry of Scientific Research and Innovation was a wonderful opportunity for advocacy of genetic issues at the decision-makers level. Beyond our expectation, a major promise of the Cameroonian government was the creation of the National Human

  9. Consent for genetic research in the Framingham Heart Study.

    PubMed

    Levy, Daniel; Splansky, Greta Lee; Strand, Nicolle K; Atwood, Larry D; Benjamin, Emelia J; Blease, Susan; Cupples, L Adrienne; D'Agostino, Ralph B; Fox, Caroline S; Kelly-Hayes, Margaret; Koski, Greg; Larson, Martin G; Mutalik, Karen M; Oberacker, Elizabeth; O'Donnell, Christopher J; Sutherland, Patrice; Valentino, Maureen; Vasan, Ramachandran S; Wolf, Philip A; Murabito, Joanne M

    2010-05-01

    Extensive efforts have been aimed at understanding the genetic underpinnings of complex diseases that affect humans. Numerous genome-wide association studies have assessed the association of genes with human disease, including the Framingham Heart Study (FHS), which genotyped 550,000 SNPs in 9,000 participants. The success of such efforts requires high rates of consent by participants, which is dependent on ethical oversight, communications, and trust between research participants and investigators. To study this we calculated percentages of participants who consented to collection of DNA and to various uses of their genetic information in two FHS cohorts between 2002 and 2009. The data included rates of consent for providing a DNA sample, creating an immortalized cell line, conducting research on various genetic conditions including those that might be considered sensitive, and for notifying participants of clinically significant genetic findings were above 95%. Only with regard to granting permission to share DNA or genetic findings with for-profit companies was the consent rate below 95%. We concluded that the FHS has maintained high rates of retention and consent for genetic research that has provided the scientific freedom to establish collaborations and address a broad range of research questions. We speculate that our high rates of consent have been achieved by establishing frequent and open communications with participants that highlight extensive oversight procedures. Our approach to maintaining high consent rates via ethical oversight of genetic research and communication with study participants is summarized in this report and should be of help to other studies engaged in similar types of research. Published 2010 Wiley-Liss, Inc. PMID:20425830

  10. Genetically modified animals and pharmacological research.

    PubMed

    Wells, Dominic J

    2010-01-01

    This chapter reviews the use of genetically modified animals and the increasingly detailed knowledge of the genomes of the domestic species. The different approaches to genetic modification are outlined as are the advantages and disadvantages of the techniques in different species. Genetically modified mice have been fundamental in understanding gene function and in generating affordable models of human disease although these are not without their drawbacks. Transgenic farm animals have been developed for nutritionally enhanced food, disease resistance and xenografting. Transgenic rabbits, goats, sheep and cows have been developed as living bioreactors producing potentially high value biopharmaceuticals, commonly referred to as "pharming". Domestic animals are also important as a target as well as for testing genetic-based therapies for both inherited and acquired disease. This latter field may be the most important of all, in the future development of novel therapies. PMID:20204589

  11. Population genetics of malaria resistance in humans.

    PubMed

    Hedrick, P W

    2011-10-01

    The high mortality and widespread impact of malaria have resulted in this disease being the strongest evolutionary selective force in recent human history, and genes that confer resistance to malaria provide some of the best-known case studies of strong positive selection in modern humans. I begin by reviewing JBS Haldane's initial contribution to the potential of malaria genetic resistance in humans. Further, I discuss the population genetics aspects of many of the variants, including globin, G6PD deficiency, Duffy, ovalocytosis, ABO and human leukocyte antigen variants. Many of the variants conferring resistance to malaria are 'loss-of-function' mutants and appear to be recent polymorphisms from the last 5000-10 000 years or less. I discuss estimation of selection coefficients from case-control data and make predictions about the change for S, C and G6PD-deficiency variants. In addition, I consider the predicted joint changes when the two β-globin alleles S and C are both variable in the same population and when there is a variation for α-thalassemia and S, two unlinked, but epistatic variants. As more becomes known about genes conferring genetic resistance to malaria in humans, population genetics approaches can contribute both to investigating past selection and predicting the consequences in future generations for these variants. PMID:21427751

  12. Population genetics of malaria resistance in humans

    PubMed Central

    Hedrick, P W

    2011-01-01

    The high mortality and widespread impact of malaria have resulted in this disease being the strongest evolutionary selective force in recent human history, and genes that confer resistance to malaria provide some of the best-known case studies of strong positive selection in modern humans. I begin by reviewing JBS Haldane's initial contribution to the potential of malaria genetic resistance in humans. Further, I discuss the population genetics aspects of many of the variants, including globin, G6PD deficiency, Duffy, ovalocytosis, ABO and human leukocyte antigen variants. Many of the variants conferring resistance to malaria are ‘loss-of-function' mutants and appear to be recent polymorphisms from the last 5000–10 000 years or less. I discuss estimation of selection coefficients from case–control data and make predictions about the change for S, C and G6PD-deficiency variants. In addition, I consider the predicted joint changes when the two β-globin alleles S and C are both variable in the same population and when there is a variation for α-thalassemia and S, two unlinked, but epistatic variants. As more becomes known about genes conferring genetic resistance to malaria in humans, population genetics approaches can contribute both to investigating past selection and predicting the consequences in future generations for these variants. PMID:21427751

  13. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease.

    PubMed

    Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-01-01

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review. PMID:26329332

  14. Implications of the apportionment of human genetic diversity for the apportionment of human phenotypic diversity

    PubMed Central

    Edge, Michael D.; Rosenberg, Noah A.

    2015-01-01

    Researchers in many fields have considered the meaning of two results about genetic variation for concepts of “race.” First, at most genetic loci, apportionments of human genetic diversity find that worldwide populations are genetically similar. Second, when multiple genetic loci are examined, it is possible to distinguish people with ancestry from different geographical regions. These two results raise an important question about human phenotypic diversity: To what extent do populations typically differ on phenotypes determined by multiple genetic loci? It might be expected that such phenotypes follow the pattern of similarity observed at individual loci. Alternatively, because they have a multilocus genetic architecture, they might follow the pattern of greater differentiation suggested by multilocus ancestry inference. To address the question, we extend a well-known classification model of Edwards (2003) by adding a selectively neutral quantitative trait. Using the extended model, we show, in line with previous work in quantitative genetics, that regardless of how many genetic loci influence the trait, one neutral trait is approximately as informative about ancestry as a single genetic locus. The results support the relevance of single-locus genetic-diversity partitioning for predictions about phenotypic diversity. PMID:25677859

  15. Human genetics shape the gut microbiome

    PubMed Central

    Goodrich, Julia K.; Waters, Jillian L.; Poole, Angela C.; Sutter, Jessica L.; Koren, Omry; Blekhman, Ran; Beaumont, Michelle; Van Treuren, William; Knight, Rob; Bell, Jordana T.; Spector, Timothy D.; Clark, Andrew G.; Ley, Ruth E.

    2014-01-01

    Summary Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation shapes the gut microbiome and interacts with it to affect host phenotype is unclear. Here, we compared microbiotas across > 1,000 fecal samples obtained from the TwinsUK population, including 416 twin-pairs. We identified many microbial taxa whose abundances were influenced by host genetics. The most heritable taxon, the family Christensenellaceae, formed a cooccurrence network with other heritable Bacteria and with methanogenic Archaea. Furthermore, Christensenellaceae and its partners were enriched in individuals with low body mass index (BMI). An obese-associated microbiome was amended with Christensenella minuta, a cultured member of the Christensenellaceae, and transplanted to germfree mice. C. minuta amendment reduced weight gain and altered the microbiome of recipient mice. Our findings indicate that host genetics influence the composition of the human gut microbiome and can do so in ways that impact host metabolism. PMID:25417156

  16. The genetics of human skin disease.

    PubMed

    DeStefano, Gina M; Christiano, Angela M

    2014-10-01

    The skin is composed of a variety of cell types expressing specific molecules and possessing different properties that facilitate the complex interactions and intercellular communication essential for maintaining the structural integrity of the skin. Importantly, a single mutation in one of these molecules can disrupt the entire organization and function of these essential networks, leading to cell separation, blistering, and other striking phenotypes observed in inherited skin diseases. Over the past several decades, the genetic basis of many monogenic skin diseases has been elucidated using classical genetic techniques. Importantly, the findings from these studies has shed light onto the many classes of molecules and essential genetic as well as molecular interactions that lend the skin its rigid, yet flexible properties. With the advent of the human genome project, next-generation sequencing techniques, as well as several other recently developed methods, tremendous progress has been made in dissecting the genetic architecture of complex, non-Mendelian skin diseases. PMID:25274756

  17. Human genetics: international projects and personalized medicine.

    PubMed

    Apellaniz-Ruiz, Maria; Gallego, Cristina; Ruiz-Pinto, Sara; Carracedo, Angel; Rodríguez-Antona, Cristina

    2016-03-01

    In this article, we present the progress driven by the recent technological advances and new revolutionary massive sequencing technologies in the field of human genetics. We discuss this knowledge in relation with drug response prediction, from the germline genetic variation compiled in the 1000 Genomes Project or in the Genotype-Tissue Expression project, to the phenome-genome archives, the international cancer projects, such as The Cancer Genome Atlas or the International Cancer Genome Consortium, and the epigenetic variation and its influence in gene expression, including the regulation of drug metabolism. This review is based on the lectures presented by the speakers of the Symposium "Human Genetics: International Projects & New Technologies" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held on the 20th and 21st of April 2015. PMID:26581075

  18. Internet solicitation of research subjects for genetic studies

    SciTech Connect

    Biesecker, L.G.; DeRenzo, E.G.

    1995-11-01

    Communication through electronic messages on the Internet has become a rapid and effective method for exchanging ideas and information in many disciplines. The Human Molecular Genetics network Diagnostics and Clinical Research Section (hum-molgen@nic.surfnet.nl) is now serving this function for the field of human molecular genetics. Our attention was drawn to the power and the pitfalls of this information exchange when we read a solicitation for research subjects by a Canadian medical student. The student was initiating a summer research project on an inherited disorder and requested information to determine the frequency of the disorder and to collect blood samples of affected patients. The student also requested samples of stored blood or DNA of affected persons. On other occasions, the hum-mol-gen service has also been used by clinicians to announce the availability of patients with a particular disorder (or their blood samples) who are interested in participating in research projects. Such uses of the Internet can serve to facilitate communication between researchers and clinicians and enhance clinical research. We believe, however, that some guidelines are necessary to protect human subjects. Investigators in the United States who are subject to U.S. Federal Government human subjects research regulations, or who are attached to an institution conducting such research, should consider some important issues before placing or responding to a request on the Internet. 1 ref.

  19. Sharing the benefits of genetic resources: from biodiversity to human genetics.

    PubMed

    Schroeder, Doris; Lasén-Díaz, Carolina

    2006-12-01

    Benefit sharing aims to achieve an equitable exchange between the granting of access to a genetic resource and the provision of compensation. The Convention on Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro, is the only international legal instrument setting out obligations for sharing the benefits derived from the use of biodiversity. The CBD excludes human genetic resources from its scope, however, this article considers whether it should be expanded to include those resources, so as to enable research subjects to claim a share of the benefits to be negotiated on a case-by-case basis. Our conclusion on this question is: 'No, the CBD should not be expanded to include human genetic resources.' There are essential differences between human and non-human genetic resources, and, in the context of research on humans, an essentially fair exchange model is already available between the health care industry and research subjects. Those who contribute to research should receive benefits in the form of accessible new health care products and services, suitable for local health needs and linked to economic prosperity (e.g. jobs). When this exchange model does not apply, as is often the case in developing countries, individually negotiated benefit sharing agreements between researchers and research subjects should not be used as 'window dressing'. Instead, national governments should focus their finances on the best economic investment they could make; the investment in population health and health research as outlined by the World Health Organization's Commission on Macroeconomics and Health; whilst international barriers to such spending need to be removed. PMID:17038005

  20. Human fertility, molecular genetics, and natural selection in modern societies.

    PubMed

    Tropf, Felix C; Stulp, Gert; Barban, Nicola; Visscher, Peter M; Yang, Jian; Snieder, Harold; Mills, Melinda C

    2015-01-01

    Research on genetic influences on human fertility outcomes such as number of children ever born (NEB) or the age at first childbirth (AFB) has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML) methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758), results show significant additive genetic effects on both traits explaining 10% (SE = 5) of the variance in the NEB and 15% (SE = 4) in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02). This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size. PMID:26039877

  1. Human Fertility, Molecular Genetics, and Natural Selection in Modern Societies

    PubMed Central

    Tropf, Felix C.; Stulp, Gert; Barban, Nicola; Visscher, Peter M.; Yang, Jian; Snieder, Harold; Mills, Melinda C.

    2015-01-01

    Research on genetic influences on human fertility outcomes such as number of children ever born (NEB) or the age at first childbirth (AFB) has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML) methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758), results show significant additive genetic effects on both traits explaining 10% (SE = 5) of the variance in the NEB and 15% (SE = 4) in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of –0.62 (SE = 0.27, p-value = 0.02). This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size. PMID:26039877

  2. [Mycotoxin research in humans].

    PubMed

    Lazo, Ramón F; Sierra, Gonzalo

    2008-03-01

    This study investigates the occurrence of aflatoxins in Ecuador. Early investigators proved the presence of aflatoxins in human and animal food, but the disturbing data lead to the formation of two research teams at Guayaquil University and the Agrarian University of Ecuador to investigate aflaxotins and other mycotoxins in food and their relationship to human health. Because the concept of mycotoxicosis as a result of the secondary metabolites produced by different species of moulds could cause different clinical patterns, the research team includes Aspergillus metabolites found in the urine of a patient with pulmonary aspergilloma. We considered that the body itself could create secondary metabolites. An ELISA method was used to detect mycotoxins with the specific reactive compounds using a company base assay. This allows the detection quantitative of such metabolites in 24 h collected urine. The patient was treated with itraconazole for nine months, after clinical, radiological and aflatoxins testing. We also investigated three other cases in children with a second level of malnutrition and only with vomitoxins results and in three investigated cases of otomycosis caused by Aspergillus niger only in one case traces of aflatoxins were found. PMID:18338920

  3. Human Research Program (HRP) Overview

    NASA Video Gallery

    The Human Research Program (HRP) is a major part of the Space Life and Physical Sciences Research and Applications Division within the Human Exploration and Operations Mission Directorate (HEOMD). ...

  4. Genetic Manipulation of Human Embryonic Stem Cells.

    PubMed

    Eiges, Rachel

    2016-01-01

    One of the great advantages of embryonic stem (ES) cells over other cell types is their accessibility to genetic manipulation. They can easily undergo genetic modifications while remaining pluripotent, and can be selectively propagated, allowing the clonal expansion of genetically altered cells in culture. Since the first isolation of ES cells in mice, many effective techniques have been developed for gene delivery and manipulation of ES cells. These include transfection, electroporation, and infection protocols, as well as different approaches for inserting, deleting, or changing the expression of genes. These methods proved to be extremely useful in mouse ES cells, for monitoring and directing differentiation, discovering unknown genes, and studying their function, and are now being extensively implemented in human ES cells (HESCs). This chapter describes the different approaches and methodologies that have been applied for the genetic manipulation of HESCs and their applications. Detailed protocols for generating clones of genetically modified HESCs by transfection, electroporation, and infection will be described, with special emphasis on the important technical details that are required for this purpose. All protocols are equally effective in human-induced pluripotent stem (iPS) cells. PMID:25520283

  5. Human Genetic Disorders of Axon Guidance

    PubMed Central

    Engle, Elizabeth C.

    2010-01-01

    This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Genes mutated in these disorders can encode axon growth cone ligands and receptors, downstream signaling molecules, and axon transport motors, as well as proteins without currently recognized roles in axon guidance. Advances in neuroimaging and genetic techniques have the potential to rapidly expand this field, and it is feasible that axon guidance disorders will soon be recognized as a new and significant category of human neurodevelopmental disorders. PMID:20300212

  6. Genetic Heterogeneity in Algerian Human Populations

    PubMed Central

    Deba, Tahria; Calafell, Francesc; Benhamamouch, Soraya; Comas, David

    2015-01-01

    The demographic history of human populations in North Africa has been characterized by complex processes of admixture and isolation that have modeled its current gene pool. Diverse genetic ancestral components with different origins (autochthonous, European, Middle Eastern, and sub-Saharan) and genetic heterogeneity in the region have been described. In this complex genetic landscape, Algeria, the largest country in Africa, has been poorly covered, with most of the studies using a single Algerian sample. In order to evaluate the genetic heterogeneity of Algeria, Y-chromosome, mtDNA and autosomal genome-wide makers have been analyzed in several Berber- and Arab-speaking groups. Our results show that the genetic heterogeneity found in Algeria is not correlated with geography or linguistics, challenging the idea of Berber groups being genetically isolated and Arab groups open to gene flow. In addition, we have found that external sources of gene flow into North Africa have been carried more often by females than males, while the North African autochthonous component is more frequent in paternally transmitted genome regions. Our results highlight the different demographic history revealed by different markers and urge to be cautious when deriving general conclusions from partial genomic information or from single samples as representatives of the total population of a region. PMID:26402429

  7. Helicopter human factors research

    NASA Technical Reports Server (NTRS)

    Nagel, David C.; Hart, Sandra G.

    1988-01-01

    Helicopter flight is among the most demanding of all human-machine integrations. The inherent manual control complexities of rotorcraft are made even more challenging by the small margin for error created in certain operations, such as nap-of-the-Earth (NOE) flight, by the proximity of the terrain. Accident data recount numerous examples of unintended conflict between helicopters and terrain and attest to the perceptual and control difficulties associated with low altitude flight tasks. Ames Research Center, in cooperation with the U.S. Army Aeroflightdynamics Directorate, has initiated an ambitious research program aimed at increasing safety margins for both civilian and military rotorcraft operations. The program is broad, fundamental, and focused on the development of scientific understandings and technological countermeasures. Research being conducted in several areas is reviewed: workload assessment, prediction, and measure validation; development of advanced displays and effective pilot/automation interfaces; identification of visual cues necessary for low-level, low-visibility flight and modeling of visual flight-path control; and pilot training.

  8. Population Genomics and the Statistical Values of Race: An Interdisciplinary Perspective on the Biological Classification of Human Populations and Implications for Clinical Genetic Epidemiological Research.

    PubMed

    Maglo, Koffi N; Mersha, Tesfaye B; Martin, Lisa J

    2016-01-01

    The biological status and biomedical significance of the concept of race as applied to humans continue to be contentious issues despite the use of advanced statistical and clustering methods to determine continental ancestry. It is thus imperative for researchers to understand the limitations as well as potential uses of the concept of race in biology and biomedicine. This paper deals with the theoretical assumptions behind cluster analysis in human population genomics. Adopting an interdisciplinary approach, it demonstrates that the hypothesis that attributes the clustering of human populations to "frictional" effects of landform barriers at continental boundaries is empirically incoherent. It then contrasts the scientific status of the "cluster" and "cline" constructs in human population genomics, and shows how cluster may be instrumentally produced. It also shows how statistical values of race vindicate Darwin's argument that race is evolutionarily meaningless. Finally, the paper explains why, due to spatiotemporal parameters, evolutionary forces, and socio-cultural factors influencing population structure, continental ancestry may be pragmatically relevant to global and public health genomics. Overall, this work demonstrates that, from a biological systematic and evolutionary taxonomical perspective, human races/continental groups or clusters have no natural meaning or objective biological reality. In fact, the utility of racial categorizations in research and in clinics can be explained by spatiotemporal parameters, socio-cultural factors, and evolutionary forces affecting disease causation and treatment response. PMID:26925096

  9. Population Genomics and the Statistical Values of Race: An Interdisciplinary Perspective on the Biological Classification of Human Populations and Implications for Clinical Genetic Epidemiological Research

    PubMed Central

    Maglo, Koffi N.; Mersha, Tesfaye B.; Martin, Lisa J.

    2016-01-01

    The biological status and biomedical significance of the concept of race as applied to humans continue to be contentious issues despite the use of advanced statistical and clustering methods to determine continental ancestry. It is thus imperative for researchers to understand the limitations as well as potential uses of the concept of race in biology and biomedicine. This paper deals with the theoretical assumptions behind cluster analysis in human population genomics. Adopting an interdisciplinary approach, it demonstrates that the hypothesis that attributes the clustering of human populations to “frictional” effects of landform barriers at continental boundaries is empirically incoherent. It then contrasts the scientific status of the “cluster” and “cline” constructs in human population genomics, and shows how cluster may be instrumentally produced. It also shows how statistical values of race vindicate Darwin's argument that race is evolutionarily meaningless. Finally, the paper explains why, due to spatiotemporal parameters, evolutionary forces, and socio-cultural factors influencing population structure, continental ancestry may be pragmatically relevant to global and public health genomics. Overall, this work demonstrates that, from a biological systematic and evolutionary taxonomical perspective, human races/continental groups or clusters have no natural meaning or objective biological reality. In fact, the utility of racial categorizations in research and in clinics can be explained by spatiotemporal parameters, socio-cultural factors, and evolutionary forces affecting disease causation and treatment response. PMID:26925096

  10. Genetic and Molecular Ecotoxicology: A Research Framework

    PubMed Central

    Anderson, Susan; Sadinski, Walter; Shugart, Lee; Brussard, Peter; Depledge, Michael; Ford, Tim; Hose, JoEllen; Stegeman, John; Suk, William; Wirgin, Isaac; Wogan, Gerald

    1994-01-01

    Participants at the Napa Conference on Genetic and Molecular Ecotoxicology assessed the status of this field in light of heightened concerns about the genetic effects of exposure to hazardous substances and recent advancements in our capabilities to measure those effects. We present here a synthesis of the ideas discussed throughout the conference, including definitions of important concepts in the field and critical research needs and opportunities. While there were many opinions expressed on these topics, there was general agreement that there are substantive new opportunities to improve the impact of genetic and molecular ecotoxicology on prediction of sublethal effects of exposure to hazardous substances. Future studies should emphasize integration of genetic ecotoxicology, ecological genetics, and molecular biology and should be directed toward improving our understanding of the ecological implications of genotoxic responses. Ecological implications may be assessed at either the population or ecosystem level; however, a population-level focus may be most pragmatic. Recent technical advancements in measuring genetic and molecular responses to toxicant exposure will spur rapid progress. These new techniques have considerable promise for increasing our understanding of both mechanisms of toxicity on genes or gene products and the relevance of detrimental effects to individual fitness. — Environ Health Perspect 102(Suppl 12):3–8 (1994) PMID:7713030

  11. A model agreement for genetic research in socially identifiable populations.

    PubMed

    Foster, M W; Bernsten, D; Carter, T H

    1998-09-01

    Genetic research increasingly focuses on population-specific human genetic diversity. However, the naming of a human population in public databases and scientific publications entails collective risks for its members. Those collective risks can be evaluated and protections can be put in place by the establishment of a dialogue with the subject population, before a research study is initiated. Here we describe an agreement to undertake genetic research with a Native American tribe. We identified the culturally appropriate public and private social units within which community members are accustomed to make decisions about health. We then engaged those units in a process of communal discourse. In their discourses about our proposed study, community members expressed most concern about culturally specific implications. We also found that, in this population, private social units were more influential in communal decision making than were public authorities. An agreement was reached that defined the scope of research, provided options for naming the population in publications (including anonymity), and addressed the distribution of royalties from intellectual property, the future use of archival samples, and specific cultural concerns. We found that informed consent by individuals could not fully address these collective issues. This approach may serve as a general model for the undertaking of population-specific genetic studies. PMID:9718343

  12. Classical and Molecular Genetic Research on General Cognitive Ability.

    PubMed

    McGue, Matt; Gottesman, Irving I

    2015-01-01

    Arguably, no psychological variable has received more attention from behavioral geneticists than what has been called "general cognitive ability" (as well as "general intelligence" or "g"), and for good reason. GCA has a rich correlational network, implying that it may play an important role in multiple domains of functioning. GCA is highly correlated with various indicators of educational attainment, yet its predictive utility is not limited to academic achievement. It is also correlated with work performance, navigating the complexities of everyday life, the absence of various social pathologies (such as criminal convictions), and even health and mortality. Although the causal basis for these associations is not always known, it is nonetheless the case that research on GCA has the potential to provide insights into the origins of a wide range of important social outcomes. In this essay, our discussion of why GCA is considered a fundamentally important dimension of behavior on which humans differ is followed by a look at behavioral genetics research on CGA. We summarize behavioral genetics research that has sought to identify and quantify the total contributions of genetic and environmental factors to individual differences in GCA as well as molecular genetic research that has sought to identify genetic variants that underlie inherited effects. PMID:26413945

  13. Human subjects research handbook: Protecting human research subjects. Second edition

    SciTech Connect

    1996-01-30

    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  14. A global reference for human genetic variation.

    PubMed

    Auton, Adam; Brooks, Lisa D; Durbin, Richard M; Garrison, Erik P; Kang, Hyun Min; Korbel, Jan O; Marchini, Jonathan L; McCarthy, Shane; McVean, Gil A; Abecasis, Gonçalo R

    2015-10-01

    The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. PMID:26432245

  15. A global reference for human genetic variation

    PubMed Central

    2016-01-01

    The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. PMID:26432245

  16. Genetic research in autism spectrum disorders

    PubMed Central

    Robinson, Elise B.; Neale, Benjamin M.; Hyman, Steven E.

    2015-01-01

    Purpose of review The recent explosion of genetic findings in autism spectrum disorder (ASD) research has improved knowledge of the disorder's underlying biology and etiologic architecture. This review introduces concepts and results from recent genetic studies and discusses the manner in which those findings can influence the trajectory of ASD research. Recent findings Large consortium studies have associated ASDs with many types of genetic risk factors, including common polygenic risk, de novo single nucleotide variants, copy number variants, and rare inherited variants. In aggregate, these results confirm the heterogeneity and complexity of ASDs. The rare variant findings in particular point to genes and pathways that begin to bridge the gap between behavior and biology. Summary Genetic studies have the potential to identify the biological underpinnings of ASDs and other neuropsychiatric disorders. The data they generate are already being used to examine disease pathways and pathogenesis. The results also speak to ASD heterogeneity and, in the future, may be used to stratify research studies and treatment trials. PMID:26371945

  17. New Directions in Science Teaching: Human Genetics Education.

    ERIC Educational Resources Information Center

    Mertens, Thomas R.

    1983-01-01

    The range, complexity, and rapid increase of controversial knowledge about human genetics require that students be taught the biomedical facts and ethical dilemmas. Human genetics education thus provides an excellent opportunity for increasing scientific literacy generally. (PB)

  18. Human Genetic Engineering: A Survey of Student Value Stances

    ERIC Educational Resources Information Center

    Wilson, Sara McCormack; And Others

    1975-01-01

    Assesses the values of high school and college students relative to human genetic engineering and recommends that biology educators explore instructional strategies merging human genetic information with value clarification techniques. (LS)

  19. Functional Analysis of the Human Genome:. Study of Genetic Disease

    NASA Astrophysics Data System (ADS)

    Tsui, Lap-Chee

    2003-04-01

    I will divide my remarks into 3 parts. First, I will give a brief summary of the Human Genome Project. Second, I will describe our work on human chromosome 7 to illustrate how we could contribute to the Project and disease research. Third, I would like to bring across the argument that study of genetic disease is an integral component of the Human Genome Project. In particular, I will use cystic fibrosis as an example to elaborate why I consider disease study is a part of functional genomics.

  20. Genetic Basis of Human Circadian Rhythm Disorders

    PubMed Central

    Jones, Christopher R.; Huang, Angela L.; Ptáček, Louis J.; Fu, Ying-Hui

    2012-01-01

    Circadian rhythm disorders constitute a group of phenotypes that usually present as altered sleep-wake schedules. Until a human genetics approach was applied to investigate these traits, the genetic components regulating human circadian rhythm and sleep behaviors remained mysterious. Steady advances in the last decade have dramatically improved our understanding of the genes involved in circadian rhythmicity and sleep regulation. Finding these genes presents new opportunities to use a wide range of approaches, including in vitro molecular studies and in vivo animal modeling, to elevate our understanding of how sleep and circadian rhythms are regulated and maintained. Ultimately, this knowledge will reveal how circadian and sleep disruption contribute to various ailments and shed light on how best to maintain and recover good health. PMID:22849821

  1. Gene Conversion in Human Genetic Disease

    PubMed Central

    Chen, Jian-Min; Férec, Claude; Cooper, David N.

    2010-01-01

    Gene conversion is a specific type of homologous recombination that involves the unidirectional transfer of genetic material from a ‘donor’ sequence to a highly homologous ‘acceptor’. We have recently reviewed the molecular mechanisms underlying gene conversion, explored the key part that this process has played in fashioning extant human genes, and performed a meta-analysis of gene-conversion events known to have caused human genetic disease. Here we shall briefly summarize some of the latest developments in the study of pathogenic gene conversion events, including (i) the emerging idea of minimal efficient sequence homology (MESH) for homologous recombination, (ii) the local DNA sequence features that appear to predispose to gene conversion, (iii) a mechanistic comparison of gene conversion and transient hypermutability, and (iv) recently reported examples of pathogenic gene conversion events. PMID:24710102

  2. Advances in gene technology: Human genetic disorders

    SciTech Connect

    Scott, W.A.; Ahmad, F.; Black, S.; Schultz, J.; Whelan, W.J.

    1984-01-01

    This book discusses the papers presented at the conference on the subject of ''advances in Gene technology: Human genetic disorders''. Molecular biology of various carcinomas and inheritance of metabolic diseases is discussed and technology advancement in diagnosis of hereditary diseases is described. Some of the titles discussed are-Immunoglobulin genes translocation and diagnosis; hemophilia; oncogenes; oncogenic transformations; experimental data on mice, hamsters, birds carcinomas and sarcomas.

  3. Patenting human genetic material: refocusing the debate

    PubMed Central

    Caulfield, Timothy; Gold, E. Richard; Cho, Mildred K.

    2008-01-01

    The biotechnology industry has become firmly established over the past twenty years and gene patents have played an important part in this phenomenon. However, concerns have been raised over the patentability of human genetic material, through public protests and international statements, but to little effect. Here we discuss some of these concerns, the patent authorities’ response to them, and ways in which to address these issues and to move the debate forward using current legal structures. PMID:11252752

  4. Genetics Research Discovered in a Bestseller | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer One morning in early January, Amar Klar sat down at his computer and found an e-mail with a curious message from a colleague. While reading a bestselling novel, The Marriage Plot by Jeffrey Eugenides, his colleague, a professor at Princeton University, found a description of research on yeast genetics that was surprisingly similar to Klar’s early research. Even the laboratory in the novel was reminiscent of Cold Spring Harbor Laboratory, where Klar had conducted his research.

  5. DNA diagnosis of human genetic individuality.

    PubMed

    Pena, S D; Prado, V F; Epplen, J T

    1995-11-01

    DNA studies of the human genome have shown polymorphic variation at thousands of sites, defining an absolute genetic uniqueness for each individual. There are many circumstances in which it may be desirable to diagnose this molecular individuality, as for instance, in criminal investigations or paternity testing. Several techniques can be used for this DNA diagnosis and we can choose among them the one that best suits the specific problem at hand. In this review we describe the main methodologies in current use to investigate human DNA polymorphisms, discussing the best application of each option, as well as their advantages and disadvantages. PMID:8751139

  6. Models to explore genetics of human aging.

    PubMed

    Karasik, David; Newman, Anne

    2015-01-01

    Genetic studies have bestowed insight into the biological mechanisms underlying inter-individual differences in susceptibility to (or resistance to) organisms’ aging. Recent advances in molecular and genetic epidemiology provide tools to explore the genetic sources of the variability in biological aging in humans. To be successful, the genetic study of a complex condition such as aging requires the clear definition of essential traits that can characterize the aging process phenotypically. Phenotypes of human aging have long relied on mortality rate or exceptional longevity. Genome-wide association studies (GWAS) have been shown to present an unbiased approach to the identification of new candidate genes for human diseases. The GWAS approach can also be used for positive health phenotypes such as longevity or a delay in age-related chronic disease, as well as for other age related changes such as loss of telomere length or lens transparency. Sequencing, either in targeted regions or across the whole genome can further identify rare variation that may contribute to the biological aging mechanisms. To date, the results of the GWAS for longevity are rather disappointing, possibly in part due to the small number of individuals with GWAS data who have reached advanced old age.Human aging phenotypes are needed that can be assessed prior to death, and should be both heritable and validated as predictors of longevity. Potentially, phenotypes that focus on “successful” or “healthy” aging will be more powerful as they can be measured in large numbers of people and also are clinically relevant.We postulate that construction of an integrated phenotype of aging can be achieved capitalizing on multiple traits that may have weak correlations, but a shared underlying genetic architecture. This is based on a hypothesis that convergent results from multiple individual aging-related traits will point out the pleiotropic signals responsible for the overall rate of aging of

  7. Offering Individual Genetic Research Results: Context Matters

    PubMed Central

    Beskow, Laura M.; Burke, Wylie

    2011-01-01

    The disclosure of individual genetic research results to participants continues to be the subject of vigorous debate, centered primarily on the nature of the results: What are the criteria for the kinds of information that should, could, or should not be offered? There are widely diverging views about how to define these categories, as reasonable people can disagree about the value of various kinds of information. Data concerning participant preferences regarding receipt of results are important, but not determinative of researchers’ fundamental obligations. We suggest that research context is a vital consideration that has not been sufficiently incorporated into the discussion. We adapt an ancillary care framework to explore what different contexts might call for with regard to offering individual genetic research results. Our analysis suggests that, beyond exceptionally rare circumstances that give rise to a duty to rescue, a “one size fits all” threshold cannot be developed for decisions about return of individual results. Instead, researchers and IRBs must consider the scope of entrustment involved in the research, the intensity and duration of interactions with participants, and the vulnerability and dependence of the study population. The strength of this approach is that research context is foreseeable at the time a study is designed. Assessments of the nature and value of the information may still be required to decide whether to offer a particular result, but perhaps will be facilitated by a more grounded understanding of researchers’ obligations in different contexts. PMID:20592417

  8. [Network Research on Human Papillomavirus].

    PubMed

    Almeida-Gutiérrez, Eduardo; Paniagua, Ramón; Furuya, María ElenaYuriko

    2015-01-01

    In order to increase the research in important health questions at a national and institutional levels, the Human Papillomavirus Research Network of the Health Research Coordination of the Instituto Mexicano del Seguro Social offers this supplement with the purpose of assisting patients that daily look for attention due to the human papillomavirus or to cervical cancer. PMID:26462505

  9. Genetic Analysis of Human Preimplantation Embryos.

    PubMed

    Garcia-Herrero, S; Cervero, A; Mateu, E; Mir, P; Póo, M E; Rodrigo, L; Vera, M; Rubio, C

    2016-01-01

    Preimplantation development comprises the initial stages of mammalian development, before the embryo implants into the mother's uterus. In normal conditions, after fertilization the embryo grows until reaching blastocyst stage. The blastocyst grows as the cells divide and the cavity expands, until it arrives at the uterus, where it "hatches" from the zona pellucida to implant into the uterine wall. Nevertheless, embryo quality and viability can be affected by chromosomal abnormalities, most of which occur during gametogenesis and early embryo development; human embryos produced in vitro are especially vulnerable. Therefore, the selection of chromosomally normal embryos for transfer in assisted reproduction can improve outcomes in poor-prognosis patients. Additionally, in couples with an inherited disorder, early diagnosis could prevent pregnancy with an affected child and would, thereby, avoid the therapeutic interruption of pregnancy. These concerns have prompted advancements in the use of preimplantation genetic diagnosis (PGD). Genetic testing is applied in two different scenarios: in couples with an inherited genetic disorder or carriers of a structural chromosomal abnormality, it is termed PGD; in infertile couples with increased risk of generating embryos with de novo chromosome abnormalities, it is termed preimplantation genetic screening, or PGS. PMID:27475859

  10. Basic Science Research and the Protection of Human Research Participants

    NASA Astrophysics Data System (ADS)

    Eiseman, Elisa

    2001-03-01

    Technological advances in basic biological research have been instrumental in recent biomedical discoveries, such as in the understanding and treatment of cancer, HIV/AIDS, and heart disease. However, many of these advances also raise several new ethical challenges. For example, genetic research may pose no physical risk beyond that of obtaining the initial blood sample, yet it can pose significant psychological and economic risks to research participants, such as stigmatization, discrimination in insurance and employment, invasion of privacy, or breach of confidentiality. These harms may occur even when investigators do not directly interact with the person whose DNA they are studying. Moreover, this type of basic research also raises broader questions, such as what is the definition of a human subject, and what kinds of expertise do Institutional Review Boards (IRBs) need to review the increasingly diverse types of research made possible by these advances in technology. The National Bioethics Advisory Commission (NBAC), a presidentially appointed federal advisory committee, has addressed these and other ethical, scientific and policy issues that arise in basic science research involving human participants. Two of its six reports, in particular, have proposed recommendations in this regard. "Research Involving Human Biological Materials: Ethical and Policy Guidance" addresses the basic research use of human tissues, cells and DNA and the protection of human participants in this type of research. In "Ethical and Policy Issues in the Oversight of Human Research" NBAC proposes a definition of research involving human participants that would apply to all scientific disciplines, including physical, biological, and social sciences, as well as the humanities and related professions, such as business and law. Both of these reports make it clear that the protection of research participants is key to conducting ethically sound research. By ensuring that all participants in

  11. Variobox: automatic detection and annotation of human genetic variants.

    PubMed

    Gaspar, Paulo; Lopes, Pedro; Oliveira, Jorge; Santos, Rosário; Dalgleish, Raymond; Oliveira, José Luís

    2014-02-01

    Triggered by the sequencing of the human genome, personalized medicine has been one of the fastest growing research areas in the last decade. Multiple software and hardware technologies have been developed by several projects, culminating in the exponential growth of genetic data. Considering the technological developments in this field, it is now fairly easy and inexpensive to obtain genetic profiles for unique individuals, such as those performed by several genetic analysis companies. The availability of computational tools that simplify genetic data analysis and the disclosure of biomedical evidences are of utmost importance. We present Variobox, a desktop tool to annotate, analyze, and compare human genes. Variobox obtains variant annotation data from WAVe, protein metadata annotations from Protein Data Bank, and sequences are obtained from Locus Reference Genomic or RefSeq databases. To explore the data, Variobox provides an advanced sequence visualization that enables agile navigation through genetic regions. DNA sequencing data can be compared with reference sequences retrieved from LRG or RefSeq records, identifying and automatically annotating new potential variants. These features and data, ranging from patient sequences to HGVS-compliant variant descriptions, are combined in an intuitive interface to analyze genes and variants. Variobox is a Java application, available at http://bioinformatics.ua.pt/variobox. PMID:24186831

  12. Human genetic disorders of sphingolipid biosynthesis.

    PubMed

    Astudillo, Leonardo; Sabourdy, Frédérique; Therville, Nicole; Bode, Heiko; Ségui, Bruno; Andrieu-Abadie, Nathalie; Hornemann, Thorsten; Levade, Thierry

    2015-01-01

    Monogenic defects of sphingolipid biosynthesis have been recently identified in human patients. These enzyme deficiencies affect the synthesis of sphingolipid precursors, ceramides or complex glycosphingolipids. They are transmitted as autosomal recessive or dominant traits, and their resulting phenotypes often replicate the abnormalities seen in murine models deficient for the corresponding enzymes. In quite good agreement with the known critical roles of sphingolipids in cells from the nervous system and the epidermis, these genetic defects clinically manifest as neurological disorders, including paraplegia, epilepsy or peripheral neuropathies, or present with ichthyosis. The present review summarizes the genetic alterations, biochemical changes and clinical symptoms of this new group of inherited metabolic disorders. Hypotheses regarding the molecular pathophysiology and potential treatments of these diseases are also discussed. PMID:25141825

  13. Human Research Program Requirements Document. Human Research Program Revision E

    NASA Technical Reports Server (NTRS)

    Vargas, Paul

    2011-01-01

    This document defines, documents, and allocates the Human Research Program (HRP) requirements to the HRP Program Elements. It also establishes the flow of requirements from the Human Exploration and Operations Mission Directorate (HEOMD) and the Office of the Chief Health and Medical Officer (OCHMO) down to the various HRP Program Elements to ensure that human research and technology countermeasure investments support the delivery of countermeasures and technologies that satisfy HEOMD's and OCHMO's exploration mission requirements.

  14. Applications of Genetic Programming in Cancer Research

    PubMed Central

    Worzel, William P.; Yu, Jianjun; Almal, Arpit A.; Chinnaiyan, Arul M.

    2012-01-01

    The theory of Darwinian evolution is the fundamental keystones of modern biology. Late in the last century, computer scientists began adapting its principles, in particular natural selection, to complex computational challenges, leading to the emergence of evolutionary algorithms. The conceptual model of selective pressure and recombination in evolutionary algorithms allows scientists to efficiently search high dimensional space for solutions to complex problems. In the last decade, genetic programming has been developed and extensively applied for analysis of molecular data to classify cancer subtypes and characterize the mechanisms of cancer pathogenesis and development. This article reviews current successes using genetic programming and discusses its potential impact in cancer research and treatment in the near future. PMID:18929677

  15. Genetically Encoded Voltage Indicators in Circulation Research

    PubMed Central

    Kaestner, Lars; Tian, Qinghai; Kaiser, Elisabeth; Xian, Wenying; Müller, Andreas; Oberhofer, Martin; Ruppenthal, Sandra; Sinnecker, Daniel; Tsutsui, Hidekazu; Miyawaki, Atsushi; Moretti, Alessandra; Lipp, Peter

    2015-01-01

    Membrane potentials display the cellular status of non-excitable cells and mediate communication between excitable cells via action potentials. The use of genetically encoded biosensors employing fluorescent proteins allows a non-invasive biocompatible way to read out the membrane potential in cardiac myocytes and other cells of the circulation system. Although the approaches to design such biosensors date back to the time when the first fluorescent-protein based Förster Resonance Energy Transfer (FRET) sensors were constructed, it took 15 years before reliable sensors became readily available. Here, we review different developments of genetically encoded membrane potential sensors. Furthermore, it is shown how such sensors can be used in pharmacological screening applications as well as in circulation related basic biomedical research. Potentials and limitations will be discussed and perspectives of possible future developments will be provided. PMID:26370981

  16. Attitudes towards the use of genetically modified animals in research.

    PubMed

    Schuppli, Catherine A; Weary, Daniel M

    2010-11-01

    Here we provide the first experimental evidence that public concerns about the use of animals in research are accentuated when genetically modified (GM) animals are used. Using an online survey, we probed participant views on two uses of pigs as research animals (to reduce agricultural pollution or to improve organ transplant success in humans) with and without GM. We surveyed 327 animal technicians, researchers, advocates, university students and others. In both scenarios and across demographics, support dropped off when the research required the use of GM pigs or GM corn. For example, 66% of participants supported using pigs to reduce phosphorus pollution, but this declined to 49% when the pigs were fed GM corn and to 20% when the research required the creation of a new GM line of pigs. Those involved in animal research were more consistently supportive compared to those who were not or those who were vegetarians. PMID:21560543

  17. Protecting Subjects’ Interests in Genetics Research

    PubMed Central

    Merz, Jon F.; Magnus, David; Cho, Mildred K.; Caplan, Arthur L.

    2002-01-01

    Biomedical researchers often assume that sponsors, subjects, families, and disease-associated advocacy groups contribute to research solely because of altruism. This view fails to capture the diverse interests of many participants in the emerging research enterprise. In the past two decades, patient groups have become increasingly active in the promotion and facilitation of genetics research. Simultaneously, a significant shift of academic biomedical science toward commercialization has occurred, spurred by U.S. federal policy changes. The concurrent rise in both the roles that subjects play and the commercial interests they have presents numerous ethical challenges. We examine the interests of different research participants, finding that these interests are not addressed by current policies and practices. We conclude that all participants should be given a voice in decisions affecting ownership, access to, and use of commercialized products and services, and that researchers and institutions should negotiate issues relating to control of research results and the sharing of benefits before the research is performed. PMID:11870592

  18. Genetics of multifactorial disorders: proceedings of the 6th Pan Arab Human Genetics Conference.

    PubMed

    Nair, Pratibha; Bizzari, Sami; Rajah, Nirmal; Assaf, Nada; Al-Ali, Mahmoud Taleb; Hamzeh, Abdul Rezzak

    2016-01-01

    The 6th Pan Arab Human Genetics Conference (PAHGC), "Genetics of Multifactorial Disorders" was organized by the Center for Arab Genomic Studies (http://www.cags.org.ae) in Dubai, United Arab Emirates from 21 to 23 January, 2016. The PAHGCs are held biennially to provide a common platform to bring together regional and international geneticists to share their knowledge and to discuss common issues. Over 800 delegates attended the first 2 days of the conference and these came from various medical and scientific backgrounds. They consisted of geneticists, molecular biologists, medical practitioners, postdoctoral researchers, technical staff (e.g., nurses and lab technicians) and medical students from 35 countries around the world. On the 3rd day, a one-day workshop on "Genetic Counseling" was delivered to 26 participants. The conference focused on four major topics, namely, diabetes, genetics of neurodevelopmental disorders, congenital anomalies and cancer genetics. Personalized medicine was a recurrent theme in most of the research presented at the conference, as was the application of novel molecular findings in clinical settings. This report discusses a summary of the presentations from the meeting. PMID:27095177

  19. A New BSCS Project: Human Genetics Education for High School.

    ERIC Educational Resources Information Center

    Biological Sciences Curriculum Study Journal, 1980

    1980-01-01

    Described is the BSCS Center for Education in Human and Medical Genetics, established to design, develop, and evaluate an instructional module in human genetics for high school students. This module will be a self-contained curricular program and will provide individualized open-ended experiences which present basic genetics content in the context…

  20. Parents' Perspectives on Participating in Genetic Research in Autism

    ERIC Educational Resources Information Center

    Trottier, Magan; Roberts, Wendy; Drmic, Irene; Scherer, Stephen W.; Weksberg, Rosanna; Cytrynbaum, Cheryl; Chitayat, David; Shuman, Cheryl; Miller, Fiona A.

    2013-01-01

    Genetic research in autism depends on the willingness of individuals with autism to participate; thus, there is a duty to assess participants' needs in the research process. We report on families' motives and expectations related to their participation in autism genetic research. Respondents valued having a genetic result, as it alleviates guilt,…

  1. Community dissemination and genetic research: moving beyond results reporting.

    PubMed

    Trinidad, Susan Brown; Ludman, Evette J; Hopkins, Scarlett; James, Rosalina D; Hoeft, Theresa J; Kinegak, Annie; Lupie, Henry; Kinegak, Ralph; Boyer, Bert B; Burke, Wylie

    2015-07-01

    The community-based participatory research (CBPR) literature notes that researchers should share study results with communities. In the case of human genetic research, results may be scientifically interesting but lack clinical relevance. The goals of this study were to learn what kinds of information community members want to receive about genetic research and how such information should be conveyed. We conducted eight focus group discussions with Yup'ik Alaska Native people in southwest Alaska (N = 60) and 6 (N = 61) with members of a large health maintenance organization in Seattle, Washington. Participants wanted to receive genetic information they "could do something about" and wanted clinically actionable information to be shared with their healthcare providers; they also wanted researchers to share knowledge about other topics of importance to the community. Although Alaska Native participants were generally less familiar with western scientific terms and less interested in web-based information sources, the main findings were the same in Alaska and Seattle: participants wished for ongoing dialogue, including opportunities for informal, small-group conversations, and receiving information that had local relevance. Effective community dissemination is more than a matter of presenting study results in lay language. Community members should be involved in both defining culturally appropriate communication strategies and in determining which information should be shared. Reframing dissemination as a two-way dialogue, rather than a one-way broadcast, supports the twin aims of advancing scientific knowledge and achieving community benefit. PMID:25900516

  2. Genetic basis of human left-right asymmetry disorders.

    PubMed

    Deng, Hao; Xia, Hong; Deng, Sheng

    2015-01-01

    Humans and other vertebrates exhibit left-right (LR) asymmetric arrangement of the internal organs, and failure to establish normal LR asymmetry leads to internal laterality disorders, including situs inversus and heterotaxy. Situs inversus is complete mirror-imaged arrangement of the internal organs along LR axis, whereas heterotaxy is abnormal arrangement of the internal thoraco-abdominal organs across LR axis of the body, most of which are associated with complex cardiovascular malformations. Both disorders are genetically heterogeneous with reduced penetrance, presumably because of monogenic, polygenic or multifactorial causes. Research in genetics of LR asymmetry disorders has been extremely prolific over the past 17 years, and a series of loci and disease genes involved in situs inversus and heterotaxy have been described. The review highlights the classification, chromosomal abnormalities, pathogenic genes and the possible mechanism of human LR asymmetry disorders. PMID:26258520

  3. Genetics of human sensitivity to ultraviolet radiation

    NASA Astrophysics Data System (ADS)

    Cleaver, James E.

    1994-07-01

    the major human health effects of solar and artificial UV light occur from the UVB and UVC wavelength ranges and involve a variety of short-term and long-term deleterious changes to the skin and eyes. the more important initial damage to cellular macromolecules involves dimerization of adjacent pyrimidines in DNA to produce cyclobutane pyrimidine dimes, (6-4) pyrimidine- pyrimidone, and (6-4) dewar photoproducts. these photoproducts can be repaired by a genetically regulated enzyme system (nucleotide excision repair) which removes oligonucleotides 29-30 nucleotides long that contain the photoproducts, and synthesizes replacement patches. At least a dozen gene products are involved in the process of recognizing photoproducts in DNA, altering local DNA helicity and cleaving the polynucleotide chain at defined positions either side of a photoproduct. Hereditary mutations in many of these genes are recognized in the human genetic disorders xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). Several of the gene products have other functions involving the regulation of gene transcription which accounts for the complex clinical presentation of repair deficient diseases that involve sensitivity of the skin and eyes to UV light, increased solar carcinogenesis (in XP), demyelination, and ganglial calcification (in CS), hair abnormalities (in TTD), and developmental and neurological abnormalities

  4. Genetic regulation of human brain development: lessons from Mendelian diseases

    PubMed Central

    Dixon-Salazar, Tracy J.; Gleeson, Joseph G.

    2016-01-01

    One of the fundamental goals in human genetics is to link gene function to phenotype, yet the function of the majority of the genes in the human body is still poorly understood. This is especially true for the developing human brain. The study of human phenotypes that result from inherited, mutated alleles is the most direct evidence for the requirement of a gene in human physiology. Thus, the study of Mendelian central nervous system(CNS) diseases can be an extremely powerful approach to elucidate such phenotypic/genotypic links and to increase our understanding of the key components required for development of the human brain. In this review, we highlight examples of how the study of inherited neurodevelopmental disorders contributes to our knowledge of both the “normal” and diseased human brain, as well as elaborate on the future of this type of research. Mendelian disease research has been, and will continue to be, key to understanding the molecular mechanisms that underlie human brain function, and will ultimately form a basis for the design of intelligent, mechanism-specific treatments for nervous system disorders. PMID:21062301

  5. Genetics of the dentofacial variation in human malocclusion

    PubMed Central

    Moreno Uribe, L. M.; Miller, S. F.

    2015-01-01

    Malocclusions affect individuals worldwide, resulting in compromised function and esthetics. Understanding the etiological factors contributing to the variation in dentofacial morphology associated with malocclusions is the key to develop novel treatment approaches. Advances in dentofacial phenotyping, which is the comprehensive characterization of hard and soft tissue variation in the craniofacial complex, together with the acquisition of large-scale genomic data have started to unravel genetic mechanisms underlying facial variation. Knowledge on the genetics of human malocclusion is limited even though results attained thus far are encouraging, with promising opportunities for future research. This review summarizes the most common dentofacial variations associated with malocclusions and reviews the current knowledge of the roles of genes in the development of malocclusions. Lastly, this review will describe ways to advance malocclusion research, following examples from the expanding fields of phenomics and genomic medicine, which aim to better patient outcomes. PMID:25865537

  6. Molecular and genetic inflammation networks in major human diseases.

    PubMed

    Zhao, Yongzhong; Forst, Christian V; Sayegh, Camil E; Wang, I-Ming; Yang, Xia; Zhang, Bin

    2016-07-19

    It has been well-recognized that inflammation alongside tissue repair and damage maintaining tissue homeostasis determines the initiation and progression of complex diseases. Albeit with the accomplishment of having captured the most critical inflammation-involved molecules, genetic susceptibilities, epigenetic factors, and environmental factors, our schemata on the role of inflammation in complex diseases remain largely patchy, in part due to the success of reductionism in terms of research methodology per se. Omics data alongside the advances in data integration technologies have enabled reconstruction of molecular and genetic inflammation networks which shed light on the underlying pathophysiology of complex diseases or clinical conditions. Given the proven beneficial role of anti-inflammation in coronary heart disease as well as other complex diseases and immunotherapy as a revolutionary transition in oncology, it becomes timely to review our current understanding of the molecular and genetic inflammation networks underlying major human diseases. In this review, we first briefly discuss the complexity of infectious diseases and then highlight recently uncovered molecular and genetic inflammation networks in other major human diseases including obesity, type II diabetes, coronary heart disease, late onset Alzheimer's disease, Parkinson's disease, and sporadic cancer. The commonality and specificity of these molecular networks are addressed in the context of genetics based on genome-wide association study (GWAS). The double-sword role of inflammation, such as how the aberrant type 1 and/or type 2 immunity leads to chronic and severe clinical conditions, remains open in terms of the inflammasome and the core inflammatome network features. Increasingly available large Omics and clinical data in tandem with systems biology approaches have offered an exciting yet challenging opportunity toward reconstruction of more comprehensive and dynamic molecular and genetic

  7. Biological databases for human research.

    PubMed

    Zou, Dong; Ma, Lina; Yu, Jun; Zhang, Zhang

    2015-02-01

    The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation. PMID:25712261

  8. Biological Databases for Human Research

    PubMed Central

    Zou, Dong; Ma, Lina; Yu, Jun; Zhang, Zhang

    2015-01-01

    The completion of the Human Genome Project lays a foundation for systematically studying the human genome from evolutionary history to precision medicine against diseases. With the explosive growth of biological data, there is an increasing number of biological databases that have been developed in aid of human-related research. Here we present a collection of human-related biological databases and provide a mini-review by classifying them into different categories according to their data types. As human-related databases continue to grow not only in count but also in volume, challenges are ahead in big data storage, processing, exchange and curation. PMID:25712261

  9. Mouse Genetic Models of Human Brain Disorders.

    PubMed

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  10. Mouse Genetic Models of Human Brain Disorders

    PubMed Central

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  11. Human Research Initiative (HRI)

    NASA Technical Reports Server (NTRS)

    Motil, Brian

    2003-01-01

    A code U initiative starting in the FY04 budget includes specific funding for 'Phase Change' and 'Multiphase Flow Research' on the ISS. NASA GRC developed a concept for two facilities based on funding/schedule constraints: 1) Two Phase Flow Facility (TphiFFy) which assumes integrating into FIR; 2) Contact Line Dynamics Experiment Facility (CLiDE) which assumes integration into MSG. Each facility will accommodate multiple experiments conducted by NRA selected PIs with an overall goal of enabling specific NASA strategic objectives. There may also be a significant ground-based component.

  12. Human Research Program Requirements Document

    NASA Technical Reports Server (NTRS)

    Rieger, Gabe

    2007-01-01

    The purpose of this document is to define, document, and allocate the Human Research Program (HRP) requirements to the HRP Program elements. It establishes the flow-down of requirements from Exploration Systems Mission Directorate (ESMD) and Office of the Chief Health and Medical Officer (OCHMO) to the various Program Elements of the HRP to ensure that human research and technology countermeasure investments are made to insure the delivery of countermeasures and technologies that satisfy ESMD s and OCHMO's exploration mission requirements.

  13. Psychological Research on Human Aggressiveness

    ERIC Educational Resources Information Center

    Hamburg, D. A.; Brodie, H. K. H.

    1973-01-01

    Discusses research relating to the effects of hormones, neurophysiology, and the environment on animal and human aggression. Indicates that the interactions of biological, psychological and social processes in the development of human aggressiveness should constitute one of the principal frontiers for science in the next two decades. (JR)

  14. Darkness in El Dorado: human genetics on trial.

    PubMed

    Morton, N E

    2001-04-01

    A recent book by a freelance journalist makes major accusations against genetic studies by J. V. Neel in the Amazon a generation ago. Contrary to these charges, there was no connection of Neel's work with human experiments conducted by the Rochester Manhattan project twenty years earlier, nor did the studies serve as a control for survivors of the atomic bombs in Japan. Neel was not a eugenicist. His program of measles vaccination reduced mortality, and was not in any sense an experiment. Given the passage of time and lack of supporting evidence, further investigation of these charges is pointless. However, the political climate in which human populations are studied has changed dramatically over the last generation. Unless guidelines reflect an international consensus, the benefits of population studies to human welfare and science will be jeopardized. The World Health Organization guidelines should be extended to cover current research. PMID:11910124

  15. The New World of Human Genetics: A dialogue between Practitioners & the General Public on Ethical, Legal & Social Implications of the Human Genome Project

    SciTech Connect

    Schofield, Amy

    2014-12-08

    The history and reasons for launching the Human Genome project and the current uses of genetic human material; Identifying and discussing the major issues stemming directly from genetic research and therapy-including genetic discrimination, medical/ person privacy, allocation of government resources and individual finances, and the effect on the way in which we perceive the value of human life; Discussing the sometimes hidden ethical, social and legislative implications of genetic research and therapy such as informed consent, screening and preservation of genetic materials, efficacy of medical procedures, the role of the government, and equal access to medical coverage.

  16. Current Progress of Genetically Engineered Pig Models for Biomedical Research

    PubMed Central

    Gün, Gökhan

    2014-01-01

    Abstract The first transgenic pigs were generated for agricultural purposes about three decades ago. Since then, the micromanipulation techniques of pig oocytes and embryos expanded from pronuclear injection of foreign DNA to somatic cell nuclear transfer, intracytoplasmic sperm injection-mediated gene transfer, lentiviral transduction, and cytoplasmic injection. Mechanistically, the passive transgenesis approach based on random integration of foreign DNA was developed to active genetic engineering techniques based on the transient activity of ectopic enzymes, such as transposases, recombinases, and programmable nucleases. Whole-genome sequencing and annotation of advanced genome maps of the pig complemented these developments. The full implementation of these tools promises to immensely increase the efficiency and, in parallel, to reduce the costs for the generation of genetically engineered pigs. Today, the major application of genetically engineered pigs is found in the field of biomedical disease modeling. It is anticipated that genetically engineered pigs will increasingly be used in biomedical research, since this model shows several similarities to humans with regard to physiology, metabolism, genome organization, pathology, and aging. PMID:25469311

  17. Drawing the line on genetic intervention in humans.

    PubMed

    Kaura, D R

    1996-03-15

    Because the science of genetics can have such profound effects on medicine and mankind, society must define the characteristics of a moral framework within which to make decisions about genetic issues. University of Manitoba medical student Deepak Kaura, who claimed third prize in CMAJ's 1995 Logie Medical Ethics Essay Contest, examines the ethics of genetic intervention in humans. PMID:8634976

  18. Drawing the line on genetic intervention in humans.

    PubMed Central

    Kaura, D R

    1996-01-01

    Because the science of genetics can have such profound effects on medicine and mankind, society must define the characteristics of a moral framework within which to make decisions about genetic issues. University of Manitoba medical student Deepak Kaura, who claimed third prize in CMAJ's 1995 Logie Medical Ethics Essay Contest, examines the ethics of genetic intervention in humans. Images p928-a PMID:8634976

  19. Genetic and environmental factors in human cleft lip and palate.

    PubMed

    Vieira, Alexandre R

    2012-01-01

    Cleft lip and palate is the most common craniofacial birth defect and its etiology has been the focus of many reports in the literature. It is well accepted that both genetics and environment play a role in the condition, however we still have not been able to translate what have been learned into clinical applications. This paper provides an interpretation of the latest research findings in humans and a perspective for where the field is going. The latest effort in gene identification and the associations between isolated cleft lip and palate and the loci harboring IRF6 (1q32) and 8q24.21 are highlighted, as well as the latest insight from more sophisticated phenotypical characterization and the inclusion of covariables related to the environment in the analysis of genetic variation. PMID:22759667

  20. Genetically modified plants and human health

    PubMed Central

    Key, Suzie; Ma, Julian K-C; Drake, Pascal MW

    2008-01-01

    Summary Genetically modified (or GM) plants have attracted a large amount of media attention in recent years and continue to do so. Despite this, the general public remains largely unaware of what a GM plant actually is or what advantages and disadvantages the technology has to offer, particularly with regard to the range of applications for which they can be used. From the first generation of GM crops, two main areas of concern have emerged, namely risk to the environment and risk to human health. As GM plants are gradually being introduced into the European Union there is likely to be increasing public concern regarding potential health issues. Although it is now commonplace for the press to adopt ‘health campaigns’, the information they publish is often unreliable and unrepresentative of the available scientific evidence. We consider it important that the medical profession should be aware of the state of the art, and, as they are often the first port of call for a concerned patient, be in a position to provide an informed opinion. This review will examine how GM plants may impact on human health both directly – through applications targeted at nutrition and enhancement of recombinant medicine production – but also indirectly, through potential effects on the environment. Finally, it will examine the most important opposition currently facing the worldwide adoption of this technology: public opinion. PMID:18515776

  1. Genetic and Fossil Evidence for the Origin of Modern Humans.

    ERIC Educational Resources Information Center

    Stringer, C. B.; Andrews, P.

    1988-01-01

    Discusses how genetic data on present human population relationships and data from the Pleistocene fossil hominid record are being used to compare two contrasting models for the origin of modern humans. (TW)

  2. TRENDS IN HUMAN RELATIONS RESEARCH.

    ERIC Educational Resources Information Center

    WINICK, CHARLES

    A REVIEW OF MAIN TRENDS IN RECENT HUMAN RELATIONS RESEARCH IN THE UNITED STATES, PARTICULARLY AS ILLUSTRATED IN THE WORK OF SIGMUND LIVINGSTON FELLOWS, IS PRESENTED. THE FOCUS IS ON STUDIES DEALING WITH ETHNIC, RACIAL, OR RELIGIOUS CATEGORIES, AND ON RESEARCH DEALING WITH INTERGROUP PREJUDICE AND DISCRIMINATION. THE THREE MAJOR TRENDS IN RESEARCH…

  3. Scaling up: human genetics as a Cold War network.

    PubMed

    Lindee, Susan

    2014-09-01

    In this commentary I explore how the papers here illuminate the processes of collection that have been so central to the history of human genetics since 1945. The development of human population genetics in the Cold War period produced databases and biobanks that have endured into the present, and that continue to be used and debated. In the decades after the bomb, scientists collected and transferred human biological materials and information from populations of interest, and as they moved these biological resources or biosocial resources acquired new meanings and uses. The papers here collate these practices and map their desires and ironies. They explore how a large international network of geneticists, biological anthropologists, virologists and other physicians and scientists interacted with local informants, research subjects and public officials. They also track the networks and standards that mobilized the transfer of information, genealogies, tissue and blood samples. As Joanna Radin suggests here, the massive collections of human biological materials and data were often understood to be resources for an "as-yet-unknown" future. The stories told here contain elements of surveillance, extraction, salvage and eschatology. PMID:24954362

  4. Knowledge Gaining by Human Genetic Studies on Tuberculosis Susceptibility

    PubMed Central

    Qu, Hui-Qi; Fisher-Hoch, Susan P; McCormick, Joseph B

    2011-01-01

    Tuberculosis (TB) is a serious health issue in the developing world. Lack of knowledge on the etiological mechanisms of TB hinders the development of effective strategies for the treatment or prevention of TB disease. Human genetic study is an indispensable approach to understand the molecular basis of common diseases. Numerous efforts were made to screen the human genome for TB susceptibility by linkage mapping. A large number of candidate-based association studies of TB were performed to examine the association of predicted functional DNA variations in candidate genes. Recently, the first genome-wide association study (GWAS) on TB was reported. The GWAS is a proof-of-principle evidence which justifies the genetic approach to understand TB. Further hypothesis-free efforts on TB research may renovate the traditional idea of TB genetic susceptibility as none of the candidate genes with important roles in containing Mycobacterium tuberculosis (MTB) infection was identified of association with active TB, while the TB-associated loci in the GWAS harbors no gene with function in MTB infection. PMID:21179108

  5. Human Laboratory Paradigms in Alcohol Research

    PubMed Central

    Plebani, Jennifer G.; Ray, Lara A.; Morean, Meghan E.; Corbin, William R.; Mackillop, James; Amlung, Michael; King, Andrea C.

    2014-01-01

    Human laboratory studies have a long and rich history in the field of alcoholism. Human laboratory studies have allowed for advances in alcohol research in a variety of ways, including elucidating of the neurobehavioral mechanisms of risk, identifying phenotypically distinct sub-types of alcohol users, investigating of candidate genes underlying experimental phenotypes for alcoholism, and testing mechanisms of action of alcoholism pharmacotherapies on clinically-relevant translational phenotypes, such as persons exhibiting positive-like alcohol effects or alcohol craving. Importantly, the field of human laboratory studies in addiction has progressed rapidly over the past decade and has built upon earlier findings of alcohol's neuropharmacological effects to advancing translational research on alcoholism etiology and treatment. To that end, the new generation of human laboratory studies has focused on applying new methodologies, further refining alcoholism phenotypes, and translating these findings to studies of alcoholism genetics, medication development, and pharmacogenetics. The combination of experimental laboratory approaches with recent developments in neuroscience and pharmacology has been particularly fruitful in furthering our understanding of the impact of individual differences in alcoholism risk and in treatment response. This review of the literature focuses on human laboratory studies of subjective intoxication, alcohol craving, anxiety, and behavioral economics. Each section discusses opportunities for phenotype refinement under laboratory conditions, as well as its application to translational science of alcoholism. A summary and recommendations for future research are also provided. PMID:22309888

  6. Legal and ethical issues in psychiatric genetic research.

    PubMed

    Shore, D; Berg, K; Wynne, D; Folstein, M F

    1993-05-01

    Genetic research may uncover the causes of severe mental disorders, and many projects have been undertaken to locate the genes responsible for schizophrenia, bipolar disorder, and Alzheimer disease. A number of sensitive legal and ethical issues have been raised, including 1) protection of confidential data concerning research subjects; 2) the assessment of types and degree of risk to subjects who participate in such studies; 3) the legal and ethical acceptability of substituted judgement on behalf of patients who may not be competent to provide informed consent; and 4) the separation of research and clinical roles in areas such as genetic counseling. Federal regulations and other guidelines are of limited value in dealing with such concerns, and many important human subjects issues will need to be dealt with by the investigator, subject to approval by a local Institutional Review Board. There does seem to be general agreement that informed consent must be obtained, potential risks of research need to be minimized, and confidentiality of sensitive data must be protected. PMID:8357032

  7. Genetic Regulation of Pituitary Gland Development in Human and Mouse

    PubMed Central

    Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C. A. F.; Dattani, Mehul T.

    2009-01-01

    Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans. PMID:19837867

  8. Inferences of Recent and Ancient Human Population History Using Genetic and Non-Genetic Data

    ERIC Educational Resources Information Center

    Kitchen, Andrew

    2008-01-01

    I have adopted complementary approaches to inferring human demographic history utilizing human and non-human genetic data as well as cultural data. These complementary approaches form an interdisciplinary perspective that allows one to make inferences of human history at varying timescales, from the events that occurred tens of thousands of years…

  9. Ethical issues arising from the participation of children in genetic research.

    PubMed

    Burke, Wylie; Diekema, Douglas S

    2006-07-01

    With new tools derived from the Human Genome Project, genetic research is expanding from the study of rare, single gene disorders to the evaluation of genetic contributors to common, complex diseases. Many genetic studies include pediatric participants. The ethical concerns related to pediatric participation in genetic research derive from the study designs commonly employed in gene discovery and from the power accorded to genetic prediction in our society. In both family-based studies and large studies combining genetic and other health-related data, special attention should be placed on recruitment procedures, informed consent, and confidentiality protections. If data repositories are created for long-term use, we recommend re-consent of pediatric participants when they reach adulthood. In addition, the potential for disclosure of individual results should be considered as part of the institutional review of genetic studies, taking into account the validity of research data and the potential that such data could be used in health care. The potential for genetic results to pose harms of personal and group stigma is also a consideration. Because genetic information is often accorded special power in our society, careful attention should be paid to how genetic information is collected and used in research involving pediatric participants. PMID:16829241

  10. Genetic Changes Shaping the Human Brain

    PubMed Central

    Bae, Byoung-il; Jayaraman, Divya; Walsh, Christopher A.

    2015-01-01

    Summary The development and function of our brain are governed by a genetic blueprint, which reflects dynamic changes over the history of evolution. Recent progress in genetics and genomics, facilitated by next-generation sequencing and single-cell sorting, has identified numerous genomic loci that are associated with a neuroanatomical or neurobehavioral phenotype. Here, we review some of the genetic changes in both protein-coding and noncoding regions that affect brain development and evolution, as well as recent progress in brain transcriptomics. Understanding these genetic changes may provide novel insights into neurological and neuropsychiatric disorders, such as autism and schizophrenia. PMID:25710529

  11. Seeking perfection: a Kantian look at human genetic engineering.

    PubMed

    Gunderson, Martin

    2007-01-01

    It is tempting to argue that Kantian moral philosophy justifies prohibiting both human germ-line genetic engineering and non-therapeutic genetic engineering because they fail to respect human dignity. There are, however, good reasons for resisting this temptation. In fact, Kant's moral philosophy provides reasons that support genetic engineering-even germ-line and non-therapeutic. This is true of Kant's imperfect duties to seek one's own perfection and the happiness of others. It is also true of the categorical imperative. Kant's moral philosophy does, however, provide limits to justifiable genetic engineering. PMID:17516148

  12. Genetics/Genomics Research in the Central Region

    USGS Publications Warehouse

    U.S. Geological Survey

    2006-01-01

    Genetics-based research within the Biological Resources Discipline (BRD) Science Centers in the Central Region incorporates many aspects of the field of genetics. Research activities range from documenting patterns of genetic variation in order to investigate relationships among species, populations and individuals to investigating the structure, function and expression of genes and their response to environmental stressors. Research in the broad areas of genetics requires multidisciplinary expertise and specialized equipment and instrumentation. Brief summaries of the capabilities of the five BRD Centers are given below.

  13. 76 FR 17930 - National Human Genome Research Institute; Notice of Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... HUMAN SERVICES National Institutes of Health National Human Genome Research Institute; Notice of Closed... privacy. Name of Committee: National Human Genome Research Institute Special Emphasis Panel; Genetic... Branch, National Human Genome Research Institute, 5635 Fishers Lane, Suite 4076, MSC 9306, Rockville,...

  14. [Advance in molecular genetic research on primary congenital glaucoma].

    PubMed

    Li, Xiulan; Liu, Haotian; Zhang, Dingding

    2016-04-01

    Primary congenital glaucoma (PCG) is one of the major diseases causing blindness in children, but its pathogenesis has remained unclear. Genetic factors play an important role in the pathogenesis of PCG. Molecular genetics of candidate genes such as CYP1B1, MYOC, LTBP2 and FOXC1 has so far been explored, but no disease-causing gene has been identified. Molecular genetic research on PCG including candidate gene screening and research strategies are reviewed here. PMID:27060330

  15. Genetic network properties of the human cortex based on regional thickness and surface area measures

    PubMed Central

    Docherty, Anna R.; Sawyers, Chelsea K.; Panizzon, Matthew S.; Neale, Michael C.; Eyler, Lisa T.; Fennema-Notestine, Christine; Franz, Carol E.; Chen, Chi-Hua; McEvoy, Linda K.; Verhulst, Brad; Tsuang, Ming T.; Kremen, William S.

    2015-01-01

    We examined network properties of genetic covariance between average cortical thickness (CT) and surface area (SA) within genetically-identified cortical parcellations that we previously derived from human cortical genetic maps using vertex-wise fuzzy clustering analysis with high spatial resolution. There were 24 hierarchical parcellations based on vertex-wise CT and 24 based on vertex-wise SA expansion/contraction; in both cases the 12 parcellations per hemisphere were largely symmetrical. We utilized three techniques—biometrical genetic modeling, cluster analysis, and graph theory—to examine genetic relationships and network properties within and between the 48 parcellation measures. Biometrical modeling indicated significant shared genetic covariance between size of several of the genetic parcellations. Cluster analysis suggested small distinct groupings of genetic covariance; networks highlighted several significant negative and positive genetic correlations between bilateral parcellations. Graph theoretical analysis suggested that small world, but not rich club, network properties may characterize the genetic relationships between these regional size measures. These findings suggest that cortical genetic parcellations exhibit short characteristic path lengths across a broad network of connections. This property may be protective against network failure. In contrast, previous research with structural data has observed strong rich club properties with tightly interconnected hub networks. Future studies of these genetic networks might provide powerful phenotypes for genetic studies of normal and pathological brain development, aging, and function. PMID:26347632

  16. An examination of chimpanzee use in human cancer research.

    PubMed

    Bailey, Jarrod

    2009-09-01

    Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human genomic studies. Papers describing potential new cancer therapies noted significant concerns regarding the chimpanzee model. Other studies described interventions that have not been pursued clinically. Finally, available evidence indicates that chimpanzees are not essential in the development of therapeutic monoclonal antibodies. It would therefore be unscientific to claim that chimpanzees are vital to cancer research. On the contrary, it is reasonable to conclude that cancer research would not suffer, if the use of chimpanzees for this purpose were prohibited in the US. Genetic differences between humans and chimpanzees, make them an unsuitable model for cancer, as well as other human diseases. PMID:19807212

  17. [Constant or break? On the relations between human genetics and eugenics in the Twentieth Century].

    PubMed

    Germann, Pascal

    2015-07-01

    The history of human genetics has been a neglected topic in history of science and medicine for a long time. Only recently, have medical historians begun to pay more attention to the history of human heredity. An important research question deals with the interconnections between human genetics and eugenics. This paper addresses this question: By focusing on a Swiss case study, the investigation of the heredity of goiter, I will argue that there existed close but also ambiguous relations between heredity research and eugenics in the twentieth century. Studies on human heredity often produced evidence that challenged eugenic aims and ideas. Concurrently, however, these studies fostered visions of genetic improvement of human populations. PMID:26111842

  18. Genetic Engineering of Plants. Agricultural Research Opportunities and Policy Concerns.

    ERIC Educational Resources Information Center

    Roberts, Leslie

    Plant scientists and science policymakers from government, private companies, and universities met at a convocation on the genetic engineering of plants. During the convocation, researchers described some of the ways genetic engineering may be used to address agricultural problems. Policymakers delineated and debated changes in research funding…

  19. Beyond race: towards a whole-genome perspective on human populations and genetic variation.

    PubMed

    Foster, Morris W; Sharp, Richard R

    2004-10-01

    The renewed emphasis on population-specific genetic variation, exemplified most prominently by the International HapMap Project, is complicated by a longstanding, uncritical reliance on existing population categories in genetic research. Race and other pre-existing population definitions (ethnicity, religion, language, nationality, culture and so on) tend to be contentious concepts that have polarized discussions about the ethics and science of research into population-specific human genetic variation. By contrast, a broader consideration of the multiple historical sources of genetic variation provides a whole-genome perspective on the ways i n which existing population definitions do, and do not, account for how genetic variation is distributed among individuals. Although genetics will continue to rely on analytical tools that make use of particular population histories, it is important to interpret findings in a broader genomic context. PMID:15510170

  20. RESEARCH ON GENETIC SEXING AND POPULATION GENETICS OF SCREWWORM AT LINCOLN, NEBRASKA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The following technical abstract refers to an invited oral presentation given at the IAEA/FAO sponsored Consultants Meeting on Genetic Sexing and Population Genetics of the Screwworm, August 2000. Responsibility for screwworm research at the USDA-ARS-Midwest Livestock Insects Research Unit (MLIRU) ...

  1. Career research interests and training of genetic counseling students.

    PubMed

    Bedard, Angela C; Huether, Carl A; Shooner, Kerry; Buncher, C Ralph; Warren, Nancy Steinberg

    2007-10-01

    Research is important to validate clinical services, provide information on the effectiveness of practice techniques, and develop the knowledge base of a clinical profession. Genetic counseling students from American Board of Genetic Counseling (ABGC) accredited training programs were surveyed to determine their career research interests and interest in pursuing a hypothetical doctoral degree in genetic counseling. Genetic counseling program directors were surveyed to assess the emphasis on research training within their programs. A substantial number (46%, n = 92) of genetic counseling students are interested in performing research in their careers and many (40%, n = 80) would pursue a doctoral degree in genetic counseling if it was available. Students and directors from programs with a thesis requirement reported a significantly higher emphasis on career research preparation than those from programs without a thesis requirement. The results of this study indicate that future genetic counselors are interested in contributing to the research base that will advance the field. This study suggests a need to strengthen research training within ABGC accredited graduate programs and explore the development of a doctoral degree option in genetic counseling. PMID:17674166

  2. Patenting genes and genetic research: good or bad for innovation?

    PubMed

    Arnold, Beth E; Ogielska-Zei, Eva

    2002-01-01

    Our goal with this article is to inform the debate over gene patenting, by providing an understanding of (a) the scope of patent claims that are actually being issued on genetic inventions in the United States, (b) the issues that impact their enforcement, and (c) the role that patents and patent licensing play in the commercialization of genetic technologies and products. We conclude by discussing whether the current legal regime effectively balances the beneficial role of patents in the development of new genetic technologies and products against negative impacts on genetic research or clinical genetic testing, or whether the current laws should be amended. PMID:12142363

  3. Lunar Human Research Requirements (LHRR)

    NASA Technical Reports Server (NTRS)

    Denkins, Pamela

    2009-01-01

    Biomedical research will be conducted during transit and on the surface of the Moon to prepare for extended stays on the Moon and to prepare for the exploration of Mars. The objective of the Human Research Program (HRP) is to preserve the health and enhance performance of astronaut explorers. Specific objectives of the HRP include developing the knowledge, capabilities, and necessary countermeasures and technologies in support of human space exploration; focusing on mitigating the highest risks to crew health and performance; and defining and improving human spaceflight medical, environmental, behavioral, and human factors standards. This document contains a detailed description of the resource accommodations, interfaces, and environments to be provided by the Constellation Program (CxP) to support the HRP research in transit and on the lunar surface. Covered, specifically, are the requirements for mass and volume transport; crew availability; ground operations, baseline data collection, and payload processing; power, and data. Volumes and mass are given for transport of conditioned samples only. They do not account for the engineering solution that the Constellation Program will implement (refrigerator/freezer volume/mass). This document does not account for requirements on the Orion vehicle for transportation to and from the International Space Station (ISS). The ISS Program has supplied requirements for this mission.

  4. Reflections on the Field of Human Genetics: A Call for Increased Disease Genetics Theory

    PubMed Central

    Schrodi, Steven J.

    2016-01-01

    Development of human genetics theoretical models and the integration of those models with experiment and statistical evaluation are critical for scientific progress. This perspective argues that increased effort in disease genetics theory, complementing experimental, and statistical efforts, will escalate the unraveling of molecular etiologies of complex diseases. In particular, the development of new, realistic disease genetics models will help elucidate complex disease pathogenesis, and the predicted patterns in genetic data made by these models will enable the concurrent, more comprehensive statistical testing of multiple aspects of disease genetics predictions, thereby better identifying disease loci. By theoretical human genetics, I intend to encompass all investigations devoted to modeling the heritable architecture underlying disease traits and studies of the resulting principles and dynamics of such models. Hence, the scope of theoretical disease genetics work includes construction and analysis of models describing how disease-predisposing alleles (1) arise, (2) are transmitted across families and populations, and (3) interact with other risk and protective alleles across both the genome and environmental factors to produce disease states. Theoretical work improves insight into viable genetic models of diseases consistent with empirical results from linkage, transmission, and association studies as well as population genetics. Furthermore, understanding the patterns of genetic data expected under realistic disease models will enable more powerful approaches to discover disease-predisposing alleles and additional heritable factors important in common diseases. In spite of the pivotal role of disease genetics theory, such investigation is not particularly vibrant. PMID:27375680

  5. Reflections on the Field of Human Genetics: A Call for Increased Disease Genetics Theory.

    PubMed

    Schrodi, Steven J

    2016-01-01

    Development of human genetics theoretical models and the integration of those models with experiment and statistical evaluation are critical for scientific progress. This perspective argues that increased effort in disease genetics theory, complementing experimental, and statistical efforts, will escalate the unraveling of molecular etiologies of complex diseases. In particular, the development of new, realistic disease genetics models will help elucidate complex disease pathogenesis, and the predicted patterns in genetic data made by these models will enable the concurrent, more comprehensive statistical testing of multiple aspects of disease genetics predictions, thereby better identifying disease loci. By theoretical human genetics, I intend to encompass all investigations devoted to modeling the heritable architecture underlying disease traits and studies of the resulting principles and dynamics of such models. Hence, the scope of theoretical disease genetics work includes construction and analysis of models describing how disease-predisposing alleles (1) arise, (2) are transmitted across families and populations, and (3) interact with other risk and protective alleles across both the genome and environmental factors to produce disease states. Theoretical work improves insight into viable genetic models of diseases consistent with empirical results from linkage, transmission, and association studies as well as population genetics. Furthermore, understanding the patterns of genetic data expected under realistic disease models will enable more powerful approaches to discover disease-predisposing alleles and additional heritable factors important in common diseases. In spite of the pivotal role of disease genetics theory, such investigation is not particularly vibrant. PMID:27375680

  6. A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases.

    PubMed

    Yamamoto, Shinya; Jaiswal, Manish; Charng, Wu-Lin; Gambin, Tomasz; Karaca, Ender; Mirzaa, Ghayda; Wiszniewski, Wojciech; Sandoval, Hector; Haelterman, Nele A; Xiong, Bo; Zhang, Ke; Bayat, Vafa; David, Gabriela; Li, Tongchao; Chen, Kuchuan; Gala, Upasana; Harel, Tamar; Pehlivan, Davut; Penney, Samantha; Vissers, Lisenka E L M; de Ligt, Joep; Jhangiani, Shalini N; Xie, Yajing; Tsang, Stephen H; Parman, Yesim; Sivaci, Merve; Battaloglu, Esra; Muzny, Donna; Wan, Ying-Wooi; Liu, Zhandong; Lin-Moore, Alexander T; Clark, Robin D; Curry, Cynthia J; Link, Nichole; Schulze, Karen L; Boerwinkle, Eric; Dobyns, William B; Allikmets, Rando; Gibbs, Richard A; Chen, Rui; Lupski, James R; Wangler, Michael F; Bellen, Hugo J

    2014-09-25

    Invertebrate model systems are powerful tools for studying human disease owing to their genetic tractability and ease of screening. We conducted a mosaic genetic screen of lethal mutations on the Drosophila X chromosome to identify genes required for the development, function, and maintenance of the nervous system. We identified 165 genes, most of whose function has not been studied in vivo. In parallel, we investigated rare variant alleles in 1,929 human exomes from families with unsolved Mendelian disease. Genes that are essential in flies and have multiple human homologs were found to be likely to be associated with human diseases. Merging the human data sets with the fly genes allowed us to identify disease-associated mutations in six families and to provide insights into microcephaly associated with brain dysgenesis. This bidirectional synergism between fly genetics and human genomics facilitates the functional annotation of evolutionarily conserved genes involved in human health. PMID:25259927

  7. A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases

    PubMed Central

    Yamamoto, Shinya; Jaiswal, Manish; Charng, Wu-Lin; Gambin, Tomasz; Karaca, Ender; Mirzaa, Ghayda; Wiszniewski, Wojciech; Sandoval, Hector; Haelterman, Nele A.; Xiong, Bo; Zhang, Ke; Bayat, Vafa; David, Gabriela; Li, Tongchao; Chen, Kuchuan; Gala, Upasana; Harel, Tamar; Pehlivan, Davut; Penney, Samantha; Vissers, Lisenka E. L. M.; de Ligt, Joep; Jhangiani, Shalini; Xie, Yajing; Tsang, Stephen H.; Parman, Yesim; Sivaci, Merve; Battaloglu, Esra; Muzny, Donna; Wan, Ying-Wooi; Liu, Zhandong; Lin-Moore, Alexander T.; Clark, Robin D.; Curry, Cynthia J.; Link, Nichole; Schulze, Karen L.; Boerwinkle, Eric; Dobyns, William B.; Allikmets, Rando; Gibbs, Richard A.; Chen, Rui; Lupski, James R.; Wangler, Michael F.; Bellen, Hugo J.

    2014-01-01

    Summary Invertebrate model systems are powerful tools for studying human disease owing to their genetic tractability and ease of screening. We conducted a mosaic genetic screen of lethal mutations on the Drosophila X-chromosome to identify genes required for the development, function, and maintenance of the nervous system. We identified 165 genes, most of whose function has not been studied in vivo. In parallel, we investigated rare variant alleles in 1,929 human exomes from families with unsolved Mendelian disease. Genes that are essential in flies and have multiple human homologs were found to be likely to be associated with human diseases. Merging the human datasets with the fly genes allowed us to identify disease-associated mutations in six families and to provide insights into microcephaly associated with brain dysgenesis. This bidirectional synergism between fly genetics and human genomics facilitates the functional annotation of evolutionarily conserved genes involved in human health. PMID:25259927

  8. Genetic knowledge and moral responsibility: ambiguity at the interface of genetic research and clinical practice.

    PubMed

    Pullman, D; Hodgkinson, K

    2006-03-01

    Despite a rapidly expanding literature on the issue of duty to warn at-risk relatives in the context of clinical genetic testing, little has been written on parallel issues with regard to the management of genetic research results. Some might view this lack as an indication that there is little to discuss in this regard. That is, standard practice is that data obtained through medical research should not be treated as though they are clinically relevant, and this standard should hold for genetic research as well. This paper challenges this conclusion and its underlying assumptions. We argue that the line between genetic research and clinical practice is often ambiguous. In some cases, research data gathered from a very small number of subjects could have immediate clinical implications. Hence, it is unethical for genetic researchers to absolve themselves of clinical responsibilities for research subjects and/or their families, on the grounds that the data were obtained for research purposes. Indeed, we argue that it could well be unethical to embark on some forms of genetic research unless advance arrangements have been made for genetic counseling and clinical follow-up. Furthermore, in some cases, it might be unethical to enroll subjects in studies if the subjects are unwilling to receive their individual results. PMID:16542381

  9. Ethical issues arising from human genetics.

    PubMed

    Arnold, A; Moseley, R

    1976-03-01

    Advances in understanding genetic disorders have been rapid in the last few years and with them the need and desire for genetic counselling have grown. Almost simultaneously, particularly in the USA, several large screening programmes have been initiated to screen large numbers of people who may be carriers of such deleterious genes as those of Tay-Sachs disease and sickle cell anaemia. The authors of this paper, clinical medical students at University College Hospital, London, spent some time studying the ethical issues raised. The first part of their study, which is not published here, relates to the biochemistry of certain genetic disorders, so leading up to the aspect of the subject which must concern readers of this journal, genetic counselling. At present genetic counselling is generally the province of the medical practitioner working with clinical biochemists, and in this paper their function is described and how programmes of screening for carriers are designed. Whether the subjects of the screening tests are found to be 'innocent' or 'guilty' psychological problems confront them, and of these the genetic counsellor must be aware. In fact the range of ethical problems raised by such counselling is wide and can only be sketched in this article. PMID:957367

  10. Commercial biobanks and genetic research: ethical and legal issues.

    PubMed

    Anderlik, Mary

    2003-01-01

    Human biological material is recognized as an important tool in research, and the demand for collections that combine samples and data is increasing. For-profit companies have assumed a leading role in assembling and managing these collections. The emergence of commercial biobanks has raised significant ethical and legal issues. The growing awareness of the importance of human biological material in research has been accompanied by a growing awareness of the deficiencies of existing archives of tissue. Commercial biobanks are attempting to position themselves as a, if not the, solution to problems that include a lack of public trust in researchers and lack of financial resources to support the prospective creation of collections that meet the highest scientific and ethical standards in the non-profit sector. Broad social and policy questions surrounding the operation of commercial biobanks have been raised however. International documents, in particular, suggest discomfort with the idea of gain from the mere transfer or exchange of human genetic material and information. Commercial involvement in the development of useful products from tissue is generally not condemned, so long as there is attention to scientific and social norms. Views on the acceptability of commercial biobanks vary. Specific issues that arise when commercial biobanks are permitted--in the areas of consent, recruitment, confidentiality, and accountability--are also relevant to the operation of public and private, non-profit biobanks. Although many uncertainties remain, consensus seems to be forming on a number of issues. For example, there appears to be agreement that blanket consent to future unspecified research uses, with no conditions, is unacceptable. Indeed, many of the leading commercial biobanks have been attentive to concerns about consent, recruitment, and confidentiality. Unfortunately, the binding nature of assurances in these areas is unclear, especially given the risk of insolvency

  11. Beliefs in genetic determinism and attitudes towards psychiatric genetic research: psychometric scale properties, construct associations, demographic correlates, and cross-cultural comparisons.

    PubMed

    Voracek, Martin; Swami, Viren; Loibl, Lisa Mariella; Furnham, Adrian

    2007-12-01

    Using two new scales, this study examined beliefs in genetic determinism and attitudes towards psychiatric genetic research in student samples from Austria, Malaysia, Romania, and the United Kingdom. For both constructs, effects of culture were detectable, whereas those related to key demographics were either small and inconsistent across samples (political orientation and religiosity) or zero (sex and age). Judged from factorial dimensionality and internal consistency, the psychometric properties of both scales were satisfactory. Belief in genetic determinism had lower prevalence and corresponded only modestly to positive attitudes towards psychiatric genetic research which had higher prevalence. The correlations of both constructs with a preference of inequality among social groups (social dominance orientation) were modest and inconsistent across samples. Both scales appear appropriate for cross-cultural applications, in particular for research into lay theories and public perceptions regarding genetic vs environmental effects on human behavior, mental disorders, and behavioral and psychiatric genetic research related to these. PMID:18232457

  12. Genetic Signatures of Exceptional Longevity in Humans

    PubMed Central

    Sebastiani, Paola; Solovieff, Nadia; DeWan, Andrew T.; Walsh, Kyle M.; Puca, Annibale; Hartley, Stephen W.; Melista, Efthymia; Andersen, Stacy; Dworkis, Daniel A.; Wilk, Jemma B.; Myers, Richard H.; Steinberg, Martin H.; Montano, Monty; Baldwin, Clinton T.; Hoh, Josephine; Perls, Thomas T.

    2012-01-01

    Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different “genetic signatures” of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity. PMID:22279548

  13. Involving study populations in the review of genetic research.

    PubMed

    Sharp, R R; Foster, M W

    2000-01-01

    Genetic research can present risks to all members of a study population, not just those who choose to participate in research. The authors suggest that community-based reviews of research protocols can help identify and minimize such research-related risks. PMID:11067631

  14. Ecological Genetics at the USGS National Wetlands Research Center

    USGS Publications Warehouse

    Travis, Steven

    2006-01-01

    The Ecological Genetics Program at the USGS National Wetlands Research Center (NWRC) employs state-of-the-art DNA fingerprinting technologies in characterizing critical management aspects of the population biology of species of concern. The overarching themes of this program have been (1) the critical role that genetic diversity plays in maintaining population viability and (2) how management strategies might incorporate genetic information in preventing the decline of desirable species or in controlling the spread of invasive species.

  15. Metabolic thrift and the genetic basis of human obesity

    PubMed Central

    O’Rourke, Robert W.

    2014-01-01

    Evolution has molded metabolic thrift within humans, a genetic heritage that, when thrust into our modern “obesogenic” environment, creates the current obesity crisis. Modern genetic analysis has identified genetic and epigenetic contributors to obesity, an understanding of which will guide the development of environmental, pharmacologic, and genetic therapeutic interventions. “The voyage was so long, food and water ran out. One hundred of the paddlers died; forty men remained. The voyagers finally reached Fitinui, then Aotona.”-From “The Story of Aka”, in The Native Culture in the Marquesas by E. S. Craighill Handy PMID:24368636

  16. Linking critical care nursing and genetics with research funding opportunities.

    PubMed

    Sigmon, H D

    1998-11-01

    The purpose of this article is threefold: to reveal how a disease that afflicts many critical care patients can be the impetus for forging into a research career; to illustrate a program of research undertaken by a nurse investigator to answer a critical care nursing question using genetic technology; and to identify exciting opportunities for research training, career development, and investigator-initiated research activities for the advanced practice critical care nurse at the National Institute of Nursing Research. The article concludes by identifying future linkages between nursing research and genetics. PMID:9855867

  17. Yeast: A Research Organism for Teaching Genetics.

    ERIC Educational Resources Information Center

    Manney, Thomas R.; Manney, Monta L.

    1992-01-01

    Explains why laboratory strains of bakers yeast, Saccharomyces cerevisiae, are particularly suited for classroom science activities. Describes the sexual life cycle of yeast and the genetic system with visible mutations. Presents an overview of activities that can be done with yeast and gives a source for teachers to obtain more information. (PR)

  18. The support of human genetic evidence for approved drug indications.

    PubMed

    Nelson, Matthew R; Tipney, Hannah; Painter, Jeffery L; Shen, Judong; Nicoletti, Paola; Shen, Yufeng; Floratos, Aris; Sham, Pak Chung; Li, Mulin Jun; Wang, Junwen; Cardon, Lon R; Whittaker, John C; Sanseau, Philippe

    2015-08-01

    Over a quarter of drugs that enter clinical development fail because they are ineffective. Growing insight into genes that influence human disease may affect how drug targets and indications are selected. However, there is little guidance about how much weight should be given to genetic evidence in making these key decisions. To answer this question, we investigated how well the current archive of genetic evidence predicts drug mechanisms. We found that, among well-studied indications, the proportion of drug mechanisms with direct genetic support increases significantly across the drug development pipeline, from 2.0% at the preclinical stage to 8.2% among mechanisms for approved drugs, and varies dramatically among disease areas. We estimate that selecting genetically supported targets could double the success rate in clinical development. Therefore, using the growing wealth of human genetic data to select the best targets and indications should have a measurable impact on the successful development of new drugs. PMID:26121088

  19. Massively parallel high-order combinatorial genetics in human cells

    PubMed Central

    Wong, Alan S L; Choi, Gigi C G; Cheng, Allen A; Purcell, Oliver; Lu, Timothy K

    2016-01-01

    The systematic functional analysis of combinatorial genetics has been limited by the throughput that can be achieved and the order of complexity that can be studied. To enable massively parallel characterization of genetic combinations in human cells, we developed a technology for rapid, scalable assembly of high-order barcoded combinatorial genetic libraries that can be quantified with high-throughput sequencing. We applied this technology, combinatorial genetics en masse (CombiGEM), to create high-coverage libraries of 1,521 two-wise and 51,770 three-wise barcoded combinations of 39 human microRNA (miRNA) precursors. We identified miRNA combinations that synergistically sensitize drug-resistant cancer cells to chemotherapy and/or inhibit cancer cell proliferation, providing insights into complex miRNA networks. More broadly, our method will enable high-throughput profiling of multifactorial genetic combinations that regulate phenotypes of relevance to biomedicine, biotechnology and basic science. PMID:26280411

  20. Crop genetic improvement for enhanced human nutrition.

    PubMed

    Toenniessen, Gary H

    2002-09-01

    In the past decade, micronutrient malnutrition has been identified as a major underlying cause of numerous human health problems in developing countries. The international agricultural research system has been highly successful in producing crop varieties with traits desired by farmers, such as higher yield and greater tolerance of poor growing conditions. These improved varieties have spread widely throughout developing countries and now provide the staple foods eaten daily by billions of people, including the poor in many difficult to reach rural areas. Modern plant breeding and biotechnology offer new opportunities to use this same international system to increase the micronutrient content and enhance the nutritional value of these staple foods. Over time, this could be an important complement to the progress that is being made in providing micronutrient supplements and fortified foods and in encouraging people to eat more diversified diets. Nutritionists and agriculturists will need to work together to define the deficiencies, target the right populations and deliver the right products. PMID:12221274

  1. 48 CFR 207.172 - Human research.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... compliance with 32 CFR Part 219, Protection of Human Subjects; and (b) Must have a Human Research Protection... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Human research. 207.172... OF DEFENSE ACQUISITION PLANNING ACQUISITION PLANNING Acquisition Plans 207.172 Human research. Any...

  2. 48 CFR 207.172 - Human research.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... compliance with 32 CFR Part 219, Protection of Human Subjects; and (b) Must have a Human Research Protection... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Human research. 207.172... OF DEFENSE ACQUISITION PLANNING ACQUISITION PLANNING Acquisition Plans 207.172 Human research. Any...

  3. 48 CFR 207.172 - Human research.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... compliance with 32 CFR Part 219, Protection of Human Subjects; and (b) Must have a Human Research Protection... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Human research. 207.172... OF DEFENSE ACQUISITION PLANNING ACQUISITION PLANNING Acquisition Plans 207.172 Human research. Any...

  4. 48 CFR 207.172 - Human research.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... compliance with 32 CFR Part 219, Protection of Human Subjects; and (b) Must have a Human Research Protection... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Human research. 207.172... OF DEFENSE ACQUISITION PLANNING ACQUISITION PLANNING Acquisition Plans 207.172 Human research. Any...

  5. 48 CFR 207.172 - Human research.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... compliance with 32 CFR Part 219, Protection of Human Subjects; and (b) Must have a Human Research Protection... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Human research. 207.172... OF DEFENSE ACQUISITION PLANNING ACQUISITION PLANNING Acquisition Plans 207.172 Human research. Any...

  6. Socially responsible genetic research with descendants of the First Australians.

    PubMed

    van Holst Pellekaan, Sheila M

    2012-01-01

    Aboriginal Australians, one of the world's indigenous peoples now outnumbered through colonization, are the most under-represented in genetic research because they feel that the benefits do not outweigh the social cost of involvement. Descendants of the First Australians have survived a period of European occupation during which time they were dispossessed of land, language and cultural identity resulting in inequities in health, education, and employment opportunities. Compared to Maori and Native American peoples, the ability to form organizations that help to control their affairs is very recent. The desire to control is understandably strong yet the 'gate-keeping' role of some organizations risks shifting the control away from smaller communities and has become increasingly politicized. In the past, research practices by Western scientists were poorly presented and have resulted in resistance to proposals that are perceived to have no beneficial outcomes for participants. In this age of advanced technological expertise in genetics, benefits to all humanity are clear to those carrying out research projects, yet not always to those being asked to participate, presenting extra challenges. Excellent guidelines for ethical conduct in research are available to assist researchers, prospective participants, and ethics committees or review boards that approve and monitor procedures. The essence of these guidelines are that research should be carried out with a spirit of integrity, respect, reciprocity, parity, recognition of survival and protection of social and cultural values, a need for control and shared responsibility. Specific Aboriginal organizations, with which researchers need to work to negotiate partnerships, vary within and between Australian states and will always expect Aboriginal personnel to be involved. People experienced in the consultation process are necessary as part of a team. By working patiently through lengthy negotiations with Aboriginal

  7. Genetic Characterization of Human Populations: From ABO to a Genetic Map of the British People

    PubMed Central

    Bodmer, Walter

    2015-01-01

    From 1900, when Landsteiner first described the ABO blood groups, to the present, the methods used to characterize the genetics of human populations have undergone a remarkable development. Concomitantly, our understanding of the history and spread of human populations across the earth has become much more detailed. As has often been said, a better understanding of the genetic relationships among the peoples of the world is one of the best antidotes to racial prejudices. Such an understanding provides us with a fascinating, improved insight into our origins as well as with valuable information about population differences that are of medical relevance. The study of genetic polymorphisms has been essential to the analysis of the relationships between human populations. The evolution of methods used to study human polymorphisms and the resulting contributions to our understanding of human health and history is the subject of this Perspectives. PMID:25657345

  8. Human Handedness: More Evidence for Genetic Involvement.

    ERIC Educational Resources Information Center

    Longstreth, Langdon E.

    1980-01-01

    A series of environmental-genetical analyses of the left-handedness of 1,950 college students indicates that left-handedness is familial: it is more frequent in families in which at least one parent is left-handed. (Author/CM)

  9. Sub-Saharan centralized biorepository for genetic and genomic research.

    PubMed

    Gasmelseed, Nagla; Elsir, Afrah Awad; Deblasio, Pasquale; Biunno, Ida

    2012-04-15

    Quality-assessed biomedical samples are essential for academia- and industry driven research on human diseases. The etiologies and the molecular genetic factors relevant in African diseases, including both infections and complex degenerative diseases as well as cancer, need to be studied using well annotated and well-preserved biosamples acquired from native African ethnic groups and compare the results with non-African populations and/or with Afro-Americans. However, a number of difficulties negatively impact on the possibility to obtain clinically annotated biological samples in most Sub-Saharan African countries. This is mainly due to major organizational problems, lack of clinical centres that can dedicate resources to research, as well as lack of facilities in which biomaterials can be properly processed and safely stored. Harmonization of biosample acquisition, storage phenotyping schemes and biocomputer infrastructures are the principal objectives of biological resource centers (BRCs). BRCs comprise biobanks of different formats (collection of blood, DNA, tissues, etc., annotated with medical, environmental, life-style and follow up data) a fundamental tool for molecular epidemiological studies aiming to increase excellence and efficacy of biomedical results, drug development and public health. BRCs provide large and highly controlled biomolecular resources necessary to meet the "omics" scientific platforms. Sudan may be a candidate nation to host such infrastructure, in view of its strategic geographical position and the already existing simple biobanking experiences connected with research groups in Central Sudan. Here, we describe the potential role of biobanks in African genetic studies aiming to dissect the eziopathogenesis of complex diseases in relation to environmental and life-style factors. PMID:21303714

  10. A Developmental-Genetic Model of Alcoholism: Implications for Genetic Research.

    ERIC Educational Resources Information Center

    Devor, Eric J.

    1994-01-01

    Research for biological-genetic markers of alcoholism is discussed in context of a multifactorial, heterogeneous, developmental model. Suggested that strategies used in linkage and association studies will require modification. Also suggested several extant associations of genetic markers represent true secondary interactive phenomena that alter…

  11. Two ethical approaches to research on human beings.

    PubMed

    O'Rourke, K D

    1988-10-01

    Since World War II the Catholic Church and national and international study groups have issued separate sets of statements regarding the ethics of research involving human subjects. The Church and the study groups agree on several points, including the following: Research on human subjects is a vital part of scientific medicine. Ethical research requires the informed consent of the subject or proxy. Research on human subjects is therapeutic or nontherapeutic. The risk of harm involved in research must be considered in regard to the potential benefit. Research on human beings should be allowed only after appropriate research on animals. Researchers should practice equity in selecting subjects and scientific problems to be studied. The human subject or proxy should be free to withdraw from the research program at any time. The two sets of statements generally disagree about nontherapeutic research on embryos and about genetic research. They also disagree on the use of in vitro fertilization and embryo transplants to initiate pregnancy. The disagreements are due to dissimilar ethical systems. The Church bases ethical analysis on a study of the effect an action has on basic human goods. As a result of this analysis, the Church maintains that some human actions are good or evil in themselves. If the action is evil insofar as the natural needs and functions of a person are concerned, it is not ethically good simply because it results in a good outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:10290386

  12. Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach

    PubMed Central

    Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio

    2015-01-01

    This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447–2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8–30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics. PMID:26452043

  13. Genetic Effects on Human Behavior: Recent Family Studies.

    ERIC Educational Resources Information Center

    Scarr, Sandra

    Although there continues to be controversy about the magnitude of genetic and environmental effects on human behavior, it is generally agreed by various scientific fields that individual differences in brain function and behavior must follow the same laws of variability as other human characteristics. Whether or not racial and ethnic group…

  14. Human longevity: Genetics or Lifestyle? It takes two to tango.

    PubMed

    Passarino, Giuseppe; De Rango, Francesco; Montesanto, Alberto

    2016-01-01

    Healthy aging and longevity in humans are modulated by a lucky combination of genetic and non-genetic factors. Family studies demonstrated that about 25 % of the variation in human longevity is due to genetic factors. The search for genetic and molecular basis of aging has led to the identification of genes correlated with the maintenance of the cell and of its basic metabolism as the main genetic factors affecting the individual variation of the aging phenotype. In addition, studies on calorie restriction and on the variability of genes associated with nutrient-sensing signaling, have shown that ipocaloric diet and/or a genetically efficient metabolism of nutrients, can modulate lifespan by promoting an efficient maintenance of the cell and of the organism. Recently, epigenetic studies have shown that epigenetic modifications, modulated by both genetic background and lifestyle, are very sensitive to the aging process and can either be a biomarker of the quality of aging or influence the rate and the quality of aging. On the whole, current studies are showing that interventions modulating the interaction between genetic background and environment is essential to determine the individual chance to attain longevity. PMID:27053941

  15. The Evolution of Human Intelligence and the Coefficient of Additive Genetic Variance in Human Brain Size

    ERIC Educational Resources Information Center

    Miller, Geoffrey F.; Penke, Lars

    2007-01-01

    Most theories of human mental evolution assume that selection favored higher intelligence and larger brains, which should have reduced genetic variance in both. However, adult human intelligence remains highly heritable, and is genetically correlated with brain size. This conflict might be resolved by estimating the coefficient of additive genetic…

  16. Human Factors Research and Nuclear Safety.

    ERIC Educational Resources Information Center

    Moray, Neville P., Ed.; Huey, Beverly M., Ed.

    The Panel on Human Factors Research Needs in Nuclear Regulatory Research was formed by the National Research Council in response to a request from the Nuclear Regulatory Commission (NRC). The NRC asked the research council to conduct an 18-month study of human factors research needs for the safe operation of nuclear power plants. This report…

  17. Publication Trends Over 55 Years of Behavioral Genetic Research.

    PubMed

    Ayorech, Ziada; Selzam, Saskia; Smith-Woolley, Emily; Knopik, Valerie S; Neiderhiser, Jenae M; DeFries, John C; Plomin, Robert

    2016-09-01

    We document the growth in published papers on behavioral genetics for 5-year intervals from 1960 through 2014. We used 1861 papers published in Behavior Genetics to train our search strategy which, when applied to Ovid PsychINFO, selected more than 45,000 publications. Five trends stand out: (1) the number of behavioral genetic publications has grown enormously; nearly 20,000 papers were published in 2010-2014. (2) The number of human quantitative genetic (QG) publications (e.g., twin and adoption studies) has steadily increased with more than 3000 papers published in 2010-2014. (3) The number of human molecular genetic (MG) publications increased substantially from about 2000 in 2000-2004 to 5000 in 2005-2009 to 9000 in 2010-2014. (4) Nonhuman publications yielded similar trends. (5) Although there has been exponential growth in MG publications, both human and nonhuman QG publications continue to grow. A searchable resource of this corpus of behavioral genetic papers is freely available online at http://www.teds.ac.uk/public_datasets.html and will be updated annually. PMID:26992731

  18. The genetics of human cancer: implications for ecotoxicology.

    PubMed Central

    McMahon, G

    1994-01-01

    The study of human cancers has provided evidence that malignant progression is associated with genetic change. It has been suggested that some genetic alterations in tumors may be the result of direct or indirect processes related to environmental chemical exposure. This hypothesis has been supported by genetic evidence in liver tumors which has associated aflatoxin B1 exposure with the detection of inactivating DNA mutations within the human p53 tumor suppressor gene. The detection of activating ras oncogene mutations at high frequency in liver tumors of feral fish suggest that the survey of mutations in genes, such as p53 or other genes, might provide a genetic signature for specific chemical exposure in tissues of aquatic animals derived from environmentally damaged sites. PMID:7713039

  19. Human genetics of infectious diseases: a unified theory.

    PubMed

    Casanova, Jean-Laurent; Abel, Laurent

    2007-02-21

    Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

  20. Human genetics: lessons from Quebec populations.

    PubMed

    Scriver, C R

    2001-01-01

    The population of Quebec, Canada (7.3 million) contains approximately 6 million French Canadians; they are the descendants of approximately 8500 permanent French settlers who colonized Nouvelle France between 1608 and 1759. Their well-documented settlements, internal migrations, and natural increase over four centuries in relative isolation (geographic, linguistic, etc.) contain important evidence of social transmission of demographic behavior that contributed to effective family size and population structure. This history is reflected in at least 22 Mendelian diseases, occurring at unusually high prevalence in its subpopulations. Immigration of non-French persons during the past 250 years has given the Quebec population further inhomogeneity, which is apparent in allelic diversity at various loci. The histories of Quebec's subpopulations are, to a great extent, the histories of their alleles. Rare pathogenic alleles with high penetrance and associated haplotypes at 10 loci (CFTR, FAH, HBB, HEXA, LDLR, LPL, PAH, PABP2, PDDR, and SACS) are expressed in probands with cystic fibrosis, tyrosinemia, beta-thalassemia, Tay-Sachs, familial hypercholesterolemia, hyperchylomicronemia, PKU, oculopharyngeal muscular dystrophy, pseudo vitamin D deficiency rickets, and spastic ataxia of Charlevoix-Saguenay, respectively) reveal the interpopulation and intrapopulation genetic diversity of Quebec. Inbreeding does not explain the clustering and prevalence of these genetic diseases; genealogical reconstructions buttressed by molecular evidence point to founder effects and genetic drift in multiple instances. Genealogical estimates of historical meioses and analysis of linkage disequilibrium show that sectors of this young population are suitable for linkage disequilibrium mapping of rare alleles. How the population benefits from what is being learned about its structure and how its uniqueness could facilitate construction of a genomic map of linkage disequilibrium are discussed

  1. Primer on Molecular Genetics; DOE Human Genome Program

    DOE R&D Accomplishments Database

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  2. Primer on molecular genetics. DOE Human Genome Program

    SciTech Connect

    Not Available

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  3. Ethical Considerations in Human Movement Research.

    ERIC Educational Resources Information Center

    Olivier, Steve

    1995-01-01

    Highlights ethical issues for human subject research, identifying principles that form the construct of a code of research ethics and evaluating against this construct past human experimentation and current research in human movement studies. The efficacy of legislation and self-regulation is examined. Particular attention is given to the context…

  4. Genetic Effects on Fine-Grained Human Cortical Regionalization.

    PubMed

    Cui, Yue; Liu, Bing; Zhou, Yuan; Fan, Lingzhong; Li, Jin; Zhang, Yun; Wu, Huawang; Hou, Bing; Wang, Chao; Zheng, Fanfan; Qiu, Chengxiang; Rao, Li-Lin; Ning, Yuping; Li, Shu; Jiang, Tianzi

    2016-09-01

    Various brain structural and functional features such as cytoarchitecture, topographic mapping, gyral/sulcal anatomy, and anatomical and functional connectivity have been used in human brain parcellation. However, the fine-grained intrinsic genetic architecture of the cortex remains unknown. In the present study, we parcellated specific regions of the cortex into subregions based on genetic correlations (i.e., shared genetic influences) between the surface area of each pair of cortical locations within the seed region. The genetic correlations were estimated by comparing the correlations of the surface area between monozygotic and dizygotic twins using bivariate twin models. Our genetic subdivisions of diverse brain regions were reproducible across 2 independent datasets and corresponded closely to fine-grained functional specializations. Furthermore, subregional genetic correlation profiles were generally consistent with functional connectivity patterns. Our findings indicate that the magnitude of the genetic covariance in brain anatomy could be used to delineate the boundaries of functional subregions of the brain and may be of value in the next generation human brain atlas. PMID:26250778

  5. A current genetic and epigenetic view on human aging mechanisms.

    PubMed

    Ostojić, Sala; Pereza, Nina; Kapović, Miljenko

    2009-06-01

    The process of aging is one of the most complex and intriguing biological phenomenons. Aging is a genetically regulated process in which the organism's maximum lifespan potential is pre-determined, while the rate of aging is influenced by environmental factors and lifestyle. Considering the complexity of mechanisms involved in the regulation of aging process, up to this date there isn't a major, unifying theory which could explain them. As genetic/epigenetic and environmental factors both inevitably influence the aging process, here we present a review on the genetic and epigenetic regulation of the most important molecular and cellular mechanisms involved in the process of aging. Based on the studies on oxidative stress, metabolism, genome stability, epigenetic modifications and cellular senescence in animal models and humans, we give an overview of key genetic and molecular pathways related to aging. As most of genetic manipulations which influence the aging process also affect reproduction, we discuss aging in humans as a post-reproductive genetically determined process. After the age of reproductive success, aging continously progresses which clinically coincides with the onset of most chronic diseases, cancers and dementions. As evolution shapes the genomes for reproductive success and not for post-reproductive survival, aging could be defined as a protective mechanism which ensures the preservation and progress of species through the modification, trasmission and improvement of genetic material. PMID:19662799

  6. Taking a Stand: The Genetics Community's Responsibility for Intelligence Research.

    PubMed

    Callier, Shawneequa L; Bonham, Vence L

    2015-01-01

    There is a longstanding debate about genetics research into intelligence. Some scholars question the value of focusing on genetic contributions to intelligence in a society where social and environmental determinants powerfully influence cognitive ability and educational outcomes. Others warn that censoring certain research questions, such as inquiries about genetic differences in intellectual potential, compromises academic freedom. Still others view interest in this subject as a corollary to a long and troublesome history of eugenics research. The dawn of a new era in genome sequencing as a commodity will sustain scientific interest in the genetics of intelligence for the foreseeable future, but deep-rooted challenges threaten the scientific merit of the research. The use of imprecise definitions of study populations, the difficult nature of studying the environment, and the potential of researcher bias are inextricably linked with concerns about the trustworthiness and utility of research in this area. Leadership by the genetics community is essential to ensure the value and trustworthiness of these studies. PMID:26413950

  7. Gene Expression and Genetic Variation in Human Atria

    PubMed Central

    Lin, Honghuang; Dolmatova, Elena V.; Morley, Michael P.; Lunetta, Kathryn L.; McManus, David D.; Magnani, Jared W.; Margulies, Kenneth B.; Hakonarson, Hakon; del Monte, Federica; Benjamin, Emelia J.; Cappola, Thomas P.; Ellinor, Patrick T.

    2013-01-01

    Background The human left and right atria have different susceptibilities to develop atrial fibrillation (AF). However, the molecular events related to structural and functional changes that enhance AF susceptibility are still poorly understood. Objective To characterize gene expression and genetic variation in human atria. Methods We studied the gene expression profiles and genetic variations in 53 left atrial and 52 right atrial tissue samples collected from the Myocardial Applied Genomics Network (MAGNet) repository. The tissues were collected from heart failure patients undergoing transplantation and from unused organ donor hearts with normal ventricular function. Gene expression was profiled using the Affymetrix GeneChip Human Genome U133A Array. Genetic variation was profiled using the Affymetrix Genome-Wide Human SNP Array 6.0. Results We found that 109 genes were differentially expressed between left and right atrial tissues. A total of 187 and 259 significant cis-associations between transcript levels and genetic variants were identified in left and right atrial tissues, respectively. We also found that a SNP at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right atrial tissues. Conclusion We found a distinct transcriptional profile between the right and left atrium, and extensive cis-associations between atrial transcripts and common genetic variants. Our results implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF. PMID:24177373

  8. Human genetics for non-scientists: Practical workshops for policy makers and opinion leaders

    SciTech Connect

    1995-12-31

    These workshops form part of a series of workshops that the Banbury and the DNA Learning Centers of Cold Spring Harbor Laboratory have held for a number of years, introducing genetics, and the ways in which scientific research is done, to non-scientists. The purpose of the workshops as stated in the grant application was: {open_quotes}Our objective is to foster a better understanding of the societal impact of human genome research by providing basic information on genetics to non-scientists whose professions or special interests interface with genetic technology.... Participants will be chosen for their interest in human genetics and for their roles as opinion leaders in their own communities. Primary care physicians are of particular interest to us for this series of workshops.{close_quotes} Two workshops were held under this grant. The first was held in 21-24 April, 1994 and attended by 20 participants, and the second was held 16-19 November, 1995, and attended by 16 participants. In each case, there was a combination of concept lectures on the foundations of human molecular genetics; lectures by invited specialists; and laboratory experiments to introduce non-scientists to the techniques used in molecular genetics.

  9. Human Aggression Across the Lifespan: Genetic Propensities and Environmental Moderators

    PubMed Central

    Tuvblad, Catherine; Baker, Laura A.

    2013-01-01

    This chapter reviews the recent evidence of genetic and environmental influences on human aggression. Findings from a large selection of the twin and adoption studies that have investigated the genetic and environmental architecture of aggressive behavior are summarized. These studies together show that about half (50%) of the variance in aggressive behavior is explained by genetic influences in both males and females, with the remaining 50% of the variance being explained by environmental factors not shared by family members. Form of aggression (reactive, proactive, direct/physical, indirect/relational), method of assessment (laboratory observation, self-report, ratings by parents and teachers), and age of the subjects—all seem to be significant moderators of the magnitude of genetic and environmental influences on aggressive behavior. Neither study design (twin vs. sibling adoption design) nor sex (male vs. female) seems to impact the magnitude of the genetic and environmental influences on aggression. There is also some evidence of gene-environment interaction (G × E) from both twin/adoption studies and molecular genetic studies. Various measures of family adversity and social disadvantage have been found to moderate genetic influences on aggressive behavior. Findings from these G × E studies suggest that not all individuals will be affected to the same degree by experiences and exposures, and that genetic predispositions may have different effects depending on the environment. PMID:22078481

  10. ANALYSIS OF THE SPECTRA OF GENETIC ACTIVITY PRODUCED BY KNOWN OR SUSPECTED HUMAN CARCINOGENS

    EPA Science Inventory

    For 24 agents classified by the International Agency for Research on Cancer as known or suspected human carcinogens, we previously catalogued the qualitative genetic bioassay data available in the literature. In the present analysis, dose information, where available, was added t...

  11. Teachers' Conceptions about the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    ERIC Educational Resources Information Center

    Castéra, Jérémy; Clément, Pierre

    2014-01-01

    This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the…

  12. The Genetics of Sun Sensitivity in Humans

    PubMed Central

    Rees, Jonathan L.

    2004-01-01

    Humans vary >100-fold in their sensitivity to the harmful effects of ultraviolet radiation. The main determinants of sensitivity are melanin pigmentation and less-well-characterized differences in skin inflammation and repair processes. Pigmentation has a high heritability, but susceptibility to cancers of the skin, a key marker of sun sensitivity, is less heritable. Despite a large number of murine coat-color mutations, only one gene in humans, the melanocortin 1 receptor (MC1R), is known to account for substantial variation in skin and hair color and in skin cancer incidence. MC1R encodes a 317–amino acid G-coupled receptor that controls the relative amounts of the two major melanin classes, eumelanin and pheomelanin. Most persons with red hair are homozygous for alleles of the MC1R gene that show varying degrees of diminished function. More than 65 human MC1R alleles with nonsynonymous changes have been identified, and current evidence suggests that many of them vary in their physiological activity, such that a graded series of responses can be achieved on the basis of (i) dosage effects (of one or two alleles) and (ii) individual differences in the pharmacological profile in response to ligand. Thus, a single locus, identified within a Mendelian framework, can contribute significantly to human pigmentary variation. PMID:15372380

  13. Molecular genetic determinants of human brain size.

    PubMed

    Tang, Bor Luen

    2006-07-01

    Cognitive skills such as tool use, syntactical languages, and self-awareness differentiate humans from other primates. The underlying basis for this cognitive difference has been widely associated with a high encephalization quotient and an anatomically distinct, exceptionally large cerebral cortex. Investigations on congenital microcephaly had revealed several genes that affect mammalian brain size when mutated. At least four of these, microcephalin (MCPH1), abnormal spindle-like microcephaly-associated (ASPM), cyclin-dependent kinase 5 regulatory associated protein 2 (CDK5RAP2), and centromere-associated protein J (CENPJ) are known to have undergone significant positive selection in the great apes and human lineages during primate evolution. MCPH1 and ASPM both have very young single nucleotide polymorphism haplotypes associated with modern humans, and these genes are presumably still evolving in Homo sapiens. Microcephalin has a role in DNA damage response and regulation of cell cycle checkpoints. The other known microcephaly-associated genes encode microtubule-associated centrosomal proteins that might regulate neural progenitor cell division and cell number. Recent reports have also unveiled a previously unknown function of ephrins and Eph in the regulation of neural progenitor cell death with a consequential effect on brain size. Understanding the mechanism for developmental control of brain organogenesis by these genes, and others such as FOXP2, shall provide fresh perspectives on the evolution of human intelligence. PMID:16716254

  14. Genetic Engineering of Animals for Medical Research: Students' Views.

    ERIC Educational Resources Information Center

    Hill, Ruaraidh; Stanisstreet, Martin; O'Sullivan, Helen; Boyes, Edward

    1999-01-01

    Reports on the results of a survey meant to ascertain the views of 16- to 18-year-old students (n=778) on using animals in medical research. Suggests that students have no greater objection to the use of genetically engineered animals over naturally bred animals in medical research. Contains 16 references. (Author/WRM)

  15. AFRICAN GENETIC DIVERSITY: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

    PubMed Central

    Campbell, Michael C.; Tishkoff, Sarah A.

    2010-01-01

    Comparative studies of ethnically diverse human populations, particularly in Africa, are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease. African populations are characterized by greater levels of genetic diversity, extensive population substructure, and less linkage disequilibrium (LD) among loci compared to non-African populations. Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets, as well as exposure to infectious disease. This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations, as well as their implications for the mapping of complex traits, including disease susceptibility. PMID:18593304

  16. [Human genetic data from a data protection law perspective].

    PubMed

    Schulte In den Bäumen, Tobias

    2007-02-01

    The collection and use of genetic data have caused much concern in the German population. Data protection is widely seen as the tool to address these fears. The term genetic data is not self-explanatory, as it depends on the different types of genetic diseases. The protection of genetic data as defined with regard to the different sets of diseases needs to fit into the preexisting data protection legislation. Still, the particularities of genetic data such as the multipersonal impact need to be considered. A balance between the information needs of society and the right to privacy requires a medically driven criteria. The medical term of indication which corresponds with the data protection term of purpose should serve as a tool in order to balance the rights of the patients and their relatives or between clients and third persons involved. Some countries have set up new legislative acts to address the challenges of human genetics. The current state of German data protection law leaves citizen rather unprotected as long as the data are used for medical purposes in a wider sense. A special law on the collection of genetic data has been discussed for several years, but it should be questioned whether the scope of a sector-specific law would serve citizens better. It seems to be preferable to adjust the existing Data Protection Act rather than drafting a specific law which covers the field of human genetics. This adaptation should reflect upon the different technical ways in which genetic data are collected and used. PMID:17238055

  17. Mendelian genetics: Paradigm, conjecture, or research program

    NASA Astrophysics Data System (ADS)

    Oldham, V.; Brouwer, W.

    Kuhn's model of the structure of scientific revolutions, Popper's hypothetic-deductive model of science, and Lakatos's methodology of competing research programs are applied to a historical episode in biology. Each of these three models offers a different explanatory system for the development, neglect, and eventual acceptance of Mendel's paradigm of inheritance. The authors conclude that both rational and nonrational criteria play an important role during times of crisis in science, when different research programs compete for acceptance. It is suggested that Kuhn's model, emphasizing the nonrational basis of science, and Popper's model, emphasizing the rational basis of science, can be used fruitfully in high school science courses.

  18. The role of genetically engineered pigs in xenotransplantation research.

    PubMed

    Cooper, David K C; Ekser, Burcin; Ramsoondar, Jagdeece; Phelps, Carol; Ayares, David

    2016-01-01

    There is a critical shortage in the number of deceased human organs that become available for the purposes of clinical transplantation. This problem might be resolved by the transplantation of organs from pigs genetically engineered to protect them from the human immune response. The pathobiological barriers to successful pig organ transplantation in primates include activation of the innate and adaptive immune systems, coagulation dysregulation and inflammation. Genetic engineering of the pig as an organ source has increased the survival of the transplanted pig heart, kidney, islet and corneal graft in non-human primates (NHPs) from minutes to months or occasionally years. Genetic engineering may also contribute to any physiological barriers that might be identified, as well as to reducing the risks of transfer of a potentially infectious micro-organism with the organ. There are now an estimated 40 or more genetic alterations that have been carried out in pigs, with some pigs expressing five or six manipulations. With the new technology now available, it will become increasingly common for a pig to express even more genetic manipulations, and these could be tested in the pig-to-NHP models to assess their efficacy and benefit. It is therefore likely that clinical trials of pig kidney, heart and islet transplantation will become feasible in the near future. PMID:26365762

  19. Your Genes, Your Choices: Exploring the Issues Raised by Genetic Research

    SciTech Connect

    Baker, C.

    1999-05-31

    Your Genes, Your Choices provides accurate information about the ethical, legal, and social implications of the Human Genome Project and genetic research in an easy-to-read style and format. Each chapter in the book begins with a brief vignette, which introduces an issue within a human story, and raises a question for the reader to think about as the basic science and information are presented in the rest of the chapter.

  20. Mendelian Genetics: Paradigm, Conjecture, or Research Program.

    ERIC Educational Resources Information Center

    Oldham, V.; Brouwer, W.

    1984-01-01

    Applies Kuhn's model of the structure of scientific revolutions, Popper's hypothetic-deductive model of science, and Lakatos' methodology of competing research programs to a historical biological episode. Suggests using Kuhn's model (emphasizing the nonrational basis of science) and Popper's model (emphasizing the rational basis of science) in…

  1. The Nazi symbiosis: politics and human genetics at the Kaiser Wilhelm Institute.

    PubMed

    Berez, Thomas M; Weiss, Sheila Faith

    2004-12-01

    The case of the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics (KWIA), from its inception in Weimar Republic Germany to its apogee under the rule of the Third Reich, is an example of how politics and human heredity can function as mutually beneficial resources. Whether it was a result of the Nazi bureaucrats' desire to legitimize their racial policy through science, or the KWIA personnel's desire to secure more funding for their research, the symbiotic relationship that developed between human genetics and Nazi politics could help explain why many scientists in the Third Reich undertook research projects that wholly transgressed the boundaries of morally acceptable science. PMID:15571767

  2. Autosomal ring chromosomes in human genetic disorders

    PubMed Central

    2015-01-01

    Ring chromosomes arise following breakage and rejoining in both chromosome arms. They are heterogeneous with variable size and genetic content and can originate from any chromosome. Phenotypes associated with ring chromosomes are highly variable as apart from any deletion caused by ring formation, imbalances from ring instability can also occur. Of interest is ring chromosome 20 which has a significant association with epilepsy with seizure onset in early childhood. Severe growth deficiency without major malformations is a common finding in the ring chromosome carrier. This phenotype associated with ring behaviour and mitotic instability and independent of the chromosome involved has been termed the “ring syndrome”. Precise genotype-phenotype correlations for ring chromosomes may not be possible as influencing factors vary depending on the extent of deletion in ring formation, ring instability and the level of mosaicism. Although ring chromosomes usually arise as de novo events, familial transmission of rings from carrier to offspring has been described and prenatal diagnosis for any pregnancies should always be considered. PMID:26835370

  3. Human genetics of tuberculosis: a long and winding road

    PubMed Central

    Abel, Laurent; El-Baghdadi, Jamila; Bousfiha, Ahmed Aziz; Casanova, Jean-Laurent; Schurr, Erwin

    2014-01-01

    Only a small fraction of individuals exposed to Mycobacterium tuberculosis develop clinical tuberculosis (TB). Over the past century, epidemiological studies have shown that human genetic factors contribute significantly to this interindividual variability, and molecular progress has been made over the past decade for at least two of the three key TB-related phenotypes: (i) a major locus controlling resistance to infection with M. tuberculosis has been identified, and (ii) proof of principle that severe TB of childhood can result from single-gene inborn errors of interferon-γ immunity has been provided; genetic association studies with pulmonary TB in adulthood have met with more limited success. Future genetic studies of these three phenotypes could consider subgroups of subjects defined on the basis of individual (e.g. age at TB onset) or environmental (e.g. pathogen strain) factors. Progress may also be facilitated by further methodological advances in human genetics. Identification of the human genetic variants controlling the various stages and forms of TB is critical for understanding TB pathogenesis. These findings should have major implications for TB control, in the definition of improved prevention strategies, the optimization of vaccines and clinical trials and the development of novel treatments aiming to restore deficient immune responses. PMID:24821915

  4. Genetics of human Bardet-Biedl syndrome, an updates.

    PubMed

    Khan, S A; Muhammad, N; Khan, M A; Kamal, A; Rehman, Z U; Khan, S

    2016-07-01

    Bardet-Biedl syndrome (BBS) is an autosomal recessive multisystemic human genetic disorder characterized by six major defects including obesity, mental retardation, renal anomalies, polydactyly, retinal degeneration and hypogenitalism. In several cases of BBS, few other features such as metabolic defects, cardiovascular anomalies, speech deficits, hearing loss, hypertension, hepatic defects and high incidence of diabetes mellitus have been reported as well. The BBS displays extensive genetic heterogeneity. To date, 19 genes have been mapped on different chromosomes causing BBS phenotypes having varied mutational load of each BBS gene. In this review, we have discussed clinical spectrum and genetics of BBS. This report presents a concise overview of the current knowledge on clinical data and its molecular genetics progress upto date. PMID:26762677

  5. Sequencing studies in human genetics: design and interpretation

    PubMed Central

    Goldstein, David B.; Allen, Andrew; Keebler, Jonathan; Margulies, Elliott H.; Petrou, Steven; Petrovski, Slavé; Sunyaev, Shamil

    2014-01-01

    Next-gene ration sequencing is becoming the primary discovery tool in human genetics. There have been many clear successes in identifying genes that are responsible for Mendelian diseases, and sequencing approaches are now poised to identify the mutations that cause undiagnosed childhood genetic diseases and those that predispose individuals to more common complex diseases. There are, however, growing concerns that the complexity and magnitude of complete sequence data could lead to an explosion of weakly justified claims of association between genetic variants and disease. Here, we provide an overview of the basic workflow in next-generation sequencing studies and emphasize, where possible, measures and considerations that facilitate accurate inferences from human sequencing studies. PMID:23752795

  6. Genetic variation and the de novo assembly of human genomes

    PubMed Central

    Chaisson, Mark J. P.; Wilson, Richard K.; Eichler, Evan E.

    2016-01-01

    The discovery of genetic variation and the assembly of genome sequences are both inextricably linked to advances in DNA-sequencing technology. Short-read massively parallel sequencing has revolutionized our ability to discover genetic variation but is insufficient to generate high-quality genome assemblies or resolve most structural variation. Full resolution of variation is only guaranteed by complete de novo assembly of a genome. Here, we review approaches to genome assembly, the nature of gaps or missing sequences, and biases in the assembly process. We describe the challenges of generating a complete de novo genome assembly using current technologies and the impact that being able to perfectly sequence the genome would have on understanding human disease and evolution. Finally, we summarize recent technological advances that improve both contiguity and accuracy and emphasize the importance of complete de novo assembly as opposed to read mapping as the primary means to understanding the full range of human genetic variation. PMID:26442640

  7. Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics.

    PubMed

    Bauer, Robert C; Khetarpal, Sumeet A; Hand, Nicholas J; Rader, Daniel J

    2016-04-01

    Human genetics has contributed to the development of multiple drugs to treat hyperlipidemia and coronary artery disease (CAD), most recently including antibodies targeting PCSK9 to reduce LDL cholesterol. Despite these successes, a large burden of CAD remains. Genetic and epidemiological studies have suggested that circulating triglyceride (TG)-rich lipoproteins (TRLs) are a causal risk factor for CAD, presenting an opportunity for novel therapeutic strategies. We discuss recent unbiased human genetics testing, including genome-wide association studies (GWAS) and whole-genome or -exome sequencing, that have identified the lipoprotein lipase (LPL) and hepatic lipogenesis pathways as important mechanisms in the regulation of circulating TRLs. Further strengthening the causal relationship between TRLs and CAD, findings such as these may provide novel targets for much-needed potential therapeutic interventions. PMID:26988439

  8. Human Subjects Issues in AIDS Research.

    ERIC Educational Resources Information Center

    Bayer, Ronald, Ed.

    1990-01-01

    Six articles are presented on the use of human subjects in research on acquired immune deficiency syndrome (AIDS). Topics include the ethics of human experimentation, female and pediatric AIDS patients, Human Immunodeficiency Virus (HIV) infection and AIDS among correctional inmates, community-based AIDS research, and clinical trials of HIV…

  9. Genetically encoded optical activation of DNA recombination in human cells.

    PubMed

    Luo, J; Arbely, E; Zhang, J; Chou, C; Uprety, R; Chin, J W; Deiters, A

    2016-06-30

    We developed two tightly regulated, light-activated Cre recombinase enzymes through site-specific incorporation of two genetically-encoded photocaged amino acids in human cells. Excellent optical off to on switching of DNA recombination was achieved. Furthermore, we demonstrated precise spatial control of Cre recombinase through patterned illumination. PMID:27277957

  10. Public Attitudes toward Human Genetic Manipulation: A Revitalization of Eugenics?

    ERIC Educational Resources Information Center

    Veglia, Geremia; And Others

    The purpose of this investigation was to measure the attitudes of college students across the United States concerning the possible use of genetic manipulation, especially in terms of enhancing human physical and intellectual characteristics. The instrument used was divided into three general areas of inquiry: the first, designed to measure the…

  11. Exploring human brain lateralization with molecular genetics and genomics.

    PubMed

    Francks, Clyde

    2015-11-01

    Lateralizations of brain structure and motor behavior have been observed in humans as early as the first trimester of gestation, and are likely to arise from asymmetrical genetic-developmental programs, as in other animals. Studies of gene expression levels in postmortem tissue samples, comparing the left and right sides of the human cerebral cortex, have generally not revealed striking transcriptional differences between the hemispheres. This is likely due to lateralization of gene expression being subtle and quantitative. However, a recent re-analysis and meta-analysis of gene expression data from the adult superior temporal and auditory cortex found lateralization of transcription of genes involved in synaptic transmission and neuronal electrophysiology. Meanwhile, human subcortical mid- and hindbrain structures have not been well studied in relation to lateralization of gene activity, despite being potentially important developmental origins of asymmetry. Genetic polymorphisms with small effects on adult brain and behavioral asymmetries are beginning to be identified through studies of large datasets, but the core genetic mechanisms of lateralized human brain development remain unknown. Identifying subtly lateralized genetic networks in the brain will lead to a new understanding of how neuronal circuits on the left and right are differently fine-tuned to preferentially support particular cognitive and behavioral functions. PMID:25950729

  12. Ethics, Ethical Human Research and Human Research Ethics Committees

    ERIC Educational Resources Information Center

    Lindorff, Margaret

    2010-01-01

    Non-medical research involves the same issues of justice, beneficence, and respect for persons that apply to non-medical research. It also may involve risk of harm to participants, and conflicts of interest for researchers. It is therefore not possible to argue that such research should be exempt from ethical review. This paper argues that…

  13. Research in China on the molecular genetics of schizophrenia

    PubMed Central

    Cui, Donghong; Jiang, Kaida

    2012-01-01

    Summary Schizophrenia is a complex disease caused by genetic and environmental factors with a global heritability of more than 80%. By the end of the 1970s, Chinese scientists reported a heritability of schizophrenia of 82.9% in the Chinese Han population. Continuous improvements in research techniques and the recruitment of larger samples have made it possible for Chinese scientists to identify a number of candidate susceptibility genes for schizophrenia. This article reviews the results in genetic research of schizophrenia by Chinese scientists over the last five decades PMID:25324626

  14. Human Research Program Exploration Medical Capability

    NASA Technical Reports Server (NTRS)

    Barsten, Kristina

    2010-01-01

    NASA s Human Research Program (HRP) conducts and coordinates research projects that provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. The Program is divided into 6 major elements, which a) Provide the Program s knowledge and capabilities to conduct research, addressing the human health and performance risks. b) Advance the readiness levels of technology and countermeasures to the point of transfer to the customer programs and organizations. The National Space Biomedical Research Institute (NSBRI) is a partner with the HRP in developing a successful research program. 3

  15. Genetic studies on the Cayo Santiago rhesus macaques: A review of 40 years of research.

    PubMed

    Widdig, Anja; Kessler, Matthew J; Bercovitch, Fred B; Berard, John D; Duggleby, Christine; Nürnberg, Peter; Rawlins, Richard G; Sauermann, Ulrike; Wang, Qian; Krawczak, Michael; Schmidtke, Jörg

    2016-01-01

    Genetic studies not only contribute substantially to our current understanding of the natural variation in behavior and health in many species, they also provide the basis of numerous in vivo models of human traits. Despite the many challenges posed by the high level of biological and social complexity, a long lifespan and difficult access in the field, genetic studies of primates are particularly rewarding because of the close evolutionary relatedness of these species to humans. The free-ranging rhesus macaque (Macaca mulatta) population on Cayo Santiago (CS), Puerto Rico, provides a unique resource in this respect because several of the abovementioned caveats are of either minor importance there, or lacking altogether, thereby allowing long-term genetic research in a primate population under constant surveillance since 1956. This review summarizes more than 40 years of genetic research carried out on CS, from early blood group typing and the genetic characterization of skeletal material via population-wide paternity testing with DNA fingerprints and short tandem repeats (STRs) to the analysis of the highly polymorphic DQB1 locus within the major histocompatibility complex (MHC). The results of the paternity studies also facilitated subsequent studies of male dominance and other factors influencing male reproductive success, of male reproductive skew, paternal kin bias, and mechanisms of paternal kin recognition. More recently, the CS macaques have been the subjects of functional genetic and gene expression analyses and have played an important role in behavioral and quantitative genetic studies. In addition, the CS colony has been used as a natural model for human adult-onset macular degeneration, glaucoma, and circadian rhythm disorder. Our review finishes off with a discussion of potential future directions of research on CS, including the transition from STRs to single nucleotide polymorphism (SNP) typing and whole genome sequencing. PMID:26031601

  16. Genetic variation in lipid desaturases and its impact on the development of human disease

    PubMed Central

    2010-01-01

    Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management. PMID:20565855

  17. Human life: genetic or social construction?

    PubMed

    Yudin, Boris

    2005-01-01

    I am going to discuss some present-day tendencies in the development of the very old debate on nature vs nurture. There is a widespread position describing the history of this debate as a pendulum-like process. Some three decades ago there was a time of overwhelming prevalence of the position stressing social factors in determining human character and behavior; now the pendulum has come to the opposite side and those who stress the role of biology, of genes are in favor. Yet in my view rather acute opposition of both positions still exists. Its existence depends not so much on new scientific discoveries as on some social and cultural factors which are more conservative than the development of science. More than that, we can even talk about competition of these two positions. PMID:17048365

  18. Psychiatric genetic research at the National Institute of Mental Health

    SciTech Connect

    Berg, K.; Mullican, C.; Maestri, N.

    1994-12-15

    For some time it has been known through the results of family, twin, and adoption studies that hereditary appears to play a significant casual role in many mental disorders, including schizophrenia, bipolar disorder, and other mood disorders, Alzheimer`s Disease, panic disorder, obsessive compulsive disorder, autism, dyslexia, and Tourette`s syndrome. The precise patterns of inheritance of these complex disorders have not been determined, nor have the relevant genes been localized or cloned. Because the genetics are complex and because there is also clearly an environmental contribution to behavior, we expect the analysis of the genetics of mental illness to be arduous and not quickly resolved. There are several compelling reasons to continue to focus our attention on uncovering the genetic factors for severe mental illness. Prominent among these are the implications for better treatment of mental disorders. The National Institute of Mental Health supports a wide range of studies on psychiatric genetic research. 16 refs.

  19. Using non-human primates to benefit humans: research and organ transplantation.

    PubMed

    Shaw, David; Dondorp, Wybo; de Wert, Guido

    2014-11-01

    Emerging biotechnology may soon allow the creation of genetically human organs inside animals, with non-human primates (henceforth simply "primates") and pigs being the best candidate species. This prospect raises the question of whether creating organs in primates in order to then transplant them into humans would be more (or less) acceptable than using them for research. In this paper, we examine the validity of the purported moral distinction between primates and other animals, and analyze the ethical acceptability of using primates to create organs for human use. PMID:24807743

  20. Simple genetics language as source of miscommunication between genetics researchers and potential research participants in informed consent documents.

    PubMed

    Morgenstern, Justin; Hegele, Robert A; Nisker, Jeff

    2015-08-01

    Informed consent is based on communication, requiring language to convey meanings and ensure understandings. The purpose of this study was to investigate the use of language in informed consent documents used in the genetics research funded by Canadian Institutes of Health Research and Genome Canada. Consent documents were requested from the principal investigators in a recent round of funding. A qualitative content analysis was performed, supported by NVivo7™. Potential barriers to informed consent were identified, including language that was vague and variable, words with both technical and common meanings, novel phrases without clear meaning, a lack of definitions, and common concepts that assume new definitions in genetics research. However, we noted that difficulties in comprehension were often obscured because the words used were generally simple and familiar. We conclude that language gaps between researcher and potential research participants may unintentionally impair comprehension and ultimately impair informed consent in genomics research. PMID:24751688

  1. Can Research on the Genetics of Intelligence Be "Socially Neutral"?

    PubMed

    Roberts, Dorothy

    2015-01-01

    The history of research on the genetics of intelligence is fraught with social bias. During the eugenics era, the hereditary theory of intelligence justified policies that encouraged the proliferation of favored races and coercively stemmed procreation by disfavored ones. In the 1970s, Berkeley psychologist Arthur Jensen argued that black students' innate cognitive inferiority limited the efficacy of federal education programs. The 1994 controversial bestseller The Bell Curve, by Richard J. Herrnstein and Charles Murray, rehashed the claim that race and class disparities stem from immutable differences in inherited intelligence, which could not be eliminated through social interventions. Today most scientists studying the genetics of intelligence distance themselves from this history of social bias by arguing that their research need not investigate intellectual differences between social groups. Rather, they argue, examining the heritability of intelligence can be socially neutral and may even help to reduce social inequities. I argue, however, that research on the genetics of intelligence cannot be socially neutral. Even if we divorce the heritability of intelligence from a eugenicist mission, measuring intelligence remains useful only as a gage of individuals' appropriate positions in society. Research into the genetics of intelligence ultimately helps to determine individuals' inherited capacity for particular social positions, even when researchers aim to modify the effects of inheritance. PMID:26413949

  2. Needed Research on the Genes and Environment in Human Psychological Development: Perspectives from Behavior Genetics. A Special Report of the USOE-Sponsored Grant Study: Critical Appraisal of Research in the Personality-Emotions-Motivation Domain.

    ERIC Educational Resources Information Center

    Loehlin, John C.; And Others

    The task group report presented in this publication is one of a series prepared by eminent psychologists who have served as consultants in the U.S.O.E.-sponsored grant study to conduct a Critical Appraisal of the Personality-Emotions-Motivation Domain. In order to attain the goal of identifying important problems and areas for new research and…

  3. Human Research Program Integrated Research Plan. Revision A January 2009

    NASA Technical Reports Server (NTRS)

    2009-01-01

    The Integrated Research Plan (IRP) describes the portfolio of Human Research Program (HRP) research and technology tasks. The IRP is the HRP strategic and tactical plan for research necessary to meet HRP requirements. The need to produce an IRP is established in HRP-47052, Human Research Program - Program Plan, and is under configuration management control of the Human Research Program Control Board (HRPCB). Crew health and performance is critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) is essential to enabling extended periods of space exploration because it provides knowledge and tools to mitigate risks to human health and performance. Risks include physiological and behavioral effects from radiation and hypogravity environments, as well as unique challenges in medical support, human factors, and behavioral or psychological factors. The Human Research Program (HRP) delivers human health and performance countermeasures, knowledge, technologies and tools to enable safe, reliable, and productive human space exploration. Without HRP results, NASA will face unknown and unacceptable risks for mission success and post-mission crew health. This Integrated Research Plan (IRP) describes HRP s approach and research activities that are intended to address the needs of human space exploration and serve HRP customers and how they are integrated to provide a risk mitigation tool. The scope of the IRP is limited to the activities that can be conducted with the resources available to the HRP; it does not contain activities that would be performed if additional resources were available. The timescale of human space exploration is envisioned to take many decades. The IRP illustrates the program s research plan through the timescale of early lunar missions of extended duration.

  4. Resources for human genetics on the World Wide Web.

    PubMed

    Osborne, L R; Lee, J R; Scherer, S W

    1997-09-01

    A little over a century ago, the HMS Beagle sailed the Pacific Ocean bringing Charles Darwin to the perfect environment in which to piece together his observations forming the theory of evolution. Now, geneticists and laypeople alike surf the equally formidable waters of the internet in search of enlightenment. Here, we attempt to help you navigate towards resources for human genetics by providing maps to three destinations: The Human Genome Project (Box 1), education (Box 2), and human genetic diseases (Box 3). For each, we highlight a few sites that we consider are the most informative and original. A more extensive list containing other useful sites has been compiled and posted on a 'jump site' at: http:/(/)www.cgdn.generes.ca/. PMID:9302686

  5. Teaching Human Genetics with Mustard: Rapid Cycling "Brassica rapa" (Fast Plants Type) as a Model for Human Genetics in the Classroom Laboratory

    ERIC Educational Resources Information Center

    Wendell, Douglas L.; Pickard, Dawn

    2007-01-01

    We have developed experiments and materials to model human genetics using rapid cycling "Brassica rapa", also known as Fast Plants. Because of their self-incompatibility for pollination and the genetic diversity within strains, "B. rapa" can serve as a relevant model for human genetics in teaching laboratory experiments. The experiment presented…

  6. Genetic fatalism and social policy: the implications of behavior genetics research.

    PubMed Central

    Alper, J. S.; Beckwith, J.

    1993-01-01

    Recent advances in molecular genetics methods have provided new means of determining the genetic bases of human behavioral traits. The impetus for the use of these approaches for specific behaviors depends, in large part, on previous familial studies on inheritance of such traits. In the past, a finding of a genetic basis for a trait was often accompanied with the idea that that trait is unchangeable. We discuss the definition of "genetic trait" and heritability and examine the relationship between these concepts and the malleability of traits for both molecular and nonmolecular approaches to behavioral genetics. We argue that the malleability of traits is as much a social and political question as it is a biological one and that whether or not a trait is genetic has little relevance to questions concerning determinism, free will, and individual responsibility for actions. We conclude by noting that "scientific objectivity" should not be used to conceal the social perspectives that underlie proposals regarding social change. PMID:7716971

  7. Conservation of Distinct Genetically-Mediated Human Cortical Pattern

    PubMed Central

    Peng, Qian; Schork, Andrew; Bartsch, Hauke; Lo, Min-Tzu; Panizzon, Matthew S.; Westlye, Lars T.; Kremen, William S.; Jernigan, Terry L.; Le Hellard, Stephanie; Steen, Vidar M.; Espeseth, Thomas; Huentelman, Matt; Agartz, Ingrid; Djurovic, Srdjan; Andreassen, Ole A.; Dale, Anders M.; Schork, Nicholas J.; Chen, Chi-Hua

    2016-01-01

    The many subcomponents of the human cortex are known to follow an anatomical pattern and functional relationship that appears to be highly conserved between individuals. This suggests that this pattern and the relationship among cortical regions are important for cortical function and likely shaped by genetic factors, although the degree to which genetic factors contribute to this pattern is unknown. We assessed the genetic relationships among 12 cortical surface areas using brain images and genotype information on 2,364 unrelated individuals, brain images on 466 twin pairs, and transcriptome data on 6 postmortem brains in order to determine whether a consistent and biologically meaningful pattern could be identified from these very different data sets. We find that the patterns revealed by each data set are highly consistent (p<10−3), and are biologically meaningful on several fronts. For example, close genetic relationships are seen in cortical regions within the same lobes and, the frontal lobe, a region showing great evolutionary expansion and functional complexity, has the most distant genetic relationship with other lobes. The frontal lobe also exhibits the most distinct expression pattern relative to the other regions, implicating a number of genes with known functions mediating immune and related processes. Our analyses reflect one of the first attempts to provide an assessment of the biological consistency of a genetic phenomenon involving the brain that leverages very different types of data, and therefore is not just statistical replication which purposefully use very similar data sets. PMID:27459196

  8. Conservation of Distinct Genetically-Mediated Human Cortical Pattern.

    PubMed

    Peng, Qian; Schork, Andrew; Bartsch, Hauke; Lo, Min-Tzu; Panizzon, Matthew S; Westlye, Lars T; Kremen, William S; Jernigan, Terry L; Le Hellard, Stephanie; Steen, Vidar M; Espeseth, Thomas; Huentelman, Matt; Håberg, Asta K; Agartz, Ingrid; Djurovic, Srdjan; Andreassen, Ole A; Dale, Anders M; Schork, Nicholas J; Chen, Chi-Hua

    2016-07-01

    The many subcomponents of the human cortex are known to follow an anatomical pattern and functional relationship that appears to be highly conserved between individuals. This suggests that this pattern and the relationship among cortical regions are important for cortical function and likely shaped by genetic factors, although the degree to which genetic factors contribute to this pattern is unknown. We assessed the genetic relationships among 12 cortical surface areas using brain images and genotype information on 2,364 unrelated individuals, brain images on 466 twin pairs, and transcriptome data on 6 postmortem brains in order to determine whether a consistent and biologically meaningful pattern could be identified from these very different data sets. We find that the patterns revealed by each data set are highly consistent (p<10-3), and are biologically meaningful on several fronts. For example, close genetic relationships are seen in cortical regions within the same lobes and, the frontal lobe, a region showing great evolutionary expansion and functional complexity, has the most distant genetic relationship with other lobes. The frontal lobe also exhibits the most distinct expression pattern relative to the other regions, implicating a number of genes with known functions mediating immune and related processes. Our analyses reflect one of the first attempts to provide an assessment of the biological consistency of a genetic phenomenon involving the brain that leverages very different types of data, and therefore is not just statistical replication which purposefully use very similar data sets. PMID:27459196

  9. The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe

    PubMed Central

    Hastings, Ros; de Wert, Guido; Fowler, Brian; Krawczak, Michael; Vermeulen, Eric; Bakker, Egbert; Borry, Pascal; Dondorp, Wybo; Nijsingh, Niels; Barton, David; Schmidtke, Jörg; van El, Carla G; Vermeesch, Joris; Stol, Yrrah; Carmen Howard, Heidi; Cornel, Martina C

    2012-01-01

    The arrival of new genetic technologies that allow efficient examination of the whole human genome (microarray, next-generation sequencing) will impact upon both laboratories (cytogenetic and molecular genetics in the first instance) and clinical/medical genetic services. The interpretation of analytical results in terms of their clinical relevance and the predicted health status poses a challenge to both laboratory and clinical geneticists, due to the wealth and complexity of the information obtained. There is a need to discuss how to best restructure the genetic services logistically and to determine the clinical utility of genetic testing so that patients can receive appropriate advice and genetic testing. To weigh up the questions and challenges of the new genetic technologies, the European Society of Human Genetics (ESHG) held a series of workshops on 10 June 2010 in Gothenburg. This was part of an ESHG satellite symposium on the ‘Changing landscape of genetic testing', co-organized by the ESHG Genetic Services Quality and Public and Professional Policy Committees. The audience consisted of a mix of geneticists, ethicists, social scientists and lawyers. In this paper, we summarize the discussions during the workshops and present some of the identified ways forward to improve and adapt the genetic services so that patients receive accurate and relevant information. This paper covers ethics, clinical utility, primary care, genetic services and the blurring boundaries between healthcare and research. PMID:22453292

  10. The changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe.

    PubMed

    Hastings, Ros; de Wert, Guido; Fowler, Brian; Krawczak, Michael; Vermeulen, Eric; Bakker, Egbert; Borry, Pascal; Dondorp, Wybo; Nijsingh, Niels; Barton, David; Schmidtke, Jörg; van El, Carla G; Vermeesch, Joris; Stol, Yrrah; Carmen Howard, Heidi; Cornel, Martina C

    2012-09-01

    The arrival of new genetic technologies that allow efficient examination of the whole human genome (microarray, next-generation sequencing) will impact upon both laboratories (cytogenetic and molecular genetics in the first instance) and clinical/medical genetic services. The interpretation of analytical results in terms of their clinical relevance and the predicted health status poses a challenge to both laboratory and clinical geneticists, due to the wealth and complexity of the information obtained. There is a need to discuss how to best restructure the genetic services logistically and to determine the clinical utility of genetic testing so that patients can receive appropriate advice and genetic testing. To weigh up the questions and challenges of the new genetic technologies, the European Society of Human Genetics (ESHG) held a series of workshops on 10 June 2010 in Gothenburg. This was part of an ESHG satellite symposium on the 'Changing landscape of genetic testing', co-organized by the ESHG Genetic Services Quality and Public and Professional Policy Committees. The audience consisted of a mix of geneticists, ethicists, social scientists and lawyers. In this paper, we summarize the discussions during the workshops and present some of the identified ways forward to improve and adapt the genetic services so that patients receive accurate and relevant information. This paper covers ethics, clinical utility, primary care, genetic services and the blurring boundaries between healthcare and research. PMID:22453292

  11. Molecular genetic study of human arginase deficiency

    PubMed Central

    Grody, Wayne W.; Klein, Deborah; Dodson, Amy E.; Kern, Rita M.; Wissmann, Paul B.; Goodman, Barbara K.; Bassand, Patrick; Marescau, Bert; Kang, Soo-Sang; Leonard, James V.; Cederbaum, Stephen D.

    1992-01-01

    We have explored the molecular pathology in 28 individuals homozygous or heterozygous for liver arginase deficiency (hyperargininemia) by a combination of Southern analysis, western blotting, DNA sequencing, and PCR. This cohort represents the majority of arginase-deficient individuals worldwide. Only 2 of 15 homozygous patients on whom red blood cells were available had antigenically cross-reacting material as ascertained by western blot analysis using anti–liver arginase antibody. Southern blots of patient genomic DNAs, cut with a variety of restriction enzymes and probed with a near-full-length (1,450-bp) human liver arginase cDNA clone, detected no gross gene deletions. Loss of a TaqI cleavage site was identified in three individuals: in a homozygous state in a Saudi Arabian patient at one site, at a different site in homozygosity in a German patient, and in heterozygosity in a patient from Australia. The changes in the latter two were localized to exon 8, through amplification of this region by PCR and electrophoretic analysis of the amplified fragment after treatment with TaqI; the precise base changes (Arg291X and Thr290Ser) were confirmed by sequencing. It it interesting that the latter nucleotide variant (Thr290Ser) was found to lie adjacent to the TaqI site rather than within it, though whether such a conservative amino acid substitution represents a true pathologic mutation remains to be determined. We conclude that arginase deficiency, though rare, is a heterogeneous disorder at the genotypic level, generally encompassing a variety of point mutations rather than substantial structural gene deletions. ImagesFigure 1Figure 3Figure 4Figure 5 PMID:1598908

  12. Genetical genomic determinants of alcohol consumption in rats and humans

    PubMed Central

    Tabakoff, Boris; Saba, Laura; Printz, Morton; Flodman, Pam; Hodgkinson, Colin; Goldman, David; Koob, George; Richardson, Heather N; Kechris, Katerina; Bell, Richard L; Hübner, Norbert; Heinig, Matthias; Pravenec, Michal; Mangion, Jonathan; Legault, Lucie; Dongier, Maurice; Conigrave, Katherine M; Whitfield, John B; Saunders, John; Grant, Bridget; Hoffman, Paula L

    2009-01-01

    Background We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs). Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. Results In the HXB/BXH recombinant inbred (RI) rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL) analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. Conclusion Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans

  13. Progress and Prospects for Genetic Modification of Nonhuman Primate Models in Biomedical Research

    PubMed Central

    Chan, Anthony W. S.

    2013-01-01

    The growing interest of modeling human diseases using genetically modified (transgenic) nonhuman primates (NHPs) is a direct result of NHPs (rhesus macaque, etc.) close relation to humans. NHPs share similar developmental paths with humans in their anatomy, physiology, genetics, and neural functions; and in their cognition, emotion, and social behavior. The NHP model within biomedical research has played an important role in the development of vaccines, assisted reproductive technologies, and new therapies for many diseases. Biomedical research has not been the primary role of NHPs. They have mainly been used for safety evaluation and pharmacokinetics studies, rather than determining therapeutic efficacy. The development of the first transgenic rhesus macaque (2001) revolutionized the role of NHP models in biomedicine. Development of the transgenic NHP model of Huntington's disease (2008), with distinctive clinical features, further suggested the uniqueness of the model system; and the potential role of the NHP model for human genetic disorders. Modeling human genetic diseases using NHPs will continue to thrive because of the latest advances in molecular, genetic, and embryo technologies. NHPs rising role in biomedical research, specifically pre-clinical studies, is foreseeable. The path toward the development of transgenic NHPs and the prospect of transgenic NHPs in their new role in future biomedicine needs to be reviewed. This article will focus on the advancement of transgenic NHPs in the past decade, including transgenic technologies and disease modeling. It will outline new technologies that may have significant impact in future NHP modeling and will conclude with a discussion of the future prospects of the transgenic NHP model. PMID:24174443

  14. Increasing global participation in genetics research through DNA barcoding.

    PubMed

    Adamowicz, Sarah J; Steinke, Dirk

    2015-12-01

    DNA barcoding--the sequencing of short, standardized DNA regions for specimen identification and species discovery--has promised to facilitate rapid access to biodiversity knowledge by diverse users. Here, we advance our opinion that increased global participation in genetics research is beneficial, both to scientists and for science, and explore the premise that DNA barcoding can help to democratize participation in genetics research. We examine publication patterns (2003-2014) in the DNA barcoding literature and compare trends with those in the broader, related domain of genomics. While genomics is the older and much larger field, the number of nations contributing to the published literature is similar between disciplines. Meanwhile, DNA barcoding exhibits a higher pace of growth in the number of publications as well as greater evenness among nations in their proportional contribution to total authorships. This exploration revealed DNA barcoding to be a highly international discipline, with growing participation by researchers in especially biodiverse nations. We briefly consider several of the challenges that may hinder further participation in genetics research, including access to training and molecular facilities as well as policy relating to the movement of genetic resources. PMID:26642251

  15. Field-based phenomics for plant genetics research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perhaps the greatest challenge for crop research in the 21st century is how to predict crop performance as a function of genetic architecture and climate change. Advances in “next generation” DNA sequencing have greatly reduced genotyping costs. Methods for characterization of plant traits (phenotyp...

  16. Psychological Issues in Cancer Genetics: Current Research and Future Priorities.

    ERIC Educational Resources Information Center

    Hopwood, Penelope

    1997-01-01

    Data concerning the psychological impact of high risk of cancer are reviewed, including implications of genetic testing, breast screening,and accuracy of women's risk estimates. Work in progress on prophylactic mastectomy and chemoprevention is reviewed. Research on cancer families, and interventions and prevention strategies for high-risk…

  17. Genetic research for wildlife and fisheries management - A primer

    USGS Publications Warehouse

    Pawlitz, Rachel J.; Hunter, Margaret E.; Johnson, Nathan A.

    2012-01-01

    Scientists at the U.S. Geological Survey (USGS) use a range of research approaches to investigate the genetics of native and non-native species that are being managed. This Fact Sheet outlines those approaches and explains the type of information they provide.

  18. Mike Gale and cereal genetics research in China

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mike was one of the leading scientists in agricultural research internationally. The significant contributions he made to wheat linkage map construction, comparative genomics among cereals, and the cloning genes of agronomic importance made him prominent in wheat genetics and agricultural biotechnol...

  19. The attitudes of people with sarcoma and their family towards genomics and incidental information arising from genetic research

    PubMed Central

    2013-01-01

    Purpose The study aimed to examine attitudes of individuals diagnosed with sarcoma and their family members towards genetics, genomic research and incidental information arising as a result of participating in genetic research. Methods A questionnaire was administered to 1200 individuals from the International Sarcoma Kindred Study (ISKS). Respondents were divided into three groups: individuals affected with sarcoma (probands), their spouses and family members. Results Approximately half of all research participants felt positively towards new discoveries in human genetics. Overall, more were positive in their attitudes towards genetic testing for inherited conditions (60%) but family members were less so. Older participants reported more highly positive attitudes more often than younger participants. Males were less likely to feel positive about new genetic discoveries and more likely to believe they could modify genetic risk by altering lifestyle factors. Almost all ISKS participants believed participants would like to be given ancillary information arising as a result of participating in genetic research. Conclusions The only difference between the study groups was the decreased likelihood of family members being highly positive about genetic testing. This may be important if predictive testing for sarcoma becomes available. Generally ISKS research participants supported the notion of returning incidental genetic information to research participants. PMID:23898988

  20. Landscape Genetics Reveals Focal Transmission of a Human Macroparasite

    PubMed Central

    Criscione, Charles D.; Anderson, Joel D.; Sudimack, Dan; Subedi, Janardan; Upadhayay, Ram P.; Jha, Bharat; Williams, Kimberly D.; Williams-Blangero, Sarah; Anderson, Timothy J. C.

    2010-01-01

    Macroparasite infections (e.g., helminths) remain a major human health concern. However, assessing transmission dynamics is problematic because the direct observation of macroparasite dispersal among hosts is not possible. We used a novel landscape genetics approach to examine transmission of the human roundworm Ascaris lumbricoides in a small human population in Jiri, Nepal. Unexpectedly, we found significant genetic structuring of parasites, indicating the presence of multiple transmission foci within a small sampling area (∼14 km2). We analyzed several epidemiological variables, and found that transmission is spatially autocorrelated around households and that transmission foci are stable over time despite extensive human movement. These results would not have been obtainable via a traditional epidemiological study based on worm counts alone. Our data refute the assumption that a single host population corresponds to a single parasite transmission unit, an assumption implicit in many classic models of macroparasite transmission. Newer models have shown that the metapopulation-like pattern observed in our data can adversely affect targeted control strategies aimed at community-wide impacts. Furthermore, the observed metapopulation structure and local mating patterns generate an excess of homozygotes that can accelerate the spread of recessive traits such as drug resistance. Our study illustrates how molecular analyses complement traditional epidemiological information in providing a better understanding of parasite transmission. Similar landscape genetic approaches in other macroparasite systems will be warranted if an accurate depiction of the transmission process is to be used to inform effective control strategies. PMID:20421919

  1. Bloat free genetic programming: application to human oral bioavailability prediction.

    PubMed

    Silva, Sara; Vanneschi, Leonardo

    2012-01-01

    Being able to predict the human oral bioavailability for a potential new drug is extremely important for the drug discovery process. This problem has been addressed by several prediction tools, with Genetic Programming providing some of the best results ever achieved. In this paper we use the newest developments of Genetic Programming, in particular the latest bloat control method, Operator Equalisation, to find out how much improvement we can achieve on this problem. We show examples of some actual solutions and discuss their quality, comparing them with previously published results. We identify some unexpected behaviours related to overfitting, and discuss the way for further improving the practical usage of the Genetic Programming approach. PMID:23356009

  2. Reverse Genetics System for Studying Human Rhinovirus Infections

    PubMed Central

    Lee, Wai-Ming; Wang, Wensheng; Bochkov, Yury A; Lee, Iris

    2015-01-01

    SUMMARY Human rhinovirus (HRV) contains a 7.2 Kb messenger-sense RNA genome which is the template for reproducing progeny viruses after it enters the cytoplasm of a host cell. Reverse genetics refers to the regeneration of progeny viruses from an artificial cDNA copy of the RNA genome of an RNA virus. It has been a powerful molecular genetic tool for studying HRV and other RNA viruses because the artificial DNA stage makes it practical to introduce specific mutations into the viral RNA genome. This chapter uses HRV-16 as the model virus to illustrate the strategy and the methods for constructing and cloning the artificial cDNA copy of a full-length HRV genome, identifying the infectious cDNA clone isolates, and selecting the most vigorous cDNA clone isolate to serve as the standard parental clone for future molecular genetic study of the virus. PMID:25261313

  3. The Evolution of Human Genetic and Phenotypic Variation in Africa

    PubMed Central

    Campbell, Michael C.

    2010-01-01

    Africa is the birthplace of modern humans, and is the source of the geographic expansion of ancestral populations into other regions of the world. Indigenous Africans are characterized by high levels of genetic diversity within and between populations. The pattern of genetic variation in these populations has been shaped by demographic events occurring over the last 200,000 years. The dramatic variation in climate, diet, and exposure to infectious disease across the continent has also resulted in novel genetic and phenotypic adaptations in extant Africans. This review summarizes some recent advances in our understanding of the demographic history and selective pressures that have influenced levels and patterns of diversity in African populations. PMID:20178763

  4. [Research advances on medical genetics in China in 2015].

    PubMed

    Li, Yuanfeng; Han, Yubo; Cao, Pengbo; Meng, Jinfeng; Li, Haibei; Qin, Geng; Zhang, Feng; Jin, Guangfu; Yang, Yong; Wu, Lingqian; Ping, Jie; Zhou, Gangqiao

    2016-05-01

    Steady progress has been achieved in the medical genetics in China in 2015, as numerous original researches were published in the world's leading journals. Chinese scientists have made significant contributions to various fields of medical genetics, such as pathogenicity of rare diseases, predisposition of common diseases, somatic mutations of cancer, new technologies and methods, disease-related microRNAs (miRNAs), disease-related long non-coding RNAs (lncRNAs), disease-related competing endogenous RNAs (ceRNAs), disease-related RNA splicing and molecular evolution. In these fields, Chinese scientists have gradually formed the tendency, from common variants to rare variants, from single omic analyses to multipleomics integration analyses, from genetic discovery to functional confirmation, from basic research to clinical application. Meanwhile, the findings of Chinese scientists have been drawn great attentions of international peers. This review aims to provide an overall picture of the front in Chinese medical genetics, and highlights the important findings and their research strategy. PMID:27232486

  5. The Trustworthiness Deficit in Postgenomic Research on Human Intelligence.

    PubMed

    Richardson, Sarah S

    2015-01-01

    In the past, work on racial and ethnic variation in brain and behavior was marginalized within genetics. Against the backdrop of genetics' eugenic legacy, wide consensus held such research to be both ethically problematic and methodologically controversial. But today it is finding new opportunistic venues in a global, transdisciplinary, data-rich postgenomic research environment in which such a consensus is increasingly strained. The postgenomic sciences display worrisome deficits in their ability to govern and negotiate standards for making postgenomic claims in the transdisciplinary space between human population variation research, studies of intelligence, neuroscience, and evolutionary biology. Today some researchers are pursuing the genomics of intelligence on a newly grand scale. They are sequencing large numbers of whole genomes of people considered highly intelligent (by varying empirical and social measures) in the hope of finding gene variants predictive of intelligence. Troubling and at times outlandish futurist claims accompany this research. Scientists involved in this research have openly discussed the possibility of marketing prenatal tests for intelligence, of genetic engineering or selective embryo implantation to increase the likelihood of a high-IQ child, and of genotyping children to guide their education. In this permissive and contested environment, what would trustworthy research on the genomics of high intelligence look like? PMID:26413942

  6. Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits.

    PubMed

    Moreno-Estrada, Andrés; Gignoux, Christopher R; Fernández-López, Juan Carlos; Zakharia, Fouad; Sikora, Martin; Contreras, Alejandra V; Acuña-Alonzo, Victor; Sandoval, Karla; Eng, Celeste; Romero-Hidalgo, Sandra; Ortiz-Tello, Patricia; Robles, Victoria; Kenny, Eimear E; Nuño-Arana, Ismael; Barquera-Lozano, Rodrigo; Macín-Pérez, Gastón; Granados-Arriola, Julio; Huntsman, Scott; Galanter, Joshua M; Via, Marc; Ford, Jean G; Chapela, Rocío; Rodriguez-Cintron, William; Rodríguez-Santana, Jose R; Romieu, Isabelle; Sienra-Monge, Juan José; del Rio Navarro, Blanca; London, Stephanie J; Ruiz-Linares, Andrés; Garcia-Herrera, Rodrigo; Estrada, Karol; Hidalgo-Miranda, Alfredo; Jimenez-Sanchez, Gerardo; Carnevale, Alessandra; Soberón, Xavier; Canizales-Quinteros, Samuel; Rangel-Villalobos, Héctor; Silva-Zolezzi, Irma; Burchard, Esteban Gonzalez; Bustamante, Carlos D

    2014-06-13

    Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide. PMID:24926019

  7. 2015 Guidelines for Establishing Genetically Modified Rat Models for Cardiovascular Research

    PubMed Central

    Flister, Michael J.; Prokop, Jeremy W.; Lazar, Jozef; Shimoyama, Mary; Dwinell, Melinda; Geurts, Aron

    2015-01-01

    The rat has long been a key physiological model for cardiovascular research; most of the inbred strains having been previously selected for susceptibility or resistance to various cardiovascular diseases (CVD). These CVD rat models offer a physiologically relevant background on which candidates of human CVD can be tested in a more clinically translatable experimental setting. However, a diverse toolbox for genetically modifying the rat genome to test molecular mechanisms has only recently become available. Here, we provide a high-level description of several strategies for developing genetically modified rat models of CVD. PMID:25920443

  8. Common genetic variants influence human subcortical brain structures.

    PubMed

    Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy

    2015-04-01

    The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  9. The influence of recombination on human genetic diversity.

    PubMed

    Spencer, Chris C A; Deloukas, Panos; Hunt, Sarah; Mullikin, Jim; Myers, Simon; Silverman, Bernard; Donnelly, Peter; Bentley, David; McVean, Gil

    2006-09-22

    In humans, the rate of recombination, as measured on the megabase scale, is positively associated with the level of genetic variation, as measured at the genic scale. Despite considerable debate, it is not clear whether these factors are causally linked or, if they are, whether this is driven by the repeated action of adaptive evolution or molecular processes such as double-strand break formation and mismatch repair. We introduce three innovations to the analysis of recombination and diversity: fine-scale genetic maps estimated from genotype experiments that identify recombination hotspots at the kilobase scale, analysis of an entire human chromosome, and the use of wavelet techniques to identify correlations acting at different scales. We show that recombination influences genetic diversity only at the level of recombination hotspots. Hotspots are also associated with local increases in GC content and the relative frequency of GC-increasing mutations but have no effect on substitution rates. Broad-scale association between recombination and diversity is explained through covariance of both factors with base composition. To our knowledge, these results are the first evidence of a direct and local influence of recombination hotspots on genetic variation and the fate of individual mutations. However, that hotspots have no influence on substitution rates suggests that they are too ephemeral on an evolutionary time scale to have a strong influence on broader scale patterns of base composition and long-term molecular evolution. PMID:17044736

  10. Genetic recombination between human and animal parasites creates novel strains of human pathogen.

    PubMed

    Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

    2015-03-01

    Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT. PMID:25816228

  11. Genetic Recombination between Human and Animal Parasites Creates Novel Strains of Human Pathogen

    PubMed Central

    Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick

    2015-01-01

    Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT. PMID:25816228

  12. [Research progress on molecular genetics of forest musk deer].

    PubMed

    Jie, Hang; Zheng, Cheng-li; Wang, Jian-ming; Feng, Xiao-lan; Zeng, De-jun; Zhao, Gui-jun

    2015-11-01

    Forest musk deer is one of the large-scale farming musk deer animals with the largest population at the same time. The male musk deer can secrete valuable medicines, which has high medicinal and economic value. Due to the loss of habitat and indiscriminate hunting, the numbers of wild population specie and the distribution have been drastically reduced. Therefore, in-depth understanding of the molecular genetics progress of forest musk deer will pave a way for musk deer protection and breeding. In this review, the progress associated with the molecular marker, genetic classification, artificial breeding, musk secretion and disease in past decades were reviewed, in order to provide a theoretical basis for subsequent molecular genetic researches in forest musk deer. PMID:27097400

  13. Rapid prototyping of database systems in human genetics data collection.

    PubMed

    Gersting, J M

    1987-06-01

    This work examines some of the problems encountered in developing small and large database application systems involving human genetics data collection efforts that include data on individuals as well as family pedigree data. Rapid prototyping of a database application requires software tools to produce the application with little or no programming. Features of MEGADATS-4 that provide for rapid prototyping and for producing stand-alone applications are examined. PMID:3668405

  14. MedlinePlus: Genetic Testing

    MedlinePlus

    ... pros and cons of testing. NIH: National Human Genome Research Institute Start Here Frequently Asked Questions about Genetic Testing (National Human Genome Research Institute) Also in Spanish Genetic Testing (For ...

  15. Human genetics and genomics a decade after the release of the draft sequence of the human genome

    PubMed Central

    2011-01-01

    Substantial progress has been made in human genetics and genomics research over the past ten years since the publication of the draft sequence of the human genome in 2001. Findings emanating directly from the Human Genome Project, together with those from follow-on studies, have had an enormous impact on our understanding of the architecture and function of the human genome. Major developments have been made in cataloguing genetic variation, the International HapMap Project, and with respect to advances in genotyping technologies. These developments are vital for the emergence of genome-wide association studies in the investigation of complex diseases and traits. In parallel, the advent of high-throughput sequencing technologies has ushered in the 'personal genome sequencing' era for both normal and cancer genomes, and made possible large-scale genome sequencing studies such as the 1000 Genomes Project and the International Cancer Genome Consortium. The high-throughput sequencing and sequence-capture technologies are also providing new opportunities to study Mendelian disorders through exome sequencing and whole-genome sequencing. This paper reviews these major developments in human genetics and genomics over the past decade. PMID:22155605

  16. Genetic alterations of protein tyrosine phosphatases in human cancers

    PubMed Central

    Zhao, Shuliang; Sedwick, David; Wang, Zhenghe

    2014-01-01

    Protein tyrosine phosphatases (PTPs) are enzymes that remove phosphate from tyrosine residues in proteins. Recent whole-exome sequencing of human cancer genomes reveals that many PTPs are frequently mutated in a variety of cancers. Among these mutated PTPs, protein tyrosine phosphatase T (PTPRT) appears to be the most frequently mutated PTP in human cancers. Beside PTPN11 which functions as an oncogene in leukemia, genetic and functional studies indicate that most of mutant PTPs are tumor suppressor genes. Identification of the substrates and corresponding kinases of the mutant PTPs may provide novel therapeutic targets for cancers harboring these mutant PTPs. PMID:25263441

  17. Milestones in Medical Research, The Human Genome and ClinicalTrials.gov | NIH MedlinePlus the Magazine

    MedlinePlus

    ... turn Javascript on. Milestones in Medical Research, The Human Genome and ClinicalTrials.gov Past Issues / Fall 2010 ... milestone in understanding the genetic foundation of all human beings; the second, a comprehensive information service to ...

  18. Human Research and Complexity Theory

    ERIC Educational Resources Information Center

    Horn, James

    2008-01-01

    The disavowal of positivist science by many educational researchers has resulted in a deepening polarization of research agendas and an epistemological divide that appears increasingly difficult to span. Despite a turning away from science altogether by some, and thus toward various forms of poststructuralist inquiry, this has not held back the…

  19. Human Research Program Integrated Research Plan. Revision C

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2011-01-01

    Crew health and performance are critical to successful human exploration beyond low Earth orbit. The Human Research Program (HRP) is essential to enabling extended periods of space exploration because it provides knowledge and tools to mitigate risks to human health and performance. Risks include physiological effects from radiation and hypogravity environments, as well as unique challenges in medical support, human factors, and behavioral or psychological factors. The Human Research Program (HRP) delivers human health and performance countermeasures, knowledge, technologies and tools to enable safe, reliable, and productive human space exploration. Without HRP results, NASA will face unknown and unacceptable risks for mission success and post-mission crew health. This Integrated Research Plan (IRP) describes (1) HRP's approach and research activities that are intended to address the needs of human space exploration and serve HRP customers and (2) the method of integration for risk mitigation. The scope of the IRP is limited to the activities that can be conducted with the resources available to the HRP; it does not contain activities that would be performed if additional resources were available. The timescale of human space exploration is envisioned to take many decades. The IRP illustrates the program s research plan through the timescale of early lunar missions of extended duration.

  20. Human Subjects Research and the Physics Classroom

    NASA Astrophysics Data System (ADS)

    Kubitskey, Beth W.; Thomsen, Marshall

    2012-09-01

    Physics Education Research is a form of social science research in that it uses human subjects. As physicists we need to be aware of the ethical and legal ramifications of performing this research, taking into account the fundamental differences between working with substances and working with people. For several decades, the federal government has regulated research involving human subjects. With current procedures, a proposal soliciting federal funds for a research project involving human subjects will be flagged by the applicants institution and checked for compliance with appropriate regulations. However, there is a large body of Physics Education Research that is not federally funded and thus may not be flagged. Nevertheless, there are ethical standards that apply to this research. This paper outlines the preliminary considerations for conducting such research.

  1. The resurgence and genetic implications of New World primates in biomedical research.

    PubMed

    Ward, Joshua M; Vallender, Eric J

    2012-12-01

    There has been a recent resurgence of interest in New World monkeys within the biomedical research community, driven by both the sequencing of the common marmoset (Callithrix jacchus) genome and a growing demand for alternatives to Old World primates. New World monkeys offer attractive advantages over Old World species, including cheaper and simpler husbandry, while still maintaining a greater evolutionary proximity to humans compared with other animal models. Although numerous commonalities across primate species exist, there are also important genetic and reproductive differences that can and should play a critical role in selecting appropriate animal models. Common marmosets in particular have significantly reduced diversity at the major histocompatibility complex (MHC) loci and are born as hematopoietic chimeras. New World primates can make ideal translational models for research, but scientists must necessarily incorporate complete understandings of their genetic and phenotypic differences from humans and other model organisms. PMID:23099234

  2. RECENT ADVANCES OF GENETIC ANCESTRY TESTING IN BIOMEDICAL RESEARCH AND DIRECT TO CONSUMER TESTING

    PubMed Central

    Via, Marc; Ziv, Elad; Burchard, Esteban González

    2010-01-01

    In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several “for profit companies” are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies is still unforeseeable. PMID:19793051

  3. Teachers' Conceptions About the Genetic Determinism of Human Behaviour: A Survey in 23 Countries

    NASA Astrophysics Data System (ADS)

    Castéra, Jérémy; Clément, Pierre

    2012-07-01

    This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed teachers' conceptions. This illustrates that innatism is present in two distinct ways: in relation to individuals (e.g. genetic determinism to justify intellectual likeness between individuals such as twins) or in relation to groups of humans (e.g. genetic determinism to justify gender differences or the superiority of some human ethnic groups). A between-factor analysis discriminates between countries, showing very significant differences. There is more innatism among teachers' conceptions in African countries and Lebanon than in European countries, Brazil and Australia. Among the other controlled parameters, only two are significantly independent of the country: the level of training and the level of knowledge of biology. A co-inertia analysis shows a strong correlation between non-citizen attitudes towards and innatist conceptions of genetic determinism regarding human groups. We discuss these findings and their implications for education.

  4. Genetic Differences Between Great Apes and Humans: Implications for Human Evolution

    SciTech Connect

    Varki, Ajit

    2004-03-17

    When considering protein sequences, humans are 99-100% identical to chimpanzees and bonobos, our closest evolutionary relatives. The evolution of humans (and the unique features of our species) from a common ancestor with these great apes involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of the differences. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly in relationship to a family of cell surface molecules called sialic acids. These differences have implications for the human condition, ranging from susceptibility or resistance to microbial pathogens; effects on endogenous receptors in the immune system; potential effects on placental signaling; the expression of oncofetal antigens in cancers; consequences of dietary intake of animal foods; and the development of the mammalian brain. This talk will provide an overview of these and other genetic differences between humans and great apes, with attention to differences potentially relevant to the evolution of humans.

  5. The autosomal genetic control of sexually dimorphic traits in humans is largely the same across the sexes.

    PubMed

    Kassam, Irfahan; McRae, Allan F

    2016-01-01

    There are substantial phenotypic differences between the male and female human. Several complex traits have recently been tested to see whether these phenotypic differences are explained by differences in genetic control between males and females. While some differences in genetic control between males and females are detected, overall the results demonstrate that the genetic control of complex traits in humans is largely the same across the sexes.Please see related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1025-x. PMID:27496044

  6. [Teaching design and practice of human blood type traits in genetics comprehensive laboratory course].

    PubMed

    Zhao, Jian; Hu, Dongmei; Yu, Dade; Dong, Mingliang; Li, Yun; Fan, Yingming; Wang, Yanwei; Zhang, Jinfeng

    2016-05-01

    Comprehensive laboratory courses, which enable students to aptly apply theoretic knowledge and master experiment skills, play an important role in the present educational reform of laboratory courses. We utilized human ABO blood type as the experimental subject, and designed the experiment--"Molecular Genotyping of Human ABO Blood Type and Analysis of Population Genetic Equilibrium". In the experiment, DNA in mucosal cells is extracted from students' saliva, and each student's genotype is identified using a series of molecular genetics technologies, including PCR amplification of target fragments, enzymatic digestion, and electrophoretic separation. Then, taking the whole class as an analogous Mendel population, a survey of genotype frequency of ABO blood type is conducted, followed with analyses of various population genetic parameters using Popgene. Through the open laboratory course, students can not only master molecular genetic experimental skills, but also improve their understanding of theoretic knowledge through independent design and optimization of molecular techniques. After five years of research and practice, a stable experimental system of molecular genetics has been established to identify six genotypes of ABO blood types, namely I(A)I(A), I(A)i, I(B)I(B), I(B)i, I(A)I(B) and ii. Laboratory courses of molecular and population genetics have been integrated by calculating the frequencies of the six genotypes and three multiple alleles and testing population genetic equilibrium. The goal of the open laboratory course with independent design and implementation by the students has been achieved. This laboratory course has proved effective and received good reviews from the students. It could be applied as a genetics laboratory course for the biology majors directly, and its ideas and methods could be promoted and applied to other biological laboratory courses. PMID:27232494

  7. Education and Human Resources Research at Rand.

    ERIC Educational Resources Information Center

    Pincus, John; Pascal, Anthony H.

    Research projects are reviewed which are representative of the Rand Corporation's education work as it affects policy, management, and research methods. Significant characteristics or results of the projects and studies are briefly described under general categories of education studies and human resources research. Education studies are grouped…

  8. Quantitative PCR for genetic markers of human fecal pollution.

    PubMed

    Shanks, Orin C; Kelty, Catherine A; Sivaganesan, Mano; Varma, Manju; Haugland, Richard A

    2009-09-01

    Assessment of health risk and fecal bacterial loads associated with human fecal pollution requires reliable host-specific analytical methods and a rapid quantification approach. We report the development of quantitative PCR assays for quantification of two recently described human-specific genetic markers targeting Bacteroidales-like cell surface-associated genes. Each assay exhibited a range of quantification from 10 to 1 x 10(6) copies of target DNA. For each assay, internal amplification controls were developed to detect the presence or absence of amplification inhibitors. The assays predominantly detected human fecal specimens and exhibited specificity levels greater than 97% when tested against 265 fecal DNA extracts from 22 different animal species. The abundance of each human-specific genetic marker in primary effluent wastewater samples collected from 20 geographically distinct locations was measured and compared to quantities estimated by real-time PCR assays specific for rRNA gene sequences from total Bacteroidales and enterococcal fecal microorganisms. Assay performances combined with the prevalence of DNA targets in sewage samples provide experimental evidence supporting the potential application of these quantitative methods for monitoring fecal pollution in ambient environmental waters. PMID:19592537

  9. Genetic and phenotypic consequences of introgression between humans and Neanderthals.

    PubMed

    Wills, Christopher

    2011-01-01

    Strong evidence for introgression of Neanderthal genes into parts of the modern human gene pool has recently emerged. The evidence indicates that some populations of modern humans have received infusions of genes from two different groups of Neanderthals. One of these Neanderthal groups lived in the Middle East and Central Europe and the other group (the Denisovans) is known to have lived in Central Asia and was probably more widespread. This review examines two questions. First, how were these introgressions detected and what does the genetic evidence tell us about their nature and extent? We will see that an unknown but possibly large fraction of the entire Neanderthal gene complement may have survived in modern humans. Even though each modern European and Asian carries only a few percent of genes that can be traced back to Neanderthals, different individuals carry different subgroups of these introgressed genes. Second, what is the likelihood that this Neanderthal genetic legacy has had phenotypic effects on modern humans? We examine evidence for and against the possibility that some of the surviving fragments of Neanderthal genomes have been preserved by natural selection, and we explore the ways in which more evidence bearing on this question will become available in the future. PMID:22099691

  10. Ethical use of tissue samples in genetic research.

    PubMed

    Azarow, Kenneth S; Olmstead, Francis L; Hume, Roderick F; Myers, Jerome; Calhoun, Bryon C; Martin, Laura S

    2003-06-01

    Many centrally based cancer protocols have begun to address the ethical issues concerning tissue banking for genetic research. A multidisciplinary subcommittee of the Madigan Army Medical Center Institutional Review Board was established to determine the scope of the problem and offer a concise, user-friendly policy with guidelines on how to control and monitor the use of stored tissue for future genetic and molecular research. Our institution participates in 69 Southern Oncology Group or National Surgical Adjuvant Breast and Bowel Project protocols and 47 Children's Oncology Group protocols. Of these protocols, 22 of 69 and 36 of 47, respectively, asked for tissue to be stored for future biologic study. Only 4 of 69 and 3 of 47, respectively, deal with specific consent for future genetic/biologic research. The multidisciplinary committee developed a policy that dealt with the following areas: exempt status, waived consent, informed consent, deceased status, family studies, and information flow. An algorithm was created to establish a system of checks and balances concerning privacy, protection and an appeals process. PMID:12834131

  11. Research on automatic human chromosome image analysis

    NASA Astrophysics Data System (ADS)

    Ming, Delie; Tian, Jinwen; Liu, Jian

    2007-11-01

    Human chromosome karyotyping is one of the essential tasks in cytogenetics, especially in genetic syndrome diagnoses. In this thesis, an automatic procedure is introduced for human chromosome image analysis. According to different status of touching and overlapping chromosomes, several segmentation methods are proposed to achieve the best results. Medial axis is extracted by the middle point algorithm. Chromosome band is enhanced by the algorithm based on multiscale B-spline wavelets, extracted by average gray profile, gradient profile and shape profile, and calculated by the WDD (Weighted Density Distribution) descriptors. The multilayer classifier is used in classification. Experiment results demonstrate that the algorithms perform well.

  12. Common genetic variants influence human subcortical brain structures

    PubMed Central

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  13. Human genetic mapping studies using single sperm typing

    SciTech Connect

    Hubert, R.S.

    1993-01-01

    Sperm typing is a powerful technique that uses the polymerase chain reaction (PCR) to analyze DNA sequences within single sperm cells in order to construct genetic maps. This methodology was used to estimate the recombination fraction between D3S2 and D3S2 which was found to be 0.28 (95% CI = 0.20-0.36). Pedigree analysis was unable to determine genetic distance between these two markers due to their low informativeness. We also showed that dinucleotide and tetranucleotide repeat polymorphisms can be analyzed in single cells without using radioactivity or denaturing gels. This provides a rich new source of DANA polymorphisms for genetic mapping by sperm typing. In addition, an approach that uses the sperm typing methodology is described that can define the physical boundaries of meiotic recombination hotspots. The hotspot at 4p16.3 near the Huntington disease gene was localized to an interval between D4S10 and D4S126. These studies demonstrated the usefulness of sperm typing as a tool for the study of human genetic.

  14. [The genetics and the dignity of the human being].

    PubMed

    Jouve de Barreda, Nicolás

    2013-01-01

    The biological elements of man are not sufficient to confront the bioethical questions around the person concept, but are necessary to accurately define the properties of the human beings and the theological, philosophical and legal aspects that are attributable to each person. The human being is a singular being. Indeed, the coexistence of two dimensions of different nature, material and spiritual, is the most important difference between the man and the rest of living beings. Moreover, in man appears a new characteristic, unique between the living beings, the ethical component. The values and guidelines of the moral and ethical behavior of the human being must be considered of natural origin since they have contributed to the success and survival of the species. The man is not only Homo sapiens but also Homo moralis. The recognition of fault, self-control, solidarity, love, generosity, altruism and honesty, among others, are innate qualities in the human beings. The unit of the human species demands the respect and the consideration of the same dignity for all its members, but only for its members. The philosophical anthropology emphasizes the singularity of each human being, each person. This agrees totally with the data of the science, which emphasize the individual and singular genetic identity of each human being. PMID:23745822

  15. Accessible Genetics Research Ethics Education (AGREE): A Web-Based Program for IRBs and Investigators

    SciTech Connect

    Sugarman, Jeremy; Lee, Linda

    2006-03-31

    The primary objective of this project was to design and evaluate a series of web-based educational modules on genetics research ethics for members of Institutional Review Boards and investigators to facilitate the development and oversight of important research that is sensitive to the relevant ethical, legal and social issues. After a needs assessment was completed in March of 2003, five online educational modules on the ethics of research in genetics were developed, tested, and made available through a host website for AGREE: http://agree.mc.duke.edu/index.html. The 5 modules are: (1) Ethics and Genetics Research in Populations; (2) Ethics in Behavioral Genetics Research; (3) Ethical Issues in Research on Gene-Environment Interactions; (4) Ethical Issues in Reproductive Genetics Research; and (5) Ethical Issues in Diagnostic and Therapeutic Research. The development process adopted a tested approach used at Duke University School of Medicine in providing education for researchers and IRB members, supplementing it with expert input and a rigorous evaluation. The host website also included a description of the AGREE; short bios on the AGREE Investigators and Expert Advisory Panel; streaming media of selected presentations from a conference, Working at the Frontiers of Law and Science: Applications of the Human Genome held October 2-3, 2003, at the University of North Carolina at Chapel Hill; and links to online resources in genomics, research ethics, ethics in genomics research, and related organizations. The web site was active beginning with the posting of the first module and was maintained throughout the project period. We have also secured agreement to keep the site active an additional year beyond the project period. AGREE met its primary objective of creating web-based educational modules related to the ethical issues in genetics research. The modules have been disseminated widely. While it is clearly easier to judge the quality of the educational experience

  16. [Influence of genetic factors on human sexual orientation. Review].

    PubMed

    Rodríguez-Larralde, Alvaro; Paradisi, Irene

    2009-09-01

    Human sexual orientation is a complex trait, influenced by several genes, experiential and sociocultural factors. These elements interact and produce a typical pattern of sexual orientation towards the opposite sex. Some exceptions exist, like bisexuality and homosexuality, which seem to be more frequent in males than females. Traditional methods for the genetic study of behavior multifactorial characteristics consist in detecting the presence of familial aggregation. In order to identify the importance of genetic and environmental factors in this aggregation, the concordance of the trait for monozygotic and dizygotic twins and for adopted sibs, reared together and apart, is compared. These types of studies have shown that familial aggregation is stronger for male than for female homosexuality. Based on the threshold method for multifactorial traits, and varying the frequency of homosexuality in the population between 4 and 10%, heritability estimates between 0.27 and 0.76 have been obtained. In 1993, linkage between homosexuality and chromosomal region Xq28 based on molecular approaches was reported. Nevertheless, this was not confirmed in later studies. Recently, a wide search of the genome has given significant or close to significant linkage values with regions 7q36, 8p12 and 10q26, which need to be studied more closely. Deviation in the proportion of X chromosome inactivation in mothers of homosexuals seems to favor the presence of genes related with sexual orientation in this chromosome. There is still much to be known about the genetics of human homosexuality. PMID:19961060

  17. Genetic instability in human ovarian cancer cell lines.

    PubMed Central

    Orth, K; Hung, J; Gazdar, A; Bowcock, A; Mathis, J M; Sambrook, J

    1994-01-01

    We have analyzed the stability of microsatellites in cell lines derived from human ovarian cancers and found that 5 out of 10 of the ovarian tumor cell lines are genetically unstable at the majority of the loci analyzed. In clones and subclones derived serially from one of these cell lines (2774; serous cystadenocarcinoma), a very high proportion of microsatellites distributed in many different regions of the genome change their size in a mercurial fashion. We conclude that genomic instability in ovarian tumors is a dynamic and ongoing process whose high frequency may have been previously underestimated by PCR-based allelotyping of bulk tumor tissue. We have identified the source of the genetic instability in one ovarian tumor as a point mutation (R524P) in the human mismatch-repair gene MSH2 (Salmonella MutS homologue), which has recently been shown to be involved in hereditary nonpolyposis colorectal cancer. Patient 2774 was a 38-year-old heterozygote, and her normal tissue carried both mutant and wild-type alleles of the human MSH2 gene. However the wild-type allele was lost at some point early during tumorigenesis so that DNA isolated either from the patient's ovarian tumor or from the 2774 cell line carries only the mutant allele of the human MSH2 gene. The genetic instability observed in the tumor and cell line DNA, together with the germ-line mutation in a mismatch-repair gene, suggest that the MSH2 gene is involved in the onset and/or progression in a subset of ovarian cancer. Images PMID:7937795

  18. The ADAMTS(L) family and human genetic disorders.

    PubMed

    Le Goff, Carine; Cormier-Daire, Valérie

    2011-10-15

    ADAMTS designates a family of 19 secreted enzymes, whose the first member ADAMTS1 was described in 1997. The ADAMTS family has a role in extracellular matrix degradation and turn over and has previously been involved in various human biological processes, including connective tissue structure, cancer, coagulation, arthritis, angiogenesis and cell migration. More recently, the ADAMTS(L) family has been described, sharing the same ancillary domain but distinct by the absence of any enzyme activity. Mutations in ADAMTS13, ADAMTS2, ADAMTS10, ADAMTS17, ADAMTSL2 and ADAMTSL4 have been identified in distinct human genetic disorders ranging from thrombotic thrombocytopenic purpura to acromelic dysplasia. The aim of our review was to emphasize the role of this family in the extracellular matrix based on human phenotypes so far identified in relation with ADAMTS(L) mutations. PMID:21880666

  19. Meganucleases Revolutionize the Production of Genetically Engineered Pigs for the Study of Human Diseases.

    PubMed

    Redel, Bethany K; Prather, Randall S

    2016-04-01

    Animal models of human diseases are critically necessary for developing an in-depth knowledge of disease development and progression. In addition, animal models are vital to the development of potential treatments or even cures for human diseases. Pigs are exceptional models as their size, physiology, and genetics are closer to that of humans than rodents. In this review, we discuss the use of pigs in human translational research and the evolving technology that has increased the efficiency of genetically engineering pigs. With the emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein 9 system technology, the cost and time it takes to genetically engineer pigs has markedly decreased. We will also discuss the use of another meganuclease, the transcription activator-like effector nucleases , to produce pigs with severe combined immunodeficiency by developing targeted modifications of the recombination activating gene 2 (RAG2).RAG2mutant pigs may become excellent animals to facilitate the development of xenotransplantation, regenerative medicine, and tumor biology. The use of pig biomedical models is vital for furthering the knowledge of, and for treating human, diseases. PMID:26516165

  20. Sarcoptes scabiei mites in humans are distributed into three genetically distinct clades.

    PubMed

    Andriantsoanirina, V; Ariey, F; Izri, A; Bernigaud, C; Fang, F; Charrel, R; Foulet, F; Botterel, F; Guillot, J; Chosidow, O; Durand, R

    2015-12-01

    Scabies is an ectoparasitic infestation caused by the mite Sarcoptes scabiei. Currently, S. scabiei is taxonomically divided into different varieties on the basis of host origin. Genetics-based research on scabies has been conducted, but the data on genetic diversity of populations of this mite in humans in Europe are lacking. We evaluated the genetic diversity of populations of S. scabiei. A large series of mites obtained from humans in France and the data of mites from various hosts and geographical areas retrieved from GenBank were included to investigate whether mites are divided into distinct populations. The study of cytochrome c oxidase subunit 1 gene polymorphisms were found to be best suited for phylogenetic analysis. S. scabiei mites were distributed into three genetically distinct clades, with most mites clustering in clades B and C. The Fst value and the Nm value calculated for mites included in clades B and C indicated a strong population structure and a very low gene flow between mites of those clades. The results of the present study not only support the rejection of the hypothesis of panmixia for S. scabiei in humans but also suggest that mites belonging to different clades are genetically isolated. Moreover, the results suggest that the subdivision of S. scabies in varieties according to animal or human hosts is not warranted. In conclusion, S. scabiei mites in humans do not constitute a homogeneous population. Further investigations are now required to assess whether different clinical forms of scabies are associated with particular haplotypes or clades. PMID:26278670

  1. Human Genetic Disorders and Knockout Mice Deficient in Glycosaminoglycan

    PubMed Central

    2014-01-01

    Glycosaminoglycans (GAGs) are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs. PMID:25126564

  2. [Genetically modified foods. Advantages and human health risks].

    PubMed

    Filip, Lorena; Miere, Doina; Indrei, L L

    2004-01-01

    One of the most important issue with which the mankind is confronting now is related to the quantitatively as well as qualitatively assurance of the food supply necessary for human species existence. In this context, by means of genetic engineering, modified genetic organisms were obtained. In the first stage, plant crops with high productivity and resistant against diseases and pests were obtained. After that, food products having modified organoleptic properties and high nutrition values were produced. The main problem concerning the long-term consumption of these products is their toxicity, which until now was not confirmed or denied. For this reason, tests are necessary to be made in order to stipulate and prevent these effects. PMID:16004228

  3. Not so simple: a quasi-experimental study of how researchers adjudicate genetic research results

    PubMed Central

    Hayeems, Robin Zoe; Miller, Fiona Alice; Li, Li; Bytautas, Jessica Peace

    2011-01-01

    Ethicists contend that researchers are obliged to report genetic research findings to individual study participants when they are clinically significant, that is, when they are clinically useful or personally meaningful to participants. Yet whether such standards are well understood and can be consistently applied remains unknown. We conducted an international, cross-sectional survey of cystic fibrosis (CF) and autism genetics researchers using a quasi-experimental design to explore factors influencing researchers' judgments. Eighty percent of researchers agreed, in principle, that clinically significant findings should be reported to individual participants. Yet judgments about when a specific finding was considered clinically significant or warranted reporting varied by scientific factors (replication, robustness, intentionality, and disease context), capacity of the research team to explain the results, and type of research ethics guidance. Further, judgments were influenced by the researchers' disease community (autism or CF), their primary role (clinical, molecular, statistical) and their beliefs regarding a general reporting obligation. In sum, judgments about the clinical significance of genetic research results, and about whether they should be reported, are influenced by scientific parameters as well as contextual factors related to the specific research project and the individual researcher. These findings call into question the assumption that the conditions under which an obligation to disclose arises are uniformly understood and actionable. Adjudicating the clinical readiness of provisional data may be a responsibility better suited to evaluative experts at arms' length of the provisional data in question, rather than a responsibility imposed upon researchers themselves. PMID:21407262

  4. Genetics Behind Barbed Wire: Masuo Kodani, Émigré Geneticists, and Wartime Genetics Research at Manzanar Relocation Center

    PubMed Central

    Smocovitis, Vassiliki Betty

    2011-01-01

    This article explores the sociopolitical backdrop of genetics research during the politically turbulent decades of the mid-20th century that saw the persecution, displacement, and relocation of unpopular minorities in both the United States and Europe. It explores how geneticists in the United States accommodated these disruptions through formal and informal émigré networks and how the subsequent war affected their research programs and their lives. It does so by focusing on the career and life of geneticist Masuo Kodani, who, as a Japanese American, found himself conducting unexpected cytogenetics research in Manzanar, a “relocation center,” or internment camp, located in the California desert, after the attack on Pearl Harbor. After the war, Kodani's subsequent career continued to be shaped by his experiences as a Japanese American and by the specific skills as a cytogeneticist that he demonstrated at a critical period in the history of 20th-century genetics. His many relocations in search of employment culminated in his work with the Atomic Bomb Casualty Commission on human chromosomes, for which he is best known. PMID:21307394

  5. Trends in human factors research.

    PubMed

    Cohen, A

    1982-06-01

    As just described, NIOSH's ongoing and new activities offer varied approaches and opportunities for gaining insights into human factor and ergonomic aspects of workplace hazards and their control. They represent a blend of surveillance work (re, the prevalence survey of chronic trauma risk), in-depth studies of known workplace problems emphasizing undue physical and psychological job demands and their consequences (re, stress from machine-paced work and musculoskeletal problems from repeated lifting), first evaluations of the consequences of new technology (re, use of video display terminals), and finally problem-solving efforts (re, the evaluation and field testing of the work practice guide for reducing lifting hazards and control technology assessment). Taken together, these efforts signal an important new commitment by NIOSH in making workplaces safe for our working men and women. PMID:6896907

  6. Aluminum, the genetic apparatus of the human CNS and Alzheimer's disease (AD).

    PubMed

    Pogue, A I; Lukiw, W J

    2016-06-01

    The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex and intricate process as genetic operations such as transcription involve the very rapid translocation and polymerization of ribonucleotides using RNA polymerases, accessory transcription protein complexes and other interrelated chromatin proteins and genetic factors. As both free ribonucleotides and polymerized single-stranded RNA chains, ribonucleotides are highly charged with phosphate, and this genetic system is extremely vulnerable to disruption by a large number of electrostatic forces, and primarily by cationic metals such as aluminum. Aluminum has been shown by independent researchers to be particularly genotoxic to the genetic apparatus, and it has become reasonably clear that aluminum disturbs genetic signaling programs in the CNS that bear a surprising resemblance to those observed in Alzheimer's disease (AD) brain. This paper will focus on a discussion of two molecular-genetic aspects of aluminum genotoxicity: (1) the observation that micro-RNA (miRNA)-mediated global gene expression patterns in aluminum-treated transgenic animal models of AD (Tg-AD) strongly resemble those found in AD; and (2) the concept of "human biochemical individuality" and the hypothesis that individuals with certain gene expression patterns may be especially sensitive and perhaps predisposed to aluminum genotoxicity. PMID:26969391

  7. Fruit Flies Help Human Sleep Research

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Fruit Flies Help Human Sleep Research Past Issues / Summer ... courtesy of NIGMS Neuroscientist Chiara Cirelli uses experimental fruit flies to study sleep. Although it may be ...

  8. Fruit Flies Help Human Sleep Research

    MedlinePlus

    ... Current Issue Past Issues Fruit Flies Help Human Sleep Research Past Issues / Summer 2007 Table of Contents ... Chiara Cirelli uses experimental fruit flies to study sleep. Although it may be tough to imagine a ...

  9. Genetically modified crops: environmental and human health concerns.

    PubMed

    Azevedo, João Lúcio; Araujo, Welington Luiz

    2003-11-01

    About 10,000 years ago subsistence farmers started to domesticate plants and it was only much later, after the discovery of the fundaments of genetics, those organisms were submitted to rational genetic improvement mainly by selecting of traits of interest. Breeders used appropriate gene combinations to produce new animal races, plant varieties and hybrids, as well as improved microorganisms such as yeasts. After the introduction of recombinant DNA techniques, the transfer of DNA between species belonging to different genera, families or kingdoms became possible. The release of transgenic plants has aroused debates about several aspects of the environmental and human risks that could result from the introduction of genetically modified crops. Less effort has been dedicated to evaluate the impact of transgenic plants on their associated microorganisms, some of which (e.g. nitrogen-fixing bacteria, mycorrhizal fungi and endophytic microbiota) are extremely important for the survival of the plant. Investigations have been made regarding the horizontal transfer of genetic material between transgenic plants and microorganisms and on the disturbance of useful symbiotic associations between plants and endophytic, epiphytic and rhizosphere communities. In most cases the results do no show any adverse effect of transgenic plants on autochthonous plant-associated microorganisms. Results from our laboratory show small changes caused by genetically modified endophytic bacteria on the indigenous endophytic population of the sweet orange Citrus sinensis. In tests using appropriated fungal strains preliminary results using extracts from transgenic plants indicate that these plants do not affect haploidization, mitotic crossing-over, mutation rate or chromosomal alterations. PMID:14644324

  10. A Genetic Basis for Mechanosensory Traits in Humans

    PubMed Central

    Frenzel, Henning; Bohlender, Jörg; Pinsker, Katrin; Wohlleben, Bärbel; Tank, Jens; Lechner, Stefan G.; Schiska, Daniela; Jaijo, Teresa; Rüschendorf, Franz; Saar, Kathrin; Jordan, Jens; Millán, José M.; Gross, Manfred; Lewin, Gary R.

    2012-01-01

    In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A. PMID:22563300

  11. Key concepts in human genetics: understanding the complex phenotype.

    PubMed

    Gibson, William T

    2009-01-01

    The recent sequencing of a reference human genome has generated a large number of DNA-based tools, which are being used to locate genes that contribute to disease. These tools have also enabled studies of the genetics of non-disease traits such as athletic fitness. Sport scientists should keep in mind three major factors when designing such studies and interpreting the literature. First of all, the methods used to assign a biological trait (be it performance related or disease related) to a specific gene are not as powerful as is commonly believed. Second, the methods used are thought to be more robust for disease-related traits than for normal physical characteristics, likely because there are many more biological factors contributing to the latter. Third, additional levels of variability continue to be uncovered in the human genome; these may ultimately contribute more to physical differences between human beings than the levels studied over the past decade. This introductory chapter will aim to equip the reader with the necessary vocabulary to understand and interpret genetic studies targeted to sport fitness and sport-related injury. PMID:19696504

  12. Educational Research: The Importance of the Humanities

    ERIC Educational Resources Information Center

    Smith, Richard

    2015-01-01

    It is one sign of the lack of understanding of the value of the humanities, to educational research and inquiry as well as to our world more widely, that such justifications of them as are offered frequently take a crudely instrumental form. The humanities (which in this essay are not distinguished from the arts) are welcomed insofar as they are…

  13. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    PubMed

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. PMID:24878678

  14. Genetic Differences Between Humans and Great Apes -- Implications for the Evolution of Humans

    NASA Astrophysics Data System (ADS)

    Varki, Ajit

    2004-06-01

    At the level of individual protein sequences, humans are 97-100% identical to the great apes, our closest evolutionary relatives. The evolution of humans (and of human intelligence) from a common ancestor with the chimpanzee and bonobo involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of any differences found. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly with respect to a family of cell surface molecules called sialic acids, as well as in the metabolism of thyroid hormones. The hormone differences have potential consequences for human brain development. The differences in sialic acid biology have multiple implications for the human condition, ranging from susceptibility or resistance to microbial pathogens, effects on endogenous receptors in the immune system, and potential effects on placental signaling, expression of oncofetal antigens in cancers, consequences of dietary intake of animal foods, and development of the mammalian brain.

  15. New technologies in molecular genetics: the impact on epilepsy research.

    PubMed

    Helbig, Ingo

    2014-01-01

    Technical advances in the last decade have finally enabled researchers to identify epilepsy-associated genetic variants by querying virtually the entire genome. In the first decade of the twenty-first century, this technical revolution began with the advent of array comparative genomic hybridization and single nucleotide polymorphism arrays. These technologies made it possible for the first time to screen for common genetic variants and rare small deletions and duplications, referred to as microdeletions and microduplications. More recently, the repertoire of technologies has expanded to exome-wide and genome-wide sequencing approaches. These technologies led to a virtual explosion of gene identifications both in familial cases and in rare severe epilepsies, referred to as epileptic encephalopathies. This chapter aims to provide an overview of the achievements of these new technologies and the challenges that the field is currently facing. PMID:25194493

  16. Genetics and Human Agency: Comment on Dar-Nimrod and Heine (2011)

    ERIC Educational Resources Information Center

    Turkheimer, Eric

    2011-01-01

    Dar-Nimrod and Heine (2011) decried genetic essentialism without denying the importance of genetics in the genesis of human behavior, and although I agree on both counts, a deeper issue remains unaddressed: how should we adjust our cognitions about our own behavior in light of genetic influence, or is it perhaps not necessary to take genetics into…

  17. Discovery and resolve: the Human Genetics Society of Australasia Oration 2011.

    PubMed

    Pearn, John

    2011-10-01

    Human genetics spans every facet of biology from molecular science, through laboratory and clinical practice, to psychology and anthropology. In each of these areas, the history of human genetics has been punctuated by paradigm shifts in knowledge. Each such new concept has been received with skepticism, often with perplexity, and sometimes with frank incredulity. Such comprise the datum milestones along the path leading to our present corpus of genetic knowledge. In parallel to the personal threats to Copernicus and Galileo in the field of astronomy in the 17th century, almost all genetic discoveries of the 19th and 20th centuries were seen as challenges to the received wisdom, and sometimes the social order, of their time and place. Researchers, scientists and clinicians encountering such new and often-heretical paradigm shifts have required considerable resolve to promote and publish their work. Just as in the field of astronomy, new directions in genetics have threatened not only the reputations and sometimes the careers of scientists, but also have been challenges to fundamental religious and sociological beliefs in society more broadly. Examples followed the discovery of biological sexual dimorphism (in plants as well as animals) by Nehemiah Grew (1641-1712). Darwinian evolution, Mendel's First and Second Laws, the existence of mitochondrial genes, apoptosis and its genetic basis, and uniparental disomy are more recent examples. Many of these new revelations, which today have led to the current understanding of fundamental biology, were discovered by individuals working in relative isolation. To promote and publish findings that fundamentally challenge received wisdom continues to require considerable resolve, if not courage. Herein lies a message for all clinicians and researchers. PMID:21962129

  18. Detecting genetic drift versus selection in human evolution

    PubMed Central

    Ackermann, Rebecca Rogers; Cheverud, James M.

    2004-01-01

    Recent paleoanthropological discoveries reveal a diverse, potentially speciose human fossil record. Such extensive morphological diversity results from the action of divergent evolutionary forces on an evolving lineage. Here, we apply quantitative evolutionary theory to test whether random evolutionary processes alone can explain the morphological diversity seen among fossil australopith and early Homo crania from the Plio–Pleistocene. We show that although selection may have played an important role in diversifying hominin facial morphology in the late Pliocene, this is not the case during the early evolution of the genus Homo, where genetic drift was probably the primary force responsible for facial diversification. PMID:15604148

  19. Human research ethics committees in technical universities.

    PubMed

    Koepsell, David; Brinkman, Willem-Paul; Pont, Sylvia

    2014-07-01

    Human research ethics has developed in both theory and practice mostly from experiences in medical research. Human participants, however, are used in a much broader range of research than ethics committees oversee, including both basic and applied research at technical universities. Although mandated in the United States, the United Kingdom, Canada, and Australia, non-medical research involving humans need not receive ethics review in much of Europe, Asia, Latin America, and Africa. Our survey of the top 50 technical universities in the world shows that, where not specifically mandated by law, most technical universities do not employ ethics committees to review human studies. As the domains of basic and applied sciences expand, ethics committees are increasingly needed to guide and oversee all such research regardless of legal requirements. We offer as examples, from our experience as an ethics committee in a major European technical university, ways in which such a committee provides needed services and can help ensure more ethical studies involving humans outside the standard medical context. We provide some arguments for creating such committees, and in our supplemental article, we provide specific examples of cases and concerns that may confront technical, engineering, and design research, as well as outline the general framework we have used in creating our committee. PMID:25746787

  20. Indiana Health Science Teachers: Their Human Genetics/Bioethics Educational Needs.

    ERIC Educational Resources Information Center

    Hendrix, Jon R.; And Others

    1982-01-01

    Results from a human genetics/bioethics needs assessment questionnaire (N = 124 out of 300) mailed to Indiana health teachers are reported. Genetic topics and human genetic diseases/defects included in health science instruction are listed in two tables. Responses to 16 science/society statements (and statements themselves) are also reported. (SK)

  1. Alu repeats as markers for human population genetics

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M.; Bazan, H.

    1993-09-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

  2. Comparative Genetics: Synergizing Human and NOD Mouse Studies for Identifying Genetic Causation of Type 1 Diabetes

    PubMed Central

    Driver, John P.; Chen, Yi-Guang; Mathews, Clayton E.

    2012-01-01

    Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come. PMID:23804259

  3. Mutation and Human Exceptionalism: Our Future Genetic Load.

    PubMed

    Lynch, Michael

    2016-03-01

    Although the human germline mutation rate is higher than that in any other well-studied species, the rate is not exceptional once the effective genome size and effective population size are taken into consideration. Human somatic mutation rates are substantially elevated above those in the germline, but this is also seen in other species. What is exceptional about humans is the recent detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition, potentially measurable on the timescale of a few generations in westernized societies, and because the brain is a particularly large mutational target, this is of particular concern. Ultimately, the price will have to be covered by further investment in various forms of medical intervention. Resolving the uncertainties of the magnitude and timescale of these effects will require the establishment of stable, standardized, multigenerational measurement procedures for various human traits. PMID:26953265

  4. Mutation and Human Exceptionalism: Our Future Genetic Load

    PubMed Central

    Lynch, Michael

    2016-01-01

    Although the human germline mutation rate is higher than that in any other well-studied species, the rate is not exceptional once the effective genome size and effective population size are taken into consideration. Human somatic mutation rates are substantially elevated above those in the germline, but this is also seen in other species. What is exceptional about humans is the recent detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition, potentially measurable on the timescale of a few generations in westernized societies, and because the brain is a particularly large mutational target, this is of particular concern. Ultimately, the price will have to be covered by further investment in various forms of medical intervention. Resolving the uncertainties of the magnitude and timescale of these effects will require the establishment of stable, standardized, multigenerational measurement procedures for various human traits. PMID:26953265

  5. The brave new era of human genetic testing.

    PubMed

    Bandelt, Hans-Jürgen; Yao, Yong-Gang; Richards, Martin B; Salas, Antonio

    2008-11-01

    The commercialization of 'big science' is in full swing, leading to situations in which the ethical principles of academia are beginning to be compromised. This is exemplified by the profitable business of genetic ancestry testing. The goals of this sort of 'big science' are not necessarily in any way novel, however. In particular, large genotyping projects have a certain start-up time when their design is frozen in, so that the projects often lag behind the development of genetic knowledge. On the other hand, extremely provisional knowledge about potential disease markers is being rapidly turned into questionable 'tests', purporting to determine risk factors for complex disorders, by private companies that are eager to get their share of a profitable market of the future. The flow of money generated by such concerns looks likely to erode traditional research operations and small-scale projects, which risk becoming pebbles on the 'big science' landscape. PMID:18937378

  6. Human Experimentation: Impact on Health Education Research.

    ERIC Educational Resources Information Center

    Vacalis, T. Demetri; Griffis, Kathleen

    1980-01-01

    The problems of the use of humans as subjects of medical research and the protection of their rights are discussed. Issues include the use of informed consent, the evaluation of risks and benefits, and the review of research plans by a committee. (JD)

  7. MedlinePlus: Genetic Counseling

    MedlinePlus

    ... Here Frequently Asked Questions about Genetic Counseling (National Human Genome Research Institute) Genetic Counseling (Centers for Disease Control and Prevention) Genetic Counseling (March of Dimes Birth Defects Foundation) Also in Spanish Making Sense of ...

  8. Human Research Program: 2010 Annual Report

    NASA Technical Reports Server (NTRS)

    2010-01-01

    2010 was a year of solid performance for the Human Research Program in spite of major changes in NASA's strategic direction for Human Spaceflight. Last year, the Program completed the final steps in solidifying the management foundation, and in 2010 we achieved exceptional performance from all elements of the research and technology portfolio. We transitioned from creating building blocks to full execution of the management tools for an applied research and technology program. As a team, we continue to deliver the answers and technologies that enable human exploration of space. While the Agency awaits strategic direction for human spaceflight, the Program is well positioned and critically important to helping the Agency achieve its goals.

  9. From Human Genetics and Genomics to Pharmacogenetics and Pharmacogenomics: Past Lessons, Future Directions

    PubMed Central

    Nebert, Daniel W.; Zhang, Ge; Vesell, Elliot S.

    2009-01-01

    A brief history of human genetics and genomics is provided, comparing recent progress in those fields with that in pharmacogenetics and pharmacogenomics, which are subsets of genetics and genomics, respectively. Sequencing of the entire human genome, the mapping of common haplotypes of single-nucleotide polymorphisms (SNPs), and cost-effective genotyping technologies leading to genome-wide association (GWA) studies—have combined convincingly in the past several years to demonstrate the requirements needed to separate true associations from the plethora of false positives. While research in human genetics has moved from monogenic to oligogenic to complex diseases, its pharmacogenetics branch has followed, usually a few years behind. The continuous discoveries, even today, of new surprises about our genome cause us to question reviews declaring that “personalized medicine is almost here” or that “individualized drug therapy will soon be a reality.” As summarized herein, numerous reasons exist to show that an “unequivocal genotype” or even an “unequivocal phenotype” is virtually impossible to achieve in current limited-size studies of human populations. This problem (of insufficiently stringent criteria) leads to a decrease in statistical power and, consequently, equivocal interpretation of most genotype-phenotype association studies. It remains unclear whether personalized medicine or individualized drug therapy will ever be achievable by means of DNA testing alone. PMID:18464043

  10. Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression

    PubMed Central

    Zhang, Zhang; Zhang, Yan; Shi, Minglei; Ye, Bingyu; Shen, Wenlong; Li, Ping; Xing, Lingyue; Zhang, Xiaopeng; Hou, Lihua; Xu, Junjie; Zhao, Zhihu; Chen, Wei

    2015-01-01

    Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility. PMID:26703731

  11. Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression.

    PubMed

    Zhang, Zhang; Zhang, Yan; Shi, Minglei; Ye, Bingyu; Shen, Wenlong; Li, Ping; Xing, Lingyue; Zhang, Xiaopeng; Hou, Lihua; Xu, Junjie; Zhao, Zhihu; Chen, Wei

    2016-01-01

    Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility. PMID:26703731

  12. Integrated Extravehicular Activity Human Research Plan: 2016

    NASA Technical Reports Server (NTRS)

    Abercromby, Andrew F. J.; Ross, Amy J.; Cupples, J. Scott; Rajulu, Sudhakar; Norcross, Jason R.; Chappell, Steven P.

    2016-01-01

    Multiple organizations within NASA and outside of NASA fund and participate in research related to extravehicular activity (EVA). In October 2015, representatives of the EVA Office, the Crew and Thermal Systems Division (CTSD), and the Human Research Program (HRP) at NASA Johnson Space Center agreed on a formal framework to improve multi-year coordination and collaboration in EVA research. At the core of the framework is an Integrated EVA Human Research Plan and a process by which it will be annually reviewed and updated. The over-arching objective of the collaborative framework is to conduct multi-disciplinary cost-effective research that will enable humans to perform EVAs safely, effectively, comfortably, and efficiently, as needed to enable and enhance human space exploration missions. Research activities must be defined, prioritized, planned and executed to comprehensively address the right questions, avoid duplication, leverage other complementary activities where possible, and ultimately provide actionable evidence-based results in time to inform subsequent tests, developments and/or research activities. Representation of all appropriate stakeholders in the definition, prioritization, planning and execution of research activities is essential to accomplishing the over-arching objective. A formal review of the Integrated EVA Human Research Plan will be conducted annually. External peer review of all HRP EVA research activities including compilation and review of published literature in the EVA Evidence Report is will also continue at a frequency determined by HRP management. Coordination with stakeholders outside of the EVA Office, CTSD, and HRP is already in effect on a study-by-study basis; closer coordination on multi-year planning with other EVA stakeholders including academia is being actively pursued. Details of the current Integrated EVA Human Research Plan are presented including description of ongoing and planned research activities in the areas of

  13. Genetic Characterization of Simian Foamy Viruses Infecting Humans

    PubMed Central

    Rua, Réjane; Betsem, Edouard; Calattini, Sara; Saib, Ali

    2012-01-01

    Simian foamy viruses (SFVs) are retroviruses that are widespread among nonhuman primates (NHPs). SFVs actively replicate in their oral cavity and can be transmitted to humans after NHP bites, giving rise to a persistent infection even decades after primary infection. Very few data on the genetic structure of such SFVs found in humans are available. In the framework of ongoing studies searching for SFV-infected humans in south Cameroon rainforest villages, we studied 38 SFV-infected hunters whose times of infection had presumably been determined. By long-term cocultures of peripheral blood mononuclear cells with BHK-21 cells, we isolated five new SFV strains and obtained complete genomes of SFV strains from chimpanzee (Pan troglodytes troglodytes; strains BAD327 and AG15), monkey (Cercopithecus nictitans; strain AG16), and gorilla (Gorilla gorilla; strains BAK74 and BAD468). These zoonotic strains share a very high degree of similarity with their NHP counterparts and have a high degree of conservation of the genetic elements important for viral replication. Interestingly, analysis of FV DNA sequences obtained before cultivation revealed variants with deletions in both the U3 region and tas that may correlate with in vivo chronicity in humans. Genomic changes in bet (a premature stop codon) and gag were also observed. To determine if such changes were specific to zoonotic strains, we studied local SFV-infected chimpanzees and found the same genomic changes. Our study reveals that natural polymorphism of SFV strains does exist at both the intersubspecies level (gag, bet) and the intrasubspecies (U3, tas) levels but does not seem to reflect a viral adaptation specific to zoonotic SFV strains. PMID:23015714

  14. Research progress in the genetics of hyperuricaemia and gout.

    PubMed

    Min, Zheng; Junwu, Ma

    2016-04-01

    Gout is one of the most common inflammatory arthritis caused by hyperuricaemia, which is affected by both genetic factors and environmental factors. Early researches show that a few of rare monogenic mutations, such as PRPS1 and HPRT1 mutations, lead to abnormal purine anabolism and then cause hyperuricaemia and gout. In recent years, genome-wide association studies (GWAS) have identified dozens of susceptibility loci and/or candidate genes associated with hyperuricemia and gout. Loss-of-function mutations in SLC2A9, SLC22A11, and SLC22A12 cause hereditary hypouricaemia, while their overexpression may increase the reabsorption of uric acid. In contrast, loss-of-function mutations in ABCG2, SLC17A1, and SLC17A3 cause urate underexcretion of renal and intestinal. These variations leading to blood uric acid excretion disorder (excess reabsorption and underexcretion) are the main genetic factors affecting hyperuicemia and gout. Moreover, to some degree, inhibins-activins growth factor system, transcription factors, cytoskeleton and gene-environment interaction can also affect the level of blood uric acid. In addition, two risk genes, RFX3 and KCNQ1, which might impair immune response and lead to functional deficiency of beta cell were recently discovered to influence hyperuiceamia and gout in Han Chinese. This paper systematically reviews genetic studies on hyperuricaemia and gout to improve our understanding of pathogenesis of hyperuricaemia and gout. PMID:27103454

  15. Can Genetics Research Benefit Educational Interventions for All?

    PubMed

    Asbury, Kathryn

    2015-01-01

    Pretty much everyone knows that our genes have at least something to do with how able or how high achieving we are. Some believe that we should not speak of this common knowledge, nor inquire into how genetic influence works or what it might mean. If we do not keep an open mind to the fact of genetic influence on academic achievement, however, then we cannot explore its possible implications. And if we do not consider the implications, then we cannot, as a society, harness any potential benefits or avoid possible pitfalls. So that's what this essay is about-exploring what behavioral genetics research might be able to offer to educational theory, policy, and practice. We cannot yet use biological information to make accurate predictions for all children. We do know, however, that academic achievement is heritable, which is to say that differences between individuals are influenced by differences in their DNA. If genes are part of the problem for some pupils (to take the negative spin on this), then it seems likely that studying them could be part of a solution. And that's what behavioral geneticists are trying to do-to chart and understand pathways from DNA to behavior and to identify interventions that can maximize outcomes for all. The fact is, though, that we have an awfully long way to go. PMID:26413947

  16. Genetic Basis of Alopecia Areata: A Roadmap for Translational Research

    PubMed Central

    Jabbari, Ali; Petukhova, Lynn; Cabral, Rita M; Clynes, Raphael; Christiano, Angela M

    2015-01-01

    Synopsis Alopecia Areata (AA) is a recurrent autoimmune type of hair loss that affects about 5.3 million people in the United States alone. Despite being the most prevalent autoimmune disease, affecting more individuals than most other autoimmune diseases combined, the molecular and cellular mechanisms underlying this complex disease are still poorly understood, and rational treatments are lacking. It is currently accepted that AA is an autoimmune disease that occurs in genetically susceptible individuals and that environmental factors play a role in the development and progression of the disease. However, further efforts are necessary to clearly pinpoint the causes and molecular pathways leading to this disease and, most importantly, to find evidence-based treatments to treat AA. Here, we will focus on the central role of genetics for gaining insight into disease pathogenesis and setting the stage for the rational development of novel effective therapeutic approaches. This is an exciting new era marking the beginning of translational research in AA based on genetic findings. PMID:23159180

  17. Human KIR repertoires: shaped by genetic diversity and evolution.

    PubMed

    Manser, Angela R; Weinhold, Sandra; Uhrberg, Markus

    2015-09-01

    Killer cell immunoglobulin-like receptors (KIRs) on natural killer (NK) cells are crucially involved in the control of cancer development and virus infection by probing cells for proper expression of HLA class I. The clonally distributed expression of KIRs leads to great combinatorial diversity that develops in the presence of the evolutionary older CD94/NKG2A receptor to create highly stochastic but tolerant repertoires of NK cells. These repertoires are present at birth and are subsequently shaped by an individuals' immunological history toward recognition of self. The single most important factor that shapes functional NK cell repertoires is the genetic diversity of KIR, which is characterized by the presence of group A and B haplotypes with complementary gene content that are present in all human populations. Group A haplotypes constitute the minimal genetic entity that provides high affinity recognition of all major human leukocyte antigen class I-encoded ligands, whereas group B haplotypes contribute to the diversification of NK cell repertoires by providing sets of stimulatory KIR genes that modify NK cell responses. We suggest a cooperative model for the balancing selection of A and B haplotypes, which is driven by the need to provide a suitable corridor of repertoire complexity in which A/A individuals with only 16 different KIR combinations coexist with A/B and B/B donors expressing up to 2048 different clone types. PMID:26284478

  18. Biobanking, consent, and commercialization in international genetics research: the Type 1 Diabetes Genetics Consortium

    PubMed Central

    Hall, Mark A; King, Nancy MP; Perdue, Letitia H; Hilner, Joan E; Akolkar, Beena; Greenbaum, Carla J; McKeon, Catherine

    2010-01-01

    Background and Purpose This article describes several ethical, legal, and social issues typical of international genetics biobanking, as encountered in the Type 1 Diabetes Genetics Consortium (T1DGC). Methods By studying the examples set and lessons learned from other international biobanking studies and by devoting considerable time and resources to identifying, addressing, and continually monitoring ethical and regulatory concerns, T1DGC was able to minimize the problems reported by some earlier studies. Conclusions Several important conclusions can be drawn based on the experience in this study: (1) Basic international standards for research ethics review and informed consent are broadly consistent across developed countries. (2) When consent forms are adapted locally and translated into different languages, discrepancies are inevitable and therefore require prompt central review and resolution before research is initiated. (3) Providing separate ‘check-box’ consent for different elements of a study creates confusion and may not be essential. (4) Creating immortalized cell lines to aid future research is broadly acceptable, both in the US and internationally. (5) Imposing some limits on the use of stored samples aids in obtaining ethics approvals worldwide. (6) Allowing potential commercial uses of donated samples is controversial in some Asian countries. (7) Obtaining government approvals can be labor-intensive and time-consuming, and can require legal and diplomatic skills. PMID:20693188

  19. Human Research Program Requirements Document (Revision C)

    NASA Technical Reports Server (NTRS)

    Vargas, Paul R.

    2009-01-01

    The purpose of this document is to define, document, and allocate the Human Research Program (HRP) requirements to the HRP Program Elements. It establishes the flow-down of requirements from Exploration Systems Mission Directorate (ESMD) and Office of the Chief Health and Medical Officer (OCHMO) to the various Program Elements of the HRP to ensure that human research and technology countermeasure investments are made to insure the delivery of countermeasures and technologies that satisfy ESMD's and OCHMO's exploration mission requirements. Requirements driving the HRP work and deliverables are derived from the exploration architecture, as well as Agency standards regarding the maintenance of human health and performance. Agency human health and performance standards will define acceptable risk for each type and duration of exploration mission. It is critical to have the best available scientific and clinical evidence in setting and validating these standards. In addition, it is imperative that the best available evidence on preventing and mitigating human health and performance risks is incorporated into exploration mission and vehicle designs. These elements form the basis of the HRP research and technology development requirements and highlight the importance of HRP investments in enabling NASA's exploration missions. This PRD defines the requirements of the HRP which is comprised of the following major Program Elements: Behavioral Health and Performance (BHP), Exploration Medical Capability (ExMC), Human Health Countermeasures (HHC), ISS Medical Project (ISSMP), Space Human Factors and Habitability (SHFH), and Space Radiation (SR).

  20. Anthropogenics: human influence on global and genetic homogenization of parasite populations.

    PubMed

    Zarlenga, Dante S; Hoberg, Eric; Rosenthal, Benjamin; Mattiucci, Simonetta; Nascetti, Giuseppe

    2014-12-01

    The distribution, abundance, and diversity of life on Earth have been greatly shaped by human activities. This includes the geographic expansion of parasites; however, measuring the extent to which humans have influenced the dissemination and population structure of parasites has been challenging. In-depth comparisons among parasite populations extending to landscape-level processes affecting disease emergence have remained elusive. New research methods have enhanced our capacity to discern human impact, where the tools of population genetics and molecular epidemiology have begun to shed light on our historical and ongoing influence. Only since the 1990s have parasitologists coupled morphological diagnosis, long considered the basis of surveillance and biodiversity studies, with state-of-the-art tools enabling variation to be examined among, and within, parasite populations. Prior to this time, populations were characterized only by phenotypic attributes such as virulence, infectivity, host range, and geographical location. The advent of genetic/molecular methodologies (multilocus allozyme electrophoresis, polymerase chain reaction-DNA [PCR-DNA] fragments analysis, DNA sequencing, DNA microsatellites, single nucleotide polymorphisms, etc.) have transformed our abilities to reveal variation among, and within, populations at local, regional, landscape, and global scales, and thereby enhanced our understanding of the biosphere. Numerous factors can affect population structure among parasites, e.g., evolutionary and ecological history, mode of reproduction and transmission, host dispersal, and life-cycle complexity. Although such influences can vary considerably among parasite taxa, anthropogenic factors are demonstrably perturbing parasite fauna. Minimal genetic structure among many geographically distinct (isolated) populations is a hallmark of human activity, hastened by geographic introductions, environmental perturbation, and global warming. Accelerating

  1. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  2. Feedback of Individual Genetic Results to Research Participants: Is It Feasible in Europe?

    PubMed Central

    Mascalzoni, Deborah; Soini, Sirpa; Machado, Helena; Kaye, Jane; Bentzen, Heidi Beate; Rial-Sebbag, Emmanuelle; D'Abramo, Flavio; Witt, Michał; Schamps, Geneviève; Katić, Višnja; Krajnovic, Dusanca; Harris, Jennifer R.

    2016-01-01

    Background: There is growing consensus that individual genetic research results that are scientifically robust, analytically valid, and clinically actionable should be offered to research participants. However, the general practice in European research projects is that results are usually not provided to research participants for many reasons. This article reports on the views of European experts and scholars who are members of the European COST Action CHIP ME IS1303 (Citizen's Health through public-private Initiatives: Public health, Market and Ethical perspectives) regarding challenges to the feedback of individual genetic results to research participants in Europe and potential strategies to address these challenges. Materials and Methods: A consultation of the COST Action members was conducted through an email survey and a workshop. The results from the consultation were analyzed following a conventional content analysis approach. Results: Legal frameworks, professional guidelines, and financial, organizational, and human resources to support the feedback of results are largely missing in Europe. Necessary steps to facilitate the feedback process include clarifying legal requirements to the feedback of results, developing harmonized European best practices, promoting interdisciplinary and cross-institutional collaboration, designing educational programs and cost-efficient IT-based platforms, involving research ethics committees, and documenting the health benefits and risks of the feedback process. Conclusions: Coordinated efforts at pan-European level are needed to enable equitable, scientifically sound, and socially robust feedback of results to research participants. PMID:27082461

  3. Nursing research and the human sciences.

    PubMed

    Malinski, Violet M

    2002-01-01

    Nursing has long been associated with the natural sciences. However, more recently some nurses have begun to identify it as a human science. The epistemological and ontological bases then shift, with clear implications for the research approaches that are regarded as the most useful. This column offers a discussion of the worldviews represented in contemporary nursing knowledge, focusing particularly on the newer paradigm that includes the view of nursing as a human science, and the place of qualitative and quantitative research. Neither the human sciences nor the natural sciences are seen as providing a sufficient base for all nursing knowledge. Both qualitative and quantitative approaches are viewed as potentially useful strategies given the nature of the phenomenon to be explored. Parallels to current discussions of worldviews and research methods in transpersonal psychology are identified. PMID:11873465

  4. The Australian joint inquiry into the Protection of Human Genetic Information.

    PubMed

    Weisbrot, David

    2003-04-01

    The Australian Law Reform Commission (ALRC) and the Australian Health Ethics Committee are currently engaged in an inquiry into the Protection of Human Genetic Information. In particular, the Attorney-General and the Minister for Health and Ageing have asked us to focus, in relation to human genetic information and tissue samples, on how best to ensure world's best practice in relation to: privacy protection; protection against unlawful discrimination; and the maintenance of high ethical standards in medical research and clinical practice. While initial concerns and controversies have related mainly to aspects of medical research (e.g. consent; re-use of samples) and access to private insurance coverage, relevant issues arise in a wide variety of contexts, including: employment; medical practice; tissue banks and genetic databases; health administration; superannuation; access to government services (e.g. schools, nursing homes); law enforcement; and use by government authorities (e.g. for immigration purposes) or other bodies (e.g. by sports associations). Under the Australian federal system, it is also the case that laws and practices may vary across states and territories. For example, neonatal genetic testing is standard, but storage and retention policies for the resulting 'Guthrie cards' differ markedly. Similarly, some states have developed highly linked health information systems (e.g. incorporating hospitals, doctors' offices and public records), while others discourage such linkages owing to concerns about privacy. The challenge for Australia is to develop policies, standards and practices that promote the intelligent use of genetic information, while providing a level of security with which the community feels comfortable. The inquiry is presently reviewing the adequacy of existing laws and regulatory mechanisms, but recognizes that it will be even more important to develop a broad mix of strategies, such as community and professional education, and the

  5. HUMAN GENETIC MARKER FOR RESISTANCE TO RADIATIONS AND CHEMICALS

    EPA Science Inventory

    The overall objective of this research is to characterize the human RAD9 gene at molecular and cellular levels, and use the information and materials gained to develop a predictive assay for assessing risks posed to individuals involved in toxic waste clean-up.Fission yeast Sch...

  6. Disentangling the Genetic Determinants of Human Aging: Biological Age as an Alternative to the Use of Survival Measures

    PubMed Central

    Karasik, David; Demissie, Serkalem; Cupples, L. Adrienne; Kiel, Douglas P.

    2005-01-01

    The choice of a phenotype is critical for the study of a complex genetically regulated process, such as aging. To date, most of the twin and family studies have focused on broad survival measures, primarily age at death or exceptional longevity. However, on the basis of recent studies of twins and families, biological age has also been shown to have a strong genetic component, with heritability estimates ranging from 27% to 57%. The aim of this review is twofold: first, to summarize growing consensus on reliable methods of biological age assessment, and second, to demonstrate validity of this phenotype for research in the genetics of aging in humans. PMID:15972604

  7. Social Diversity in Humans: Implications and Hidden Consequences for Biological Research

    PubMed Central

    Duster, Troy

    2014-01-01

    Humans are both similar and diverse in such a vast number of dimensions that for human geneticists and social scientists to decide which of these dimensions is a worthy focus of empirical investigation is a formidable challenge. For geneticists, one vital question, of course, revolves around hypothesizing which kind of social diversity might illuminate genetic variation—and vice versa (i.e., what genetic variation illuminates human social diversity). For example, are there health outcomes that can be best explained by genetic variation—or for social scientists, are health outcomes mainly a function of the social diversity of lifestyles and social circumstances of a given population? Indeed, what is a “population,” how is it bounded, and are those boundaries most appropriate or relevant for human genetic research, be they national borders, religious affiliation, ethnic or racial identification, or language group, to name but a few? For social scientists, the matter of what constitutes the relevant borders of a population is equally complex, and the answer is demarcated by the goal of the research project. Although race and caste are categories deployed in both human genetics and social science, the social meaning of race and caste as pathways to employment, health, or education demonstrably overwhelms the analytic and explanatory power of genetic markers of difference between human aggregates. PMID:24789817

  8. The latest progress in sugarcane molecular genetics research at the USDA-ARS, Sugarcane Research Laboratory

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In 2005, two sugar molecular genetics tools were developed in the USDA-ARS, Southeast Area, Sugarcane Research Laboratory at Houma, LA. One is the high throughput fluorescence- and capillary electrophoregrams (CE)-based SSR genotyping tool and the other is single pollen collection and SSR genotyping...

  9. Physiology of SLC12 transporters: lessons from inherited human genetic mutations and genetically engineered mouse knockouts

    PubMed Central

    Gagnon, Kenneth B.

    2013-01-01

    Among the over 300 members of the solute carrier (SLC) group of integral plasma membrane transport proteins are the nine electroneutral cation-chloride cotransporters belonging to the SLC12 gene family. Seven of these transporters have been functionally described as coupling the electrically silent movement of chloride with sodium and/or potassium. Although in silico analysis has identified two additional SLC12 family members, no physiological role has been ascribed to the proteins encoded by either the SLC12A8 or the SLC12A9 genes. Evolutionary conservation of this gene family from protists to humans confirms their importance. A wealth of physiological, immunohistochemical, and biochemical studies have revealed a great deal of information regarding the importance of this gene family to human health and disease. The sequencing of the human genome has provided investigators with the capability to link several human diseases with mutations in the genes encoding these plasma membrane proteins. The availability of bacterial artificial chromosomes, recombination engineering techniques, and the mouse genome sequence has simplified the creation of targeting constructs to manipulate the expression/function of these cation-chloride cotransporters in the mouse in an attempt to recapitulate some of these human pathologies. This review will summarize the three human disorders that have been linked to the mutation/dysfunction of the Na-Cl, Na-K-2Cl, and K-Cl cotransporters (i.e., Bartter's, Gitleman's, and Andermann's syndromes), examine some additional pathologies arising from genetically modified mouse models of these cotransporters including deafness, blood pressure, hyperexcitability, and epithelial transport deficit phenotypes. PMID:23325410

  10. Genetic variants influencing effectiveness of exercise training programmes in obesity – an overview of human studies

    PubMed Central

    Ahmetov, II; Zmijewski, P

    2016-01-01

    Frequent and regular physical activity has significant benefits for health, including improvement of body composition and help in weight control. Consequently, promoting training programmes, particularly in those who are genetically predisposed, is a significant step towards controlling the presently increasing epidemic of obesity. Although the physiological responses of the human body to exercise are quite well described, the genetic background of these reactions still remains mostly unknown. This review not only summarizes the current evidence, through a literature review and the results of our studies on the influence of gene variants on the characteristics and range of the body's adaptive response to training, but also explores research organization problems, future trends, and possibilities. We describe the most reliable candidate genetic markers that are involved in energy balance pathways and body composition changes in response to training programmes, such as FTO, MC4R, ACE, PPARG, LEP, LEPR, ADRB2, and ADRB3. This knowledge can have an enormous impact not only on individualization of exercise programmes to make them more efficient and safer, but also on improved recovery, traumatology, medical care, diet, supplementation and many other areas. Nevertheless, the current studies still represent only the first steps towards a better understanding of the genetic factors that influence obesity-related traits, as well as gene variant x physical activity interactions, so further research is necessary. PMID:27601774

  11. Genetic variants influencing effectiveness of exercise training programmes in obesity - an overview of human studies.

    PubMed

    Leońska-Duniec, A; Ahmetov, I I; Zmijewski, P

    2016-09-01

    Frequent and regular physical activity has significant benefits for health, including improvement of body composition and help in weight control. Consequently, promoting training programmes, particularly in those who are genetically predisposed, is a significant step towards controlling the presently increasing epidemic of obesity. Although the physiological responses of the human body to exercise are quite well described, the genetic background of these reactions still remains mostly unknown. This review not only summarizes the current evidence, through a literature review and the results of our studies on the influence of gene variants on the characteristics and range of the body's adaptive response to training, but also explores research organization problems, future trends, and possibilities. We describe the most reliable candidate genetic markers that are involved in energy balance pathways and body composition changes in response to training programmes, such as FTO, MC4R, ACE, PPARG, LEP, LEPR, ADRB2, and ADRB3. This knowledge can have an enormous impact not only on individualization of exercise programmes to make them more efficient and safer, but also on improved recovery, traumatology, medical care, diet, supplementation and many other areas. Nevertheless, the current studies still represent only the first steps towards a better understanding of the genetic factors that influence obesity-related traits, as well as gene variant x physical activity interactions, so further research is necessary. PMID:27601774

  12. Human milk research for answering questions about human health.

    PubMed

    Wang, Richard Y; Bates, Michael N; Goldstein, Daniel A; Haynes, Suzanne G; Hench, Karen D; Lawrence, Ruth A; Paul, Ian M; Qian, Zhengmin

    2005-10-22

    Concerns regarding human milk in our society are diverse, ranging from the presence of environmental chemicals to the health of breastfed infants and the economic value of breastfeeding to society. The panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on 24--26 September 2004, considered how human milk research may contribute to environmental health initiatives to benefit society. The panel concluded that infant, maternal, and community health can benefit from studies using human milk biomonitoring. Unlike other biological specimens, human milk provides information regarding exposure of the mother and breastfed infant to environmental chemicals. Some of the health topics relevant to this field of research include disorders of growth and development in infants, cancer origins in women, and characterization of the trend of exposure to environmental chemicals in the community. The research focus will determine the design of the study and the need for the collection of alternative biological specimens and the long-term storage of these specimens. In order to strengthen the ability to interpret study results, it is important to identify reference ranges for the chemicals measured and to control for populations with high environmental chemical exposure, because the amount of data on environmental chemical levels in human milk that is available for comparison is extremely limited. In addition, it will be necessary to validate models used to assess infant exposure from breastfeeding because of the variable nature of current models. Information on differences between individual and population risk estimates for toxicity needs to be effectively communicated to the participant. Human milk research designed to answer questions regarding health will require additional resources to meet these objectives. PMID:16176918

  13. Wide disparity of clinical genetics services and EU rare disease research funding across Europe.

    PubMed

    Lynch, Sally Ann; Borg, Isabella

    2016-04-01

    The origins of clinical genetics services vary throughout Europe with some emerging from paediatric medicine and others from an academic laboratory setting. In 2011, the cross-border patients' rights directive recommended the creation of European Research Networks (ERNs) to improve patient care throughout EU. In 2013, the EU recommendation on the care for rare diseases came into place. The process of designating EU centres of expertise in rare diseases is being implemented to allow centres to enter ERNs. Hence, this is an opportune time to reflect on the current status of genetic services and research funding throughout Europe as 80 % of rare diseases have a genetic origin. Our aims were to determine (a) whether EU countries are prepared in terms of appropriate clinical genetic staffing to fulfil the European Union Committee of Experts on Rare Diseases (EUCERD) criteria that will allow national centres to be designated as centres of expertise, (b) which EU countries are successful in grant submissions to EU rare disease research funding and (c) country of origin of researchers from the EU presenting their research work as a spoken presentation at the European Society of Human Genetics annual conference. Our results show there is wide disparity of staffing levels per head of population in clinical genetics units throughout Europe. EU rare disease research funding is not being distributed equitably and the opportunity to present research is skewed with many countries not achieving spoken presentations despite abstract submissions. Inequity in the care of patients with rare diseases exists in Europe. Many countries will struggle to designate centres of expertise as their staffing mix and levels will not meet the EUCERD criteria which may prevent them from entering ERNs. The establishment of a small number of centres of expertise centrally, which is welcome, should not occur at the expense of an overall improvement in EU rare disease patient care. Caution should be

  14. [Social engineers--providers--bioethicists. Human genetics experts in West-Germany and Denmark between 1950 and 1990].

    PubMed

    Thomaschke, Dirk

    2013-01-01

    The author compares the history of human genetics in the Federal Republic of Germany and Denmark from the 1950s to the 1980s. The paper combines a discourse analysis with the exploration of human genetics experts' subject forms along the lines of current considerations within cultural studies. In the 1950s and 1960s, human geneticists acted in close cooperation with other political, judicial and administrative expert groups. They monitored the 'overall genetic development' of the population and cautioned about 'genetic crises'. Laypersons were supposed to submit to 'objectively reasonable' behavioral patterns--to their own as well as society's benefit. In the 1970s, the experts turned into 'providers' of a 'precise, purely medical, diagnostic service'. The patients mainly appeared as 'de-personalized' sources of a common human demand for 'safe eugenic information'. In the 1980s, the demand and supply paradigm manifested psychological and ethical side effects. Human geneticists became aware of the social and historical interrelations of their research and practices. The results of this study contribute to a more complex understanding of the dominant 'individualization narrative' of human genetics history. In this context, the development in Germany and Denmark displays two complementary forms of a transnational discourse. PMID:25643481

  15. Perceived barriers to Internet-based health communication on human genetics.

    PubMed

    Bernhardt, Jay M; Lariscy, Ruth Ann Weaver; Parrott, Roxanne L; Silk, Kami J; Felter, Elizabeth M

    2002-01-01

    The Internet has emerged as potential vehicle for distributing health communication to millions of individuals because it is interactive, user controlled, and offers breadth and depth of information. However, its widespread use by the public may be limited due to three overarching concerns: privacy and confidentiality, information accuracy and perceptions of credibility, including limited credibility of some government-sponsored web sites. To explore the potential of using the Internet, especially for delivering information on human genetics communication, 15 focus groups and one interview were conducted with African American and European American adult males and females in a southeastern town. We found that the participants recognized great potential in the Internet for health communication on human genetics, but they also voiced concerns about the credibility and accuracy of online information, lack of trust in many web sites, and fear of safeguarding privacy. Their concerns are summarized here, along with potential remedies health communicators could implement and should research further. The Internet cannot achieve its full potential for human genetics communication until the public's concerns are addressed and resolved. PMID:12356290

  16. The humankind genome: from genetic diversity to the origin of human diseases.

    PubMed

    Belizário, Jose E

    2013-12-01

    Genome-wide association studies have failed to establish common variant risk for the majority of common human diseases. The underlying reasons for this failure are explained by recent studies of resequencing and comparison of over 1200 human genomes and 10 000 exomes, together with the delineation of DNA methylation patterns (epigenome) and full characterization of coding and noncoding RNAs (transcriptome) being transcribed. These studies have provided the most comprehensive catalogues of functional elements and genetic variants that are now available for global integrative analysis and experimental validation in prospective cohort studies. With these datasets, researchers will have unparalleled opportunities for the alignment, mining, and testing of hypotheses for the roles of specific genetic variants, including copy number variations, single nucleotide polymorphisms, and indels as the cause of specific phenotypes and diseases. Through the use of next-generation sequencing technologies for genotyping and standardized ontological annotation to systematically analyze the effects of genomic variation on humans and model organism phenotypes, we will be able to find candidate genes and new clues for disease's etiology and treatment. This article describes essential concepts in genetics and genomic technologies as well as the emerging computational framework to comprehensively search websites and platforms available for the analysis and interpretation of genomic data. PMID:24433206

  17. Integrating Spaceflight Human System Risk Research

    NASA Technical Reports Server (NTRS)

    Mindock, J.; Lumpkins, S.; Anton, W.; Havenhill, M.; Shelhamer, M.; Canga, M.

    2016-01-01

    NASA is working to increase the likelihoods of human health and performance success during exploration missions, and subsequent crew long-term health. To manage the risks in achieving these goals, a system modeled after a Continuous Risk Management framework is in place. "Human System Risks" (Risks) have been identified, and approximately 30 are being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Ties between the research efforts supporting each Risk have been identified, however, this has been in an ad hoc fashion. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioral, vehicle, and organizational aspects of the exploration missions must be integrated across Risks and disciplines. We will discuss how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information is allowing us to identify and visualize connections between Risks and research efforts in a systematic and standardized way. We will discuss the applications of the visualizations and insights to research planning, solicitation, and decision-making processes.

  18. Integrating Spaceflight Human System Risk Research

    NASA Technical Reports Server (NTRS)

    Mindock, Jennifer; Lumpkins, Sarah; Anton, Wilma; Havenhill, Maria; Shelhamer, Mark; Canga, Michael

    2016-01-01

    NASA is working to increase the likelihood of human health and performance success during exploration missions as well as to maintain the subsequent long-term health of the crew. To manage the risks in achieving these goals, a system modelled after a Continuous Risk Management framework is in place. "Human System Risks" (Risks) have been identified, and approximately 30 are being actively addressed by NASA's Human Research Program (HRP). Research plans for each of HRP's Risks have been developed and are being executed. Inter-disciplinary ties between the research efforts supporting each Risk have been identified; however, efforts to identify and benefit from these connections have been mostly ad hoc. There is growing recognition that solutions developed to address the full set of Risks covering medical, physiological, behavioural, vehicle, and organizational aspects of exploration missions must be integrated across Risks and disciplines. This paper discusses how a framework of factors influencing human health and performance in space is being applied as the backbone for bringing together sometimes disparate information relevant to the individual Risks. The resulting interrelated information enables identification and visualization of connections between Risks and research efforts in a systematic and standardized manner. This paper also discusses the applications of the visualizations and insights into research planning, solicitation, and decision-making processes.

  19. Genetic Characterization and Classification of Human and Animal Sapoviruses.

    PubMed

    Oka, Tomoichiro; Lu, Zhongyan; Phan, Tung; Delwart, Eric L; Saif, Linda J; Wang, Qiuhong

    2016-01-01

    Sapoviruses (SaVs) are enteric caliciviruses that have been detected in multiple mammalian species, including humans, pigs, mink, dogs, sea lions, chimpanzees, and rats. They show a high level of diversity. A SaV genome commonly encodes seven nonstructural proteins (NSs), including the RNA polymerase protein NS7, and two structural proteins (VP1 and VP2). We classified human and animal SaVs into 15 genogroups (G) based on available VP1 sequences, including three newly characterized genomes from this study. We sequenced the full length genomes of one new genogroup V (GV), one GVII and one GVIII porcine SaV using long range RT-PCR including newly designed forward primers located in the conserved motifs of the putative NS3, and also 5' RACE methods. We also determined the 5'- and 3'-ends of sea lion GV SaV and canine GXIII SaV. Although the complete genomic sequences of GIX-GXII, and GXV SaVs are unavailable, common features of SaV genomes include: 1) "GTG" at the 5'-end of the genome, and a short (9~14 nt) 5'-untranslated region; and 2) the first five amino acids (M [A/V] S [K/R] P) of the putative NS1 and the five amino acids (FEMEG) surrounding the putative cleavage site between NS7 and VP1 were conserved among the chimpanzee, two of five genogroups of pig (GV and GVIII), sea lion, canine, and human SaVs. In contrast, these two amino acid motifs were clearly different in three genogroups of porcine (GIII, GVI and GVII), and bat SaVs. Our results suggest that several animal SaVs have genetic similarities to human SaVs. However, the ability of SaVs to be transmitted between humans and animals is uncertain. PMID:27228126

  20. Genetic Characterization and Classification of Human and Animal Sapoviruses

    PubMed Central

    Oka, Tomoichiro; Lu, Zhongyan; Phan, Tung; Delwart, Eric L.; Saif, Linda J.; Wang, Qiuhong

    2016-01-01

    Sapoviruses (SaVs) are enteric caliciviruses that have been detected in multiple mammalian species, including humans, pigs, mink, dogs, sea lions, chimpanzees, and rats. They show a high level of diversity. A SaV genome commonly encodes seven nonstructural proteins (NSs), including the RNA polymerase protein NS7, and two structural proteins (VP1 and VP2). We classified human and animal SaVs into 15 genogroups (G) based on available VP1 sequences, including three newly characterized genomes from this study. We sequenced the full length genomes of one new genogroup V (GV), one GVII and one GVIII porcine SaV using long range RT-PCR including newly designed forward primers located in the conserved motifs of the putative NS3, and also 5' RACE methods. We also determined the 5’- and 3’-ends of sea lion GV SaV and canine GXIII SaV. Although the complete genomic sequences of GIX-GXII, and GXV SaVs are unavailable, common features of SaV genomes include: 1) “GTG” at the 5′-end of the genome, and a short (9~14 nt) 5′-untranslated region; and 2) the first five amino acids (M [A/V] S [K/R] P) of the putative NS1 and the five amino acids (FEMEG) surrounding the putative cleavage site between NS7 and VP1 were conserved among the chimpanzee, two of five genogroups of pig (GV and GVIII), sea lion, canine, and human SaVs. In contrast, these two amino acid motifs were clearly different in three genogroups of porcine (GIII, GVI and GVII), and bat SaVs. Our results suggest that several animal SaVs have genetic similarities to human SaVs. However, the ability of SaVs to be transmitted between humans and animals is uncertain. PMID:27228126

  1. Organizational Issues and Human Resource Development Research Questions. A Guide for Researchers in Human Resource Development.

    ERIC Educational Resources Information Center

    Jacobs, Ronald L., Ed.

    The nine papers in this monograph, written by members of the University Council for Research in Human Resource Development, respond to the following questions: What is the most important organizational issue of the 1990s, and what human resource development (HRD) research questions might be generated from this issue? The papers are as follows: (1)…

  2. Genetic diversity of Toxoplasma gondii in animals and humans

    PubMed Central

    Sibley, L. David; Khan, Asis; Ajioka, James W.; Rosenthal, Benjamin M.

    2009-01-01

    Toxoplasma gondii is one of the most widespread parasites of domestic, wild, and companion animals, and it also commonly infects humans. Toxoplasma gondii has a complex life cycle. Sexual development occurs only in the cat gut, while asexual replication occurs in many vertebrate hosts. These features combine to create an unusual population structure. The vast majority of strains in North America and Europe fall into three recently derived, clonal lineages known as types I, II and III. Recent studies have revealed that South American strains are more genetically diverse and comprise distinct genotypes. These differences have been shaped by infrequent sexual recombination, population sweeps and biogeography. The majority of human infections that have been studied in North America and Europe are caused by type II strains, which are also common in agricultural animals from these regions. In contrast, several diverse genotypes of T. gondii are associated with severe infections in humans in South America. Defining the population structure of T. gondii from new regions has important implications for transmission, immunogenicity and pathogenesis. PMID:19687043

  3. A REVIEW OF THE GENETIC AND RELATED EFFECTS OF 1,3-BUTADIENE IN RODENTS AND HUMANS

    EPA Science Inventory

    In this paper, the metabolism and genetic toxicity of 1,3-butadiene (BD) and its oxidative metabolites in humans and rodents is reviewed with attention to newer data that have been published since the latest evaluation of BD by the International Agency for Research on Cancer (IAR...

  4. Fast computation of genetic likelihoods on human pedigree data.

    PubMed

    Goradia, T M; Lange, K; Miller, P L; Nadkarni, P M

    1992-01-01

    Gene mapping and genetic epidemiology require large-scale computation of likelihoods based on human pedigree data. Although computation of such likelihoods has become increasingly sophisticated, fast calculations are still impeded by complex pedigree structures, by models with many underlying loci and by missing observations on key family members. The current paper 'introduces' a new method of array factorization that substantially accelerates linkage calculations with large numbers of markers. This method is not limited to nuclear families or to families with complete phenotyping. Vectorization and parallelization are two general-purpose hardware techniques for accelerating computations. These techniques can assist in the rapid calculation of genetic likelihoods. We describe our experience using both of these methods with the existing program MENDEL. A vectorized version of MENDEL was run on an IBM 3090 supercomputer. A parallelized version of MENDEL was run on parallel machines of different architectures and on a network of workstations. Applying these revised versions of MENDEL to two challenging linkage problems yields substantial improvements in computational speed. PMID:1555846

  5. Transgenic animal models of neurodegeneration based on human genetic studies

    PubMed Central

    Richie, Christopher T.; Hoffer, Barry J.; Airavaara, Mikko

    2011-01-01

    The identification of genes linked to neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) has led to the development of animal models for studying mechanism and evaluating potential therapies. None of the transgenic models developed based on disease-associated genes have been able to fully recapitulate the behavioral and pathological features of the corresponding disease. However, there has been enormous progress made in identifying potential therapeutic targets and understanding some of the common mechanisms of neurodegeneration. In this review, we will discuss transgenic animal models for AD, ALS, HD and PD that are based on human genetic studies. All of the diseases discussed have active or complete clinical trials for experimental treatments that benefited from transgenic models of the disease. PMID:20931247

  6. Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach.

    PubMed

    Chaturvedi, Swati; Singh, Ashok K; Keshari, Amit K; Maity, Siddhartha; Sarkar, Srimanta; Saha, Sudipta

    2016-01-01

    One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches. PMID:27051561

  7. Correlation of physical and genetic maps of human chromosome 16

    SciTech Connect

    Sutherland, G.R.

    1991-01-01

    This project aimed to divide chromosome 16 into approximately 50 intervals of {approximately}2Mb in size by constructing a series of mouse/human somatic cell hybrids each containing a rearranged chromosome 16. Using these hybrids, DNA probes would be regionally mapped by Southern blot or PCR analysis. Preference would be given to mapping probes which demonstrated polymorphisms for which the CEPH panel of families had been typed. This would allow a correlation of the physical and linkage maps of this chromosome. The aims have been substantially achieved. 49 somatic cell hybrids have been constructed which have allowed definition of 46, and potentially 57, different physical intervals on the chromosome. 164 loci have been fully mapped into these intervals. A correlation of the physical and genetic maps of the chromosome is in an advanced stage of preparation. The somatic cell hybrids constructed have been widely distributed to groups working on chromosome 16 and other genome projects.

  8. Thermosensory and mechanosensory perception in human genetic disease

    PubMed Central

    Tan, Perciliz L.; Katsanis, Nicholas

    2009-01-01

    Peripheral sensory perception is established through an elaborate network of specialized neurons that mediate the translation of extraorganismal stimuli through the use of a broad array of receptors and downstream effector molecules. Studies of human genetic disorders, as well as mouse and other animal models, have identified some of the key molecules necessary for peripheral innervation and function. These findings have, in turn, yielded new insights into the developmental networks and homeostatic mechanisms necessary for the transformation of external stimuli into interpretable electrical impulses. In this review, we will summarize and discuss some of the genes/proteins implicated in two particular aspects of sensory perception, thermosensation and mechanosensation, highlighting pathways whose perturbation leads to both isolated and syndromic sensory deficits. PMID:19808790

  9. Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach

    PubMed Central

    Chaturvedi, Swati; Singh, Ashok K.; Maity, Siddhartha; Sarkar, Srimanta

    2016-01-01

    One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches. PMID:27051561

  10. Stakeholder views on the creation and use of genetically-engineered animals in research.

    PubMed

    Ormandy, Elisabeth H

    2016-05-01

    This interview-based study examined the diversity of views relating to the creation and use of genetically-engineered (GE) animals in biomedical science. Twenty Canadian participants (eight researchers, five research technicians and seven members of the public) took part in the interviews, in which four main themes were discussed: a) how participants felt about the genetic engineering of animals as a practice; b) governance of the creation and use of GE animals in research, and whether current guidelines are sufficient; c) the Three Rs (Replacement, Reduction, Refinement) and how they are applied during the creation and use of GE animals in research; and d) whether public opinion should play a greater role in the creation and use of GE animals. Most of the participants felt that the creation and use of GE animals for biomedical research purposes (as opposed to food purposes) is acceptable, provided that tangible human health benefits are gained. However, obstacles to Three Rs implementation were identified, and the participants agreed that more effort should be placed on engaging the public on the use of GE animals in research. PMID:27256452

  11. GOOD GIFTS FOR THE COMMON GOOD: Blood and Bioethics in the Market of Genetic Research

    PubMed Central

    REDDY, DEEPA S.

    2008-01-01

    This article is based on ethnographic fieldwork conducted with the Indian community in Houston, as part of a NIH–NHGRI-sponsored ethics study and sample collection initiative entitled “Indian and Hindu Perspectives on Genetic Variation Research.” At the heart of this research is one central exchange—blood samples donated for genetic research—that draws both the Indian community and a community of researchers into an encounter with bioethics. I consider the meanings that come to be associated with blood donation as it passes through various hands, agendas, and associated ethical filters on its way to the lab bench: how and why blood is solicited, how the giving and taking of blood is rationalized, how blood as material substance is alienated, processed, documented, and made available for the promised ends of basic science research. Examining corporeal substances and asking what sorts of gifts and problems these represent, I argue, sheds some light on two imbricated tensions expressed by a community of Indians, on the one hand, and of geneticists and basic science researchers, on the other hand: that gifts ought to be free (but are not), and that science ought to be pure (but is not). In this article, I explore how experiences of bioethics are variously shaped by the histories and habits of Indic giving, prior sample collection controversies, commitments to “good science” and the common “good of humanity,” and negotiations of the sites where research findings circulate. PMID:18458755

  12. On the relative roles of background selection and genetic hitchhiking in shaping human cytomegalovirus genetic diversity.

    PubMed

    Renzette, Nicholas; Kowalik, Timothy F; Jensen, Jeffrey D

    2016-01-01

    A central focus of population genetics has been examining the contribution of selective and neutral processes in shaping patterns of intraspecies diversity. In terms of selection specifically, surveys of higher organisms have shown considerable variation in the relative contributions of background selection and genetic hitchhiking in shaping the distribution of polymorphisms, although these analyses have rarely been extended to bacteria and viruses. Here, we study the evolution of a ubiquitous, viral pathogen, human cytomegalovirus (HCMV), by analysing the relationship among intraspecies diversity, interspecies divergence and rates of recombination. We show that there is a strong correlation between diversity and divergence, consistent with expectations of neutral evolution. However, after correcting for divergence, there remains a significant correlation between intraspecies diversity and recombination rates, with additional analyses suggesting that this correlation is largely due to the effects of background selection. In addition, a small number of loci, centred on long noncoding RNAs, also show evidence of selective sweeps. These data suggest that HCMV evolution is dominated by neutral mechanisms as well as background selection, expanding our understanding of linked selection to a novel class of organisms. PMID:26211679

  13. Human Support Technology Research, Development and Demonstration

    NASA Technical Reports Server (NTRS)

    Joshi, Jitendra; Trinh, Eugene

    2004-01-01

    The Human Support Technology research, development, and demonstration program address es the following areas at TRL: Advanced Power and Propulsion. Cryogenic fluid management. Closed-loop life support and Habitability. Extravehicular activity systems. Scientific data collection and analysis. and Planetary in-situ resource utilization.

  14. Information Technology and the Human Research Facility

    NASA Technical Reports Server (NTRS)

    Klee, Margaret

    2002-01-01

    This slide presentation reviews how information technology supports the Human Research Facility (HRF) and specifically the uses that contractor has for the information. There is information about the contractor, the HRF, some of the experiments that were performed using the HRF on board the Shuttle, overviews of the data architecture, and software both commercial and specially developed software for the specific experiments.

  15. Research opportunities in human behavior and performance

    NASA Technical Reports Server (NTRS)

    Christensen, J. M. (Editor); Talbot, J. M. (Editor)

    1985-01-01

    Extant information on the subject of psychological aspects of manned space flight are reviewed; NASA's psychology research program is examined; significant gaps in knowledge are identified; and suggestions are offered for future research program planning. Issues of human behavior and performance related to the United States space station, to the space shuttle program, and to both near and long term problems of a generic nature in applicable disciplines of psychology are considered. Topics covered include: (1) human performance requirements for a 90 day mission; (2) human perceptual, cognitive, and motor capabilities and limitations in space; (3) crew composition, individual competencies, crew competencies, selection criteria, and special training; (4) environmental factors influencing behavior; (5) psychosocial aspects of multiperson space crews in long term missions; (6) career determinants in NASA; (7) investigational methodology and equipment; and (8) psychological support.

  16. Evolutionary genetics of the human Rh blood group system

    PubMed Central

    Perry, George H.; Xue, Yali; Smith, Richard S.; Meyer, Wynn K.; Çalışkan, Minal; Yanez-Cuna, Omar; Lee, Arthur S.; Gutiérrez-Arcelus, María; Ober, Carole; Hollox, Edward J.; Tyler-Smith, Chris; Lee, Charles

    2012-01-01

    The evolutionary history of variation in the human Rh blood group system, determined by variants in the RHD and RHCE genes, has long been an unresolved puzzle in human genetics. Prior to medical treatments and interventions developed in the last century, the D-positive children of D-negative women were at risk for hemolytic disease of the newborn, if the mother produced anti-D antibodies following sensitization to the blood of a previous D-positive child. Given the deleterious fitness consequences of this disease, the appreciable frequencies in European populations of the responsible RHD gene deletion variant (for example, 0.43 in our study) seem surprising. In this study, we used new molecular and genomic data generated from four HapMap population samples to test the idea that positive selection for an as-of-yet unknown fitness benefit of the RHD deletion may have offset the otherwise negative fitness effects of hemolytic disease of the newborn. We found no evidence that positive natural selection affected the frequency of the RHD deletion. Thus, the initial rise to intermediate frequency of the RHD deletion in European populations may simply be explained by genetic drift/ founder effect, or by an older or more complex sweep that we are insufficiently powered to detect. However, our simulations recapitulate previous findings that selection on the RHD deletion is frequency dependent, and weak or absent near 0.5. Therefore, once such a frequency was achieved, it could have been maintained by a relatively small amount of genetic drift. We unexpectedly observed evidence for positive selection on the C allele of RHCE in non-African populations (on chromosomes with intact copies of the RHD gene) in the form of an unusually high FST value and the high frequency of a single haplotype carrying the C allele. RhCE function is not well understood, but the C/c antigenic variant is clinically relevant and can result in hemolytic disease of the newborn, albeit much less commonly

  17. Genetic implication of a novel thiamine transporter in human hypertension

    PubMed Central

    Zhang, Kuixing; Huentelman, Matthew J.; Rao, Fangwen; Sun, Eric I.; Corneveaux, Jason J.; Schork, Andrew J.; Wei, Zhiyun; Waalen, Jill; Miramontes-Gonzalez, Jose Pablo; Hightower, C. Makena; Maihofer, Adam X.; Mahata, Manjula; Pastinen, Tomi; Ehret, Georg B.; Schork, Nicholas J.; Eskin, Eleazar; Nievergelt, Caroline M.; Saier, Milton H.; O'Connor, Daniel T.

    2014-01-01

    Objectives We coupled two strategies – trait extremes and genome-wide pooling – to discover a novel BP locus that encodes a previously uncharacterized thiamine transporter. Background Hypertension is a heritable trait that remains the most potent and widespread cardiovascular risk factor, though details of its genetic determination are poorly understood. Methods Representative genomic DNA pools were created from male and female subjects in the highest and lowest 5th %iles of BP in a primary care population of >50,000 individuals. The peak associated SNPs were typed in individual DNA samples, as well as twins/siblings phenotyped for cardiovascular and autonomic traits. Biochemical properties of the associated transporter were evaluated in cellular assays. Results After chip hybridization and calculation of relative allele scores, the peak associations were typed in individual samples, revealing association of hypertension, SBP, and DBP to the previously uncharacterized solute carrier SLC35F3. The BP genetic association at SLC35F3 was validated by meta-analysis in an independent sample from the original source population, as well as the ICBP (across North America and Western Europe). Sequence homology to a putative yeast thiamine (vitamin B1) transporter prompted us to express human SLC35F3 in E. coli, which catalyzed [3H]-thiamine uptake. SLC35F3 risk allele (T/T) homozygotes displayed decreased erythrocyte thiamine content on microbiological assay. In twin pairs, the SLC35F3 risk allele predicted heritable cardiovascular traits previously associated with thiamine deficiency, including elevated cardiac stroke volume with decreased vascular resistance, and elevated pressor responses to environmental (cold) stress. Allelic expression imbalance (AEI) confirmed that cis-variation at the human SLC35F3 locus influenced expression of that gene, and the AEI peak coincided with the hypertension peak. Conclusions Novel strategies were coupled to position a new

  18. Virology research and virulent human pandemics.

    PubMed Central

    Mims, C. A.

    1995-01-01

    The possibility that a devastating human pandemic could arise, causing massive loss of human life, is discussed. Such a major threat to the human species is likely to be a virus, and would spread by the respiratory route. It need not necessarily cause massive loss of life, but if it caused serious illness or incapacity it would still have a major impact. A possible source is from an existing respiratory pathogen, but it would more probably arise from an infection that is maintained in an arthropod or vertebrate host, but which at present either does not infect humans, or if it does it fails to be effectively transmitted between them. More research should therefore focus on the pathogenetic factors and the viral determinants that promote respiratory transmission. PMID:8557069

  19. [Characteristics of molecular genetics and research progress on mitochondrial diseases].

    PubMed

    Zhang, Meng; Si, Yanmei; Zhao, Juan

    2016-10-01

    Mitochondrial diseases is a group of metabolic disorders caused by abnormal structure and dysfunction of mitochondrial DNA (mtDNA). Abnormalities of mtDNA include point mutations, deletions, and rearrangements and depletion of mtDNA. These may affect the ability of mitochondria to generate energy in cells of various tissues and organs. As many factors are involved in the regulation of mtDNA mutations, most mitochondrial diseases may manifest great genetic heterogeneity and a wide spectrum of clinical manifestations. On the other hand, for the low prevalence of single disease, these disorders may be easily missed or with delayed diagnosis. This review focuses on the pathological mutations and benign variations of mtDNA, and research progress on such disorders. PMID:27577231

  20. [Advances in research on the genetics of peripheral arterial disease].

    PubMed

    Yin, Li; Han, Qi; Li, Xueyang; Liu, Zhenjie

    2015-12-01

    Peripheral arterial disease (PAD) shows increasing morbidity and mortality. Clinical manifestations of PAD, such as intermittent claudication, rest pain and nonhealing ulcer, contribute to impaired quality of life, and ischemic stroke caused by PAD can be life-threatening. Unfortunately, PAD patients often receive suboptimal treatment, and pathogenesis of the disease is still unclear. Over the past decade, the evolving technology and interdisciplinary collaboration have enabled improvement of diagnosis and treatment for PAD. This review makes a brief summary of the current status and progress in genetics research on PAD, which included candidate gene studies, linkage analyses, genome-wide association studies, and applications and development prospects of epigenetics, mitochondrial DNA and other new technologies. PMID:26663072

  1. Insights into the epidemiology and genetic make-up of Oesophagostomum bifurcum from human and non-human primates using molecular tools.

    PubMed

    Gasser, R B; de Gruijter, J M; Polderman, A M

    2006-04-01

    The nodule worm Oesophagostomum bifurcum (Nematoda: Strongylida) is a parasite of major human health importance predominantly in northern Togo and Ghana. Currently, it is estimated that 0.25 million people are infected with this nematode, and at least 1 million people are at risk of infection. Infection with this parasite causes significant disease as a consequence of encysted larvae in the wall of the large intestine. In spite of the health problems caused by O. bifurcum, there have been significant gaps in the knowledge of the biology, transmission and population genetics of the parasite. This review provides an account of some recent insights into the epidemiology and genetics of the parasite from human and non-human primate hosts in specific regions of Africa using molecular tools. Recent research findings are discussed mainly in relation to non-human primates being reservoirs of infection, and the consequences for the prevention and control of oesophagostomiasis in humans are briefly discussed. PMID:16332292

  2. Using yeast genetics to generate a research environment.

    PubMed

    Manney, T R; Manney, M L

    1993-05-01

    Many of the same features of the yeast Saccharomyces cerevisiae that have made it so useful as a genetics and molecular biology research organism make it equally useful as a teaching organism. Furthermore, the fact that it is a modern research organism makes it all the more exciting to students and teachers. The unique characteristic of yeast as a unicellular, eukaryotic organism with a complete sexual life cycle is ideal for teaching. A simple monohybrid cross to explore dominance and recessiveness, a dihybrid cross to demonstrate independent assortment, pigmented adenine auxotrophs for investigating the fundamentals of gene action, and easily measured responses to ultraviolet radiation provide an array of appropriate laboratory tools that put real science in the hands of students and teachers. Direct collaborations between scientists and science teachers bring together complementing knowledge and experience, providing an effective and efficient way to adapt and simplify techniques and procedures to accommodate time and money constraints. Collaborations quickly identify technical and theoretical problems that must be solved for implementation in classrooms. They also provide a continuing stimulus to teachers and students to participate in the research process. PMID:8514146

  3. Using Yeast Genetics to Generate a Research Environment

    PubMed Central

    Manney, T. R.; Manney, M. L.

    1993-01-01

    Many of the same features of the yeast Saccharomyces cerevisiae that have made it so useful as a genetics and molecular biology research organism make it equally useful as a teaching organism. Furthermore, the fact that it is a modern research organism makes it all the more exciting to students and teachers. The unique characteristic of yeast as a unicellular, eukaryotic organism with a complete sexual life cycle is ideal for teaching. A simple monohybrid cross to explore dominance and recessiveness, a dihybrid cross to demonstrate independent assortment, pigmented adenine auxotrophs for investigating the fundamentals of gene action, and easily measured responses to ultraviolet readiation provide an array of appropriate laboratory tools that put real science in the hands of students and teachers. Direct collaborations between scientists and science teachers bring together complementing knowledge and experience, providing an effective and efficient way to adapt and simplify techniques and procedures to accommodate time and money constraints. Collaborations quickly identify technical and theoretical problems that must be solved for implementation in classrooms. They also provide a continuing stimulus to teachers and students to participate in the research process. PMID:8514146

  4. Pathophysiology of asthma: lessons from genetic research with particular focus on severe asthma.

    PubMed

    Melén, E; Pershagen, G

    2012-08-01

    There is good evidence that both inherited and environmental factors influence the risk of developing asthma. Only recently, large well-designed studies have been undertaken with the power to identify the genetic causes for asthma, and methods developed in parallel with the Human Genome Project, such as gene expression and epigenetic studies, have made large-scale analyses of functional genetics possible. In this review, we discuss the recent findings from genetic and genomic research studies of asthma, particularly severe asthma, and highlight specific genes for which there are multiple lines of evidence for involvement in asthma pathogenesis. Bio-ontologic enrichment analyses of the most recently identified asthma-related genes point to attributes such as 'molecular and signal transducer activity' and 'immune system processes', which indicates the importance of immunoregulation and inflammatory response in the pathogenesis of asthma. Finally, we discuss how genetic and environmental factors jointly influence asthma susceptibility and summarize how the results may increase understanding of the pathophysiology of asthma-related diseases. PMID:22632610

  5. Human-Robot Interaction Directed Research Project

    NASA Technical Reports Server (NTRS)

    Rochlis, Jennifer; Ezer, Neta; Sandor, Aniko

    2011-01-01

    Human-robot interaction (HRI) is about understanding and shaping the interactions between humans and robots (Goodrich & Schultz, 2007). It is important to evaluate how the design of interfaces and command modalities affect the human s ability to perform tasks accurately, efficiently, and effectively (Crandall, Goodrich, Olsen Jr., & Nielsen, 2005) It is also critical to evaluate the effects of human-robot interfaces and command modalities on operator mental workload (Sheridan, 1992) and situation awareness (Endsley, Bolt , & Jones, 2003). By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed that support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for design. Because the factors associated with interfaces and command modalities in HRI are too numerous to address in 3 years of research, the proposed research concentrates on three manageable areas applicable to National Aeronautics and Space Administration (NASA) robot systems. These topic areas emerged from the Fiscal Year (FY) 2011 work that included extensive literature reviews and observations of NASA systems. The three topic areas are: 1) video overlays, 2) camera views, and 3) command modalities. Each area is described in detail below, along with relevance to existing NASA human-robot systems. In addition to studies in these three topic areas, a workshop is proposed for FY12. The workshop will bring together experts in human-robot interaction and robotics to discuss the state of the practice as applicable to research in space robotics. Studies proposed in the area of video overlays consider two factors in the implementation of augmented reality (AR) for operator displays during teleoperation. The first of these factors is the type of navigational guidance provided by AR symbology. In the proposed

  6. Functional modules, mutational load and human genetic disease

    PubMed Central

    Zaghloul, Norann A.; Katsanis, Nicholas

    2013-01-01

    The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically-relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. PMID:20226561

  7. Pigmentation, pleiotropy, and genetic pathways in humans and mice

    SciTech Connect

    Barsh, G.S.

    1995-10-01

    Some of the most striking polymorphisms in human populations affect the color of our eyes, hair, or skin. Despite some simple lessons from high school biology (blue eyes are recessive; brown are dominant), the genetic basis of such phenotypic variability has, for the most part, eluded Mendelian description. A logical place to search for the keys to understanding common variation in human pigmentation are genes in which defects cause uncommon conditions such as albinism or piebaldism. The area under this lamppost has recently gotten larger, with two articles, one in this issue of the Journal, that describe the map position for Hermansky-Pudlak syndrome (HPS) and with the recent cloning of a gene that causes X-linked ocular albinism (OA1). In addition, a series of three recent articles in Cell demonstrate (1) that defects in the gene encoding the endothelin B (ET{sub B}) receptor cause hypopigmentation and Hirschsprung disease in a Mennonite population and the mouse mutation piebald(s) and (2) that a defect in the edn3 gene, which encodes one of the ligands for the ET{sub B} receptor, causes the lethal spotting (ls) mouse mutation. 47 refs., 1 fig.

  8. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  9. Canonical genetic signatures of the adult human brain.

    PubMed

    Hawrylycz, Michael; Miller, Jeremy A; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L; Jegga, Anil G; Aronow, Bruce J; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F; Dierker, Donna L; Menche, Jörg; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R; Jones, Allan; Van Essen, David C; Koch, Christof; Lein, Ed

    2015-12-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  10. EPA'S GENETIC DIVERSITY RESEARCH PROGRAM: ECOLOGICAL INDICATOR DEVELOPMENT

    EPA Science Inventory

    Genetic diversity is a fundamental component of biodiversity that is affected by environmental stressors in predictable ways and limits potential responses of a population to future stressors. Understanding patterns of genetic diversity enhances the value and interpretation of o...

  11. The State of Federal Research Funding in Genetics as Reflected by Members of the Genetics Society of America.

    PubMed

    Rine, Jasper; Fagen, Adam P

    2015-08-01

    Scientific progress runs on the intellect, curiosity, and passion of its practitioners fueled by the research dollars of its sponsors. The concern over research funding in biology in general and genetics in particular led us to survey the membership of the Genetics Society of America for information about the federal support of genetics at the level of individual principal investigators. The results paint a mosaic of circumstances-some good, others not so good-that describes some of our present challenges with sufficient detail to suggest useful steps that could address the challenges. PMID:26178966

  12. The State of Federal Research Funding in Genetics as Reflected by Members of the Genetics Society of America

    PubMed Central

    Rine, Jasper; Fagen, Adam P.

    2015-01-01

    Scientific progress runs on the intellect, curiosity, and passion of its practitioners fueled by the research dollars of its sponsors. The concern over research funding in biology in general and genetics in particular led us to survey the membership of the Genetics Society of America for information about the federal support of genetics at the level of individual principal investigators. The results paint a mosaic of circumstances—some good, others not so good—that describes some of our present challenges with sufficient detail to suggest useful steps that could address the challenges. PMID:26178966

  13. Genetics of Adiposity in Large Animal Models for Human Obesity-Studies on Pigs and Dogs.

    PubMed

    Stachowiak, M; Szczerbal, I; Switonski, M

    2016-01-01

    The role of domestic mammals in the development of human biomedical sciences has been widely documented. Among these model species the pig and dog are of special importance. Both are useful for studies on the etiology of human obesity. Genome sequences of both species are known and advanced genetic tools [eg, microarray SNP for genome wide association studies (GWAS), next generation sequencing (NGS), etc.] are commonly used in such studies. In the domestic pig the accumulation of adipose tissue is an important trait, which influences meat quality and fattening efficiency. Numerous quantitative trait loci (QTLs) for pig fatness traits were identified, while gene polymorphisms associated with these traits were also described. The situation is different in dog population. Generally, excessive accumulation of adipose tissue is considered, similar to humans, as a complex disease. However, research on the genetic background of canine obesity is still in its infancy. Between-breed differences in terms of adipose tissue accumulation are well known in both animal species. In this review we show recent advances of studies on adipose tissue accumulation in pigs and dogs, and their potential importance for studies on human obesity. PMID:27288831

  14. Human Genetics and Islam: Scientific and Medical Aspects

    PubMed Central

    Ghareeb, Bilal A.A.

    2011-01-01

    Objective: To relate diverse aspects of genetics and its applications to concepts in the Glorious Qur’an and the ḥadīth. Study Design: The author compared passages from the Glorious Qur’an and ḥadīth with modern concepts in genetics, such as recessive inheritance, genetic counseling, genetic variation, cytoplasmic inheritance, sex chromosomes, genetics-environment interactions, gender determination, and the hypothesis of “pairing in the universe.” Conclusions: A fresh understanding of Islamic scripture reveals references to principles of genetics that predate contemporary discoveries. This highlights the need for further exploration of possible links between science and religion. PMID:23610491

  15. African Americans’ Responses to Genetic Explanations of Lung Cancer Disparities and Willingness to Participate in Clinical Genetics Research

    PubMed Central

    White, Della Brown; Koehly, Laura M.; Omogbehin, Adedamola; McBride, Colleen M.

    2012-01-01

    Purpose To assess whether reactions to genetic explanations for disparities in lung cancer incidence among family members of African American patients with lung cancer are associated with willingness to participate in clinical genetics research. Methods Data are reported for 67 self-identified African Americans ages 18 to 55 years who completed a telephone survey assessing reactions to explanations (i.e., genetics, toxin exposure, menthol cigarettes, race-related stress) for lung cancer disparities. Majority was female (70%), current smokers (57%), and patients’ biological relatives (70%). Results Family members’ rated the four explanations similarly, each as believable, fair and not too worrisome. Participants also indicated a high level of willingness to participate in genetics research (M= 4.1 ± 1.0; Scale 1–5). Endorsements of genetics explanations for disparities as believable and fair, and toxin exposure as believable were associated significantly with willingness to participate in genetics research. Conclusion These results suggest that strategies to encourage African Americans’ participation in genetics research would do well to inform potential participants of how their involvement might be used to better understand important environmental factors that affect health disparities. PMID:20613544

  16. Retinoblastoma genetics in India: From research to implementation.

    PubMed

    Dimaras, Helen

    2015-03-01

    Retinoblastoma is the prototypic genetic cancer. India carries the biggest burden of retinoblastoma globally, with an estimated 1500 new cases annually. Recent advances in retinoblastoma genetics are reviewed, focusing specifically on information with clinical significance to patients. The Indian literature on retinoblastoma clinical genetics is also highlighted, with a comment on challenges and future directions. The review concludes with recommendations to help clinicians implement and translate retinoblastoma genetics to their practice. PMID:25971166

  17. Analysis of the Genetic Basis of Disease in the Context of Worldwide Human Relationships and Migration

    PubMed Central

    Corona, Erik; Chen, Rong; Sikora, Martin; Morgan, Alexander A.; Patel, Chirag J.; Ramesh, Aditya; Bustamante, Carlos D.; Butte, Atul J.

    2013-01-01

    Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation. PMID:23717210

  18. International Space Station Research Benefits for Humanity

    NASA Technical Reports Server (NTRS)

    Thumm, Tracy; Robinson, Julie A.; Johnson-Green, Perry; Buckley, Nicole; Karabadzhak, George; Nakamura, Tai; Kamigaichi, Shigeki; Sorokin, Igor V.; Zell, Martin; Fuglesang, Christer; Sabbagh, Jean; Pignataro, Salvatore

    2012-01-01

    The ISS partnership has seen a substantial increase in research accomplished, crew efforts devoted to research, and results of ongoing research and technology development. The ISS laboratory is providing a unique environment for research and international collaboration that benefits humankind. Benefits come from the engineering development, the international partnership, and from the research results. Benefits can be of three different types: scientific discovery, applications to life on Earth, and applications to future exploration. Working across all ISS partners, we identified key themes where the activities on the ISS improve the lives of people on Earth -- not only within the partner nations, but also in other nations of the world. Three major themes of benefits to life on earth emerged from our review: benefits to human health, education, and Earth observation and disaster response. Other themes are growing as use of the ISS continues. Benefits to human health range from advancements in surgical technology, improved telemedicine, and new treatments for disease. Earth observations from the ISS provide a wide range of observations that include: marine vessel tracking, disaster monitoring and climate change. The ISS participates in a number of educational activities aimed to inspire students of all ages to learn about science, technology, engineering and mathematics. To date over 63 countries have directly participated in some aspect of ISS research or education. In summarizing these benefits and accomplishments, ISS partners are also identifying ways to further extend the benefits to people in developing countries for the benefits of humankind.

  19. Human Hallucinogen Research: Guidelines for Safety

    PubMed Central

    Johnson, Matthew W.; Richards, William A.; Griffiths, Roland R.

    2010-01-01

    There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (“bad trip”), which could lead to potentially dangerous behavior such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment, and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science. PMID:18593734

  20. Inconsistencies in pedigree symbols in human genetics publications: A need for standardization

    SciTech Connect

    Steinhaus, K.A.; Bennett, R.L.; Resta, R.G.

    1995-04-10

    To determine consistency in usage of pedigree symbols by genetics professionals, we reviewed pedigrees printed in 10 human genetic and medical journals and 24 medical genetics textbooks. We found no consistent symbolization for common situations such as pregnancy, spontaneous abortion, death, or test results. Inconsistency in pedigree design can create difficulties in the interpretation of family studies and detract from the pedigree`s basic strength of simple and accurate communication of medical information. We recommend the development of standard pedigree symbols, and their incorporation into genetic publications, professional genetics training programs, pedigree software programs, and genetic board examinations. 5 refs., 11 figs., 2 tabs.

  1. [Ethical principles in human scientific research].

    PubMed

    Cruz-Coke, R

    1994-07-01

    Hippocrates was the first physician to use the scientific method to find rational and not religious or mythic causes, for the etiology of diseases. Hippocrates and Aristoteles did not dare to dissect the human body. Afterwards however, many scientists such as Herophilus, Erasitastrus, Vesalus and Fallopio, performed experiments in human beings using vivisection. According to that age's ideas, there was no cruelty in performing vivisection in criminals, since useful knowledge for the progress of medicine and relief of diseases was obtained. Only during the nineteenth century and with Claude Bernard (1865), the ethical principles of systematic scientific research in humans were defined. These principles were violated by nazi physicians during Hitler's dictatorship in Germany (1933-1945). As a response to these horrors, the Ethical Codes of Nuremberg (1947) and Geneva (1948), that reestablished all the strength of Hippocratic principles, were dictated. The Nuremberg rules enact that a research subject must give a voluntary consent, that the experiment must by necessary and exempt of death risk, that the research must be qualified and that the experiment must be discontinued if there is a risk for the subject. The Geneva statement is a modernized hippocratic oath that protects patient's life above all. These classical rules, in force at the present time, are the essential guides that must be applied by physicians and researchers. PMID:7732235

  2. Genetic polymorphisms of human UDP-glucuronosyltransferase (UGT) genes and cancer risk.

    PubMed

    Hu, Dong Gui; Mackenzie, Peter I; McKinnon, Ross A; Meech, Robyn

    2016-01-01

    Identification of genetic polymorphisms that contribute to the risk of developing cancers is important for cancer prevention. The most recent human genome GRCh38/hg38 assembly (2013) reveals thousands of genetic polymorphisms in human uridine diphosphoglucuronosyltransferase (UGT) genes. Among these, a large number of polymorphisms at the UGT1A and UGT2B genes have been shown to modulate UGT gene promoter activity or enzymatic activity. Glucuronidation plays an important role in the metabolism and clearance of endogenous and exogenous carcinogenic compounds, and this reaction is primarily catalyzed by the UGT1A and UGT2B enzymes. Therefore, it has long been hypothesized that UGT polymorphisms that reduce the capacity to glucuronidate carcinogens and other types of cancer-promoting molecules (e.g. sex hormones) are associated with an increased risk of developing cancers. A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT polymorphisms may be cancer causative polymorphisms, or be linked to as yet undefined causative polymorphisms, either in UGT genes or neighboring genes. This article presents a comprehensive review of these case-control studies, discusses current areas of uncertainty, and highlights future research directions in this field. PMID:26828111

  3. Usability: Human Research Program - Space Human Factors and Habitability

    NASA Technical Reports Server (NTRS)

    Sandor, Aniko; Holden, Kritina L.

    2009-01-01

    The Usability project addresses the need for research in the area of metrics and methodologies used in hardware and software usability testing in order to define quantifiable and verifiable usability requirements. A usability test is a human-in-the-loop evaluation where a participant works through a realistic set of representative tasks using the hardware/software under investigation. The purpose of this research is to define metrics and methodologies for measuring and verifying usability in the aerospace domain in accordance with FY09 focus on errors, consistency, and mobility/maneuverability. Usability metrics must be predictive of success with the interfaces, must be easy to obtain and/or calculate, and must meet the intent of current Human Systems Integration Requirements (HSIR). Methodologies must work within the constraints of the aerospace domain, be cost and time efficient, and be able to be applied without extensive specialized training.

  4. Atlas of Cryptic Genetic Relatedness Among 1000 Human Genomes

    PubMed Central

    Fedorova, Larisa; Qiu, Shuhao; Dutta, Rajib; Fedorov, Alexei

    2016-01-01

    A novel computational method for detecting identical-by-descent (IBD) chromosomal segments between sequenced genomes is presented. It utilizes the distribution patterns of very rare genetic variants (vrGVs), which have minor allele frequencies <0.2%. Contrary to the existing probabilistic approaches our method is rather deterministic, because it considers a group of very rare events which cannot happen together only by chance. This method has been applied for exhaustive computational search of shared IBD segments among 1,092 sequenced individuals from 14 populations. It demonstrated that clusters of vrGVs are unique and powerful markers of genetic relatedness, that uncover IBD chromosomal segments between and within populations, irrespective of whether divergence was recent or occurred hundreds-to-thousands of years ago. We found that several IBD segments are shared by practically any possible pair of individuals belonging to the same population. Moreover, shared short IBD segments (median size 183 kb) were found in 10% of inter-continental human pairs, each comprising of a person from sub-Saharan Africa and a person from Southern Europe. The shortest shared IBD segments (median size 54 kb) were found in 0.42% of inter-continental pairs composed of individuals from Chinese/Japanese populations and Africans from Kenya and Nigeria. Knowledge of inheritance of IBD segments is important in clinical case–control and cohort studies, since unknown distant familial relationships could compromise interpretation of collected data. Clusters of vrGVs should be useful markers for familial relationship and common multifactorial disorders. PMID:26907499

  5. Atlas of Cryptic Genetic Relatedness Among 1000 Human Genomes.

    PubMed

    Fedorova, Larisa; Qiu, Shuhao; Dutta, Rajib; Fedorov, Alexei

    2016-03-01

    A novel computational method for detecting identical-by-descent (IBD) chromosomal segments between sequenced genomes is presented. It utilizes the distribution patterns of very rare genetic variants (vrGVs), which have minor allele frequencies <0.2%. Contrary to the existing probabilistic approaches our method is rather deterministic, because it considers a group of very rare events which cannot happen together only by chance. This method has been applied for exhaustive computational search of shared IBD segments among 1,092 sequenced individuals from 14 populations. It demonstrated that clusters of vrGVs are unique and powerful markers of genetic relatedness, that uncover IBD chromosomal segments between and within populations, irrespective of whether divergence was recent or occurred hundreds-to-thousands of years ago. We found that several IBD segments are shared by practically any possible pair of individuals belonging to the same population. Moreover, shared short IBD segments (median size 183 kb) were found in 10% of inter-continental human pairs, each comprising of a person from sub-Saharan Africa and a person from Southern Europe. The shortest shared IBD segments (median size 54 kb) were found in 0.42% of inter-continental pairs composed of individuals from Chinese/Japanese populations and Africans from Kenya and Nigeria. Knowledge of inheritance of IBD segments is important in clinical case-control and cohort studies, since unknown distant familial relationships could compromise interpretation of collected data. Clusters of vrGVs should be useful markers for familial relationship and common multifactorial disorders. PMID:26907499

  6. If I Could in a Small Way Help”: Motivations for and Beliefs about Sample Donation for Genetic Research

    PubMed Central

    Michie, Marsha; Henderson, Gail; Garrett, Joanne; Corbie-Smith, Giselle

    2012-01-01

    Human genome research depends upon participants who donate genetic samples, but few studies have explored in depth the motivations of genetic research donors. This mixed methods study examines telephone interviews with 752 sample donors in a U.S. genetic epidemiology study investigating colorectal cancer. Quantitative and qualitative results indicate that most participants wanted to help society, and that many also wanted information about their own health, even though such information was not promised. Qualitative analysis reveals that donors believed their samples contributed to a scientific “common good”; imagined samples as information rather than tissues; and often blurred distinctions between research and diagnostic testing of samples. Differences between African American and White perspectives were distinct from educational and other possible explanatory factors. PMID:21680977

  7. Personalized Exposure Assessment: Promising Approaches for Human Environmental Health Research

    PubMed Central

    Weis, Brenda K.; Balshaw, David; Barr, John R.; Brown, David; Ellisman, Mark; Lioy, Paul; Omenn, Gilbert; Potter, John D.; Smith, Martyn T.; Sohn, Lydia; Suk, William A.; Sumner, Susan; Swenberg, James; Walt, David R.; Watkins, Simon; Thompson, Claudia; Wilson, Samuel H.

    2005-01-01

    New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a “toolbox” of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure–disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs. PMID:16002370

  8. [Update of the work of the ethics research in evaluating genetic research and its role as an external ethics committee biobank].

    PubMed

    Alfonso Farnós, Iciar; Hernández Gil, Arantza; Rodríguez Velasco, María

    2013-01-01

    Research on human genome and its applications open great perspectives to improve human beings' health. However, these advances must never endanger the respect of dignity, freedom and rights of the participants in medical research, assuring prohibition of any way of discrimination because of genetic features. The Independent Research Boards (IRB), responsible for safeguarding rights, safety and well-being of the subjects taking part in the biomedical research, assess independently submitted genetic studies, clinical trials whose primary objective is obtaining genetic information and genetic sub-studies of clinical trials with drugs. Biobanks, as safeguarding means to preserve biological samples in suitable quality conditions, must be assigned to two external committees, a scientific one and an ethics one. External ethics committees of biobanks have to make the ethical assessment of the submissions of samples transfers and associated data, in order to carry out research projects. On the other hand, they have to advise biobanks on the compliance of ethical and legal principles, which, in many committees, has turned into the performance of informed consent forms which are in accordance with current laws. PMID:24868962

  9. The Latin American School of Human and Medical Genetics: promoting education and collaboration in genetics and ethics applied to health sciences across the continent.

    PubMed

    Giugliani, Roberto; Baldo, Guilherme; Vairo, Filippo; Lujan Lopez, Monica; Matte, Ursula

    2015-07-01

    The Latin American Network of Human Genetics (RELAGH) created the Latin American School of Human and Medical Genetics (ELAG) to prepare young researchers and professionals of Latin America to deal with the growing challenge of the genomic medicine. ELAG promotes an annually course since 2005, which received 838 students from 17 Latin American countries over these 10 years. ELAG plays an important role to provide education in genetics applied to health sciences to fellows who live in countries with a less favorable economic situation. Influenced, among others, by the humanitarian perspective of José Maria Cantú, one of its founders, ELAG has always favored the discussion of ethical and social issues related to genetics in Latin America. Few initiatives in Latin America lasted 10 consecutive years. One of the factors responsible for the ELAG's success has been its group of faculty members, who contribute to a friendly environment prone to facilitating the exchange of their own experiences with young researchers. PMID:26007289

  10. Genetically-Based Biologic Technologies. Biology and Human Welfare.

    ERIC Educational Resources Information Center

    Mayer, William V.; McInerney, Joseph D.

    The purpose of this six-part booklet is to review the current status of genetically-based biologic technologies and to suggest how information about these technologies can be inserted into existing educational programs. Topic areas included in the six parts are: (1) genetically-based technologies in the curriculum; (2) genetic technologies…

  11. Research opportunities in human behavior and performances

    NASA Technical Reports Server (NTRS)

    Christensen, J. M.; Talbot, J. M.

    1985-01-01

    The NASA research program in the biological and medical aspects of space flight includes investigations of human behavior and performance. The research focuses on psychological and psychophysiological responses to operational and environmental stresses and demands of spaceflight, and encompasses problems in perception, cognition, motivation, psychological stability, small group dynamics, and performance. The primary objective is to acquire the knowledge and methodology to aid in achieving high productivity and essential psychological support of space and ground crews in the Space Shuttle and space station programs. The Life Sciences Research Office (LSRO) of the Federation of American Societies for Experimental Biology reviewed its program in psychology and identified its research for future program planning to be in line with NASA's goals.

  12. An Exploration of Attitudes Among Black Americans Towards Psychiatric Genetic Research

    PubMed Central

    Murphy, Eleanor; Thompson, Azure

    2011-01-01

    With increasing emphasis on understanding genetic contribution to disease, inclusion of all racial and ethnic groups in molecular genetic research is necessary to ensure parity in distribution of research benefits. Blacks are underrepresented in large-scale genetic studies of psychiatric disorders. In an effort to understand the reasons for the underrepresentation, this study explored black participants’ attitudes towards genetic research of psychiatric disorders. Twenty-six adults, the majority of whom were black (n = 18) were recruited from a New York City community to participate in six 90-minute focus groups. This paper reports findings about respondents’ understanding of genetics and genetic research, and opinions about psychiatric genetic research. Primary themes revealed participants’ perceived lack of knowledge about genetics, concerns about potentially harmful study procedures, and confidentiality surrounding mental illness in families. Participation incentives included provision of treatment or related service, monetary compensation, and reporting of results to participants. These findings suggest that recruitment of subjects into genetic studies should directly address procedures, privacy, benefits and follow-up with results. Further, there is critical need to engage communities with education about genetics and mental illness, and provide opportunities for continued discussion about concerns related to genetic research. PMID:19614555

  13. Future directions in human-environment research.

    PubMed

    Moran, Emilio F; Lopez, Maria Claudia

    2016-01-01

    Human-environment research in the 21st century will need to change in major ways. It will need to integrate the natural and the social sciences; it will need to engage stakeholders and citizens in the design of research and in the delivery of science for the benefit of society; it will need to address ethical and democratic goals; and it will need to address a myriad of important theoretical and methodological challenges that continue to impede progress in the advance of sustainability science. PMID:26422805

  14. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach

    PubMed Central

    Saeb, Amr T. M.; Al-Naqeb, Dhekra

    2016-01-01

    Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases. PMID:27313952

  15. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach.

    PubMed

    Saeb, Amr T M; Al-Naqeb, Dhekra

    2016-01-01

    Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases. PMID:27313952

  16. Inbreeding and the genetic complexity of human hypertension.

    PubMed Central

    Rudan, Igor; Smolej-Narancic, Nina; Campbell, Harry; Carothers, Andrew; Wright, Alan; Janicijevic, Branka; Rudan, Pavao

    2003-01-01

    Considerable uncertainty exists regarding the genetic architecture underlying common late-onset human diseases. In particular, the contribution of deleterious recessive alleles has been predicted to be greater for late-onset than for early-onset traits. We have investigated the contribution of recessive alleles to human hypertension by examining the effects of inbreeding on blood pressure (BP) as a quantitative trait in 2760 adult individuals from 25 villages within Croatian island isolates. We found a strong linear relationship between the inbreeding coefficient (F) and both systolic and diastolic BP, indicating that recessive or partially recessive quantitative trait locus (QTL) alleles account for 10-15% of the total variation in BP in this population. An increase in F of 0.01 corresponded to an increase of approximately 3 mm Hg in systolic and 2 mm Hg in diastolic BP. Regression of F on BP indicated that at least several hundred (300-600) recessive QTL contribute to BP variability. A model of the distribution of locus effects suggests that the 8-16 QTL of largest effect together account for a maximum of 25% of the dominance variation, while the remaining 75% of the variation is mediated by QTL of very small effect, unlikely to be detectable using current technologies and sample sizes. We infer that recent inbreeding accounts for 36% of all hypertension in this population. The global impact of inbreeding on hypertension may be substantial since, although inbreeding is declining in Western societies, an estimated 1 billion people globally show rates of consanguineous marriages >20%. PMID:12663539

  17. Genetic Regulation of Charged Particle Mutagenesis in Human Cells

    NASA Technical Reports Server (NTRS)

    Kronenberg, Amy; Gauny, S.; Cherbonnel-Lasserre, C.; Liu, W.; Wiese, C.

    1999-01-01

    Our studies use a series of syngeneic, and where possible, isogenic human B-lymphoblastoid cell lines to assess the genetic factors that modulate susceptibility apoptosis and their impact on the mutagenic risks of low fluence exposures to 1 GeV Fe ions and 55 MeV protons. These ions are representative of the types of charged particle radiation that are of particular significance for human health in the space radiation environment. The model system employs cell lines derived from the male donor WIL-2. These cells have a single X chromosome and they are hemizygous for one mutation marker, hypoxanthine phosphoribosyltransferase (HPRT). TK6 and WTK1 cells were each derived from descendants of WIL-2 and were each selected as heterozygotes for a second mutation marker, the thymidine kinase (TK) gene located on chromosome 17q. The HPRT and TK loci can detect many different types of mutations, from single basepair substitutions up to large scale loss of heterozygosity (LOH). The single expressing copy of TK in the TK6 and WTKI cell lines is found on the same copy of chromosome 17, and this allele can be identified by a restriction fragment length polymorphism (RFLP) identified when high molecular weight DNA is digested by the SacI restriction endonuclease and hybridized against the cDNA probe for TK. A large series of polymorphic linked markers has been identified that span more than 60 cM of DNA (approx. 60 megabasepairs) and distinguish the copy of chromosome 17 bearing the initially active TK allele from the copy of chromosome 17 bearing the silent TK allele in both TK6 and WTKI cells. TK6 cells express normal p53 protein while WTKI cells express homozygous mutant p53. Expression of mutant p53 can increase susceptibility to x-ray-induced mutations. It's been suggested that the increased mutagenesis in p53 mutant cells might be due to reduced apoptosis.

  18. Live vaccines for human metapneumovirus designed by reverse genetics.

    PubMed

    Buchholz, Ursula J; Nagashima, Kunio; Murphy, Brian R; Collins, Peter L

    2006-10-01

    Human metapneumovirus (HMPV) was first described in 2001 and has quickly become recognized as an important cause of respiratory tract disease worldwide, especially in the pediatric population. A vaccine against HMPV is required to prevent severe disease associated with infection in infancy. The primary strategy is to develop a live-attenuated virus for intranasal immunization, which is particularly well suited against a respiratory virus. Reverse genetics provides a means of developing highly characterized 'designer' attenuated vaccine candidates. To date, several promising vaccine candidates have been developed, each using a different mode of attenuation. One candidate involves deletion of the G glycoprotein, providing attenuation that is probably based on reduced efficiency of attachment. A second candidate involves deletion of the M2-2 protein, which participates in regulating RNA synthesis and whose deletion has the advantageous property of upregulating transcription and increasing antigen synthesis. A third candidate involves replacing the P protein gene of HMPV with its counterpart from the related avian metapneumovirus, thereby introducing attenuation owing to its chimeric nature and host range restriction. Another live vaccine strategy involves using an attenuated parainfluenza virus as a vector to express HMPV protective antigens, providing a bivalent pediatric vaccine. Additional modifications to provide improved vaccines will also be discussed. PMID:17181442

  19. GENETIC ASSOCIATION BETWEEN HUMAN CHITINASES AND LUNG FUNCTION IN COPD

    PubMed Central

    Aminuddin, F.; Akhabir, L.; Stefanowicz, D.; Paré, P.D.; Connett, J.E.; Anthonisen, N.R.; Fahy, J.V.; Seibold, M.A.; Burchard, E.G.; Eng, C.; Gulsvik, A.; Bakke, P.; Cho, M. H.; Litonjua, A.; Lomas, D.A.; Anderson, W. H.; Beaty, T.H.; Crapo, J.D.; Silverman, E.K.; Sandford, A.J.

    2013-01-01

    Two primary chitinases have been identified in humans – acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host’s immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to Chronic Obstructive Pulmonary Disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the Caucasian LHS population, the baseline forced expiratory volume in one second (FEV1) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV1 and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV1. Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups. PMID:22200767

  20. Human emotion detector based on genetic algorithm using lip features

    NASA Astrophysics Data System (ADS)

    Brown, Terrence; Fetanat, Gholamreza; Homaifar, Abdollah; Tsou, Brian; Mendoza-Schrock, Olga

    2010-04-01

    We predicted human emotion using a Genetic Algorithm (GA) based lip feature extractor from facial images to classify all seven universal emotions of fear, happiness, dislike, surprise, anger, sadness and neutrality. First, we isolated the mouth from the input images using special methods, such as Region of Interest (ROI) acquisition, grayscaling, histogram equalization, filtering, and edge detection. Next, the GA determined the optimal or near optimal ellipse parameters that circumvent and separate the mouth into upper and lower lips. The two ellipses then went through fitness calculation and were followed by training using a database of Japanese women's faces expressing all seven emotions. Finally, our proposed algorithm was tested using a published database consisting of emotions from several persons. The final results were then presented in confusion matrices. Our results showed an accuracy that varies from 20% to 60% for each of the seven emotions. The errors were mainly due to inaccuracies in the classification, and also due to the different expressions in the given emotion database. Detailed analysis of these errors pointed to the limitation of detecting emotion based on the lip features alone. Similar work [1] has been done in the literature for emotion detection in only one person, we have successfully extended our GA based solution to include several subjects.

  1. The human genetic history of the Americas: the final frontier.

    PubMed

    O'Rourke, Dennis H; Raff, Jennifer A

    2010-02-23

    The Americas, the last continents to be entered by modern humans, were colonized during the late Pleistocene via a land bridge across what is now the Bering strait. However, the timing and nature of the initial colonization events remain contentious. The Asian origin of the earliest Americans has been amply established by numerous classical marker studies of the mid-twentieth century. More recently, mtDNA sequences, Y-chromosome and autosomal marker studies have provided a higher level of resolution in confirming the Asian origin of indigenous Americans and provided more precise time estimates for the emergence of Native Americans. But these data raise many additional questions regarding source populations, number and size of colonizing groups and the points of entry to the Americas. Rapidly accumulating molecular data from populations throughout the Americas, increased use of demographic models to test alternative colonization scenarios, and evaluation of the concordance of archaeological, paleoenvironmental and genetic data provide optimism for a fuller understanding of the initial colonization of the Americas. PMID:20178768

  2. Human genome research and the public interest: Progress notes from an American Science Policy Experiment

    SciTech Connect

    Juengst, E.T. )

    1994-01-01

    This essay reviews the efforts of the US Human Genome Project to anticipate and address the ethical, legal, and social implications of new advances in human genetics. Since 1990, approximately $10 million has been awarded by the National Institutes of Health and the DOE, in support of 65 research, education, and public discussion projects. These projects address four major areas of need: (1) the need for both client-centered assessments of new genetic services and for improved knowledge of the psychosocial and ethnocultural factors that shape clients' clinical genetic experiences; (2) the need for clear professional policies regarding human-subject research, clinical practical standards, and public health goals in human genetics; (3) the need for social policy protection against unfair access to and use of personal genetic information; (4) the need for improved public and professional understanding and discussion of these issues. The Human Genome Project's goal is to have defined, by 1995, policy options and programs capable of addressing these needs. 47 refs.

  3. Unequal Treatment of Human Research Subjects

    PubMed Central

    Resnik, David B.

    2015-01-01

    Unequal treatment of human research subjects is a significant ethical concern, because justice requires that equals be treated equally. If two research subjects are the same in the relevant respects, they should be treated equally. However, not all human subjects are the same in relevant respects: people differ with respect to age, health, gender, race, mental abilities, socioeconomic status, and other characteristics. Disputes sometimes arise concerning the issue of whether subjects are the same in relevant respects and should therefore be treated equally. Allegedly unequal treatment occurs when subjects are treated differently and there is a serious dispute about whether subjects are the same in relevant respects. Patently unequal treatment occurs when there is no significant dispute about whether subjects are the same in relevant respects and they are treated unequally. Research regulations can help to minimize patently unequal treatment by providing rules for investigators, institutional review boards, institutions, and sponsors to follow. However, patently unequal treatment may still occur because the regulations are subject to interpretation. Additional guidance may be necessary to minimize patently unequal treatment of research subjects. PMID:24879129

  4. Research Issues in Genetic Testing of Adolescents for Obesity

    PubMed Central

    Segal, Mary E.; Sankar, Pamela; Reed, Danielle R.

    2006-01-01

    Obesity is often established in adolescence, and advances are being made in identifying its genetic underpinnings. We examine issues related to the eventual likelihood of genetic tests for obesity targeted to adolescents: family involvement; comprehension of the test’s meaning; how knowledge of genetic status may affect psychological adaptation; minors’ ability to control events; parental/child autonomy; ability to make informed medical decisions; self-esteem; unclear distinctions between early/late onset for this condition; and social stigmatization. The public health arena will be important in educating families about possible future genetic tests for obesity. PMID:15478685

  5. International Space Station -- Human Research Facility (HRF)

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Arn Harris Hoover of Lockheed Martin Company demonstrates an engineering mockup of the Human Research Facility (HRF) that will be installed in Destiny, the U.S. Laboratory Module on the International Space Station (ISS). Using facilities similar to research hardware available in laboratories on Earth, the HRF will enable systematic study of cardiovascular, musculoskeletal, neurosensory, pulmonary, radiation, and regulatory physiology to determine biomedical changes resulting from space flight. Research results obtained using this facility are relevant to the health and the performance of the astronaut as well as future exploration of space. Because this is a mockup, the actual flight hardware may vary as desings are refined. (Credit: NASA/Marshall Space Flight Center)

  6. Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders

    PubMed Central

    Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M.; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura

    2015-01-01

    The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. PMID:25568173

  7. Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.

    PubMed

    Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola

    2015-08-01

    The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. PMID:25568173

  8. Translational genetic approaches to substance use disorders: bridging the gap between mice and humans

    PubMed Central

    Palmer, Abraham A.; de Wit, Harriet

    2012-01-01

    While substance abuse disorders only occur in humans, mice and other model organisms can make valuable contributions to genetic studies of these disorders. In this review, we consider a few specific examples of how model organisms have been used in conjunction with studies in humans to study the role of genetic factors in substance use disorders. In some examples genes that were first discovered in mice were subsequently studied in humans. In other examples genes or specific polymorphisms in genes were first studied in humans and then modeled in mice. Using anatomically and temporally specific genetic, pharmacological and other environmental manipulations in conjunction with histological analyses, mechanistic insights that would be difficult to obtain in humans have been obtained in mice. We hope these examples illustrate how novel biological insights about the effect of genes on substance use disorders can be obtained when mouse and human genetic studies are successfully integrated. PMID:22170288

  9. Using Fuzzy Gaussian Inference and Genetic Programming to Classify 3D Human Motions

    NASA Astrophysics Data System (ADS)

    Khoury, Mehdi; Liu, Honghai

    This research introduces and builds on the concept of Fuzzy Gaussian Inference (FGI) (Khoury and Liu in Proceedings of UKCI, 2008 and IEEE Workshop on Robotic Intelligence in Informationally Structured Space (RiiSS 2009), 2009) as a novel way to build Fuzzy Membership Functions that map to hidden Probability Distributions underlying human motions. This method is now combined with a Genetic Programming Fuzzy rule-based system in order to classify boxing moves from natural human Motion Capture data. In this experiment, FGI alone is able to recognise seven different boxing stances simultaneously with an accuracy superior to a GMM-based classifier. Results seem to indicate that adding an evolutionary Fuzzy Inference Engine on top of FGI improves the accuracy of the classifier in a consistent way.

  10. The Population Reference Sample, POPRES: A Resource for Population, Disease, and Pharmacological Genetics Research

    PubMed Central

    Nelson, Matthew R.; Bryc, Katarzyna; King, Karen S.; Indap, Amit; Boyko, Adam R.; Novembre, John; Briley, Linda P.; Maruyama, Yuka; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Oksenberg, Jorge R.; Hauser, Stephen L.; Stirnadel, Heide A.; Kooner, Jaspal S.; Chambers, John C.; Jones, Brendan; Mooser, Vincent; Bustamante, Carlos D.; Roses, Allen D.; Burns, Daniel K.; Ehm, Margaret G.; Lai, Eric H.

    2008-01-01

    Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections. To facilitate exploratory genetics research, we have assembled a DNA resource from a large number of subjects participating in multiple studies throughout the world. This growing resource was initially genotyped with a commercially available genome-wide 500,000 single-nucleotide polymorphism panel. This project includes nearly 6,000 subjects of African-American, East Asian, South Asian, Mexican, and European origin. Seven informative axes of variation identified via principal-component analysis (PCA) of these data confirm the overall integrity of the data and highlight important features of the genetic structure of diverse populations. The potential value of such extensively genotyped collections is illustrated by selection of genetically matched population controls in a genome-wide analysis of abacavir-associated hypersensitivity reaction. We find that matching based on country of origin, identity-by-state distance, and multidimensional PCA do similarly well to control the type I error rate. The genotype and demographic data from this reference sample are freely available through the NCBI database of Genotypes and Phenotypes (dbGaP). PMID:18760391

  11. [Development of genetic research in ophthalmology with special reference to Switzerland].

    PubMed

    Klein, D

    1990-05-01

    The relationship between ophthalmology and genetics has always been a very active one, and existed even before Mendel's laws of inheritance were known. The pedigree method in particular yielded satisfactory results even to the first researchers. Later, Helmholtz's invention of the ophthalmoscope (in 1851) and the rediscovery of Mendel's laws of heredity (in 1900) made major contributions to the progress of human genetics in ophthalmology. Credit is due to J. F. Horner of Zurich (1831-1886) for having first established the X-chromosomal inheritance of colorblindness. Subsequently, the development of genetic research was advanced in particular by Alfred Vogt, Professor of Ophthalmology in Zurich (1879-1943) and Adolf Franceschetti in Geneva (1896-1968) and their co-workers. We are indebted to Vogt for the first description of albinismus solum bulbi. Credit is also due to him for having made early diagnosis of myotonic dystrophy (Steinert) possible, a major discovery for genetic counseling. He was the first to detect, by slit-lamp examination, characteristic lens changes in the form of whitish, red, and green opacities in the anterior and posterior subcapsular regions. Franceschetti's achievements include the description of several clinical syndromes, of which mandibulofacial dysostosis has become well known. Among the hereditary retinal dystrophies, he described fundus flavimaculatus (yellowish lesions disseminated in the deeper layers of the posterior pole) as a new entity, attributed to degeneration of the pigment epithelium. In addition to more than 500 articles, he was also co-author, with J. François and J. Babel, of a monumental handbook in two volumes titled Hérédodégénérescences choriorétiniennes (of which an English translation appeared in 1974).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2195224

  12. Puzzling role of genetic risk factors in human longevity: "risk alleles" as pro-longevity variants.

    PubMed

    Ukraintseva, Svetlana; Yashin, Anatoliy; Arbeev, Konstantin; Kulminski, Alexander; Akushevich, Igor; Wu, Deqing; Joshi, Gaurang; Land, Kenneth C; Stallard, Eric

    2016-02-01

    Complex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity. Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in the effect of gene on vulnerability to death with age (especially, from "bad" to "good"); (iii) gene-gene interaction; and (iv) gene-environment interaction, among other factors. A review of current knowledge provides many examples of genetic factors that may increase the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it. Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that the influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease "risk allele" can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention. PMID:26306600

  13. Analysis of Dengue Virus Genetic Diversity during Human and Mosquito Infection Reveals Genetic Constraints

    PubMed Central

    Sessions, October M.; Wilm, Andreas; Kamaraj, Uma Sangumathi; Choy, Milly M.; Chow, Angelia; Chong, Yuwen; Ong, Xin Mei; Nagarajan, Niranjan; Cook, Alex R.; Ooi, Eng Eong

    2015-01-01

    Dengue viruses (DENV) cause debilitating and potentially life-threatening acute disease throughout the tropical world. While drug development efforts are underway, there are concerns that resistant strains will emerge rapidly. Indeed, antiviral drugs that target even conserved regions in other RNA viruses lose efficacy over time as the virus mutates. Here, we sought to determine if there are regions in the DENV genome that are not only evolutionarily conserved but genetically constrained in their ability to mutate and could hence serve as better antiviral targets. High-throughput sequencing of DENV-1 genome directly from twelve, paired dengue patients’ sera and then passaging these sera into the two primary mosquito vectors showed consistent and distinct sequence changes during infection. In particular, two residues in the NS5 protein coding sequence appear to be specifically acquired during infection in Ae. aegypti but not Ae. albopictus. Importantly, we identified a region within the NS3 protein coding sequence that is refractory to mutation during human and mosquito infection. Collectively, these findings provide fresh insights into antiviral targets and could serve as an approach to defining evolutionarily constrained regions for therapeutic targeting in other RNA viruses. PMID:26327586

  14. 75 FR 37813 - Secretary's Advisory Committee on Human Research Protections

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-30

    ... HUMAN SERVICES Secretary's Advisory Committee on Human Research Protections AGENCY: Department of Health... hereby given that the Secretary's Advisory Committee on Human Research Protections (SACHRP) will hold its..., Office for Human Research Protections (OHRP), or Julia Gorey, J.D., Executive Director, SACHRP;...

  15. Challenges of Research and Human Capital Development in Nigeria

    ERIC Educational Resources Information Center

    Chikwe, Christian K.; Ogidi, Reuben C.; Nwachukwu, K.

    2015-01-01

    The paper discussed the challenges of research and human capital development in Nigeria. Research and human capital development are critical to the development of any nation. Research facilitates human capital development. A high rating in human capital development indices places a country among the leading countries of the world. The paper…

  16. Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

    PubMed Central

    Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

    2014-01-01

    Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

  17. The Impact of a Web-Based Research Simulation in Bioinformatics on Students' Understanding of Genetics

    NASA Astrophysics Data System (ADS)

    Gelbart, Hadas; Brill, Gilat; Yarden, Anat

    2009-11-01

    Providing learners with opportunities to engage in activities similar to those carried out by scientists was addressed in a web-based research simulation in genetics developed for high school biology students. The research simulation enables learners to apply their genetics knowledge while giving them an opportunity to participate in an authentic genetics study using bioinformatics tools. The main purpose of the study outlined here is to examine how learning using this research simulation influences students’ understanding of genetics, and how students’ approaches to learning using the simulation influence their learning outcomes. Using both quantitative and qualitative procedures, we were able to show that while learning using the simulation students expanded their understanding of the relationships between molecular mechanisms and phenotype, and refined their understanding of certain genetic concepts. Two types of learners, research-oriented and task-oriented, were identified on the basis of the differences in the ways they seized opportunities to recognize the research practices, which in turn influenced their learning outcomes. The research-oriented learners expanded their genetics knowledge more than the task-oriented learners. The learning approach taken by the research-oriented learners enabled them to recognize the epistemology that underlies authentic genetic research, while the task-oriented learners referred to the research simulation as a set of simple procedural tasks. Thus, task-oriented learners should be encouraged by their teachers to cope with the scientists’ steps, while learning genetics through the simulation in a class setting.

  18. Developing genetic competency in undergraduate nursing students through the context of human disease and the constructivist framework

    NASA Astrophysics Data System (ADS)

    Tribble, Leta Meole

    Nowhere is the influence of genetics more extensively seen than in medicine. More precise diagnostic testing, prevention methods, and risk counseling have resulted from recent decades of genetics research, including the Human Genome Project (HGP). The expansion in genetics knowledge and related technologies will drive a major paradigm shift from diagnosis and treatment to preventive medicine. Resulting from this predicted shift are educational challenges for healthcare professionals including both physicians and nurses. The largest group of healthcare providers is registered professional nurses whose work allows a unique and holistic view of patients and families, often caring for patients throughout the life span. Nurses need to understand basic genetic concepts including the role of genes in common diseases, to identify individuals at risk through the collection of informed family histories, to provide information about genetic testing and informed consent, and to know when and how to make appropriate referrals to genetic specialists. The purpose of this study was to expand the clinical application and use of genetic principles in patient management and care. To do this, a survey of South Carolina nursing educators from twenty two nursing programs was conducted to determine the extent of genetic content in the curriculum. The second part of the study was teaching a semester course in human genetics to undergraduate nursing students, a need identified in the literature review and supported by results of the nursing programs survey. Through the use of clinical case studies, PBL activities, and "shrink wrapped" lectures, all congruent with the constructivist viewpoint of learning, student's objective post-intervention measurements indicated significant improvement in content knowledge with an effect size of 1.6 and significant improvement in their ability to analyze and draw the family history in a pedigree format. An attitudinal tool used to assess student

  19. The rise of developmental genetics - a historical account of the fusion of embryology and cell biology with human genetics and the emergence of the Stem Cell Initiative.

    PubMed

    Kidson, S H; Ballo, R; Greenberg, L J

    2016-01-01

    Genetics and cell biology are very prominent areas of biological research with rapid advances being driven by a flood of theoretical, technological and informational knowledge. Big biology and small biology continue to feed off each other. In this paper, we provide a brief overview of the productive interactions that have taken place between human geneticists and cell biologists at UCT, and credit is given to the enabling environment created led by Prof. Peter Beighton. The growth of new disciplines and disciplinary mergers that have swept away division of the past to make new exciting syntheses are discussed. We show how our joint research has benefitted from worldwide advances in developmental genetics, cloning and stem cell technologies, genomics, bioinformatics and imaging. We conclude by describing the role of the UCT Stem Cell Initiative and show how we are using induced pluripotent cells to carry out disease-in-the- dish studies on retinal degeneration and fibrosis. PMID:27245528

  20. GENETIC ASSOCIATION ANALYSIS OF COPY NUMBER VARIATION (CNVs) IN HUMAN DISEASE PATHOGENESIS

    PubMed Central

    Ionita-Laza, Iuliana; Rogers, Angela J.; Lange, Christoph; Raby, Benjamin A.; Lee, Charles

    2009-01-01

    Structural genetic variation, including copy number variation (CNV), constitutes a substantial fraction of total genetic variability and the importance of structural genetic variants in modulating human disease is increasingly being recognized. Early successes in identifying disease-associated CNVs via a candidate gene approach mandate that future disease association studies need to include structural genetic variation. Such analyses should not rely on previously developed methodologies that were designed to evaluate single nucleotide polymorphisms (SNPs). Instead, development of novel technical, statistical, and epidemiologic methods will be necessary to optimally capture this newly-appreciated form of genetic variation in a meaningful manner. PMID:18822366

  1. Interpreting noncoding genetic variation in complex traits and human disease.

    PubMed

    Ward, Lucas D; Kellis, Manolis

    2012-11-01

    Association studies provide genome-wide information about the genetic basis of complex disease, but medical research has focused primarily on protein-coding variants, owing to the difficulty of interpreting noncoding mutations. This picture has changed with advances in the systematic annotation of functional noncoding elements. Evolutionary conservation, functional genomics, chromatin state, sequence motifs and molecular quantitative trait loci all provide complementary information about the function of noncoding sequences. These functional maps can help with prioritizing variants on risk haplotypes, filtering mutations encountered in the clinic and performing systems-level analyses to reveal processes underlying disease associations. Advances in predictive modeling can enable data-set integration to reveal pathways shared across loci and alleles, and richer regulatory models can guide the search for epistatic interactions. Lastly, new massively parallel reporter experiments can systematically validate regulatory predictions. Ultimately, advances in regulatory and systems genomics can help unleash the value of whole-genome sequencing for personalized genomic risk assessment, diagnosis and treatment. PMID:23138309

  2. Future human bone research in space

    NASA Technical Reports Server (NTRS)

    LeBlanc, A.; Shackelford, L.; Schneider, V.

    1998-01-01

    Skylab crewmembers demonstrated negative calcium (Ca) balance reaching about -300 mg/day by flight day 84. Limited bone density (BMD) measurements documented that bone was not lost equally from all parts of the skeleton. Subsequent BMD studies during long duration Russian flights documented the regional extent of bone loss. These studies demonstrated mean losses in the spine, femur neck, trochanter, and pelvis of about 1%-1.6% with large differences between individuals as well as between bone sites in a given individual. Limited available data indicate postflight bone recovery occurred in some individuals, but may require several years for complete restoration. Long duration bedrest studies showed a similar pattern of bone loss and calcium balance (-180 mg/day) as spaceflight. During long duration bedrest, resorption markers were elevated, formation markers were unchanged, 1,25 vitamin D (VitD) and calcium absorption were decreased, and serum ionized Ca was increased. Although this information is a good beginning, additional spaceflight research is needed to assess architectural and subregional bone changes, elucidate mechanisms, and develop efficient as well as effective countermeasures. Space research poses a number of unique problems not encountered in ground-based laboratory research. Therefore, researchers contemplating human spaceflight research need to consider a number of unique problems related to spaceflight in their experimental design.

  3. Development of a Rotating Human Research Facility

    NASA Technical Reports Server (NTRS)

    Mulenburg, Gerald M.; Caldwell, William F.; Tucker, John; Wade, Charles E. (Technical Monitor)

    1994-01-01

    A unique facility has been developed at the NASA Ames Research Center to provide scientists with unusual research opportunities at greater than Earth's gravity. In addition to its use for basic research, this facility will help provide answers to many of the questions posed by proponents of rotating human space vehicles. This paper describes the design and planned use of this facility, the Spaceflight Environmental Simulator. Using an existing 52-foot diameter cylindrical rotating platform design centrifuge, the revised facility design includes the provision of two human habitats for long duration studies of the effects of hypergravity. Up to four humans (per habitat) will be able to live at up to 2 G for as long as one month without stopping the centrifuge. Each habitat, constructed of lightweight honeycomb sandwich panels, is nominally 9 ft high x 11 ft wide x 25 1/2 ft long. A radial positioning system provides for positioning each habitat at a distance of 15 to 21 feet from the centrifuge's axis of rotation to the midpoint of the habitat's interior floor. As centrifugal acceleration changes with rotation rate, a habitat floor-mounted accelerometer signal provides automatic servo controlled adjustment of each habitat's angle of inclination to provide an environment for the habitat's crew and cargo in which the resultant gravity vector is normal to the habitat floor at all times. Design of the habitats and modifications to the centrifuge are complete, and are currently under construction. Design philosophy and operational rationale are presented along with complete descriptions of the facility and its systems.

  4. The Impact of a Web-Based Research Simulation in Bioinformatics on Students' Understanding of Genetics

    ERIC Educational Resources Information Center

    Gelbart, Hadas; Brill, Gilat; Yarden, Anat

    2009-01-01

    Providing learners with opportunities to engage in activities similar to those carried out by scientists was addressed in a web-based research simulation in genetics developed for high school biology students. The research simulation enables learners to apply their genetics knowledge while giving them an opportunity to participate in an authentic…

  5. The 'Out of Africa' Hypothesis, Human Genetic Diversity, and Comparative Economic Development

    PubMed Central

    Ashraf, Quamrul; Galor, Oded

    2013-01-01

    This research argues that deep-rooted factors, determined tens of thousands of years ago, had a significant effect on the course of economic development from the dawn of human civilization to the contemporary era. It advances and empirically establishes the hypothesis that, in the course of the exodus of Homo sapiens out of Africa, variation in migratory distance from the cradle of humankind to various settlements across the globe affected genetic diversity and has had a long-lasting effect on the pattern of comparative economic development that is not captured by geographical, institutional, and cultural factors. In particular, the level of genetic diversity within a society is found to have a hump-shaped effect on development outcomes in both the pre-colonial and the modern era, reflecting the trade-off between the beneficial and the detrimental effects of diversity on productivity. While the intermediate level of genetic diversity prevalent among Asian and European populations has been conducive for development, the high degree of diversity among African populations and the low degree of diversity among Native American populations have been a detrimental force in the development of these regions. PMID:25506083

  6. An atlas of genetic correlations across human diseases and traits.

    PubMed

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri; Gusev, Alexander; Day, Felix R; Loh, Po-Ru; Duncan, Laramie; Perry, John R B; Patterson, Nick; Robinson, Elise B; Daly, Mark J; Price, Alkes L; Neale, Benjamin M

    2015-11-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual-level genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique-cross-trait LD Score regression-for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses, as there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment. PMID:26414676

  7. An Atlas of Genetic Correlations across Human Diseases and Traits

    PubMed Central

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri; Gusev, Alexander; Day, Felix R.; Loh, Po-Ru; Duncan, Laramie; Perry, John R.B.; Patterson, Nick; Robinson, Elise B.; Daly, Mark J.; Price, Alkes L.; Neale, Benjamin M.

    2015-01-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique – cross-trait LD Score regression – for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity and associations between educational attainment and several diseases. These results highlight the power of genome-wide analyses, since there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment. PMID:26414676

  8. An analysis of the human genetics content of 13 general biology textbooks.

    PubMed

    Mertens, T R; Bowman, D

    1981-01-01

    Professionals in genetics, medicine, and biology education have in recent years called for placing greater emphasis on human genetics in the education of the nation's citizenry. Since a large collegiate audience for such education is found in the general biology classroom, we elected to analyze 13 current and widely used general biology textbooks to determine their human genetics content. The analyses revealed that from 6.68 to 15.51 percent of the books' pages were devoted to genetics, but only 0.75 to 3.44 percent of the pages dealt specifically with human genetics. The number of human genetic traits discussed in the books ranged from four to 24, with a mean of 15.77. Nine different chromosome aberrations were cited, with Down, Klinefelter, and Turner syndromes being mentioned most often. Twenty autosomal dominant, fifteen autosomal recessive, and seven X-linked traits were used as examples in the various textbooks. Most frequently cited single-gene conditions were the ABO blood groups, sickle cell anemia, phenylketonuria, hemophilia, and red/green colorblindness. The books varied considerably in the emphasis given to social applications of medical genetics. Based on the findings of this study, we offer several recommendations for the improvement of the human genetics content of general biology textbooks and courses. PMID:7328307

  9. Molecular genetics of the human MHC complement gene cluster.

    PubMed

    Yu, C Y

    1998-01-01

    The human major histocompatibility complex (MHC) complement gene cluster (MCGC) is a highly variable region that is characterized by polymorphisms, variations in gene size and gene number, and associations with diseases. Deficiencies in complement C2 are either due to abolition of C2 protein synthesis by mini-deletions that caused frameshift mutations, or blocked secretion of the C2 protein by single amino acid substitutions. One, two or three C4 genes may be present in a human MCGC haplotype and these genes may code for C4A, C4B, or both. Deficiencies of C4A or C4B proteins are attributed to the expression of identical C4 isotypes or allotypes from the C4 loci, the absence or deletion of a C4 gene, 2-bp insertion at exon 29 or 1-bp deletion at exon 20 that caused frameshift mutations. The C4 genes are either 21 or 14.6 kb in size due to the presence of endogenous retrovirus HERV-K(C4) in the intron 9 of long C4 genes. A deletion or duplication of a C4 gene is always accompanied by its neighboring genes, RP at the 5' region, and CYP21 and TNX at the 3' region. These four genes form a genetic unit termed the RCCX module. In an RCCX bimodular structure, the pseudogene CYP21A, and partially duplicated gene segments TNXA and RP2 are present between the two C4 loci. The RCCX modular variations in gene number and gene size contributed to unequal crossovers and exchanges of polymorphic sequences/mutations, resulting in the homogenization of C4 polymorphisms and acquisitions of deleterious mutations in RP1, C4A, C4B, CYP21B and TNXB genes. RD, SKI2W, DOM3Z and RP1 are the four novel genes found between Bf and C4. RD and Ski2w proteins may be related to RNA splicing, RNA turnover and regulation of translation. The functions of Dom3z and RP1 are being investigated. The complete genomic DNA sequence between C2 and TNX is now available. This should facilitate a complete documentation of polymorphisms, mutations and disease associations for the MCGC. PMID:10072631

  10. Role of genetic variants in ADIPOQ in human eating behavior.

    PubMed

    Rohde, Kerstin; Keller, Maria; Horstmann, Annette; Liu, Xuanshi; Eichelmann, Fabian; Stumvoll, Michael; Villringer, Arno; Kovacs, Peter; Tönjes, Anke; Böttcher, Yvonne

    2015-01-01

    The beneficial effects of adiponectin and its negative correlation with BMI are well described. Adiponectin serum levels are altered in eating disorders such as anorexia nervosa, bulimia nervosa or binge eating. Here, we tested the hypothesis that (1) adiponectin serum levels correlate with human eating behavior factors and (2) that genetic variants of the ADIPOQ locus influence both serum levels and eating behavior. We analyzed 11 SNPs within ADIPOQ and in the 5' UTR and measured serum adiponectin levels in 1,036 individuals from the German Sorbs population. The German version of the three-factor eating questionnaire (FEV) was completed by 548 Sorbs. For replication purposes, we included an independent replication cohort from Germany (N = 350). In the Sorbs, we observed positive correlations of restraint with adiponectin serum levels (P = 0.001; r = 0.148) which, however, did not withstand adjustment for covariates (P = 0.083; r = 0.077). In addition, four SNPs were nominally associated with serum adiponectin levels (all P < 0.05). Of these, two variants (rs3774261; rs1501229, all P < 0.05) were also related to disinhibition. Furthermore, three variants were exclusively associated with hunger (rs2036373, P = 0.049) and disinhibition (rs822396; rs864265, all P < 0.05). However, none of these associations withstood Bonferroni corrections for multiple testing (all P > 9.3 × 10(-4)). In our replication cohort, we observed similar effect directions at rs1501229 for disinhibition and hunger. A meta-analysis resulted in nominal statistical significance P = 0.036 (Z score 2.086) and P = 0.017 (Z score 2.366), respectively. Given the observed relationship of the SNPs with adiponectin levels and eating behavior, our data support a potential role of adiponectin in human eating behavior. Whether the relationship with eating behavior is mediated by the effects of circulating adiponectin warrants further investigations. PMID:25542302

  11. Public and Biobank Participant Attitudes toward Genetic Research Participation and Data Sharing

    PubMed Central

    Lemke, A.A.; Wolf, W.A.; Hebert-Beirne, J.; Smith, M.E.

    2010-01-01

    Research assessing attitudes toward consent processes for high-throughput genomic-wide technologies and widespread sharing of data is limited. In order to develop a better understanding of stakeholder views toward these issues, this cross-sectional study assessed public and biorepository participant attitudes toward research participation and sharing of genetic research data. Forty-nine individuals participated in 6 focus groups; 28 in 3 public focus groups and 21 in 3 NUgene biorepository participant focus groups. In the public focus groups, 75% of participants were women, 75% had some college education or more, 46% were African-American and 29% were Hispanic. In the NUgene focus groups, 67% of participants were women, 95% had some college education or more, and the majority (76%) of participants was Caucasian. Five major themes were identified in the focus group data: (a) a wide spectrum of understanding of genetic research; (b) pros and cons of participation in genetic research; (c) influence of credibility and trust of the research institution; (d) concerns about sharing genetic research data and need for transparency in the Policy for Sharing of Data in National Institutes of Health-Supported or Conducted Genome-Wide Association Studies; (e) a need for more information and education about genetic research. In order to increase public understanding and address potential concerns about genetic research, future efforts should be aimed at involving the public in genetic research policy development and in identifying or developing appropriate educational strategies to meet the public's needs. PMID:20805700

  12. Genetics

    MedlinePlus

    Homozygous; Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  13. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  14. Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12–15, 2009, Yaoundé, Cameroon

    PubMed Central

    Sirugo, Giorgio; Williams, Scott M.; Royal, Charmaine D. M.; Newport, Melanie J.; Hennig, Branwen J.; Mariani-Costantini, Renato; Buonaguro, Franco M.; Velez Edwards, Digna R.; Ibrahim, Muntaser; Soodyall, Himla; Wonkam, Ambroise; Ramesar, Raj; Rotimi, Charles N.

    2010-01-01

    The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural meeting in Accra, Ghana,1 has the stated missions of (1) disseminating information about human genetics research in Africa, (2) establishing a mentorship network providing educational resources, including the development of appropriate technology transfer, (3) providing advocacy for human genetic research in Africa, and (4) encouraging collaborative research. Despite its young age, the AfSHG has developed a strong cadre of active researchers, both within and outside of Africa, with more than 400 members (from 16 countries across Africa as well as 8 other countries), and has held six successful meetings, five in Africa and one in the United States. PMID:20682860

  15. How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria

    PubMed Central

    Kwiatkowski, Dominic P.

    2005-01-01

    Malaria is a major killer of children worldwide and the strongest known force for evolutionary selection in the recent history of the human genome. The past decade has seen growing evidence of ethnic differences in susceptibility to malaria and of the diverse genetic adaptations to malaria that have arisen in different populations: epidemiological confirmation of the hypotheses that G6PD deficiency, α+ thalassemia, and hemoglobin C protect against malaria mortality; the application of novel haplotype-based techniques demonstrating that malaria-protective genes have been subject to recent positive selection; the first genetic linkage maps of resistance to malaria in experimental murine models; and a growing number of reported associations with resistance and susceptibility to human malaria, particularly in genes involved in immunity, inflammation, and cell adhesion. The challenge for the next decade is to build the global epidemiological infrastructure required for statistically robust genomewide association analysis, as a way of discovering novel mechanisms of protective immunity that can be used in the development of an effective malaria vaccine. PMID:16001361

  16. High volume molecular genetic identification of single nucleotide polymorphisms using Genetic Bit Analysis Application to human genetic diagnosis

    SciTech Connect

    Boyce-Jacino, M.T.; Reynolds, J.; Nikiforov, T.

    1994-09-01

    The most common type of genetic disease-associated mutation is the single nucleotide polymorphism (SNP). Because most genetic diseases can be caused by multiple SNPs in the same gene, effective routine diagnosis of complex genetic diseases is dependent on a simple and reliable method of interrogating SNP sites. Molecular Tool`s solid phase assay capable of direct genotyping (single base sequencing) of SNP sites, Genetic Bit Analysis (GBA), involves hybridization-capture of a single-stranded PCR product to a sequence-specific, microtiter plate-bound oligonucleotide primer. The captured PCR product then acts as template for single-base extension of the capture primer across the polymorphic site, enabling direct determination of the base composition of the polymorphism through a simple colormetric assay. Genotyping in a high volume, semi-automated, processing system with a current capacity of 100 SNP interrogations per technician per day enables the screening of candidate mutations rapidly and cost-effectively, critically important to comprehensive genetic diagnosis. Using this gel-free technology, we have developed prototype diagnostic tests for CFTR and ApoE polymorphisms which enable direct sequencing of the polymorphic base at each site of interest. Routine clinical diagnosis of genetically complex diseases such as cystic fibrosis is dependent on this combination of robust biochemistry and simple format. Additionally, the ability to transfer the format and biochemistry to any disease gene of interest enables the broad application of this technology to clinical diagnostics, especially for genetically complex diseases.

  17. Human-Robot Interaction Directed Research Project

    NASA Technical Reports Server (NTRS)

    Sandor, Aniko; Cross, Ernest V., II; Chang, M. L.

    2014-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces and command modalities affect the human's ability to perform tasks accurately, efficiently, and effectively when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. This DRP concentrates on three areas associated with interfaces and command modalities in HRI which are applicable to NASA robot systems: 1) Video Overlays, 2) Camera Views, and 3) Command Modalities. The first study focused on video overlays that investigated how Augmented Reality (AR) symbology can be added to the human-robot interface to improve teleoperation performance. Three types of AR symbology were explored in this study, command guidance (CG), situation guidance (SG), and both (SCG). CG symbology gives operators explicit instructions on what commands to input, whereas SG symbology gives operators implicit cues so that operators can infer the input commands. The combination of CG and SG provided operators with explicit and implicit cues allowing the operator to choose which symbology to utilize. The objective of the study was to understand how AR symbology affects the human operator's ability to align a robot arm to a target using a flight stick and the ability to allocate attention between the symbology and external views of the world. The study evaluated the effects type of symbology (CG and SG) has on operator tasks performance and attention allocation during teleoperation of a robot arm. The second study expanded on the first study by evaluating the effects of the type of

  18. Understanding our Genetic Inheritance: The U.S. Human Genome Project, The First Five Years FY 1991--1995

    DOE R&D Accomplishments Database

    1990-04-01

    The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will by of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that affect mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focused on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. The basic data produced will be collected in electronic databases that will make the information readily accessible on convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project.

  19. Understanding our genetic inheritance: The US Human Genome Project, The first five years FY 1991--1995

    SciTech Connect

    1990-04-01

    The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will by of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that affect mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focused on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. The basic data produced will be collected in electronic databases that will make the information readily accessible on convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project.

  20. Can Man Control His Biological Evolution? A Symposium on Genetic Engineering. Xeroxing Human Beings

    ERIC Educational Resources Information Center

    Freund, Paul A.

    1972-01-01

    If the aim of new research is to improve the genetic inheritance of future generations, then decisions regarding who should decide what research should be done needs to be established. Positive and negative eugenics need to be considered thoroughly. (PS)

  1. Genetics of PTSD: Fear Conditioning as a Model for Future Research.

    PubMed

    Amstadter, Ananda B; Nugent, Nicole R; Koenen, Karestan C

    2009-06-01

    In the last decade, the number of publications in psychiatric genetics has nearly tripled but little attention has been paid to the role of genetic factors in the etiology of posttraumatic stress disorder (PTSD). The present review summarizes the current state of genetic research on PTSD. First, we outline information regarding genetic influences provided by family investigations and by twin studies. Second, we propose the fear-conditioning model of PTSD as a framework for the nomination of candidate genes that may be related to the disorder. Third, we review lines of evidence from three neurobiological systems involved in fear conditioning, and we summarize published investigations of genetic variants studied in association with PTSD in these three systems. Finally, we review gene-by-environment interaction research, a promising novel approach to genetic research in PTSD. PMID:19779593

  2. Mouse models with human immunity and their application in biomedical research

    PubMed Central

    Zhang, Baojun; Duan, Ziyuan; Zhao, Yong

    2009-01-01

    Biomedical research in human beings is largely restricted to in vitro studies that lack complexity of a living organism. To overcome this limitation, humanized mouse models are developed based on immunodeficient characteristics of severe combined immunodeficiency (SCID) or recombination activating gene (Rag)null mice, which can accept xenografts. Peripheral constitution of human immunity in SCID or Ragnull mice has been achieved by transplantation of mature human immune cells, foetal human thymus, bone marrow, liver tissues, lymph nodes or a combination of these, although efficiency needs to be improved. These mouse models with constituted human immunity (defined as humanized mice in the present text) have been widely used to investigate the basic principles of human immunobiology as well as complex pathomechanisms and potential therapies of human diseases. Here, elements of an ideal humanized mouse model are highlighted including genetic and non-genetic modification of recipient mice, transplantation strategies and proposals to improve engraftments. The applications of the humanized mice to study the development and response of human immune cells, human autoimmune diseases, virus infections, transplantation biology and tumour biology are reviewed as well. PMID:18419795

  3. Potential International Approaches to Ownership/Control of Human Genetic Resources.

    PubMed

    Rhodes, Catherine

    2016-09-01

    In its governance activities for genetic resources, the international community has adopted various approaches to their ownership, including: free access; common heritage of mankind; intellectual property rights; and state sovereign rights. They have also created systems which combine elements of these approaches. While governance of plant and animal genetic resources is well-established internationally, there has not yet been a clear approach selected for human genetic resources. Based on assessment of the goals which international governance of human genetic resources ought to serve, and the implications for how they will be accessed and utilised, it is argued that common heritage of mankind will be the most appropriate approach to adopt to their ownership/control. It does this with the aim of stimulating discussion in this area and providing a starting point for deeper consideration of how a common heritage of mankind, or similar, regime for human genetic resources would function and be implemented. PMID:26297608

  4. Research Review: Genetic Vulnerability or Differential Susceptibility in Child Development--The Case of Attachment

    ERIC Educational Resources Information Center

    Bakermans-Kranenburg, Marian J.; van IJzendoorn, Marinus H.

    2007-01-01

    Gene-environment interactions interpreted in terms of differential susceptibility may play a large part in the explanation of individual differences in human development. Reviewing studies on the behavioral and molecular genetics of attachment, we present evidence for interactions between genetic and environmental factors explaining individual…

  5. Toward pre-conceptual genetic analysis of human spermatozoa.

    PubMed

    Dozortsev, Dmitri; Serafim, Rui; Cardoso, J Jakson; Abdelmassih, Soraya; Nagy, Peter; Diamond, Michael P; Abdelmassih, Roger

    2003-01-01

    Nuclei of mature mammalian spermatozoa are extraordinarily resistant to chemical and thermal injury. Additionally, decondensation of spermatozoa DNA can be accompanied by little or no visual changes of the sperm head. This study tested whether human spermatozoa could be recovered following several cycles of primer extension preamplification (PEP) and used to achieve fertilization and subsequent development of human oocytes. An attempt was also made to amplify PEP buffer after spermatozoon removal. The results demonstrate that the sperm head can be successfully recovered following treatment with KOH or proteinase K followed by one to four cycles of PEP. It is also shown that following this treatment, the spermatozoa can be injected into the oocytes and will transform into a pronucleus if the oocyte is activated by sperm cytosolic fraction. In some cases, it was also possible to obtain polymerase chain reaction signals using a buffer after sperm cells were removed following several cycles of PEP. Although sperm participation in development was confirmed by fluorescence in-situ hybridization, light microscopy revealed some degree of damage to spermatozoal chromosomes. It is concluded that pre-conceptual analysis of sperm cells may be possible, but more research is necessary to determine the optimal conditions that would preserve sperm DNA integrity while allowing accurate diagnoses. PMID:14656400

  6. Beliefs and attitudes towards participating in genetic research – a population based cross-sectional study

    PubMed Central

    2013-01-01

    Background Biobanks have the potential to offer a venue for chronic disease biomarker discovery, which would allow for disease early detection and for identification of carriers of a certain predictor biomarker. To assess the general attitudes towards genetic research and participation in biobanks in the Long Island/Queens area of New York, and what factors would predict a positive view of such research, participants from the NSLIJ hospital system were surveyed. Methods Participants were recruited at six hospital centers in the NSLIJ system during the summers of 2009 and again in 2011 (n = 1,041). Those who opted to participate were given a questionnaire containing 22 questions assessing demographics, lifestyle and attitudes towards genetic research. These questions addressed individual participant’s beliefs about the importance of genetic research, willingness to participate in genetic research themselves, and their views on informed consent issues. Results Respondents took a generally positive view of genetic research in general, as well as their own participation in such research. Those with reservations were most likely to cite concerns over the privacy of their medical and genetic information. Those who were married tended to view genetic research as important, while those in the younger age group viewed it as less important. Prior blood donation of respondents was found to be a predictor of their approval for genetic research. Demographic factors were not found to be predictive of personal willingness to participate in genetic research, or of approval for the opt-out approach to consent. Conclusions While respondents were generally inclined to approve of genetic research, and those who disapproved did not do so based on an underlying moral objection to such research, there is a disconnect between the belief in the importance of genetic research and the willingness of individuals to participate themselves. This indicates a continued concern for the ways

  7. [Ethics and laws related to human subject research].

    PubMed

    Chiu, Hui-Ju; Lee, Ya-Ling; Chang, Su-Fen

    2011-10-01

    Advances in medical technology rely on human subject research to test the effects on real patients of unproven new drugs, equipment and techniques. Illegal human subject research happens occasionally and has led to subject injury and medical disputes. Familiarity with the laws and established ethics related to human subject research can minimize both injury and disputes. History is a mirror that permits reflection today on past experience. Discussing the Nuremberg Code, the Declaration of Helsinki and Belmont Report, this article describes the laws, ethics, history and news related to human subject research as well as the current definition and characteristics of human subject research. Increasing numbers of nurses serve as research nurses and participate in human subject research. The authors hope this article can increase research nurse knowledge regarding laws and ethics in order to protect human research subjects adequately. PMID:22024809

  8. Can Using Human Examples Diminish the Number of Misconceptions Held Concerning Mendelian Genetics Concepts?

    ERIC Educational Resources Information Center

    Moore, John M.

    2000-01-01

    Explores high school biology and the teaching of genetics. The question is asked, Can the use of relevant, meaningful human genetics concepts diminish the number of misconceptions formed between new and existing concepts? Can the application of the Ausubelian learning theory also decrease the acquisition of misconceptions? (SAH)

  9. Perspectives of Decisional Surrogates and Patients Regarding Critical Illness Genetic Research

    PubMed Central

    Freeman, Bradley D.; Bolcic-Jankovic, Dragana; Kennedy, Carie R.; LeBlanc, Jessica; Eastman, Alexander; Barillas, Jennifer; Wittgen, Catherine M.; indsey, Kathryn; Mahmood, Rumel S.; Clarridge, Brian R.

    2015-01-01

    Background Critical illness research is challenging due to disease severity and because patients are frequently incapacitated. Surrogates called upon to provide consent might not accurately represent patient preferences. Though commonplace, genetic data collection adds complexity in this context. We undertook this investigation to understand whether surrogate decision makers would be receptive to permitting participation in a critical illness genetics study and whether their decision making was consistent with that of the patient represented. Methods We invited individuals identified as surrogates for critically ill adults, if required, as well as patients once recovered to participate in a survey designed to understand attitudes about genetic research. Associations between dependent (receptivity to participation, concordance of responses) and independent variables were tested using bivariate and multivariate logistic regression analyses. Results Most of the entire surrogate sample (n=439) reported familiarity with research, including genetic research; tended to view research as useful; and were receptive to allowing their family member participate (with 39.6% and 38.1% stating that this would be “very” and “somewhat likely,” respectively) even absent direct benefit. Willingness to participate was similar comparing genetic and non-genetic studies (χ2 [1,n=439]=0.00127, p=0.972), though respondents expressed worry regarding lack of confidentiality of genetic data. Responses were concordant in 70.8% of the 192 surrogate-patient pairs analyzed. In multivariate analysis, African American race was associated with less receptivity to genetic data collection (p<0.05). No factors associated with concordance of surrogate-patient response were identified. Conclusions Surrogates’ receptivity to critical illness research was not influenced by whether the study entailed collection of genetic data. While more than two-thirds of surrogate-patient responses for

  10. 77 FR 37408 - Secretary's Advisory Committee on Human Research Protections

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-21

    ... HUMAN SERVICES Secretary's Advisory Committee on Human Research Protections AGENCY: Office of the Assistant Secretary for Health, Office of the Secretary, Department of Health and Human Services. ACTION..., notice is hereby given that the Secretary's Advisory Committee on Human Research Protections...

  11. 75 FR 59264 - Secretary's Advisory Committee on Human Research Protections

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... HUMAN SERVICES Secretary's Advisory Committee on Human Research Protections AGENCY: Department of Health and Human Services, Office of the Secretary, Office of the Assistant Secretary for Health. ACTION..., notice is hereby given that the Secretary's Advisory Committee on Human Research Protections...

  12. 77 FR 58383 - Secretary's Advisory Committee on Human Research Protections

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... HUMAN SERVICES Secretary's Advisory Committee on Human Research Protections AGENCY: Office of the Assistant Secretary for Health, Office of the Secretary, Department of Health and Human Services. ACTION..., notice is hereby given that the Secretary's Advisory Committee on Human Research Protections...

  13. Potential consumers' attitudes toward psychiatric genetic research and testing and factors influencing their intentions to test.

    PubMed

    Laegsgaard, Mett Marri; Kristensen, Ann Suhl; Mors, Ole

    2009-02-01

    Psychiatric genetic research brings on the possibility of psychiatric genetic testing. The optimal and responsible utilization of genetic testing depends on knowledge of the potential consumers' attitudes and expectations regarding testing. The aim of this study was to assess potential consumers' attitudes and expectations toward psychiatric genetics and factors influencing their intentions to test. A questionnaire constructed to assess attitudes and intentions toward psychiatric genetic testing was mailed or given in person to individuals participating in different genetic studies aiming at identifying genes predisposing for mental illness. A total of 397 persons diagnosed with major depression, bipolar disorder, schizophrenia, or anxiety disorder participated in the survey. A large majority of the sample expressed an intention for themselves and their children to participate in psychiatric genetic testing. Support for prenatal testing was considerably less strong. A large minority expressed intention to test regardless of treatment possibilities. Intentions to test were positively associated with being a parent, trust in researchers, and expecting to feel better prepared for fighting the disorder when knowing of the presence of risk genes. Intentions were negatively associated with the fear of psychiatric genetic research bringing on too many difficult choices and fearing not to be able to cope with the results of a psychiatric genetic test. These results indicate that psychiatric genetic testing is not just perceived as a way to better treatment. Other expectations may motivate testing even though the clinical validity of the test is poor. PMID:19309275

  14. Human genetics education for middle and secondary science teachers. Third annual report, April 1, 1994--March 30, 1995

    SciTech Connect

    Collins, D.L.; Segebrecht, L.; Schimke, R.N.

    1994-12-01

    This project is designed to increase teachers` knowledge of the Human Genome Project (HGP) with a focus on the ethical, legal and social implications of genetic technology. The project provides educators with the newest information on human genetics including applications of genetic technology, updated teaching resources and lesson plans, peer teaching ideas to disseminate genetic information to students and other educators, and established liaisons with genetic professionals.

  15. Oral and Craniofacial Clinical Signs Associated to Genetic Conditions in Human Identification Part I: A Review

    PubMed Central

    Ayoub, Fouad; Aoun, Nicole; el Husseini, Hassan; Jassar, Houssam; Sayah, Fida; Salameh, Ziad

    2015-01-01

    Background: Forensic dentistry is one of the most reliable methods used in human identification when other technique as fingerprint, DNA, visual identification cannot be used. Genetic disorders have several manifestations that can target the intra-oral cavity, the cranio-facial area or any location in the human body. Materials and Methods: A literature search of the scientific database (Medline and Science Direct) for the years 1990 to 2014 was carried out to find out all the available papers that indicate oral, cranio-facial signs, genetic and human identification. Results: A table with 10 genetic conditions was described with oral and cranio-facial signs that can help forensic specialist in human identification. Conclusion: This review showed a correlation between genetics, facial and intra-oral signs that would help forensic ondontologist in the identification procedures. PMID:26028912

  16. Half of the T-cell repertoire combinatorial diversity is genetically determined in humans and humanized mice.

    PubMed

    Pham, Hang-Phuong; Manuel, Manuarii; Petit, Nicolas; Klatzmann, David; Cohen-Kaminsky, Sylvia; Six, Adrien; Marodon, Gilles

    2012-03-01

    In humanized mice, the T-cell repertoire is derived from genetically identical human progenitors in distinct animals. Thus, careful comparison of the T-cell repertoires of humanized mice with those of humans may reveal the contribution of genetic determinism on T-cell repertoire formation. Here, we performed a comprehensive assessment of the distribution of V-J combinations of the human β chain of the T-cell receptor (hTRBV) in NOD.SCID.γc(-/-) (NSG) humanized mice. We observed that numerous V-J combinations were equally distributed in the thymus and in the periphery of humanized mice compared with human references. A global analysis of the data, comparing repertoire perturbation indices in humanized NSG mice and unrelated human PBMCs, reveals that 50% of the hTRBV families significantly overlapped. Using multivariate ranking and bootstrap analyses, we found that 18% of all possible V-J combinations contributed close to 50% of the expressed diversity, with significant over-representation of BV5-J1.1+1.2 and BV6-J1.1+1.2 rearrangements. Finally, comparison of CD3(-) and CD3(+) thymocyte repertoires indicated that the observed V-J combination overlap was already present before TCR-MHC selection in the thymus. Altogether, our results show that half of the T-cell repertoire combinatorial diversity in humans is genetically determined. PMID:22105329

  17. Molecular Genetic Tools and Techniques for Marchantia polymorpha Research.

    PubMed

    Ishizaki, Kimitsune; Nishihama, Ryuichi; Yamato, Katsuyuki T; Kohchi, Takayuki

    2016-02-01

    Liverworts occupy a basal position in the evolution of land plants, and are a key group to address a wide variety of questions in plant biology. Marchantia polymorpha is a common, easily cultivated, dioecious liverwort species, and is emerging as an experimental model organism. The haploid gametophytic generation dominates the diploid sporophytic generation in its life cycle. Genetically homogeneous lines in the gametophyte generation can be established easily and propagated through asexual reproduction, which aids genetic and biochemical experiments. Owing to its dioecy, male and female sexual organs are formed in separate individuals, which enables crossing in a fully controlled manner. Reproductive growth can be induced at the desired times under laboratory conditions, which helps genetic analysis. The developmental process from a single-celled spore to a multicellular body can be observed directly in detail. As a model organism, molecular techniques for M. polymorpha are well developed; for example, simple and efficient protocols of Agrobacterium-mediated transformation have been established. Based on them, various strategies for molecular genetics, such as introduction of reporter constructs, overexpression, gene silencing and targeted gene modification, are available. Herein, we describe the technologies and resources for reverse and forward genetics in M. polymorpha, which offer an excellent experimental platform to study the evolution and diversity of regulatory systems in land plants. PMID:26116421

  18. Human-Robot Interaction Directed Research Project

    NASA Technical Reports Server (NTRS)

    Sandor, Aniko; Cross, Ernest V., II; Chang, Mai Lee

    2014-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces and command modalities affect the human's ability to perform tasks accurately, efficiently, and effectively when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. This DRP concentrates on three areas associated with interfaces and command modalities in HRI which are applicable to NASA robot systems: 1) Video Overlays, 2) Camera Views, and 3) Command Modalities. The first study focused on video overlays that investigated how Augmented Reality (AR) symbology can be added to the human-robot interface to improve teleoperation performance. Three types of AR symbology were explored in this study, command guidance (CG), situation guidance (SG), and both (SCG). CG symbology gives operators explicit instructions on what commands to input, whereas SG symbology gives operators implicit cues so that operators can infer the input commands. The combination of CG and SG provided operators with explicit and implicit cues allowing the operator to choose which symbology to utilize. The objective of the study was to understand how AR symbology affects the human operator's ability to align a robot arm to a target using a flight stick and the ability to allocate attention between the symbology and external views of the world. The study evaluated the effects type of symbology (CG and SG) has on operator tasks performance and attention allocation during teleoperation of a robot arm. The second study expanded on the first study by evaluating the effects of the type of

  19. [Research progress of genetic engineering on medicinal plants].

    PubMed

    Teng, Zhong-qiu; Shen, Ye

    2015-02-01

    The application of genetic engineering technology in modern agriculture shows its outstanding role in dealing with food shortage. Traditional medicinal plant cultivation and collection have also faced with challenges, such as lack of resources, deterioration of environment, germplasm of recession and a series of problems. Genetic engineering can be used to improve the disease resistance, insect resistance, herbicides resistant ability of medicinal plant, also can improve the medicinal plant yield and increase the content of active substances in medicinal plants. Thus, the potent biotechnology can play an important role in protection and large area planting of medicinal plants. In the development of medicinal plant genetic engineering, the safety of transgenic medicinal plants should also be paid attention to. A set of scientific safety evaluation and judgment standard which is suitable for transgenic medicinal plants should be established based on the recognition of the particularity of medicinal plants. PMID:26137675

  20. [The role of genetic factors in human radioresistance].

    PubMed

    Tel'nov, V I

    2005-01-01

    The role of genetic factors in the development of chronic radiation disease (CRD), mostly caused by occupational external gamma-exposure, was evaluated. The data of molecular genetic survey of a cohort of 985 workers at the nuclear power plant, the Mayak PA, were analyzed. Among the genetic markers tested, an association between the haptoglobin (Hp) genetic system and the development of CRD was established. It was demonstrated that the contribution of genetic factors to the CRD onset was realized not within the whole, but in a relatively narrow dose interval (70 to 400 cGy), i.e., was relative. Furthermore, at equal irradiation doses, relatively higher risk of CRD was observed among the Hp 2-2 phenotype carriers (1.96) compared to lower risk among the Hp 1-1 and Hp 2-1 phenotype carriers (0.64). It was shown that with the increase of the irradiation dose, genotypic differences in the CRD frequency decreased to the point of their complete disappearance. Comparison of the roles of the genetic factors in the onset of such deterministic irradiation effect as CRD, with their roles in the onset of lung cancer in tobacco smokers revealed similar patterns. A scheme of the relationships between the effector intensity and the differences in the genetically determined radioresistance is presented. The data obtained do not support the idea that the survivals of the atomic bombing of Hiroshima and Nagasaki were the most radioresistant individuals, who are not representative for evaluating the radiation risk. PMID:15771255