WorldWideScience

Sample records for public human genome

  1. Human Contamination in Public Genome Assemblies.

    Science.gov (United States)

    Kryukov, Kirill; Imanishi, Tadashi

    2016-01-01

    Contamination in genome assembly can lead to wrong or confusing results when using such genome as reference in sequence comparison. Although bacterial contamination is well known, the problem of human-originated contamination received little attention. In this study we surveyed 45,735 available genome assemblies for evidence of human contamination. We used lineage specificity to distinguish between contamination and conservation. We found that 154 genome assemblies contain fragments that with high confidence originate as contamination from human DNA. Majority of contaminating human sequences were present in the reference human genome assembly for over a decade. We recommend that existing contaminated genomes should be revised to remove contaminated sequence, and that new assemblies should be thoroughly checked for presence of human DNA before submitting them to public databases.

  2. The human genome as public: Justifications and implications.

    Science.gov (United States)

    Bayefsky, Michelle J

    2017-03-01

    Since the human genome was decoded, great emphasis has been placed on the unique, personal nature of the genome, along with the benefits that personalized medicine can bring to individuals and the importance of safeguarding genetic privacy. As a result, an equally important aspect of the human genome - its common nature - has been underappreciated and underrepresented in the ethics literature and policy dialogue surrounding genetics and genomics. This article will argue that, just as the personal nature of the genome has been used to reinforce individual rights and justify important privacy protections, so too the common nature of the genome can be employed to support protections of the genome at a population level and policies designed to promote the public's wellbeing. In order for public health officials to have the authority to develop genetics policies for the sake of the public good, the genome must have not only a common, but also a public, dimension. This article contends that DNA carries a public dimension through the use of two conceptual frameworks: the common heritage (CH) framework and the common resource (CR) framework. Both frameworks establish a public interest in the human genome, but the CH framework can be used to justify policies aimed at preserving and protecting the genome, while the CR framework can be employed to justify policies for utilizing the genome for the public benefit. A variety of possible policy implications are discussed, with special attention paid to the use of large-scale genomics databases for public health research. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  3. Democratizing Human Genome Project Information: A Model Program for Education, Information and Debate in Public Libraries.

    Science.gov (United States)

    Pollack, Miriam

    The "Mapping the Human Genome" project demonstrated that librarians can help whomever they serve in accessing information resources in the areas of biological and health information, whether it is the scientists who are developing the information or a member of the public who is using the information. Public libraries can guide library…

  4. Integrating Public Health and Deliberative Public Bioethics: Lessons from the Human Genome Project Ethical, Legal, and Social Implications Program.

    Science.gov (United States)

    Meagher, Karen M; Lee, Lisa M

    2016-01-01

    Public health policy works best when grounded in firm public health standards of evidence and widely shared social values. In this article, we argue for incorporating a specific method of ethical deliberation--deliberative public bioethics--into public health. We describe how deliberative public bioethics is a method of engagement that can be helpful in public health. Although medical, research, and public health ethics can be considered some of what bioethics addresses, deliberative public bioethics offers both a how and where. Using the Human Genome Project Ethical, Legal, and Social Implications program as an example of effective incorporation of deliberative processes to integrate ethics into public health policy, we examine how deliberative public bioethics can integrate both public health and bioethics perspectives into three areas of public health practice: research, education, and health policy. We then offer recommendations for future collaborations that integrate deliberative methods into public health policy and practice.

  5. Mapping and sequencing the human genome: Science, ethics, and public policy. Final report

    Energy Technology Data Exchange (ETDEWEB)

    McInerney, J.D.

    1993-03-31

    Development of Mapping and Sequencing the Human Genome: Science, Ethics, and Public Policy followed the standard process of curriculum development at the Biological Sciences Curriculum Study (BSCS), the process is described. The production of this module was a collaborative effort between BSCS and the American Medical Association (AMA). Appendix A contains a copy of the module. Copies of reports sent to the Department of Energy (DOE) during the development process are contained in Appendix B; all reports should be on file at DOE. Appendix B also contains copies of status reports submitted to the BSCS Board of Directors.

  6. Decoding the human genome

    CERN Multimedia

    CERN. Geneva. Audiovisual Unit; Antonerakis, S E

    2002-01-01

    Decoding the Human genome is a very up-to-date topic, raising several questions besides purely scientific, in view of the two competing teams (public and private), the ethics of using the results, and the fact that the project went apparently faster and easier than expected. The lecture series will address the following chapters: Scientific basis and challenges. Ethical and social aspects of genomics.

  7. Human Germline Genome Editing.

    Science.gov (United States)

    Ormond, Kelly E; Mortlock, Douglas P; Scholes, Derek T; Bombard, Yvonne; Brody, Lawrence C; Faucett, W Andrew; Garrison, Nanibaa' A; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E

    2017-08-03

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  8. Big Data Analysis of Human Genome Variations

    KAUST Repository

    Gojobori, Takashi

    2016-01-01

    Since the human genome draft sequence was in public for the first time in 2000, genomic analyses have been intensively extended to the population level. The following three international projects are good examples for large-scale studies of human

  9. Human genome. 1993 Program report

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    The purpose of this report is to update the Human Genome 1991-92 Program Report and provide new information on the DOE genome program to researchers, program managers, other government agencies, and the interested public. This FY 1993 supplement includes abstracts of 60 new or renewed projects and listings of 112 continuing and 28 completed projects. These two reports, taken together, present the most complete published view of the DOE Human Genome Program through FY 1993. Research is progressing rapidly toward 15-year goals of mapping and sequencing the DNA of each of the 24 different human chromosomes.

  10. The human genome project

    International Nuclear Information System (INIS)

    Worton, R.

    1996-01-01

    The Human Genome Project is a massive international research project, costing 3 to 5 billion dollars and expected to take 15 years, which will identify the all the genes in the human genome - i.e. the complete sequence of bases in human DNA. The prize will be the ability to identify genes causing or predisposing to disease, and in some cases the development of gene therapy, but this new knowledge will raise important ethical issues

  11. Integrating Public Health and Deliberative Public Bioethics: Lessons from the Human Genome Project Ethical, Legal, and Social Implications Program

    OpenAIRE

    Meagher, Karen M.; Lee, Lisa M.

    2016-01-01

    Public health policy works best when grounded in firm public health standards of evidence and widely shared social values. In this article, we argue for incorporating a specific method of ethical deliberation—deliberative public bioethics—into public health. We describe how deliberative public bioethics is a method of engagement that can be helpful in public health. Although medical, research, and public health ethics can be considered some of what bioethics addresses, deliberative public bio...

  12. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  13. Human genome I

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    An international conference, Human Genome I, was held Oct. 2-4, 1989 in San Diego, Calif. Selected speakers discussed: Current Status of the Genome Project; Technique Innovations; Interesting regions; Applications; and Organization - Different Views of Current and Future Science and Procedures. Posters, consisting of 119 presentations, were displayed during the sessions. 119 were indexed for inclusion to the Energy Data Base

  14. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  15. Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The DOE Human Genome program has grown tremendously, as shown by the marked increase in the number of genome-funded projects since the last workshop held in 1991. The abstracts in this book describe the genome research of DOE-funded grantees and contractors and invited guests, and all projects are represented at the workshop by posters. The 3-day meeting includes plenary sessions on ethical, legal, and social issues pertaining to the availability of genetic data; sequencing techniques, informatics support; and chromosome and cDNA mapping and sequencing.

  16. Human Germline Genome Editing

    OpenAIRE

    Ormond, Kelly E.; Mortlock, Douglas P.; Scholes, Derek T.; Bombard, Yvonne; Brody, Lawrence C.; Faucett, W. Andrew; Garrison, Nanibaa’ A.; Hercher, Laura; Isasi, Rosario; Middleton, Anna; Musunuru, Kiran; Shriner, Daniel; Virani, Alice; Young, Caroline E.

    2017-01-01

    With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Gen...

  17. Annotating individual human genomes.

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A; Topol, Eric J; Schork, Nicholas J

    2011-10-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. ANNOTATING INDIVIDUAL HUMAN GENOMES*

    Science.gov (United States)

    Torkamani, Ali; Scott-Van Zeeland, Ashley A.; Topol, Eric J.; Schork, Nicholas J.

    2014-01-01

    Advances in DNA sequencing technologies have made it possible to rapidly, accurately and affordably sequence entire individual human genomes. As impressive as this ability seems, however, it will not likely to amount to much if one cannot extract meaningful information from individual sequence data. Annotating variations within individual genomes and providing information about their biological or phenotypic impact will thus be crucially important in moving individual sequencing projects forward, especially in the context of the clinical use of sequence information. In this paper we consider the various ways in which one might annotate individual sequence variations and point out limitations in the available methods for doing so. It is arguable that, in the foreseeable future, DNA sequencing of individual genomes will become routine for clinical, research, forensic, and personal purposes. We therefore also consider directions and areas for further research in annotating genomic variants. PMID:21839162

  19. Viral hepatitis C gets personal--the value of human genomics to public health.

    Science.gov (United States)

    Zhang, L; Gwinn, M; Hu, D J

    2013-01-01

    About 180 million people worldwide are chronically infected with hepatitis C virus (HCV), with 3-4 million newly infected each year. Only 15-25% of acute HCV infections clear spontaneously, and the remainder persists as chronic HCV infection. More than 350,000 people die every year from hepatitis C-related liver failure and cancer. There is currently no vaccine and the standard-of-care therapies--peg-interferon alpha (pegIFN) plus ribavirin (RBV)--are expensive and have serious side effects. Also, they may be effective in only 40-50% of patients infected with HCV genotype 1, the most common HCV genotype in the US. Interleukin 28B (IL28B) genotype was recently and convincingly associated with response to pegIFN and RBV therapy. It has emerged as a robust pretreatment predictor of sustained virological response (SVR, i.e. virologic clearance) to pegIFN and RBV as well as to new triple therapy regimens that include a direct-acting antiviral agent with pegIFN and RBV and increase SVR rates as much as 75% in patients infected with HCV genotype 1. Testing for IL28B genotype may contribute to clinical decision-making and could inform clinical guidelines and public health policies. © 2013 S. Karger AG, Basel.

  20. 76 FR 28056 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-05-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Counselors, National Human Genome Research Institute. The meeting will be closed to the public as indicated... National Human Genome Research Institute, including consideration of personnel qualifications and...

  1. 78 FR 70063 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-11-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Counselors, National Human Genome Research Institute. The meeting will be closed to the public as indicated... NATIONAL HUMAN GENOME RESEARCH INSTITUTE, including consideration of personnel qualifications and...

  2. 75 FR 13558 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-03-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Counselors, National Human Genome Research Institute. The meeting will be closed to the public as indicated... National Human Genome Research Institute, including consideration of personnel qualifications and...

  3. National Human Genome Research Institute

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  4. Insights from Human/Mouse genome comparisons

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.

    2003-03-30

    Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestry of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.

  5. Big Data Analysis of Human Genome Variations

    KAUST Repository

    Gojobori, Takashi

    2016-01-25

    Since the human genome draft sequence was in public for the first time in 2000, genomic analyses have been intensively extended to the population level. The following three international projects are good examples for large-scale studies of human genome variations: 1) HapMap Data (1,417 individuals) (http://hapmap.ncbi.nlm.nih.gov/downloads/genotypes/2010-08_phaseII+III/forward/), 2) HGDP (Human Genome Diversity Project) Data (940 individuals) (http://www.hagsc.org/hgdp/files.html), 3) 1000 genomes Data (2,504 individuals) http://ftp.1000genomes.ebi.ac.uk/vol1/ftp/release/20130502/ If we can integrate all three data into a single volume of data, we should be able to conduct a more detailed analysis of human genome variations for a total number of 4,861 individuals (= 1,417+940+2,504 individuals). In fact, we successfully integrated these three data sets by use of information on the reference human genome sequence, and we conducted the big data analysis. In particular, we constructed a phylogenetic tree of about 5,000 human individuals at the genome level. As a result, we were able to identify clusters of ethnic groups, with detectable admixture, that were not possible by an analysis of each of the three data sets. Here, we report the outcome of this kind of big data analyses and discuss evolutionary significance of human genomic variations. Note that the present study was conducted in collaboration with Katsuhiko Mineta and Kosuke Goto at KAUST.

  6. DEFINING THE CHEMICAL SPACE OF PUBLIC GENOMIC ...

    Science.gov (United States)

    The current project aims to chemically index the genomics content of public genomic databases to make these data accessible in relation to other publicly available, chemically-indexed toxicological information. By defining the chemical space of public genomic data, it is possible to identify classes of chemicals on which to develop methodologies for the integration of chemogenomic data into predictive toxicology. The chemical space of public genomic data will be presented as well as the methodologies and tools developed to identify this chemical space.

  7. Genome engineering in human cells.

    Science.gov (United States)

    Song, Minjung; Kim, Young-Hoon; Kim, Jin-Soo; Kim, Hyongbum

    2014-01-01

    Genome editing in human cells is of great value in research, medicine, and biotechnology. Programmable nucleases including zinc-finger nucleases, transcription activator-like effector nucleases, and RNA-guided engineered nucleases recognize a specific target sequence and make a double-strand break at that site, which can result in gene disruption, gene insertion, gene correction, or chromosomal rearrangements. The target sequence complexities of these programmable nucleases are higher than 3.2 mega base pairs, the size of the haploid human genome. Here, we briefly introduce the structure of the human genome and the characteristics of each programmable nuclease, and review their applications in human cells including pluripotent stem cells. In addition, we discuss various delivery methods for nucleases, programmable nickases, and enrichment of gene-edited human cells, all of which facilitate efficient and precise genome editing in human cells.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Genomic hypomethylation in the human germline associates with selective structural mutability in the human genome.

    Directory of Open Access Journals (Sweden)

    Jian Li

    Full Text Available The hotspots of structural polymorphisms and structural mutability in the human genome remain to be explained mechanistically. We examine associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination (NAHR mediated by low-copy repeats (LCRs. Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability. Specifically, methylation deserts, the ~1% fraction of the human genome with the lowest methylation in the germline, show a tenfold enrichment for structural rearrangements that occurred in the human genome since the branching of chimpanzee and are highly enriched for fast-evolving loci that regulate tissue-specific gene expression. Analysis of copy number variants (CNVs from 400 human samples identified using a custom-designed array comparative genomic hybridization (aCGH chip, combined with publicly available structural variation data, indicates that association of structural mutability with germline hypomethylation is comparable in magnitude to the association of structural mutability with LCR-mediated NAHR. Moreover, rare CNVs occurring in the genomes of individuals diagnosed with schizophrenia, bipolar disorder, and developmental delay and de novo CNVs occurring in those diagnosed with autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between the epigenome, selective mutability, evolution, and human disease.

  10. The Human Genome Project and Biology Education.

    Science.gov (United States)

    McInerney, Joseph D.

    1996-01-01

    Highlights the importance of the Human Genome Project in educating the public about genetics. Discusses four challenges that science educators must address: teaching for conceptual understanding, the nature of science, the personal and social impact of science and technology, and the principles of technology. Contains 45 references. (JRH)

  11. Human Genome Education Program

    Energy Technology Data Exchange (ETDEWEB)

    Richard Myers; Lane Conn

    2000-05-01

    The funds from the DOE Human Genome Program, for the project period 2/1/96 through 1/31/98, have provided major support for the curriculum development and field testing efforts for two high school level instructional units: Unit 1, ''Exploring Genetic Conditions: Genes, Culture and Choices''; and Unit 2, ''DNA Snapshots: Peaking at Your DNA''. In the original proposal, they requested DOE support for the partial salary and benefits of a Field Test Coordinator position to: (1) complete the field testing and revision of two high school curriculum units, and (2) initiate the education of teachers using these units. During the project period of this two-year DOE grant, a part-time Field-Test Coordinator was hired (Ms. Geraldine Horsma) and significant progress has been made in both of the original proposal objectives. Field testing for Unit 1 has occurred in over 12 schools (local and non-local sites with diverse student populations). Field testing for Unit 2 has occurred in over 15 schools (local and non-local sites) and will continue in 12-15 schools during the 96-97 school year. For both curricula, field-test sites and site teachers were selected for their interest in genetics education and in hands-on science education. Many of the site teachers had no previous experience with HGEP or the unit under development. Both of these first-year biology curriculum units, which contain genetics, biotechnology, societal, ethical and cultural issues related to HGP, are being implemented in many local and non-local schools (SF Bay Area, Southern California, Nebraska, Hawaii, and Texas) and in programs for teachers. These units will reach over 10,000 students in the SF Bay Area and continues to receive support from local corporate and private philanthropic organizations. Although HGEP unit development is nearing completion for both units, data is still being gathered and analyzed on unit effectiveness and student learning. The final field

  12. What does it mean to be genomically literate?: National Human Genome Research Institute Meeting Report.

    Science.gov (United States)

    Hurle, Belen; Citrin, Toby; Jenkins, Jean F; Kaphingst, Kimberly A; Lamb, Neil; Roseman, Jo Ellen; Bonham, Vence L

    2013-08-01

    Genomic discoveries will increasingly advance the science of medicine. Limited genomic literacy may adversely impact the public's understanding and use of the power of genetics and genomics in health care and public health. In November 2011, a meeting was held by the National Human Genome Research Institute to examine the challenge of achieving genomic literacy for the general public, from kindergarten to grade 12 to adult education. The role of the media in disseminating scientific messages and in perpetuating or reducing misconceptions was also discussed. Workshop participants agreed that genomic literacy will be achieved only through active engagement between genomics experts and the varied constituencies that comprise the public. This report summarizes the background, content, and outcomes from this meeting, including recommendations for a research agenda to inform decisions about how to advance genomic literacy in our society.

  13. Human Genome Research: Decoding DNA

    Science.gov (United States)

    dropdown arrow Site Map A-Z Index Menu Synopsis Human Genome Research: Decoding DNA Resources with of the DNA double helix during April 2003. James D. Watson, Francis Crick, and Maurice Wilkins were company Celera announced the completion of a "working draft" reference DNA sequence of the human

  14. Genomics Research: World Survey of Public Funding

    Directory of Open Access Journals (Sweden)

    Cook-Deegan Robert M

    2008-10-01

    Full Text Available Abstract Background Over the past two decades, genomics has evolved as a scientific research discipline. Genomics research was fueled initially by government and nonprofit funding sources, later augmented by private research and development (R&D funding. Citizens and taxpayers of many countries have funded much of the research, and have expectations about access to the resulting information and knowledge. While access to knowledge gained from all publicly funded research is desired, access is especially important for fields that have broad social impact and stimulate public dialogue. Genomics is one such field, where public concerns are raised for reasons such as health care and insurance implications, as well as personal and ancestral identification. Thus, genomics has grown rapidly as a field, and attracts considerable interest. Results One way to study the growth of a field of research is to examine its funding. This study focuses on public funding of genomics research, identifying and collecting data from major government and nonprofit organizations around the world, and updating previous estimates of world genomics research funding, including information about geographical origins. We initially identified 89 publicly funded organizations; we requested information about each organization's funding of genomics research. Of these organizations, 48 responded and 34 reported genomics research expenditures (of those that responded but did not supply information, some did not fund such research, others could not quantify it. The figures reported here include all the largest funders and we estimate that we have accounted for most of the genomics research funding from government and nonprofit sources. Conclusion Aggregate spending on genomics research from 34 funding sources averaged around $2.9 billion in 2003 – 2006. The United States spent more than any other country on genomics research, corresponding to 35% of the overall worldwide public

  15. Human genomics projects and precision medicine.

    Science.gov (United States)

    Carrasco-Ramiro, F; Peiró-Pastor, R; Aguado, B

    2017-09-01

    The completion of the Human Genome Project (HGP) in 2001 opened the floodgates to a deeper understanding of medicine. There are dozens of HGP-like projects which involve from a few tens to several million genomes currently in progress, which vary from having specialized goals or a more general approach. However, data generation, storage, management and analysis in public and private cloud computing platforms have raised concerns about privacy and security. The knowledge gained from further research has changed the field of genomics and is now slowly permeating into clinical medicine. The new precision (personalized) medicine, where genome sequencing and data analysis are essential components, allows tailored diagnosis and treatment according to the information from the patient's own genome and specific environmental factors. P4 (predictive, preventive, personalized and participatory) medicine is introducing new concepts, challenges and opportunities. This review summarizes current sequencing technologies, concentrates on ongoing human genomics projects, and provides some examples in which precision medicine has already demonstrated clinical impact in diagnosis and/or treatment.

  16. Genomics and the human genome project: implications for psychiatry

    OpenAIRE

    Kelsoe, J R

    2004-01-01

    In the past decade the Human Genome Project has made extraordinary strides in understanding of fundamental human genetics. The complete human genetic sequence has been determined, and the chromosomal location of almost all human genes identified. Presently, a large international consortium, the HapMap Project, is working to identify a large portion of genetic variation in different human populations and the structure and relationship of these variants to each other. The Human Genome Project h...

  17. Introduction: Digital Humanities, Public Humanities

    Directory of Open Access Journals (Sweden)

    Alex Christie

    2014-07-01

    Full Text Available NANO: New American Notes Online: An Interdisciplinary Academic Journal for Big Ideas in a Small World. This special issue shows how both public and digital humanities research can be rendered more persuasive through engagement with cultures beyond the academy. More specifically, the aim of this special issue is to demonstrate how investments in technologies and computation are not necessarily antithetical to investments in critical theory and social justice.

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

    Science.gov (United States)

    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

  19. HGVA: the Human Genome Variation Archive

    OpenAIRE

    Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gr?f, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

    2017-01-01

    Abstract High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic...

  20. 77 FR 64816 - National Human Genome Research Institute; Notice of Meeting

    Science.gov (United States)

    2012-10-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., National Human Genome Research Institute. The meeting will be open to the public as indicated below, with... invasion of personal privacy. Name of Committee: Board of Scientific Counselors, National Human Genome...

  1. 75 FR 2147 - National Human Genome Research Institute; Notice of Meetings

    Science.gov (United States)

    2010-01-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Council for Human Genome Research. The meetings will be open to the public as indicated below, with... Extramural Research, National Human Genome Research Institute, 5635 Fishers Lane, Suite 4076, MSC 9305...

  2. 76 FR 65204 - National Human Genome Research Institute; Notice of Meeting

    Science.gov (United States)

    2011-10-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., National Human Genome Research Institute. The meeting will be open to the public as indicated below, with... invasion of personal privacy. Name of Committee: Board of Scientific Counselors, National Human Genome...

  3. 75 FR 44800 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-07-29

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... for Human Genome Research. The meeting will be closed to the public in accordance with the provisions... Committee: National Advisory Council for Human Genome Research. Date: August 18, 2010. Time: 1 p.m. to 3 p.m...

  4. 75 FR 60467 - National Human Genome Research Institute; Notice of Meeting

    Science.gov (United States)

    2010-09-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., National Human Genome Research Institute. The meeting will be open to the public as indicated below, with... invasion of personal privacy. Name of Committee: Board of Scientific Counselors, National Human Genome...

  5. The Human Genome Diversity Project

    Energy Technology Data Exchange (ETDEWEB)

    Cavalli-Sforza, L. [Stanford Univ., CA (United States)

    1994-12-31

    The Human Genome Diversity Project (HGD Project) is an international anthropology project that seeks to study the genetic richness of the entire human species. This kind of genetic information can add a unique thread to the tapestry knowledge of humanity. Culture, environment, history, and other factors are often more important, but humanity`s genetic heritage, when analyzed with recent technology, brings another type of evidence for understanding species` past and present. The Project will deepen the understanding of this genetic richness and show both humanity`s diversity and its deep and underlying unity. The HGD Project is still largely in its planning stages, seeking the best ways to reach its goals. The continuing discussions of the Project, throughout the world, should improve the plans for the Project and their implementation. The Project is as global as humanity itself; its implementation will require the kinds of partnerships among different nations and cultures that make the involvement of UNESCO and other international organizations particularly appropriate. The author will briefly discuss the Project`s history, describe the Project, set out the core principles of the Project, and demonstrate how the Project will help combat the scourge of racism.

  6. All about the Human Genome Project (HGP)

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  7. About human genome Acerca del genoma humano

    Directory of Open Access Journals (Sweden)

    Mojica Tobias

    2000-12-01

    Full Text Available The sequence ofthe human genome, an undertaking ofadvanced countries, is nearly complete. In fact The Human Genome Project has around 85% ofthe genome sequenced 4 times on the average, with an accuracy of roughly 1 in 1000 nucleotides. Celera Genomics, on the other hand, has 99% of the sequence of one person, with an accuracy of slightly less than 1 in 100. The Human Genome project trives to produce a physical map for public consumption following a step by step strategy, in which the researcher sequences short DNA fragments belonging to Iarger fragments of known relative
    position. Celera Genomics wants to have very rapidly a physical map which can be quickly used to develop genetic tests and drugs, which can be later sold. We feel that the sequence ofthe human genome is something, which will widen the gap between advanced and backward countries.En este artículo se revisan los eventos, alrededor del secuenciamiento del genoma humano, que han llevado a tanta excitación en los medios noticiosos y académicos en meses recientes. Se explican las estrategias que han llevado a que tengamos dos borradores diferentes pero complementarios, la estrategia llevada a cabo con el dinero
    de los contribuyentes que consiste en establecer el orden de fragmentos grandes de DNA antes de ser secuenciados y la estrategia llevada a cabo con dineros aportados por la industria privada, con la intención de explotar gananciosamente el conocimiento derivado del genoma humano. El genoma humano a mediados del año 2000 es
    un borrador incompleto que cubre aliededor del 85% de la secuencia con una precisión de un error en 1000 y el 99% de la secuencia con una precisión menor de 1 en 100 nucleótidos, También se discuten algunas de las posibles avenidas

  8. Rapid detection of structural variation in a human genome using nanochannel-based genome mapping technology

    DEFF Research Database (Denmark)

    Cao, Hongzhi; Hastie, Alex R.; Cao, Dandan

    2014-01-01

    mutations; however, none of the current detection methods are comprehensive, and currently available methodologies are incapable of providing sufficient resolution and unambiguous information across complex regions in the human genome. To address these challenges, we applied a high-throughput, cost......-effective genome mapping technology to comprehensively discover genome-wide SVs and characterize complex regions of the YH genome using long single molecules (>150 kb) in a global fashion. RESULTS: Utilizing nanochannel-based genome mapping technology, we obtained 708 insertions/deletions and 17 inversions larger...... fosmid data. Of the remaining 270 SVs, 260 are insertions and 213 overlap known SVs in the Database of Genomic Variants. Overall, 609 out of 666 (90%) variants were supported by experimental orthogonal methods or historical evidence in public databases. At the same time, genome mapping also provides...

  9. The bonobo genome compared with the chimpanzee and human genomes

    Science.gov (United States)

    Prüfer, Kay; Munch, Kasper; Hellmann, Ines; Akagi, Keiko; Miller, Jason R.; Walenz, Brian; Koren, Sergey; Sutton, Granger; Kodira, Chinnappa; Winer, Roger; Knight, James R.; Mullikin, James C.; Meader, Stephen J.; Ponting, Chris P.; Lunter, Gerton; Higashino, Saneyuki; Hobolth, Asger; Dutheil, Julien; Karakoç, Emre; Alkan, Can; Sajjadian, Saba; Catacchio, Claudia Rita; Ventura, Mario; Marques-Bonet, Tomas; Eichler, Evan E.; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Junhold, Jörg; Patterson, Nick; Siebauer, Michael; Good, Jeffrey M.; Fischer, Anne; Ptak, Susan E.; Lachmann, Michael; Symer, David E.; Mailund, Thomas; Schierup, Mikkel H.; Andrés, Aida M.; Kelso, Janet; Pääbo, Svante

    2012-01-01

    Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours1–4, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other. PMID:22722832

  10. Tempo and mode of genomic mutations unveil human evolutionary history.

    Science.gov (United States)

    Hara, Yuichiro

    2015-01-01

    Mutations that have occurred in human genomes provide insight into various aspects of evolutionary history such as speciation events and degrees of natural selection. Comparing genome sequences between human and great apes or among humans is a feasible approach for inferring human evolutionary history. Recent advances in high-throughput or so-called 'next-generation' DNA sequencing technologies have enabled the sequencing of thousands of individual human genomes, as well as a variety of reference genomes of hominids, many of which are publicly available. These sequence data can help to unveil the detailed demographic history of the lineage leading to humans as well as the explosion of modern human population size in the last several thousand years. In addition, high-throughput sequencing illustrates the tempo and mode of de novo mutations, which are producing human genetic variation at this moment. Pedigree-based human genome sequencing has shown that mutation rates vary significantly across the human genome. These studies have also provided an improved timescale of human evolution, because the mutation rate estimated from pedigree analysis is half that estimated from traditional analyses based on molecular phylogeny. Because of the dramatic reduction in sequencing cost, sequencing on-demand samples designed for specific studies is now also becoming popular. To produce data of sufficient quality to meet the requirements of the study, it is necessary to set an explicit sequencing plan that includes the choice of sample collection methods, sequencing platforms, and number of sequence reads.

  11. Human Genome Sequencing in Health and Disease

    Science.gov (United States)

    Gonzaga-Jauregui, Claudia; Lupski, James R.; Gibbs, Richard A.

    2013-01-01

    Following the “finished,” euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges. PMID:22248320

  12. Human genome and genetic sequencing research and informed consent

    International Nuclear Information System (INIS)

    Iwakawa, Mayumi

    2003-01-01

    On March 29, 2001, the Ethical Guidelines for Human Genome and Genetic Sequencing Research were established. They have intended to serve as ethical guidelines for all human genome and genetic sequencing research practice, for the purpose of upholding respect for human dignity and rights and enforcing use of proper methods in the pursuit of human genome and genetic sequencing research, with the understanding and cooperation of the public. The RadGenomics Project has prepared a research protocol and informed consent document that follow these ethical guidelines. We have endeavored to protect the privacy of individual information, and have established a procedure for examination of research practices by an ethics committee. Here we report our procedure in order to offer this concept to the patients. (authors)

  13. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute's genomic medicine portfolio.

    Science.gov (United States)

    Manolio, Teri A

    2016-10-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual's genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of "Genomic Medicine Meetings," under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and difficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI's genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. Published by Elsevier Ireland Ltd.

  14. Human genome program report. Part 2, 1996 research abstracts

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-01

    This report contains Part 2 of a two-part report to reflect research and progress in the US Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 2 consists of 1996 research abstracts. Attention is focused on the following: sequencing; mapping; informatics; ethical, legal, and social issues; infrastructure; and small business innovation research.

  15. Human genome program report. Part 1, overview and progress

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-01

    This report contains Part 1 of a two-part report to reflect research and progress in the U.S. Department of Energy Human Genome Program from 1994 through 1996, with specified updates made just before publication. Part 1 consists of the program overview and report on progress.

  16. Radiation-induced instability of human genome

    International Nuclear Information System (INIS)

    Ryabchenko, N.N.; Demina, Eh.A.

    2014-01-01

    A brief review is dedicated to the phenomenon of radiation-induced genomic instability where the increased level of genomic changes in the offspring of irradiated cells is characteristic. Particular attention is paid to the problems of genomic instability induced by the low-dose radiation, role of the bystander effect in formation of radiation-induced instability, and its relationship with individual radiosensitivity. We believe that in accordance with the paradigm of modern radiobiology the increased human individual radiosensitivity can be formed due to the genome instability onset and is a significant risk factor for radiation-induced cancer

  17. Unexplored therapeutic opportunities in the human genome

    DEFF Research Database (Denmark)

    Oprea, Tudor I; Bologa, Cristian G; Brunak, Søren

    2018-01-01

    A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially d...... as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development....

  18. Body maps on the human genome.

    Science.gov (United States)

    Cherniak, Christopher; Rodriguez-Esteban, Raul

    2013-12-20

    Chromosomes have territories, or preferred locales, in the cell nucleus. When these sites are taken into account, some large-scale structure of the human genome emerges. The synoptic picture is that genes highly expressed in particular topologically compact tissues are not randomly distributed on the genome. Rather, such tissue-specific genes tend to map somatotopically onto the complete chromosome set. They seem to form a "genome homunculus": a multi-dimensional, genome-wide body representation extending across chromosome territories of the entire spermcell nucleus. The antero-posterior axis of the body significantly corresponds to the head-tail axis of the nucleus, and the dorso-ventral body axis to the central-peripheral nucleus axis. This large-scale genomic structure includes thousands of genes. One rationale for a homuncular genome structure would be to minimize connection costs in genetic networks. Somatotopic maps in cerebral cortex have been reported for over a century.

  19. The characterization of twenty sequenced human genomes.

    Directory of Open Access Journals (Sweden)

    Kimberly Pelak

    2010-09-01

    Full Text Available We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.

  20. Origins of the Human Genome Project.

    Science.gov (United States)

    Watson, J D; Cook-Deegan, R M

    1991-01-01

    The Human Genome Project has become a reality. Building on a debate that dates back to 1985, several genome projects are now in full stride around the world, and more are likely to form in the next several years. Italy began its genome program in 1987, and the United Kingdom and U.S.S.R. in 1988. The European communities mounted several genome projects on yeast, bacteria, Drosophila, and Arabidospis thaliana (a rapidly growing plant with a small genome) in 1988, and in 1990 commenced a new 2-year program on the human genome. In the United States, we have completed the first year of operation of the National Center for Human Genome Research at the National Institutes of Health (NIH), now the largest single funding source for genome research in the world. There have been dedicated budgets focused on genome-scale research at NIH, the U.S. Department of Energy, and the Howard Hughes Medical Institute for several years, and results are beginning to accumulate. There were three annual meetings on genome mapping and sequencing at Cold Spring Harbor, New York, in the spring of 1988, 1989, and 1990; the talks have shifted from a discussion about how to approach problems to presenting results from experiments already performed. We have finally begun to work rather than merely talk. The purpose of genome projects is to assemble data on the structure of DNA in human chromosomes and those of other organisms. A second goal is to develop new technologies to perform mapping and sequencing. There have been impressive technical advances in the past 5 years since the debate about the human genome project began. We are on the verge of beginning pilot projects to test several approaches to sequencing long stretches of DNA, using both automation and manual methods. Ordered sets of yeast artificial chromosome and cosmid clones have been assembled to span more than 2 million base pairs of several human chromosomes, and a region of 10 million base pairs has been assembled for

  1. Genomic and expression analyses of Tursiops truncatus T cell receptor gamma (TRG) and alpha/delta (TRA/TRD) loci reveal a similar basic public γδ repertoire in dolphin and human.

    Science.gov (United States)

    Linguiti, Giovanna; Antonacci, Rachele; Tasco, Gianluca; Grande, Francesco; Casadio, Rita; Massari, Serafina; Castelli, Vito; Consiglio, Arianna; Lefranc, Marie-Paule; Ciccarese, Salvatrice

    2016-08-15

    The bottlenose dolphin (Tursiops truncatus) is a mammal that belongs to the Cetartiodactyla and have lived in marine ecosystems for nearly 60 millions years. Despite its popularity, our knowledge about its adaptive immunity and evolution is very limited. Furthermore, nothing is known about the genomics and evolution of dolphin antigen receptor immunity. Here we report a evolutionary and expression study of Tursiops truncatus T cell receptor gamma (TRG) and alpha/delta (TRA/TRD) genes. We have identified in silico the TRG and TRA/TRD genes and analyzed the relevant mature transcripts in blood and in skin from four subjects. The dolphin TRG locus is the smallest and simplest of all mammalian loci as yet studied. It shows a genomic organization comprising two variable (V1 and V2), three joining (J1, J2 and J3) and a single constant (C), genes. Despite the fragmented nature of the genome assemblies, we deduced the TRA/TRD locus organization, with the recent TRDV1 subgroup genes duplications, as it is expected in artiodactyls. Expression analysis from blood of a subject allowed us to assign unambiguously eight TRAV genes to those annotated in the genomic sequence and to twelve new genes, belonging to five different subgroups. All transcripts were productive and no relevant biases towards TRAV-J rearrangements are observed. Blood and skin from four unrelated subjects expression data provide evidence for an unusual ratio of productive/unproductive transcripts which arise from the TRG V-J gene rearrangement and for a "public" gamma delta TR repertoire. The productive cDNA sequences, shared both in the same and in different individuals, include biases of the TRGV1 and TRGJ2 genes. The high frequency of TRGV1-J2/TRDV1- D1-J4 productive rearrangements in dolphins may represent an interesting oligo-clonal population comparable to that found in human with the TRGV9- JP/TRDV2-D-J T cells and in primates. Although the features of the TRG and TRA/TRD loci organization reflect

  2. Expert paper for the Future Panel on Public Health Genomics

    NARCIS (Netherlands)

    Stemerding, D.; Krom, A.

    2013-01-01

    Developments in public health genomics (PHG) hold the promise to be beneficial for individuals and to promote public health. Central to this paper is the idea that given the range of uncertainties and ambiguities related to genome-based information and technologies (GBIT), the responsible

  3. Mainstreaming sex and gender analysis in public health genomics

    NARCIS (Netherlands)

    Verdonk, P.; Klinge, I.

    2012-01-01

    Background: The integration of genome-based knowledge into public health or public health genomics (PHG) aims to contribute to disease prevention, health promotion, and risk reduction associated with genetic disease susceptibility. Men and women differ, for instance, in susceptibilities for heart

  4. HGVA: the Human Genome Variation Archive.

    Science.gov (United States)

    Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gräf, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

    2017-07-03

    High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic data for key reference projects in a clean, fast and integrated fashion. HGVA provides an efficient and intuitive web-interface for easy data mining, a comprehensive RESTful API and client libraries in Python, Java and JavaScript for fast programmatic access to its knowledge base. HGVA calculates population frequencies for these projects and enriches their data with variant annotation provided by CellBase, a rich and fast annotation solution. HGVA serves as a proof-of-concept of the genome analysis developments being carried out by the University of Cambridge together with UK's 100 000 genomes project and the National Institute for Health Research BioResource Rare-Diseases, in particular, deploying open-source for Computational Biology (OpenCB) software platform for storing and analyzing massive genomic datasets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Human-specific HERV-K insertion causes genomic variations in the human genome.

    Directory of Open Access Journals (Sweden)

    Wonseok Shin

    Full Text Available Human endogenous retroviruses (HERV sequences account for about 8% of the human genome. Through comparative genomics and literature mining, we identified a total of 29 human-specific HERV-K insertions. We characterized them focusing on their structure and flanking sequence. The results showed that four of the human-specific HERV-K insertions deleted human genomic sequences via non-classical insertion mechanisms. Interestingly, two of the human-specific HERV-K insertion loci contained two HERV-K internals and three LTR elements, a pattern which could be explained by LTR-LTR ectopic recombination or template switching. In addition, we conducted a polymorphic test and observed that twelve out of the 29 elements are polymorphic in the human population. In conclusion, human-specific HERV-K elements have inserted into human genome since the divergence of human and chimpanzee, causing human genomic changes. Thus, we believe that human-specific HERV-K activity has contributed to the genomic divergence between humans and chimpanzees, as well as within the human population.

  6. Reflections from Turkish Public Health Genomics Task Force

    Directory of Open Access Journals (Sweden)

    Bayram Serdar Savas

    2006-12-01

    Full Text Available

    Dear Sirs,

    The forth phase of the epidemiological and demographic transition has brought populations to a lower fertility status with extended life expectancy.The diseases of this phase are chronic and complex diseases, which mainly stem from the complex interaction of the human genome with life style factors. Cardiovascular and cerebrovascular diseases, cancers, diabetes and osteoporosis are among major chronic and complex diseases,which account for approximately 86% of all deaths and 77% of the burden of disease in Europe (Preventing chronic diseases: a vital investment. Geneva,World Health Organization, 2005.

    The way we view health and disease from the perspective of chronic and complex diseases, the main determinants of health - including those that are biological and social, is illustrated in Figure 1. The strong interaction of biological and genetic factors with life style factors in the development of chronic and complex diseases has brought us to a new understanding of ‘genetics’, where genetics is not only related to the study of rare hereditary disorders, as understood in ‘conventional’ medical genetics.As science reveals more about the genetic basis of these common diseases, genetics and genomics are increasingly becoming a part of daily practice in various branches of medicine.At this point,new issues and problems arise related to various aspects of this new potential practice; such as the implications for nutrigenetics and pharmacogenetics; the clinical utility and validity of genetic tests; as well as the ethical, legal and social aspects of public health genomics.

     Public Health Genomics European Network (PHGEN, an EU project that runs from January 2006 to December 2008, aims to deal with these issues in the European context.This networking exercise covers all EU Member States, Applicant Countries and EFTA-EEA (European Free Trade Association-European Economic Area countries.

  7. Analysing human genomes at different scales

    DEFF Research Database (Denmark)

    Liu, Siyang

    The thriving of the Next-Generation sequencing (NGS) technologies in the past decade has dramatically revolutionized the field of human genetics. We are experiencing a wave of several large-scale whole genome sequencing studies of humans in the world. Those studies vary greatly regarding cohort...... will be reflected by the analysis of real data. This thesis covers studies in two human genome sequencing projects that distinctly differ in terms of studied population, sample size and sequencing depth. In the first project, we sequenced 150 Danish individuals from 50 trio families to 78x coverage....... The sophisticated experimental design enables high-quality de novo assembly of the genomes and provides a good opportunity for mapping the structural variations in the human population. We developed the AsmVar approach to discover, genotype and characterize the structural variations from the assemblies. Our...

  8. Initial genomics of the human nucleolus.

    Directory of Open Access Journals (Sweden)

    Attila Németh

    2010-03-01

    Full Text Available We report for the first time the genomics of a nuclear compartment of the eukaryotic cell. 454 sequencing and microarray analysis revealed the pattern of nucleolus-associated chromatin domains (NADs in the linear human genome and identified different gene families and certain satellite repeats as the major building blocks of NADs, which constitute about 4% of the genome. Bioinformatic evaluation showed that NAD-localized genes take part in specific biological processes, like the response to other organisms, odor perception, and tissue development. 3D FISH and immunofluorescence experiments illustrated the spatial distribution of NAD-specific chromatin within interphase nuclei and its alteration upon transcriptional changes. Altogether, our findings describe the nature of DNA sequences associated with the human nucleolus and provide insights into the function of the nucleolus in genome organization and establishment of nuclear architecture.

  9. Initial Genomics of the Human Nucleolus

    Science.gov (United States)

    Németh, Attila; Conesa, Ana; Santoyo-Lopez, Javier; Medina, Ignacio; Montaner, David; Péterfia, Bálint; Solovei, Irina; Cremer, Thomas; Dopazo, Joaquin; Längst, Gernot

    2010-01-01

    We report for the first time the genomics of a nuclear compartment of the eukaryotic cell. 454 sequencing and microarray analysis revealed the pattern of nucleolus-associated chromatin domains (NADs) in the linear human genome and identified different gene families and certain satellite repeats as the major building blocks of NADs, which constitute about 4% of the genome. Bioinformatic evaluation showed that NAD–localized genes take part in specific biological processes, like the response to other organisms, odor perception, and tissue development. 3D FISH and immunofluorescence experiments illustrated the spatial distribution of NAD–specific chromatin within interphase nuclei and its alteration upon transcriptional changes. Altogether, our findings describe the nature of DNA sequences associated with the human nucleolus and provide insights into the function of the nucleolus in genome organization and establishment of nuclear architecture. PMID:20361057

  10. Justice and the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, T.F.; Lappe, M. (eds.)

    1992-01-01

    Most of the essays gathered in this volume were first presented at a conference, Justice and the Human Genome, in Chicago in early November, 1991. The goal of the, conference was to consider questions of justice as they are and will be raised by the Human Genome Project. To achieve its goal of identifying and elucidating the challenges of justice inherent in genomic research and its social applications the conference drew together in one forum members from academia, medicine, and industry with interests divergent as rate-setting for insurance, the care of newborns, and the history of ethics. The essays in this volume address a number of theoretical and practical concerns relative to the meaning of genomic research.

  11. Justice and the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, T.F.; Lappe, M. [eds.

    1992-12-31

    Most of the essays gathered in this volume were first presented at a conference, Justice and the Human Genome, in Chicago in early November, 1991. The goal of the, conference was to consider questions of justice as they are and will be raised by the Human Genome Project. To achieve its goal of identifying and elucidating the challenges of justice inherent in genomic research and its social applications the conference drew together in one forum members from academia, medicine, and industry with interests divergent as rate-setting for insurance, the care of newborns, and the history of ethics. The essays in this volume address a number of theoretical and practical concerns relative to the meaning of genomic research.

  12. Inversion variants in human and primate genomes.

    Science.gov (United States)

    Catacchio, Claudia Rita; Maggiolini, Flavia Angela Maria; D'Addabbo, Pietro; Bitonto, Miriana; Capozzi, Oronzo; Signorile, Martina Lepore; Miroballo, Mattia; Archidiacono, Nicoletta; Eichler, Evan E; Ventura, Mario; Antonacci, Francesca

    2018-05-18

    For many years, inversions have been proposed to be a direct driving force in speciation since they suppress recombination when heterozygous. Inversions are the most common large-scale differences among humans and great apes. Nevertheless, they represent large events easily distinguishable by classical cytogenetics, whose resolution, however, is limited. Here, we performed a genome-wide comparison between human, great ape, and macaque genomes using the net alignments for the most recent releases of genome assemblies. We identified a total of 156 putative inversions, between 103 kb and 91 Mb, corresponding to 136 human loci. Combining literature, sequence, and experimental analyses, we analyzed 109 of these loci and found 67 regions inverted in one or multiple primates, including 28 newly identified inversions. These events overlap with 81 human genes at their breakpoints, and seven correspond to sites of recurrent rearrangements associated with human disease. This work doubles the number of validated primate inversions larger than 100 kb, beyond what was previously documented. We identified 74 sites of errors, where the sequence has been assembled in the wrong orientation, in the reference genomes analyzed. Our data serve two purposes: First, we generated a map of evolutionary inversions in these genomes representing a resource for interrogating differences among these species at a functional level; second, we provide a list of misassembled regions in these primate genomes, involving over 300 Mb of DNA and 1978 human genes. Accurately annotating these regions in the genome references has immediate applications for evolutionary and biomedical studies on primates. © 2018 Catacchio et al.; Published by Cold Spring Harbor Laboratory Press.

  13. BioQ: tracing experimental origins in public genomic databases using a novel data provenance model.

    Science.gov (United States)

    Saccone, Scott F; Quan, Jiaxi; Jones, Peter L

    2012-04-15

    Public genomic databases, which are often used to guide genetic studies of human disease, are now being applied to genomic medicine through in silico integrative genomics. These databases, however, often lack tools for systematically determining the experimental origins of the data. We introduce a new data provenance model that we have implemented in a public web application, BioQ, for assessing the reliability of the data by systematically tracing its experimental origins to the original subjects and biologics. BioQ allows investigators to both visualize data provenance as well as explore individual elements of experimental process flow using precise tools for detailed data exploration and documentation. It includes a number of human genetic variation databases such as the HapMap and 1000 Genomes projects. BioQ is freely available to the public at http://bioq.saclab.net.

  14. Human Genome Editing and Ethical Considerations.

    Science.gov (United States)

    Krishan, Kewal; Kanchan, Tanuj; Singh, Bahadur

    2016-04-01

    Editing human germline genes may act as boon in some genetic and other disorders. Recent editing of the genome of the human embryo with the CRISPR/Cas9 editing tool generated a debate amongst top scientists of the world for the ethical considerations regarding its effect on the future generations. It needs to be seen as to what transformation human gene editing brings to humankind in the times to come.

  15. Development and application of Human Genome Epidemiology

    Science.gov (United States)

    Xu, Jingwen

    2017-12-01

    Epidemiology is a science that studies distribution of diseases and health in population and its influencing factors, it also studies how to prevent and cure disease and promote health strategies and measures. Epidemiology has developed rapidly in recent years and it is an intercross subject with various other disciplines to form a series of branch disciplines such as Genetic epidemiology, molecular epidemiology, drug epidemiology and tumor epidemiology. With the implementation and completion of Human Genome Project (HGP), Human Genome Epidemiology (HuGE) has emerged at this historic moment. In this review, the development of Human Genome Epidemiology, research content, the construction and structure of relevant network, research standards, as well as the existing results and problems are briefly outlined.

  16. 76 FR 38399 - Assessing the Current Research, Policy, and Practice Environment in Public Health Genomics

    Science.gov (United States)

    2011-06-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention [Docket Number CDC-2011-0008] Assessing the Current Research, Policy, and Practice Environment in Public Health... information helpful to assess the current research, policy, and practice environment in public health genomics...

  17. Genome Editing in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Carlson-Stevermer, Jared; Saha, Krishanu

    2017-01-01

    Genome editing in human pluripotent stem cells (hPSCs) enables the generation of reporter lines and knockout cell lines. Zinc finger nucleases, transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 technology have recently increased the efficiency of proper gene editing by creating double strand breaks (DSB) at defined sequences in the human genome. These systems typically use plasmids to transiently transcribe nucleases within the cell. Here, we describe the process for preparing hPSCs for transient expression of nucleases via electroporation and subsequent analysis to create genetically modified stem cell lines.

  18. Stakeholder engagement in policy development: challenges and opportunities for human genomics

    OpenAIRE

    Lemke, Amy A.; Harris-Wai, Julie N.

    2015-01-01

    Along with rapid advances in human genomics, policies governing genomic data and clinical technologies have proliferated. Stakeholder engagement is widely lauded as an important methodology for improving clinical, scientific, and public health policy decision making. The purpose of this paper is to examine how stakeholder engagement is used to develop policies in genomics research and public health areas, as well as to identify future priorities for conducting evidence-based stakeholder engag...

  19. Beyond Our Borders? Public Resistance to Global Genomic Data Sharing.

    Directory of Open Access Journals (Sweden)

    Mary A Majumder

    2016-11-01

    Full Text Available Prospects have never seemed better for a truly global approach to science to improve human health, with leaders of national initiatives laying out their vision of a worldwide network of related projects. An extensive literature addresses obstacles to global genomic data sharing, yet a series of public polls suggests that the scientific community may be overlooking a significant barrier: potential public resistance to data sharing across national borders. In several large United States surveys, university researchers in other countries were deemed the least acceptable group of data users, and a just-completed US survey found a marked increase in privacy and security concerns related to data access by non-US researchers. Furthermore, diminished support for sharing beyond national borders is not unique to the US, although the limited data from outside the US suggest variation across countries as well as demographic groups. Possible sources of resistance include apprehension about privacy and security protections. Strategies for building public support include making the affirmative case for global data sharing, addressing privacy, security, and other legitimate concerns, and investigating public concerns in greater depth.

  20. Implications of the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Kitcher, P.

    1998-11-01

    The Human Genome Project (HGP), launched in 1991, aims to map and sequence the human genome by 2006. During the fifteen-year life of the project, it is projected that $3 billion in federal funds will be allocated to it. The ultimate aims of spending this money are to analyze the structure of human DNA, to identify all human genes, to recognize the functions of those genes, and to prepare for the biology and medicine of the twenty-first century. The following summary examines some of the implications of the program, concentrating on its scientific import and on the ethical and social problems that it raises. Its aim is to expose principles that might be used in applying the information which the HGP will generate. There is no attempt here to translate the principles into detailed proposals for legislation. Arguments and discussion can be found in the full report, but, like this summary, that report does not contain any legislative proposals.

  1. Attitudes towards the Human Genome Project.

    Science.gov (United States)

    Shahroudi, Julie; Shaw, Geraldine

    Attitudes concerning the Human Genome Project were reported by faculty (N=40) and students (N=66) from a liberal arts college. Positive attitudes toward the project involved privacy, insurance and health, economic purposes, reproductive purposes, genetic counseling, religion and overall opinions. Negative attitudes were expressed regarding…

  2. Unexplored therapeutic opportunities in the human genome.

    Science.gov (United States)

    Oprea, Tudor I; Bologa, Cristian G; Brunak, Søren; Campbell, Allen; Gan, Gregory N; Gaulton, Anna; Gomez, Shawn M; Guha, Rajarshi; Hersey, Anne; Holmes, Jayme; Jadhav, Ajit; Jensen, Lars Juhl; Johnson, Gary L; Karlson, Anneli; Leach, Andrew R; Ma'ayan, Avi; Malovannaya, Anna; Mani, Subramani; Mathias, Stephen L; McManus, Michael T; Meehan, Terrence F; von Mering, Christian; Muthas, Daniel; Nguyen, Dac-Trung; Overington, John P; Papadatos, George; Qin, Jun; Reich, Christian; Roth, Bryan L; Schürer, Stephan C; Simeonov, Anton; Sklar, Larry A; Southall, Noel; Tomita, Susumu; Tudose, Ilinca; Ursu, Oleg; Vidovic, Dušica; Waller, Anna; Westergaard, David; Yang, Jeremy J; Zahoránszky-Köhalmi, Gergely

    2018-05-01

    A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.

  3. Viral symbiosis and the holobiontic nature of the human genome.

    Science.gov (United States)

    Ryan, Francis Patrick

    2016-01-01

    The human genome is a holobiontic union of the mammalian nuclear genome, the mitochondrial genome and large numbers of endogenized retroviral genomes. This article defines and explores this symbiogenetic pattern of evolution, looking at the implications for human genetics, epigenetics, embryogenesis, physiology and the pathogenesis of inborn errors of metabolism and many other diseases. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  4. "Orphan" retrogenes in the human genome.

    Science.gov (United States)

    Ciomborowska, Joanna; Rosikiewicz, Wojciech; Szklarczyk, Damian; Makałowski, Wojciech; Makałowska, Izabela

    2013-02-01

    Gene duplicates generated via retroposition were long thought to be pseudogenized and consequently decayed. However, a significant number of these genes escaped their evolutionary destiny and evolved into functional genes. Despite multiple studies, the number of functional retrogenes in human and other genomes remains unclear. We performed a comparative analysis of human, chicken, and worm genomes to identify "orphan" retrogenes, that is, retrogenes that have replaced their progenitors. We located 25 such candidates in the human genome. All of these genes were previously known, and the majority has been intensively studied. Despite this, they have never been recognized as retrogenes. Analysis revealed that the phenomenon of replacing parental genes with their retrocopies has been taking place over the entire span of animal evolution. This process was often species specific and contributed to interspecies differences. Surprisingly, these retrogenes, which should evolve in a more relaxed mode, are subject to a very strong purifying selection, which is, on average, two and a half times stronger than other human genes. Also, for retrogenes, they do not show a typical overall tendency for a testis-specific expression. Notably, seven of them are associated with human diseases. Recognizing them as "orphan" retrocopies, which have different regulatory machinery than their parents, is important for any disease studies in model organisms, especially when discoveries made in one species are transferred to humans.

  5. Identification of endogenous retroviral reading frames in the human genome

    Directory of Open Access Journals (Sweden)

    Wiuf Carsten

    2004-10-01

    Full Text Available Abstract Background Human endogenous retroviruses (HERVs comprise a large class of repetitive retroelements. Most HERVs are ancient and invaded our genome at least 25 million years ago, except for the evolutionary young HERV-K group. The far majority of the encoded genes are degenerate due to mutational decay and only a few non-HERV-K loci are known to retain intact reading frames. Additional intact HERV genes may exist, since retroviral reading frames have not been systematically annotated on a genome-wide scale. Results By clustering of hits from multiple BLAST searches using known retroviral sequences we have mapped 1.1% of the human genome as retrovirus related. The coding potential of all identified HERV regions were analyzed by annotating viral open reading frames (vORFs and we report 7836 loci as verified by protein homology criteria. Among 59 intact or almost-intact viral polyproteins scattered around the human genome we have found 29 envelope genes including two novel gammaretroviral types. One encodes a protein similar to a recently discovered zebrafish retrovirus (ZFERV while another shows partial, C-terminal, homology to Syncytin (HERV-W/FRD. Conclusions This compilation of HERV sequences and their coding potential provide a useful tool for pursuing functional analysis such as RNA expression profiling and effects of viral proteins, which may, in turn, reveal a role for HERVs in human health and disease. All data are publicly available through a database at http://www.retrosearch.dk.

  6. Genomic uracil and human disease

    DEFF Research Database (Denmark)

    Hagen, Lars; Pena Diaz, Javier; Kavli, Bodil

    2006-01-01

    Uracil is present in small amounts in DNA due to spontaneous deamination of cytosine and incorporation of dUMP during replication. While deamination generates mutagenic U:G mismatches, incorporated dUMP results in U:A pairs that are not directly mutagenic, but may be cytotoxic. In most cells, mut...... retroviral infections. Ung(-/-) mice have a similar phenotype and develop B-cell lymphomas late in life. However, there is no evidence indicating that UNG deficiency causes lymphomas in humans....

  7. Research for genetic instability of human genome

    Energy Technology Data Exchange (ETDEWEB)

    Hori, T.; Takahashi, E.; Tsuji, H.; Yamauchi, M. (National Inst. of Radiological Sciences, Chiba (Japan)); Murata, M.

    1992-01-01

    In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author).

  8. Helminth Genomics: The Implications for Human Health

    Science.gov (United States)

    Brindley, Paul J.; Mitreva, Makedonka; Ghedin, Elodie; Lustigman, Sara

    2009-01-01

    More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings. PMID:19855829

  9. Research for genetic instability of human genome

    International Nuclear Information System (INIS)

    Hori, T.; Takahashi, E.; Tsuji, H.; Yamauchi, M.; Murata, M.

    1992-01-01

    In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author)

  10. Whole genome sequencing in clinical and public health microbiology.

    Science.gov (United States)

    Kwong, J C; McCallum, N; Sintchenko, V; Howden, B P

    2015-04-01

    Genomics and whole genome sequencing (WGS) have the capacity to greatly enhance knowledge and understanding of infectious diseases and clinical microbiology.The growth and availability of bench-top WGS analysers has facilitated the feasibility of genomics in clinical and public health microbiology.Given current resource and infrastructure limitations, WGS is most applicable to use in public health laboratories, reference laboratories, and hospital infection control-affiliated laboratories.As WGS represents the pinnacle for strain characterisation and epidemiological analyses, it is likely to replace traditional typing methods, resistance gene detection and other sequence-based investigations (e.g., 16S rDNA PCR) in the near future.Although genomic technologies are rapidly evolving, widespread implementation in clinical and public health microbiology laboratories is limited by the need for effective semi-automated pipelines, standardised quality control and data interpretation, bioinformatics expertise, and infrastructure.

  11. The ethical introduction of genome-based information and technologies into public health.

    Science.gov (United States)

    Howard, H C; Swinnen, E; Douw, K; Vondeling, H; Cassiman, J-J; Cambon-Thomsen, A; Borry, P

    2013-01-01

    With the human genome project running from 1989 until its completion in 2003, and the incredible advances in sequencing technology and in bioinformatics during the last decade, there has been a shift towards an increase focus on studying common complex disorders which develop due to the interplay of many different genes as well as environmental factors. Although some susceptibility genes have been identified in some populations for disorders such as cancer, diabetes and cardiovascular diseases, the integration of this information into the health care system has proven to be much more problematic than for single gene disorders. Furthermore, with the 1000$ genome supposedly just around the corner, and whole genome sequencing gradually being integrated into research protocols as well as in the clinical context, there is a strong push for the uptake of additional genomic testing. Indeed, the advent of public health genomics, wherein genomics would be integrated in all aspects of health care and public health, should be taken seriously. Although laudable, these advances also bring with them a slew of ethical and social issues that challenge the normative frameworks used in clinical genetics until now. With this in mind, we highlight herein 5 principles that are used as a primer to discuss the ethical introduction of genome-based information and genome-based technologies into public health. Copyright © 2013 S. Karger AG, Basel.

  12. GenPlay Multi-Genome, a tool to compare and analyze multiple human genomes in a graphical interface.

    Science.gov (United States)

    Lajugie, Julien; Fourel, Nicolas; Bouhassira, Eric E

    2015-01-01

    Parallel visualization of multiple individual human genomes is a complex endeavor that is rapidly gaining importance with the increasing number of personal, phased and cancer genomes that are being generated. It requires the display of variants such as SNPs, indels and structural variants that are unique to specific genomes and the introduction of multiple overlapping gaps in the reference sequence. Here, we describe GenPlay Multi-Genome, an application specifically written to visualize and analyze multiple human genomes in parallel. GenPlay Multi-Genome is ideally suited for the comparison of allele-specific expression and functional genomic data obtained from multiple phased genomes in a graphical interface with access to multiple-track operation. It also allows the analysis of data that have been aligned to custom genomes rather than to a standard reference and can be used as a variant calling format file browser and as a tool to compare different genome assembly, such as hg19 and hg38. GenPlay is available under the GNU public license (GPL-3) from http://genplay.einstein.yu.edu. The source code is available at https://github.com/JulienLajugie/GenPlay. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Comparison of phasing strategies for whole human genomes.

    Science.gov (United States)

    Choi, Yongwook; Chan, Agnes P; Kirkness, Ewen; Telenti, Amalio; Schork, Nicholas J

    2018-04-01

    Humans are a diploid species that inherit one set of chromosomes paternally and one homologous set of chromosomes maternally. Unfortunately, most human sequencing initiatives ignore this fact in that they do not directly delineate the nucleotide content of the maternal and paternal copies of the 23 chromosomes individuals possess (i.e., they do not 'phase' the genome) often because of the costs and complexities of doing so. We compared 11 different widely-used approaches to phasing human genomes using the publicly available 'Genome-In-A-Bottle' (GIAB) phased version of the NA12878 genome as a gold standard. The phasing strategies we compared included laboratory-based assays that prepare DNA in unique ways to facilitate phasing as well as purely computational approaches that seek to reconstruct phase information from general sequencing reads and constructs or population-level haplotype frequency information obtained through a reference panel of haplotypes. To assess the performance of the 11 approaches, we used metrics that included, among others, switch error rates, haplotype block lengths, the proportion of fully phase-resolved genes, phasing accuracy and yield between pairs of SNVs. Our comparisons suggest that a hybrid or combined approach that leverages: 1. population-based phasing using the SHAPEIT software suite, 2. either genome-wide sequencing read data or parental genotypes, and 3. a large reference panel of variant and haplotype frequencies, provides a fast and efficient way to produce highly accurate phase-resolved individual human genomes. We found that for population-based approaches, phasing performance is enhanced with the addition of genome-wide read data; e.g., whole genome shotgun and/or RNA sequencing reads. Further, we found that the inclusion of parental genotype data within a population-based phasing strategy can provide as much as a ten-fold reduction in phasing errors. We also considered a majority voting scheme for the construction of a

  14. Pig genome sequence - analysis and publication strategy

    DEFF Research Database (Denmark)

    Archibald, Alan L.; Bolund, Lars; Churcher, Carol

    2010-01-01

    preferentially selected for sequencing. In accordance with the Bermuda and Fort Lauderdale agreements and the more recent Toronto Statement the data have been released into public sequence repositories (Genbank/EMBL, NCBI/Ensembl trace repositories) in a timely manner and in advance of publication. CONCLUSIONS...

  15. An overview of the human genome project

    Energy Technology Data Exchange (ETDEWEB)

    Batzer, M.A.

    1994-01-01

    The human genome project is one of the most ambitious scientific projects to date, with the ultimate goal being a nucleotide sequence for all four billion bases of human DNA. In the process of determining the nucleotide sequence for each base, the location, function, and regulatory regions from the estimated 100,000 human genes will be identified. The genome project itself relies upon maps of the human genetic code derived from several different levels of resolution. Genetic linkage analysis provides a low resolution genome map. The information for genetic linkage maps is derived from the analysis of chromosome specific markers such as Sequence Tagged Sites (STSs), Variable Number of Tandem Repeats (VNTRs) or other polymorphic (highly informative) loci in a number of different-families. Using this information the location of an unknown disease gene can be limited to a region comprised of one million base pairs of DNA or less. After this point, one must construct or have access to a physical map of the region of interest. Physical mapping involves the construction of an ordered overlapping (contiguous) set of recombinant DNA clones. These clones may be derived from a number of different vectors including cosmids, Bacterial Artificial Chromosomes (BACs), P1 derived Artificial Chromosomes (PACs), somatic cell hybrids, or Yeast Artificial Chromosomes (YACs). The ultimate goal for physical mapping is to establish a completely overlapping (contiguous) set of clones for the entire genome. After a gene or region of interest has been localized using physical mapping the nucleotide sequence is determined. The overlap between genetic mapping, physical mapping and DNA sequencing has proven to be a powerful tool for the isolation of disease genes through positional cloning.

  16. Annotating the human genome with Disease Ontology

    Science.gov (United States)

    Osborne, John D; Flatow, Jared; Holko, Michelle; Lin, Simon M; Kibbe, Warren A; Zhu, Lihua (Julie); Danila, Maria I; Feng, Gang; Chisholm, Rex L

    2009-01-01

    Background The human genome has been extensively annotated with Gene Ontology for biological functions, but minimally computationally annotated for diseases. Results We used the Unified Medical Language System (UMLS) MetaMap Transfer tool (MMTx) to discover gene-disease relationships from the GeneRIF database. We utilized a comprehensive subset of UMLS, which is disease-focused and structured as a directed acyclic graph (the Disease Ontology), to filter and interpret results from MMTx. The results were validated against the Homayouni gene collection using recall and precision measurements. We compared our results with the widely used Online Mendelian Inheritance in Man (OMIM) annotations. Conclusion The validation data set suggests a 91% recall rate and 97% precision rate of disease annotation using GeneRIF, in contrast with a 22% recall and 98% precision using OMIM. Our thesaurus-based approach allows for comparisons to be made between disease containing databases and allows for increased accuracy in disease identification through synonym matching. The much higher recall rate of our approach demonstrates that annotating human genome with Disease Ontology and GeneRIF for diseases dramatically increases the coverage of the disease annotation of human genome. PMID:19594883

  17. De novo assembly of a haplotype-resolved human genome.

    Science.gov (United States)

    Cao, Hongzhi; Wu, Honglong; Luo, Ruibang; Huang, Shujia; Sun, Yuhui; Tong, Xin; Xie, Yinlong; Liu, Binghang; Yang, Hailong; Zheng, Hancheng; Li, Jian; Li, Bo; Wang, Yu; Yang, Fang; Sun, Peng; Liu, Siyang; Gao, Peng; Huang, Haodong; Sun, Jing; Chen, Dan; He, Guangzhu; Huang, Weihua; Huang, Zheng; Li, Yue; Tellier, Laurent C A M; Liu, Xiao; Feng, Qiang; Xu, Xun; Zhang, Xiuqing; Bolund, Lars; Krogh, Anders; Kristiansen, Karsten; Drmanac, Radoje; Drmanac, Snezana; Nielsen, Rasmus; Li, Songgang; Wang, Jian; Yang, Huanming; Li, Yingrui; Wong, Gane Ka-Shu; Wang, Jun

    2015-06-01

    The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-genome shotgun strategies, based solely on next-generation sequencing and hierarchical assembly methods. We applied our sequencing method to the genome of an Asian individual and generated a 5.15-Gb assembled genome with a haplotype N50 of 484 kb. Our analysis identified previously undetected indels and 7.49 Mb of novel coding sequences that could not be aligned to the human reference genome, which include at least six predicted genes. This haplotype-resolved genome represents the most complete de novo human genome assembly to date. Application of our approach to identify individual haplotype differences should aid in translating genotypes to phenotypes for the development of personalized medicine.

  18. A Secure Alignment Algorithm for Mapping Short Reads to Human Genome.

    Science.gov (United States)

    Zhao, Yongan; Wang, Xiaofeng; Tang, Haixu

    2018-05-09

    The elastic and inexpensive computing resources such as clouds have been recognized as a useful solution to analyzing massive human genomic data (e.g., acquired by using next-generation sequencers) in biomedical researches. However, outsourcing human genome computation to public or commercial clouds was hindered due to privacy concerns: even a small number of human genome sequences contain sufficient information for identifying the donor of the genomic data. This issue cannot be directly addressed by existing security and cryptographic techniques (such as homomorphic encryption), because they are too heavyweight to carry out practical genome computation tasks on massive data. In this article, we present a secure algorithm to accomplish the read mapping, one of the most basic tasks in human genomic data analysis based on a hybrid cloud computing model. Comparing with the existing approaches, our algorithm delegates most computation to the public cloud, while only performing encryption and decryption on the private cloud, and thus makes the maximum use of the computing resource of the public cloud. Furthermore, our algorithm reports similar results as the nonsecure read mapping algorithms, including the alignment between reads and the reference genome, which can be directly used in the downstream analysis such as the inference of genomic variations. We implemented the algorithm in C++ and Python on a hybrid cloud system, in which the public cloud uses an Apache Spark system.

  19. Genome-wide associations of gene expression variation in humans.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    2005-12-01

    Full Text Available The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis- to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

  20. Genome-Wide Associations of Gene Expression Variation in Humans.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis- to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

  1. Public attitudes to genomic science: an experiment in information provision.

    Science.gov (United States)

    Sturgis, Patrick; Brunton-Smith, Ian; Fife-Schaw, Chris

    2010-03-01

    We use an experimental panel study design to investigate the effect of providing "value-neutral" information about genomic science in the form of a short film to a random sample of the British public. We find little evidence of attitude change as a function of information provision. However, our results show that information provision significantly increased dropout from the study amongst less educated respondents. Our findings have implications both for our understanding of the knowledge-attitude relationship in public opinion toward genomic science and for science communication more generally.

  2. Report on the Human Genome Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Tinoco, I.; Cahill, G.; Cantor, C.; Caskey, T.; Dulbecco, R.; Engelhardt, D. L.; Hood, L.; Lerman, L. S.; Mendelsohn, M. L.; Sinsheimer, R. L.; Smith, T.; Soll, D.; Stormo, G.; White, R. L.

    1987-04-01

    The report urges DOE and the Nation to commit to a large. multi-year. multidisciplinary. technological undertaking to order and sequence the human genome. This effort will first require significant innovation in general capability to manipulate DNA. major new analytical methods for ordering and sequencing. theoretical developments in computer science and mathematical biology, and great expansions in our ability to store and manipulate the information and to interface it with other large and diverse genetic databases. The actual ordering and sequencing involves the coordinated processing of some 3 billion bases from a reference human genome. Science is poised on the rudimentary edge of being able to read and understand human genes. A concerted. broadly based. scientific effort to provide new methods of sufficient power and scale should transform this activity from an inefficient one-gene-at-a-time. single laboratory effort into a coordinated. worldwide. comprehensive reading of "the book of man". The effort will be extraordinary in scope and magnitude. but so will be the benefit to biological understanding. new technology and the diagnosis and treatment of human disease.

  3. The Human Genome Project (HGP): dividends and challenges: a ...

    African Journals Online (AJOL)

    The Human Genome Project (HGP): dividends and challenges: a review. ... Genomic studies have given profound insights into the genetic organization of ... with it will be an essential part of modern medicine and biology for years to come.

  4. Harvard Personal Genome Project: lessons from participatory public research

    Science.gov (United States)

    2014-01-01

    Background Since its initiation in 2005, the Harvard Personal Genome Project has enrolled thousands of volunteers interested in publicly sharing their genome, health and trait data. Because these data are highly identifiable, we use an ‘open consent’ framework that purposefully excludes promises about privacy and requires participants to demonstrate comprehension prior to enrollment. Discussion Our model of non-anonymous, public genomes has led us to a highly participatory model of researcher-participant communication and interaction. The participants, who are highly committed volunteers, self-pursue and donate research-relevant datasets, and are actively engaged in conversations with both our staff and other Personal Genome Project participants. We have quantitatively assessed these communications and donations, and report our experiences with returning research-grade whole genome data to participants. We also observe some of the community growth and discussion that has occurred related to our project. Summary We find that public non-anonymous data is valuable and leads to a participatory research model, which we encourage others to consider. The implementation of this model is greatly facilitated by web-based tools and methods and participant education. Project results are long-term proactive participant involvement and the growth of a community that benefits both researchers and participants. PMID:24713084

  5. Harvard Personal Genome Project: lessons from participatory public research.

    Science.gov (United States)

    Ball, Madeleine P; Bobe, Jason R; Chou, Michael F; Clegg, Tom; Estep, Preston W; Lunshof, Jeantine E; Vandewege, Ward; Zaranek, Alexander; Church, George M

    2014-02-28

    Since its initiation in 2005, the Harvard Personal Genome Project has enrolled thousands of volunteers interested in publicly sharing their genome, health and trait data. Because these data are highly identifiable, we use an 'open consent' framework that purposefully excludes promises about privacy and requires participants to demonstrate comprehension prior to enrollment. Our model of non-anonymous, public genomes has led us to a highly participatory model of researcher-participant communication and interaction. The participants, who are highly committed volunteers, self-pursue and donate research-relevant datasets, and are actively engaged in conversations with both our staff and other Personal Genome Project participants. We have quantitatively assessed these communications and donations, and report our experiences with returning research-grade whole genome data to participants. We also observe some of the community growth and discussion that has occurred related to our project. We find that public non-anonymous data is valuable and leads to a participatory research model, which we encourage others to consider. The implementation of this model is greatly facilitated by web-based tools and methods and participant education. Project results are long-term proactive participant involvement and the growth of a community that benefits both researchers and participants.

  6. The human genome: Some assembly required. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    The Human Genome Project promises to be one of the most rewarding endeavors in modern biology. The cost and the ethical and social implications, however, have made this project the source of considerable debate both in the scientific community and in the public at large. The 1994 Graduate Student Symposium addresses the scientific merits of the project, the technical issues involved in accomplishing the task, as well as the medical and social issues which stem from the wealth of knowledge which the Human Genome Project will help create. To this end, speakers were brought together who represent the diverse areas of expertise characteristic of this multidisciplinary project. The keynote speaker addresses the project`s motivations and goals in the larger context of biological and medical sciences. The first two sessions address relevant technical issues, data collection with a focus on high-throughput sequencing methods and data analysis with an emphasis on identification of coding sequences. The third session explores recent advances in the understanding of genetic diseases and possible routes to treatment. Finally, the last session addresses some of the ethical, social and legal issues which will undoubtedly arise from having a detailed knowledge of the human genome.

  7. Governance in genomics: a conceptual challenge for public health genomics law

    Directory of Open Access Journals (Sweden)

    Tobias Schulte in den Bäumen

    2006-12-01

    Full Text Available Increasing levels of genomic knowledge has led to awareness that new governance issues need to be taken into consideration. While some countries have created new statutory laws in the last 10 years, science supports the idea that genomic data should be treated like other medical data. In this article we discuss the three core models of governance in medical law on a conceptual level. The three models, the Medical, Public Health and Fundamental Rights Model stress different values, or in legal terms serve different principles. The Medical Model stands for expert knowledge and the standardisation of quality in healthcare. The Public Health Model fosters a social point of view as it advocates distribution justice in healthcare and an awareness of healthcare as a broader concept. The Fundamental Rights Model focuses on individual rights such as the right to privacy and autonomy. We argue that none of the models can be used in a purist fashion as governance in genomics should enable society and individuals to protect individual rights, to strive for a distribution justice and to ensure the quality of genomic services in one coherent process. Thus, genomic governance in genomics requires procedural law and a set of applicable principles. The principle which underlies all three models is the principle of medical beneficence. Therefore genomic governance should refer to it as a key principle when conflicting rights of individuals or communities need to be balanced.

  8. Origins of the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Cook-Deegan, Robert

    1993-07-01

    The human genome project was borne of technology, grew into a science bureaucracy in the US and throughout the world, and is now being transformed into a hybrid academic and commercial enterprise. The next phase of the project promises to veer more sharply toward commercial application, harnessing both the technical prowess of molecular biology and the rapidly growing body of knowledge about DNA structure to the pursuit of practical benefits. Faith that the systematic analysis of DNA structure will prove to be a powerful research tool underlies the rationale behind the genome project. The notion that most genetic information is embedded in the sequence of CNA base pairs comprising chromosomes is a central tenet. A rough analogy is to liken an organism's genetic code to computer code. The coal of the genome project, in this parlance, is to identify and catalog 75,000 or more files (genes) in the software that directs construction of a self-modifying and self-replicating system -- a living organism.

  9. Origins of the Human Genome Project

    Science.gov (United States)

    Cook-Deegan, Robert (Affiliation: Institute of Medicine, National Academy of Sciences)

    1993-07-01

    The human genome project was borne of technology, grew into a science bureaucracy in the United States and throughout the world, and is now being transformed into a hybrid academic and commercial enterprise. The next phase of the project promises to veer more sharply toward commercial application, harnessing both the technical prowess of molecular biology and the rapidly growing body of knowledge about DNA structure to the pursuit of practical benefits. Faith that the systematic analysis of DNA structure will prove to be a powerful research tool underlies the rationale behind the genome project. The notion that most genetic information is embedded in the sequence of CNA base pairs comprising chromosomes is a central tenet. A rough analogy is to liken an organism's genetic code to computer code. The coal of the genome project, in this parlance, is to identify and catalog 75,000 or more files (genes) in the software that directs construction of a self-modifying and self-replicating system -- a living organism.

  10. Genomic landscape of human diversity across Madagascar

    Science.gov (United States)

    Pierron, Denis; Heiske, Margit; Razafindrazaka, Harilanto; Rakoto, Ignace; Rabetokotany, Nelly; Ravololomanga, Bodo; Rakotozafy, Lucien M.-A.; Rakotomalala, Mireille Mialy; Razafiarivony, Michel; Rasoarifetra, Bako; Raharijesy, Miakabola Andriamampianina; Razafindralambo, Lolona; Ramilisonina; Fanony, Fulgence; Lejamble, Sendra; Thomas, Olivier; Mohamed Abdallah, Ahmed; Rocher, Christophe; Arachiche, Amal; Tonaso, Laure; Pereda-loth, Veronica; Schiavinato, Stéphanie; Brucato, Nicolas; Ricaut, Francois-Xavier; Kusuma, Pradiptajati; Sudoyo, Herawati; Ni, Shengyu; Boland, Anne; Deleuze, Jean-Francois; Beaujard, Philippe; Grange, Philippe; Adelaar, Sander; Stoneking, Mark; Rakotoarisoa, Jean-Aimé; Radimilahy, Chantal; Letellier, Thierry

    2017-01-01

    Although situated ∼400 km from the east coast of Africa, Madagascar exhibits cultural, linguistic, and genetic traits from both Southeast Asia and Eastern Africa. The settlement history remains contentious; we therefore used a grid-based approach to sample at high resolution the genomic diversity (including maternal lineages, paternal lineages, and genome-wide data) across 257 villages and 2,704 Malagasy individuals. We find a common Bantu and Austronesian descent for all Malagasy individuals with a limited paternal contribution from Europe and the Middle East. Admixture and demographic growth happened recently, suggesting a rapid settlement of Madagascar during the last millennium. However, the distribution of African and Asian ancestry across the island reveals that the admixture was sex biased and happened heterogeneously across Madagascar, suggesting independent colonization of Madagascar from Africa and Asia rather than settlement by an already admixed population. In addition, there are geographic influences on the present genomic diversity, independent of the admixture, showing that a few centuries is sufficient to produce detectable genetic structure in human populations. PMID:28716916

  11. Virtual Northern analysis of the human genome.

    Directory of Open Access Journals (Sweden)

    Evan H Hurowitz

    2007-05-01

    Full Text Available We applied the Virtual Northern technique to human brain mRNA to systematically measure human mRNA transcript lengths on a genome-wide scale.We used separation by gel electrophoresis followed by hybridization to cDNA microarrays to measure 8,774 mRNA transcript lengths representing at least 6,238 genes at high (>90% confidence. By comparing these transcript lengths to the Refseq and H-Invitational full-length cDNA databases, we found that nearly half of our measurements appeared to represent novel transcript variants. Comparison of length measurements determined by hybridization to different cDNAs derived from the same gene identified clones that potentially correspond to alternative transcript variants. We observed a close linear relationship between ORF and mRNA lengths in human mRNAs, identical in form to the relationship we had previously identified in yeast. Some functional classes of protein are encoded by mRNAs whose untranslated regions (UTRs tend to be longer or shorter than average; these functional classes were similar in both human and yeast.Human transcript diversity is extensive and largely unannotated. Our length dataset can be used as a new criterion for judging the completeness of cDNAs and annotating mRNA sequences. Similar relationships between the lengths of the UTRs in human and yeast mRNAs and the functions of the proteins they encode suggest that UTR sequences serve an important regulatory role among eukaryotes.

  12. Virtual Northern analysis of the human genome.

    Science.gov (United States)

    Hurowitz, Evan H; Drori, Iddo; Stodden, Victoria C; Donoho, David L; Brown, Patrick O

    2007-05-23

    We applied the Virtual Northern technique to human brain mRNA to systematically measure human mRNA transcript lengths on a genome-wide scale. We used separation by gel electrophoresis followed by hybridization to cDNA microarrays to measure 8,774 mRNA transcript lengths representing at least 6,238 genes at high (>90%) confidence. By comparing these transcript lengths to the Refseq and H-Invitational full-length cDNA databases, we found that nearly half of our measurements appeared to represent novel transcript variants. Comparison of length measurements determined by hybridization to different cDNAs derived from the same gene identified clones that potentially correspond to alternative transcript variants. We observed a close linear relationship between ORF and mRNA lengths in human mRNAs, identical in form to the relationship we had previously identified in yeast. Some functional classes of protein are encoded by mRNAs whose untranslated regions (UTRs) tend to be longer or shorter than average; these functional classes were similar in both human and yeast. Human transcript diversity is extensive and largely unannotated. Our length dataset can be used as a new criterion for judging the completeness of cDNAs and annotating mRNA sequences. Similar relationships between the lengths of the UTRs in human and yeast mRNAs and the functions of the proteins they encode suggest that UTR sequences serve an important regulatory role among eukaryotes.

  13. The Human Genome Initiative of the Department of Energy

    Science.gov (United States)

    1988-01-01

    The structural characterization of genes and elucidation of their encoded functions have become a cornerstone of modern health research, biology and biotechnology. A genome program is an organized effort to locate and identify the functions of all the genes of an organism. Beginning with the DOE-sponsored, 1986 human genome workshop at Santa Fe, the value of broadly organized efforts supporting total genome characterization became a subject of intensive study. There is now national recognition that benefits will rapidly accrue from an effective scientific infrastructure for total genome research. In the US genome research is now receiving dedicated funds. Several other nations are implementing genome programs. Supportive infrastructure is being improved through both national and international cooperation. The Human Genome Initiative of the Department of Energy (DOE) is a focused program of Resource and Technology Development, with objectives of speeding and bringing economies to the national human genome effort. This report relates the origins and progress of the Initiative.

  14. The PCNA pseudogenes in the human genome

    Directory of Open Access Journals (Sweden)

    Stoimenov Ivaylo

    2012-02-01

    Full Text Available Abstract Background The proliferating cell nuclear antigen (PCNA is a key protein in the eukaryotic DNA replication and cell proliferation. Following the cloning and characterisation of the human PCNA gene, the question of the existence of pseudogenes in the human genome was raised. Findings In this short communication we summarise the existing information about the PCNA pseudogenes and critically assess their status. Conclusions We propose the existence of at least four valid PCNA pseudogenes, PCNAP1, PCNAP2, LOC392454 and LOC390102. We would like to recommend assignment of a name for LOC392454 as "proliferating cell nuclear antigen pseudogene 3" (alias PCNAP3 and a name for LOC390102 as "proliferating cell nuclear antigen pseudogene 4" (alias PCNAP4. We prompt for more critical evaluation of the existence of a PCNA pseudogene, designated as PCNAP.

  15. Comparative genomics of emerging human ehrlichiosis agents.

    Directory of Open Access Journals (Sweden)

    Julie C Dunning Hotopp

    2006-02-01

    Full Text Available Anaplasma (formerly Ehrlichia phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens.

  16. A set of BAC clones spanning the human genome.

    NARCIS (Netherlands)

    Krzywinski, M.; Bosdet, I.; Smailus, D.; Chiu, R.; Mathewson, C.; Wye, N.; Barber, S.; Brown-John, M.; Chan, S.; Chand, S.; Cloutier, A.; Girn, N.; Lee, D.; Masson, A.; Mayo, M.; Olson, T.; Pandoh, P.; Prabhu, A.L.; Schoenmakers, E.F.P.M.; Tsai, M.Y.; Albertson, D.; Lam, W.W.; Choy, C.O.; Osoegawa, K.; Zhao, S.; Jong, P.J. de; Schein, J.; Jones, S.; Marra, M.A.

    2004-01-01

    Using the human bacterial artificial chromosome (BAC) fingerprint-based physical map, genome sequence assembly and BAC end sequences, we have generated a fingerprint-validated set of 32 855 BAC clones spanning the human genome. The clone set provides coverage for at least 98% of the human

  17. The Human Genome Project: how do we protect Australians?

    Science.gov (United States)

    Stott Despoja, N

    It is the moon landing of the nineties: the ambitious Human Genome Project--identifying the up to 100,000 genes that make up human DNA and the sequences of the three billion base-pairs that comprise the human genome. However, unlike the moon landing, the effects of the genome project will have a fundamental impact on the way we see ourselves and each other.

  18. Implementing genomics and pharmacogenomics in the clinic: The National Human Genome Research Institute’s genomic medicine portfolio

    Science.gov (United States)

    Manolio, Teri A.

    2016-01-01

    Increasing knowledge about the influence of genetic variation on human health and growing availability of reliable, cost-effective genetic testing have spurred the implementation of genomic medicine in the clinic. As defined by the National Human Genome Research Institute (NHGRI), genomic medicine uses an individual’s genetic information in his or her clinical care, and has begun to be applied effectively in areas such as cancer genomics, pharmacogenomics, and rare and undiagnosed diseases. In 2011 NHGRI published its strategic vision for the future of genomic research, including an ambitious research agenda to facilitate and promote the implementation of genomic medicine. To realize this agenda, NHGRI is consulting and facilitating collaborations with the external research community through a series of “Genomic Medicine Meetings,” under the guidance and leadership of the National Advisory Council on Human Genome Research. These meetings have identified and begun to address significant obstacles to implementation, such as lack of evidence of efficacy, limited availability of genomics expertise and testing, lack of standards, and diffficulties in integrating genomic results into electronic medical records. The six research and dissemination initiatives comprising NHGRI’s genomic research portfolio are designed to speed the evaluation and incorporation, where appropriate, of genomic technologies and findings into routine clinical care. Actual adoption of successful approaches in clinical care will depend upon the willingness, interest, and energy of professional societies, practitioners, patients, and payers to promote their responsible use and share their experiences in doing so. PMID:27612677

  19. Public Access for Teaching Genomics, Proteomics, and Bioinformatics

    Science.gov (United States)

    Campbell, A. Malcolm

    2003-01-01

    When the human genome project was conceived, its leaders wanted all researchers to have equal access to the data and associated research tools. Their vision of equal access provides an unprecedented teaching opportunity. Teachers and students have free access to the same databases that researchers are using. Furthermore, the recent movement to…

  20. Recurrent DNA inversion rearrangements in the human genome

    DEFF Research Database (Denmark)

    Flores, Margarita; Morales, Lucía; Gonzaga-Jauregui, Claudia

    2007-01-01

    Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome...... to human genomic variation is discussed........ In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located...

  1. Human Rhinovirus B and C Genomes from Rural Coastal Kenya

    NARCIS (Netherlands)

    Agoti, Charles N.; Kiyuka, Patience K.; Kamau, Everlyn; Munywoki, Patrick K.; Bett, Anne; van der Hoek, Lia; Kellam, Paul; Nokes, D. James; Cotten, Matthew

    2016-01-01

    Primer-independent agnostic deep sequencing was used to generate three human rhinovirus (HRV) B genomes and one HRV C genome from samples collected in a household respiratory survey in rural coastal Kenya. The study provides the first rhinovirus genomes from Kenya and will help improve the

  2. Genomic stability of adipogenic human adenovirus 36.

    Science.gov (United States)

    Nam, J-H; Na, H-N; Atkinson, R L; Dhurandhar, N V

    2014-02-01

    Human adenovirus Ad36 increases adiposity in several animal models, including rodents and non-human primates. Importantly, Ad36 is associated with human obesity, which has prompted research to understand its epidemiology and to develop a vaccine to prevent a subgroup of obesity. For this purpose, understanding the genomic stability of Ad36 in vivo and in vitro infections is critical. Here, we examined whether in vitro cell passaging over a 14-year period introduced any genetic variation in Ad36. We sequenced the whole genome of Ad36-which was plaque purified in 1998 from the original strain obtained from American Type Culture Collection, and passaged approximately 12 times over the past 14 years (Ad36-2012). This DNA sequence was compared with a previously published sequence of Ad36 likely obtained from the same source (Ad36-1988). Compared with Ad36-1988, only two nucleotides were altered in Ad36-2012: a T insertion at nucleotide 1862, which may induce early termination of the E1B viral protein, and a T➝C transition at nucleotide 26 136. Virus with the T insertion (designated Ad36-2012-T6) was mixed with wild-type virus lacking the T insertion (designated Ad36-2012-T5) in the viral stock. The transition at nucleotide 26 136 does not change the encoded amino acid (aspartic acid) in the pVIII viral protein. The rate of genetic variation in Ad36 is ∼2.37 × 10(-6) mutations/nucleotide/passage. Of particular importance, there were no mutations in the E4orf1 gene, the critical gene for producing obesity. This very-low-variation rate should reduce concerns about genetic variability when developing Ad36 vaccines or developing assays for detecting Ad36 infection in populations.

  3. Genome editing of human pluripotent stem cells to generate human cellular disease models

    Directory of Open Access Journals (Sweden)

    Kiran Musunuru

    2013-07-01

    Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  4. 75 FR 8374 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-02-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Officer, Scientific Review Branch, National Human Genome Research Institute, National Institutes of Health...

  5. 77 FR 5035 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-02-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research... Officer, Scientific Review Branch, National Human Genome Research Institute, National Institutes of Health...

  6. 78 FR 64222 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-10-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research... Review, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, 301...

  7. 77 FR 20646 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-04-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research.... Agenda: To review and evaluate grant applications. Place: National Human Genome Research Institute, 5635...

  8. 77 FR 58402 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-09-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research...: To review and evaluate grant applications. Place: National Human Genome Research Institute, 5635...

  9. 76 FR 65204 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-10-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... constitute a clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome... Review Officer, Scientific Review Branch, National Human Genome Research Institute, 5635 Fishers Lane...

  10. 77 FR 12604 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-03-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. >Name of Committee: National Human Genome Research... review and evaluate contract proposals. Place: National Human Genome Reseach Institute, 5635 Fishers Lane...

  11. 78 FR 55752 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-09-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research.... Pozzatti, Ph.D., Scientific Review Officer, Scientific Review Branch, National Human Genome Research...

  12. 78 FR 56905 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-09-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research....m. Agenda: To review and evaluate grant applications. Place: National Human Genome Research...

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

    Science.gov (United States)

    2011-03-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Review Officer, Scientific Review Branch, National Human Genome Research Institute, 5635 Fishers Lane...

  14. 77 FR 59933 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-10-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research....D., Scientific Review Officer, Scientific Review Branch, National Human Genome Research Institute...

  15. 78 FR 107 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-01-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... evaluate grant applications. Place: National Human Genome Research Institute, 3rd Floor Conference Room....D., Scientific Review Officer, Scientific Review Branch, National Human Genome Research Institute...

  16. 76 FR 58023 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-09-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial..., Scientific Review Officer, Office of Scientific Review, National Human Genome Research Institute, National...

  17. 77 FR 28888 - National Human Genome Research Institute Notice of Closed Meeting

    Science.gov (United States)

    2012-05-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial...: To review and evaluate grant applications. Place: National Human Genome Research Institute, 3635...

  18. 78 FR 9707 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-02-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research... Officer, Scientific Review Branch, National Human Genome Research Institute, 5635 Fishers Lane, Suite 4076...

  19. 77 FR 71604 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-12-03

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special..., Scientific Review Branch, National Human Genome Research Institute, National Institutes of Health, 5635...

  20. 76 FR 5390 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-01-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Place: National Human Genome Research Institute Special Emphasis... Officer, Scientific Review Branch, National Human Genome Research Institute, 5635 Fishers Lane, Suite 4076...

  1. 76 FR 29772 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-05-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research... of Scientific Review, National Human Genome Research Institute, National Institutes of Health...

  2. Genomic features of human limb specific enhancers.

    Science.gov (United States)

    Ali, Shahid; Amina, Bibi; Anwar, Saneela; Minhas, Rashid; Parveen, Nazia; Nawaz, Uzma; Azam, Syed Sikandar; Abbasi, Amir Ali

    2016-10-01

    To elucidate important cellular and molecular interactions that regulate patterning and skeletal development, vertebrate limbs served as a model organ. A growing body of evidence from detailed studies on a subset of limb regulators like the HOXD cluster or SHH, reveals the importance of enhancers in limb related developmental and disease processes. Exploiting the recent genome-wide availability of functionally confirmed enhancer dataset, this study establishes regulatory interactions for dozens of human limb developmental genes. From these data, it appears that the long-range regulatory interactions are fairly common during limb development. This observation highlights the significance of chromosomal breaks/translocations in human limb deformities. Transcriptional factor (TF) analysis predicts that the differentiation of early nascent limb-bud into future territories entail distinct TF interaction networks. Conclusively, an important motivation for annotating the human limb specific regulatory networks is to pave way for the systematic exploration of their role in disease and evolution. Copyright © 2016. Published by Elsevier Inc.

  3. Forces shaping the fastest evolving regions in the human genome

    DEFF Research Database (Denmark)

    Pollard, Katherine S; Salama, Sofie R; King, Bryan

    2006-01-01

    Comparative genomics allow us to search the human genome for segments that were extensively changed in the last approximately 5 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. We found 202...... genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements...... contributed to accelerated evolution of the fastest evolving elements in the human genome....

  4. Genome Architecture and Its Roles in Human Copy Number Variation

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-12-01

    Full Text Available Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs, are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

  5. The Human Genome Project: An Imperative for International Collaboration.

    Science.gov (United States)

    Allende, J. E.

    1989-01-01

    Discussed is the Human Genome Project which aims to decipher the totality of the human genetic information. The historical background, the objectives, international cooperation, ethical discussion, and the role of UNESCO are included. (KR)

  6. Complete Genome Sequence of the Human Gut Symbiont Roseburia hominis

    DEFF Research Database (Denmark)

    Travis, Anthony J.; Kelly, Denise; Flint, Harry J

    2015-01-01

    We report here the complete genome sequence of the human gut symbiont Roseburia hominis A2-183(T) (= DSM 16839(T) = NCIMB 14029(T)), isolated from human feces. The genome is represented by a 3,592,125-bp chromosome with 3,405 coding sequences. A number of potential functions contributing to host...

  7. Child Development and Structural Variation in the Human Genome

    Science.gov (United States)

    Zhang, Ying; Haraksingh, Rajini; Grubert, Fabian; Abyzov, Alexej; Gerstein, Mark; Weissman, Sherman; Urban, Alexander E.

    2013-01-01

    Structural variation of the human genome sequence is the insertion, deletion, or rearrangement of stretches of DNA sequence sized from around 1,000 to millions of base pairs. Over the past few years, structural variation has been shown to be far more common in human genomes than previously thought. Very little is currently known about the effects…

  8. Widespread of horizontal gene transfer in the human genome.

    Science.gov (United States)

    Huang, Wenze; Tsai, Lillian; Li, Yulong; Hua, Nan; Sun, Chen; Wei, Chaochun

    2017-04-04

    A fundamental concept in biology is that heritable material is passed from parents to offspring, a process called vertical gene transfer. An alternative mechanism of gene acquisition is through horizontal gene transfer (HGT), which involves movement of genetic materials between different species. Horizontal gene transfer has been found prevalent in prokaryotes but very rare in eukaryote. In this paper, we investigate horizontal gene transfer in the human genome. From the pair-wise alignments between human genome and 53 vertebrate genomes, 1,467 human genome regions (2.6 M bases) from all chromosomes were found to be more conserved with non-mammals than with most mammals. These human genome regions involve 642 known genes, which are enriched with ion binding. Compared to known horizontal gene transfer regions in the human genome, there were few overlapping regions, which indicated horizontal gene transfer is more common than we expected in the human genome. Horizontal gene transfer impacts hundreds of human genes and this study provided insight into potential mechanisms of HGT in the human genome.

  9. Human Ecology: Acid Rain and Public Policy.

    Science.gov (United States)

    Bybee, Rodger W.

    1983-01-01

    A connection between science and society can be seen in the human and ecological dimensions of one contemporary problem: acid rain. Introduces a human ecological theme and relationships between acid rain and public policy, considering scientific understanding and public awareness, scientific research and public policy, and national politics and…

  10. Genomics in Public Health: Perspective from the Office of Public Health Genomics at the Centers for Disease Control and Prevention (CDC

    Directory of Open Access Journals (Sweden)

    Ridgely Fisk Green

    2015-09-01

    Full Text Available The national effort to use genomic knowledge to save lives is gaining momentum, as illustrated by the inclusion of genomics in key public health initiatives, including Healthy People 2020, and the recent launch of the precision medicine initiative. The Office of Public Health Genomics (OPHG at the Centers for Disease Control and Prevention (CDC partners with state public health departments and others to advance the translation of genome-based discoveries into disease prevention and population health. To do this, OPHG has adopted an “identify, inform, and integrate” model: identify evidence-based genomic applications ready for implementation, inform stakeholders about these applications, and integrate these applications into public health at the local, state, and national level. This paper addresses current and future work at OPHG for integrating genomics into public health programs.

  11. Genomics in Public Health: Perspective from the Office of Public Health Genomics at the Centers for Disease Control and Prevention (CDC).

    Science.gov (United States)

    Green, Ridgely Fisk; Dotson, W David; Bowen, Scott; Kolor, Katherine; Khoury, Muin J

    2015-01-01

    The national effort to use genomic knowledge to save lives is gaining momentum, as illustrated by the inclusion of genomics in key public health initiatives, including Healthy People 2020, and the recent launch of the precision medicine initiative. The Office of Public Health Genomics (OPHG) at the Centers for Disease Control and Prevention (CDC) partners with state public health departments and others to advance the translation of genome-based discoveries into disease prevention and population health. To do this, OPHG has adopted an "identify, inform, and integrate" model: identify evidence-based genomic applications ready for implementation, inform stakeholders about these applications, and integrate these applications into public health at the local, state, and national level. This paper addresses current and future work at OPHG for integrating genomics into public health programs.

  12. Genomics England's implementation of its public engagement strategy: Blurred boundaries between engagement for the United Kingdom's 100,000 Genomes project and the need for public support.

    Science.gov (United States)

    Samuel, Gabrielle Natalie; Farsides, Bobbie

    2018-04-01

    The United Kingdom's 100,000 Genomes Project has the aim of sequencing 100,000 genomes from National Health Service patients such that whole genome sequencing becomes routine clinical practice. It also has a research-focused goal to provide data for scientific discovery. Genomics England is the limited company established by the Department of Health to deliver the project. As an innovative scientific/clinical venture, it is interesting to consider how Genomics England positions itself in relation to public engagement activities. We set out to explore how individuals working at, or associated with, Genomics England enacted public engagement in practice. Our findings show that individuals offered a narrative in which public engagement performed more than one function. On one side, public engagement was seen as 'good practice'. On the other, public engagement was presented as core to the project's success - needed to encourage involvement and ultimately recruitment. We discuss the implications of this in this article.

  13. Public awareness of human papillomavirus.

    Science.gov (United States)

    Cuschieri, K S; Horne, A W; Szarewski, A; Cubie, H A

    2006-01-01

    The main objective of this study was to review the evidence relating to the level of awareness of human papillomavirus (HPV) in the general population and the implications for the potential introduction of HPV vaccination and HPV testing as part of screening. PubMed search performed on terms: 'HPV education', 'HPV awareness' 'Genital Warts Awareness' Results: Public awareness of HPV is generally very low, particularly with respect to its relation to abnormal smears and cervical cancer although knowledge levels vary to some extent according to sociodemographic characteristics. There is also much confusion around which types cause warts and the types that can cause cancer. The sexually transmissible nature of the infection is of major concern and confusion to women. Due to the lack of current awareness of HPV, significant education initiatives will be necessary should HPV vaccination and/or HPV testing be introduced. Organized edification of health-care workers and the media, who constitute the two most preferred sources of information, will be crucial.

  14. The Past, Present, and Future of Human Centromere Genomics

    Directory of Open Access Journals (Sweden)

    Megan E. Aldrup-MacDonald

    2014-01-01

    Full Text Available The centromere is the chromosomal locus essential for chromosome inheritance and genome stability. Human centromeres are located at repetitive alpha satellite DNA arrays that compose approximately 5% of the genome. Contiguous alpha satellite DNA sequence is absent from the assembled reference genome, limiting current understanding of centromere organization and function. Here, we review the progress in centromere genomics spanning the discovery of the sequence to its molecular characterization and the work done during the Human Genome Project era to elucidate alpha satellite structure and sequence variation. We discuss exciting recent advances in alpha satellite sequence assembly that have provided important insight into the abundance and complex organization of this sequence on human chromosomes. In light of these new findings, we offer perspectives for future studies of human centromere assembly and function.

  15. (Public) Health and Human Rights in Practice.

    Science.gov (United States)

    Annas, George J; Mariner, Wendy K

    2016-02-01

    Public health's reliance on law to define and carry out public activities makes it impossible to define a set of ethical principles unique to public health. Public health ethics must be encompassed within--and consistent with--a broader set of principles that define the power and limits of governmental institutions. These include human rights, health law, and even medical ethics. The human right to health requires governments not only to respect individual human rights and personal freedoms, but also, importantly, to protect people from harm from external sources and third parties, and to fulfill the health needs of the population. Even if human rights are the natural language for public health, not all public health professionals are comfortable with the language of human rights. Some argue that individual human rights--such as autonomy and privacy--unfairly limit the permissible means to achieve the goal of health protection. We argue that public health should welcome and promote the human rights framework. In almost every instance, this will make public health more effective in the long run, because the goals of public health and human rights are the same: to promote human flourishing. Copyright © 2016 by Duke University Press.

  16. Human Genome Epidemiology : A scientific foundation for using genetic information to improve health and prevent disease

    Directory of Open Access Journals (Sweden)

    Stefania Boccia

    2005-03-01

    Full Text Available

    Human health is determined by the interplay of genetic factors and the environment. In this context the recent advances in human genomics are expected to play a central role in medicine and public health by providing genetic information for disease prediction and prevention.

    After the completion of the human genome sequencing, a fundamental step will be represented by the translation of these discoveries into meaningful actions to improve health and prevent diseases, and the field of epidemiology plays a central role in this effort. These are some of the issues addressed by Human Genome Epidemiology –A scientific foundation for using genetic information to improve health and prevent disease, a volume edited by Prof. M. Khoury, Prof. J. Little, Prof.W. Burke and published by Oxford university Press 2004.

    This book describes the important role that epidemiological methods play in the continuum from gene discovery to the development and application of genetic tests. The Authors calls this continuum human genome epidemiology (HuGE to denote an evolving field of inquiry that uses systematic applications of epidemiological methods to assess the impact of human genetic variation on health and disease.

    The book is divided into four sections and it is structured to allow readers to proceed systematically from the fundamentals of genome technology and discovery, to the epidemiological approaches, to gene characterisation, to the evaluation of genetic tests and their use in health services and public health.

  17. Recent and ongoing selection in the human genome

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Hellmann, Ines; Hubisz, Melissa

    2007-01-01

    The recent availability of genome-scale genotyping data has led to the identification of regions of the human genome that seem to have been targeted by selection. These findings have increased our understanding of the evolutionary forces that affect the human genome, have augmented our knowledge...... of gene function and promise to increase our understanding of the genetic basis of disease. However, inferences of selection are challenged by several confounding factors, especially the complex demographic history of human populations, and concordance between studies is variable. Although such studies...

  18. Explaining human uniqueness: genome interactions with environment, behaviour and culture.

    Science.gov (United States)

    Varki, Ajit; Geschwind, Daniel H; Eichler, Evan E

    2008-10-01

    What makes us human? Specialists in each discipline respond through the lens of their own expertise. In fact, 'anthropogeny' (explaining the origin of humans) requires a transdisciplinary approach that eschews such barriers. Here we take a genomic and genetic perspective towards molecular variation, explore systems analysis of gene expression and discuss an organ-systems approach. Rejecting any 'genes versus environment' dichotomy, we then consider genome interactions with environment, behaviour and culture, finally speculating that aspects of human uniqueness arose because of a primate evolutionary trend towards increasing and irreversible dependence on learned behaviours and culture - perhaps relaxing allowable thresholds for large-scale genomic diversity.

  19. Localizing recent adaptive evolution in the human genome

    DEFF Research Database (Denmark)

    Williamson, Scott H; Hubisz, Melissa J; Clark, Andrew G

    2007-01-01

    , clusters of olfactory receptors, genes involved in nervous system development and function, immune system genes, and heat shock genes. We also observe consistent evidence of selective sweeps in centromeric regions. In general, we find that recent adaptation is strikingly pervasive in the human genome......-nucleotide polymorphism ascertainment, while also providing fine-scale estimates of the position of the selected site, we analyzed a genomic dataset of 1.2 million human single-nucleotide polymorphisms genotyped in African-American, European-American, and Chinese samples. We identify 101 regions of the human genome...

  20. Human Rights and Public Education

    Science.gov (United States)

    Bowring, Bill

    2012-01-01

    This article attempts a contrast to the contribution by Hugh Starkey. Rather than his account of the inexorable rise of human rights discourse, and of the implementation of human rights standards, human rights are here presented as always and necessarily scandalous and highly contested. First, I explain why the UK has lagged so far behind its…

  1. Transposable element activity, genome regulation and human health.

    Science.gov (United States)

    Wang, Lu; Jordan, I King

    2018-03-02

    A convergence of novel genome analysis technologies is enabling population genomic studies of human transposable elements (TEs). Population surveys of human genome sequences have uncovered thousands of individual TE insertions that segregate as common genetic variants, i.e. TE polymorphisms. These recent TE insertions provide an important source of naturally occurring human genetic variation. Investigators are beginning to leverage population genomic data sets to execute genome-scale association studies for assessing the phenotypic impact of human TE polymorphisms. For example, the expression quantitative trait loci (eQTL) analytical paradigm has recently been used to uncover hundreds of associations between human TE insertion variants and gene expression levels. These include population-specific gene regulatory effects as well as coordinated changes to gene regulatory networks. In addition, analyses of linkage disequilibrium patterns with previously characterized genome-wide association study (GWAS) trait variants have uncovered TE insertion polymorphisms that are likely causal variants for a variety of common complex diseases. Gene regulatory mechanisms that underlie specific disease phenotypes have been proposed for a number of these trait associated TE polymorphisms. These new population genomic approaches hold great promise for understanding how ongoing TE activity contributes to functionally relevant genetic variation within and between human populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. DFAST: a flexible prokaryotic genome annotation pipeline for faster genome publication.

    Science.gov (United States)

    Tanizawa, Yasuhiro; Fujisawa, Takatomo; Nakamura, Yasukazu

    2018-03-15

    We developed a prokaryotic genome annotation pipeline, DFAST, that also supports genome submission to public sequence databases. DFAST was originally started as an on-line annotation server, and to date, over 7000 jobs have been processed since its first launch in 2016. Here, we present a newly implemented background annotation engine for DFAST, which is also available as a standalone command-line program. The new engine can annotate a typical-sized bacterial genome within 10 min, with rich information such as pseudogenes, translation exceptions and orthologous gene assignment between given reference genomes. In addition, the modular framework of DFAST allows users to customize the annotation workflow easily and will also facilitate extensions for new functions and incorporation of new tools in the future. The software is implemented in Python 3 and runs in both Python 2.7 and 3.4-on Macintosh and Linux systems. It is freely available at https://github.com/nigyta/dfast_core/under the GPLv3 license with external binaries bundled in the software distribution. An on-line version is also available at https://dfast.nig.ac.jp/. yn@nig.ac.jp. Supplementary data are available at Bioinformatics online.

  3. Public health nursing, ethics and human rights.

    Science.gov (United States)

    Ivanov, Luba L; Oden, Tami L

    2013-05-01

    Public health nursing has a code of ethics that guides practice. This includes the American Nurses Association Code of Ethics for Nurses, Principles of the Ethical Practice of Public Health, and the Scope and Standards of Public Health Nursing. Human rights and Rights-based care in public health nursing practice are relatively new. They reflect human rights principles as outlined in the Universal Declaration of Human Rights and applied to public health practice. As our health care system is restructured and there are new advances in technology and genetics, a focus on providing care that is ethical and respects human rights is needed. Public health nurses can be in the forefront of providing care that reflects an ethical base and a rights-based approach to practice with populations. © 2013 Wiley Periodicals, Inc.

  4. Building the sequence map of the human pan-genome

    DEFF Research Database (Denmark)

    Li, Ruiqiang; Li, Yingrui; Zheng, Hancheng

    2010-01-01

    analysis of predicted genes indicated that the novel sequences contain potentially functional coding regions. We estimate that a complete human pan-genome would contain approximately 19-40 Mb of novel sequence not present in the extant reference genome. The extensive amount of novel sequence contributing...

  5. Genome Editing: A New Approach to Human Therapeutics.

    Science.gov (United States)

    Porteus, Matthew

    2016-01-01

    The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

  6. ELSI Bibliography: Ethical legal and social implications of the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Yesley, M.S. [comp.

    1993-11-01

    This second edition of the ELSI Bibliography provides a current and comprehensive resource for identifying publications on the major topics related to the ethical, legal and social issues (ELSI) of the Human Genome Project. Since the first edition of the ELSI Bibliography was printed last year, new publications and earlier ones identified by additional searching have doubled our computer database of ELSI publications to over 5600 entries. The second edition of the ELSI Bibliography reflects this growth of the underlying computer database. Researchers should note that an extensive collection of publications in the database is available for public use at the General Law Library of Los Alamos National Laboratory (LANL).

  7. Predicting Tissue-Specific Enhancers in the Human Genome

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  8. National human genome projects: an update and an agenda.

    Science.gov (United States)

    An, Joon Yong

    2017-01-01

    Population genetic and human genetic studies are being accelerated with genome technology and data sharing. Accordingly, in the past 10 years, several countries have initiated genetic research using genome technology and identified the genetic architecture of the ethnic groups living in the corresponding country or suggested the genetic foundation of a social phenomenon. Genetic research has been conducted from epidemiological studies that previously described the health or disease conditions in defined population. This perspective summarizes national genome projects conducted in the past 10 years and introduces case studies to utilize genomic data in genetic research.

  9. Public Lecture: Human Space Exploration

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    Should you wish to attend to this lecture only (and not the full colloquium), please register here: https://indico.cern.ch/event/386996/registration/ Participants to the full colloquium are automatically registered to the public lectures.

  10. The lawful uses of knowledge from the Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Grad, F.P.

    1994-04-15

    Part I of this study deals with the right to know or not to know personal genetic information, and examines available legal protections of the right of privacy and the adverse effect of the disclosure of genetic information both on employment and insurance interests and on self esteem and protection of personal integrity. The study examines the rationale for the legal protection of privacy as the protection of a public interest. It examines the very limited protections currently available for privacy interests, including genetic privacy interests, and concludes that there is a need for broader, more far-reaching legal protections. The second part of the study is based on the assumption that as major a project as the Human Genome Project, spending billions of dollars on science which is health related, will indeed be applied for preventive and therapeutic public health purposes, as it has been in the past. It also addresses the recurring fear that public health initiatives in the genetic area must evolve a new eugenic agenda, that we must not repeat the miserable discriminatory experiences of the past.

  11. A decade of human genome project conclusion: Scientific diffusion about our genome knowledge.

    Science.gov (United States)

    Moraes, Fernanda; Góes, Andréa

    2016-05-06

    The Human Genome Project (HGP) was initiated in 1990 and completed in 2003. It aimed to sequence the whole human genome. Although it represented an advance in understanding the human genome and its complexity, many questions remained unanswered. Other projects were launched in order to unravel the mysteries of our genome, including the ENCyclopedia of DNA Elements (ENCODE). This review aims to analyze the evolution of scientific knowledge related to both the HGP and ENCODE projects. Data were retrieved from scientific articles published in 1990-2014, a period comprising the development and the 10 years following the HGP completion. The fact that only 20,000 genes are protein and RNA-coding is one of the most striking HGP results. A new concept about the organization of genome arose. The ENCODE project was initiated in 2003 and targeted to map the functional elements of the human genome. This project revealed that the human genome is pervasively transcribed. Therefore, it was determined that a large part of the non-protein coding regions are functional. Finally, a more sophisticated view of chromatin structure emerged. The mechanistic functioning of the genome has been redrafted, revealing a much more complex picture. Besides, a gene-centric conception of the organism has to be reviewed. A number of criticisms have emerged against the ENCODE project approaches, raising the question of whether non-conserved but biochemically active regions are truly functional. Thus, HGP and ENCODE projects accomplished a great map of the human genome, but the data generated still requires further in depth analysis. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:215-223, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

  12. Human · mouse genome analysis and radiation biology. Proceedings

    International Nuclear Information System (INIS)

    Hori, Tada-aki

    1994-03-01

    This issue is the collection of the papers presented at the 25th NIRS symposium on Human, Mouse Genome Analysis and Radiation Biology. The 14 of the presented papers are indexed individually. (J.P.N.)

  13. The Human Genome Project: big science transforms biology and medicine

    OpenAIRE

    Hood, Leroy; Rowen, Lee

    2013-01-01

    The Human Genome Project has transformed biology through its integrated big science approach to deciphering a reference human genome sequence along with the complete sequences of key model organisms. The project exemplifies the power, necessity and success of large, integrated, cross-disciplinary efforts - so-called ‘big science’ - directed towards complex major objectives. In this article, we discuss the ways in which this ambitious endeavor led to the development of novel technologies and a...

  14. Crossed wires: 3D genome misfolding in human disease.

    Science.gov (United States)

    Norton, Heidi K; Phillips-Cremins, Jennifer E

    2017-11-06

    Mammalian genomes are folded into unique topological structures that undergo precise spatiotemporal restructuring during healthy development. Here, we highlight recent advances in our understanding of how the genome folds inside the 3D nucleus and how these folding patterns are miswired during the onset and progression of mammalian disease states. We discuss potential mechanisms underlying the link among genome misfolding, genome dysregulation, and aberrant cellular phenotypes. We also discuss cases in which the endogenous 3D genome configurations in healthy cells might be particularly susceptible to mutation or translocation. Together, these data support an emerging model in which genome folding and misfolding is critically linked to the onset and progression of a broad range of human diseases. © 2017 Norton and Phillips-Cremins.

  15. The Human Genome Project: big science transforms biology and medicine.

    Science.gov (United States)

    Hood, Leroy; Rowen, Lee

    2013-01-01

    The Human Genome Project has transformed biology through its integrated big science approach to deciphering a reference human genome sequence along with the complete sequences of key model organisms. The project exemplifies the power, necessity and success of large, integrated, cross-disciplinary efforts - so-called 'big science' - directed towards complex major objectives. In this article, we discuss the ways in which this ambitious endeavor led to the development of novel technologies and analytical tools, and how it brought the expertise of engineers, computer scientists and mathematicians together with biologists. It established an open approach to data sharing and open-source software, thereby making the data resulting from the project accessible to all. The genome sequences of microbes, plants and animals have revolutionized many fields of science, including microbiology, virology, infectious disease and plant biology. Moreover, deeper knowledge of human sequence variation has begun to alter the practice of medicine. The Human Genome Project has inspired subsequent large-scale data acquisition initiatives such as the International HapMap Project, 1000 Genomes, and The Cancer Genome Atlas, as well as the recently announced Human Brain Project and the emerging Human Proteome Project.

  16. Ancient Human Genome Sequence of an Extinct Palaeo-Eskimo

    DEFF Research Database (Denmark)

    Rasmussen, Morten; Li, Yingrui; Lindgreen, Stinus

    2010-01-01

    We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome...... possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence...

  17. Automated whole-genome multiple alignment of rat, mouse, and human

    Energy Technology Data Exchange (ETDEWEB)

    Brudno, Michael; Poliakov, Alexander; Salamov, Asaf; Cooper, Gregory M.; Sidow, Arend; Rubin, Edward M.; Solovyev, Victor; Batzoglou, Serafim; Dubchak, Inna

    2004-07-04

    We have built a whole genome multiple alignment of the three currently available mammalian genomes using a fully automated pipeline which combines the local/global approach of the Berkeley Genome Pipeline and the LAGAN program. The strategy is based on progressive alignment, and consists of two main steps: (1) alignment of the mouse and rat genomes; and (2) alignment of human to either the mouse-rat alignments from step 1, or the remaining unaligned mouse and rat sequences. The resulting alignments demonstrate high sensitivity, with 87% of all human gene-coding areas aligned in both mouse and rat. The specificity is also high: <7% of the rat contigs are aligned to multiple places in human and 97% of all alignments with human sequence > 100kb agree with a three-way synteny map built independently using predicted exons in the three genomes. At the nucleotide level <1% of the rat nucleotides are mapped to multiple places in the human sequence in the alignment; and 96.5% of human nucleotides within all alignments agree with the synteny map. The alignments are publicly available online, with visualization through the novel Multi-VISTA browser that we also present.

  18. Genome editing: a robust technology for human stem cells.

    Science.gov (United States)

    Chandrasekaran, Arun Pandian; Song, Minjung; Ramakrishna, Suresh

    2017-09-01

    Human pluripotent stem cells comprise induced pluripotent and embryonic stem cells, which have tremendous potential for biological and therapeutic applications. The development of efficient technologies for the targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. Genome editing of stem cells is possible with the help of synthetic nucleases that facilitate site-specific modification of a gene of interest. Recent advances in genome editing techniques have improved the efficiency and speed of the development of stem cells for human disease models. Zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system are powerful tools for editing DNA at specific loci. Here, we discuss recent technological advances in genome editing with site-specific nucleases in human stem cells.

  19. Human genome project: revolutionizing biology through leveraging technology

    Science.gov (United States)

    Dahl, Carol A.; Strausberg, Robert L.

    1996-04-01

    The Human Genome Project (HGP) is an international project to develop genetic, physical, and sequence-based maps of the human genome. Since the inception of the HGP it has been clear that substantially improved technology would be required to meet the scientific goals, particularly in order to acquire the complete sequence of the human genome, and that these technologies coupled with the information forthcoming from the project would have a dramatic effect on the way biomedical research is performed in the future. In this paper, we discuss the state-of-the-art for genomic DNA sequencing, technological challenges that remain, and the potential technological paths that could yield substantially improved genomic sequencing technology. The impact of the technology developed from the HGP is broad-reaching and a discussion of other research and medical applications that are leveraging HGP-derived DNA analysis technologies is included. The multidisciplinary approach to the development of new technologies that has been successful for the HGP provides a paradigm for facilitating new genomic approaches toward understanding the biological role of functional elements and systems within the cell, including those encoded within genomic DNA and their molecular products.

  20. Defining functional DNA elements in the human genome

    Science.gov (United States)

    Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E.; Dekker, Job; Dunham, Ian; Elnitski, Laura L.; Farnham, Peggy J.; Feingold, Elise A.; Gerstein, Mark; Giddings, Morgan C.; Gilbert, David M.; Gingeras, Thomas R.; Green, Eric D.; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D.; Myers, Richard M.; Pazin, Michael J.; Ren, Bing; Stamatoyannopoulos, John A.; Weng, Zhiping; White, Kevin P.; Hardison, Ross C.

    2014-01-01

    With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease. PMID:24753594

  1. The human noncoding genome defined by genetic diversity.

    Science.gov (United States)

    di Iulio, Julia; Bartha, Istvan; Wong, Emily H M; Yu, Hung-Chun; Lavrenko, Victor; Yang, Dongchan; Jung, Inkyung; Hicks, Michael A; Shah, Naisha; Kirkness, Ewen F; Fabani, Martin M; Biggs, William H; Ren, Bing; Venter, J Craig; Telenti, Amalio

    2018-03-01

    Understanding the significance of genetic variants in the noncoding genome is emerging as the next challenge in human genomics. We used the power of 11,257 whole-genome sequences and 16,384 heptamers (7-nt motifs) to build a map of sequence constraint for the human species. This build differed substantially from traditional maps of interspecies conservation and identified regulatory elements among the most constrained regions of the genome. Using new Hi-C experimental data, we describe a strong pattern of coordination over 2 Mb where the most constrained regulatory elements associate with the most essential genes. Constrained regions of the noncoding genome are up to 52-fold enriched for known pathogenic variants as compared to unconstrained regions (21-fold when compared to the genome average). This map of sequence constraint across thousands of individuals is an asset to help interpret noncoding elements in the human genome, prioritize variants and reconsider gene units at a larger scale.

  2. Review Human Oesophagostomiasis: A Serious Public Health ...

    African Journals Online (AJOL)

    Review Human Oesophagostomiasis: A Serious Public Health Problem in Tropical ... Historical events were described from its first record in Ethiopia in 1905. ... information on patterns of distribution and relation of transmission to seasons and ...

  3. Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation.

    Science.gov (United States)

    Kidd, Jeffrey M; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F; Peckham, Heather E; Omberg, Larsson; Bormann Chung, Christina A; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G; Russell, Archie; Reynolds, Andy; Clark, Andrew G; Reese, Martin G; Lincoln, Stephen E; Butte, Atul J; De La Vega, Francisco M; Bustamante, Carlos D

    2012-10-05

    Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  4. Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

    Science.gov (United States)

    Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

    2013-01-01

    In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

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

    Directory of Open Access Journals (Sweden)

    Allana Roach

    Full Text Available 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.

  6. Human genome and open source: balancing ethics and business.

    Science.gov (United States)

    Marturano, Antonio

    2011-01-01

    The Human Genome Project has been completed thanks to a massive use of computer techniques, as well as the adoption of the open-source business and research model by the scientists involved. This model won over the proprietary model and allowed a quick propagation and feedback of research results among peers. In this paper, the author will analyse some ethical and legal issues emerging by the use of such computer model in the Human Genome property rights. The author will argue that the Open Source is the best business model, as it is able to balance business and human rights perspectives.

  7. Genomic divergences among cattle, dog and human estimated from large-scale alignments of genomic sequences

    Directory of Open Access Journals (Sweden)

    Shade Larry L

    2006-06-01

    Full Text Available Abstract Background Approximately 11 Mb of finished high quality genomic sequences were sampled from cattle, dog and human to estimate genomic divergences and their regional variation among these lineages. Results Optimal three-way multi-species global sequence alignments for 84 cattle clones or loci (each >50 kb of genomic sequence were constructed using the human and dog genome assemblies as references. Genomic divergences and substitution rates were examined for each clone and for various sequence classes under different functional constraints. Analysis of these alignments revealed that the overall genomic divergences are relatively constant (0.32–0.37 change/site for pairwise comparisons among cattle, dog and human; however substitution rates vary across genomic regions and among different sequence classes. A neutral mutation rate (2.0–2.2 × 10(-9 change/site/year was derived from ancestral repetitive sequences, whereas the substitution rate in coding sequences (1.1 × 10(-9 change/site/year was approximately half of the overall rate (1.9–2.0 × 10(-9 change/site/year. Relative rate tests also indicated that cattle have a significantly faster rate of substitution as compared to dog and that this difference is about 6%. Conclusion This analysis provides a large-scale and unbiased assessment of genomic divergences and regional variation of substitution rates among cattle, dog and human. It is expected that these data will serve as a baseline for future mammalian molecular evolution studies.

  8. From hacking the human genome to editing organs.

    Science.gov (United States)

    Tobita, Takamasa; Guzman-Lepe, Jorge; Collin de l'Hortet, Alexandra

    2015-01-01

    In the recent decades, human genome engineering has been one of the major interesting research subjects, essentially because it raises new possibilities for personalized medicine and biotechnologies. With the development of engineered nucleases such as the Zinc Finger Nucleases (ZFNs), the Transcription activator-like effector nucleases (TALENs) and more recently the Clustered Regularly Interspaced short Palindromic Repeats (CRISPR), the field of human genome edition has evolved very rapidly. Every new genetic tool is broadening the scope of applications on human tissues, even before we can completely master each of these tools. In this review, we will present the recent advances regarding human genome edition tools, we will discuss the numerous implications they have in research and medicine, and we will mention the limits and concerns about such technologies.

  9. Sequencing and analysis of an Irish human genome.

    LENUS (Irish Health Repository)

    Tong, Pin

    2010-01-01

    Recent studies generating complete human sequences from Asian, African and European subgroups have revealed population-specific variation and disease susceptibility loci. Here, choosing a DNA sample from a population of interest due to its relative geographical isolation and genetic impact on further populations, we extend the above studies through the generation of 11-fold coverage of the first Irish human genome sequence.

  10. The diploid genome sequence of an individual human.

    Directory of Open Access Journals (Sweden)

    Samuel Levy

    2007-09-01

    Full Text Available Presented here is a genome sequence of an individual human. It was produced from approximately 32 million random DNA fragments, sequenced by Sanger dideoxy technology and assembled into 4,528 scaffolds, comprising 2,810 million bases (Mb of contiguous sequence with approximately 7.5-fold coverage for any given region. We developed a modified version of the Celera assembler to facilitate the identification and comparison of alternate alleles within this individual diploid genome. Comparison of this genome and the National Center for Biotechnology Information human reference assembly revealed more than 4.1 million DNA variants, encompassing 12.3 Mb. These variants (of which 1,288,319 were novel included 3,213,401 single nucleotide polymorphisms (SNPs, 53,823 block substitutions (2-206 bp, 292,102 heterozygous insertion/deletion events (indels(1-571 bp, 559,473 homozygous indels (1-82,711 bp, 90 inversions, as well as numerous segmental duplications and copy number variation regions. Non-SNP DNA variation accounts for 22% of all events identified in the donor, however they involve 74% of all variant bases. This suggests an important role for non-SNP genetic alterations in defining the diploid genome structure. Moreover, 44% of genes were heterozygous for one or more variants. Using a novel haplotype assembly strategy, we were able to span 1.5 Gb of genome sequence in segments >200 kb, providing further precision to the diploid nature of the genome. These data depict a definitive molecular portrait of a diploid human genome that provides a starting point for future genome comparisons and enables an era of individualized genomic information.

  11. Learning about human population history from ancient and modern genomes.

    Science.gov (United States)

    Stoneking, Mark; Krause, Johannes

    2011-08-18

    Genome-wide data, both from SNP arrays and from complete genome sequencing, are becoming increasingly abundant and are now even available from extinct hominins. These data are providing new insights into population history; in particular, when combined with model-based analytical approaches, genome-wide data allow direct testing of hypotheses about population history. For example, genome-wide data from both contemporary populations and extinct hominins strongly support a single dispersal of modern humans from Africa, followed by two archaic admixture events: one with Neanderthals somewhere outside Africa and a second with Denisovans that (so far) has only been detected in New Guinea. These new developments promise to reveal new stories about human population history, without having to resort to storytelling.

  12. A periodic pattern of SNPs in the human genome

    DEFF Research Database (Denmark)

    Madsen, Bo Eskerod; Villesen, Palle; Wiuf, Carsten

    2007-01-01

    By surveying a filtered, high-quality set of SNPs in the human genome, we have found that SNPs positioned 1, 2, 4, 6, or 8 bp apart are more frequent than SNPs positioned 3, 5, 7, or 9 bp apart. The observed pattern is not restricted to genomic regions that are known to cause sequencing...... periodic DNA. Our results suggest that not all SNPs in the human genome are created by independent single nucleotide mutations, and that care should be taken in analysis of SNPs from periodic DNA. The latter may have important consequences for SNP and association studies....... or alignment errors, for example, transposable elements (SINE, LINE, and LTR), tandem repeats, and large duplicated regions. However, we found that the pattern is almost entirely confined to what we define as "periodic DNA." Periodic DNA is a genomic region with a high degree of periodicity in nucleotide usage...

  13. Public humanization policies: integrative literature review.

    Science.gov (United States)

    Moreira, Márcia Adriana Dias Meirelles; Lustosa, Abdon Moreira; Dutra, Fernando; Barros, Eveline de Oliveira; Batista, Jaqueline Brito Vidal; Duarte, Marcella Costa Souto

    2015-10-01

    The study aimed to investigate the scientific literature on Public Humanization Policies, available in online periodicals, from 2009 to 2012, in the health field. This is an integrative literature review conducted in the Virtual Health Library databases: Latin-America and Caribbean Health Sciences (Lilacs) and the Scientific Electronic Library Online (SciELO) and Portal Capes. Data were collected in July 2013. To this end, the following Health Sciences Descriptors (DeCS) were used: "Humanization of Care," "Public Policies," "National Humanization Policy". The sample consisted of 27 articles about the investigated theme. From the publications selected for the research, three categories emerged according to their respective approaches: National Human-ization Policy: history and processes involved in its implementation; National Humanization Policy: health professionals contribution; Humanization and in the care process. The study showed that the National Humanization Policy is an important benchmark in the development of health practices. For this reason, there is a pressing multiplication of related reflections on ways to promote human-ization in health services.

  14. Anonymizing patient genomic data for public sharing association studies.

    Science.gov (United States)

    Fernandez-Lozano, Carlos; Lopez-Campos, Guillermo; Seoane, Jose A; Lopez-Alonso, Victoria; Dorado, Julian; Martín-Sanchez, Fernando; Pazos, Alejandro

    2013-01-01

    The development of personalized medicine is tightly linked with the correct exploitation of molecular data, especially those associated with the genome sequence along with these use of genomic data there is an increasing demand to share these data for research purposes. Transition of clinical data to research is based in the anonymization of these data so the patient cannot be identified, the use of genomic data poses a great challenge because its nature of identifying data. In this work we have analyzed current methods for genome anonymization and propose a one way encryption method that may enable the process of genomic data sharing accessing only to certain regions of genomes for research purposes.

  15. Primer on molecular genetics. DOE Human Genome Program

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. National human genome projects: an update and an agenda

    OpenAIRE

    An, Joon Yong

    2017-01-01

    Population genetic and human genetic studies are being accelerated with genome technology and data sharing. Accordingly, in the past 10 years, several countries have initiated genetic research using genome technology and identified the genetic architecture of the ethnic groups living in the corresponding country or suggested the genetic foundation of a social phenomenon. Genetic research has been conducted from epidemiological studies that previously described the health or disease conditions...

  17. Genomics for public health improvement: relevant international ethical and policy issues around genome-wide association studies and biobanks.

    Science.gov (United States)

    Pang, T

    2013-01-01

    Genome-wide association studies and biobanks are at the forefront of genomics research and possess unprecedented potential to improve public health. However, for public health genomics to ultimately fulfill its potential, technological and scientific advances alone are insufficient. Scientists, ethicists, policy makers, and regulators must work closely together with research participants and communities in order to craft an equitable and just ethical framework, and a sustainable environment for effective policies. Such a framework should be a 'hybrid' form which balances equity and solidarity with entrepreneurship and scientific advances. A good balance between research and policy on one hand, and privacy, protection and trust on the other is the key for public health improvement based on advances in genomics science. Copyright © 2013 S. Karger AG, Basel.

  18. Saccharomyces genome database informs human biology

    OpenAIRE

    Skrzypek, Marek S; Nash, Robert S; Wong, Edith D; MacPherson, Kevin A; Hellerstedt, Sage T; Engel, Stacia R; Karra, Kalpana; Weng, Shuai; Sheppard, Travis K; Binkley, Gail; Simison, Matt; Miyasato, Stuart R; Cherry, J Michael

    2017-01-01

    Abstract The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is an expertly curated database of literature-derived functional information for the model organism budding yeast, Saccharomyces cerevisiae. SGD constantly strives to synergize new types of experimental data and bioinformatics predictions with existing data, and to organize them into a comprehensive and up-to-date information resource. The primary mission of SGD is to facilitate research into the biology of yeast and...

  19. In the Beginning was the Genome: Genomics and the Bi-textuality of Human Existence.

    Science.gov (United States)

    Zwart, H A E Hub

    2018-04-01

    This paper addresses the cultural impact of genomics and the Human Genome Project (HGP) on human self-understanding. Notably, it addresses the claim made by Francis Collins (director of the HGP) that the genome is the language of God and the claim made by Max Delbrück (founding father of molecular life sciences research) that Aristotle must be credited with having predicted DNA as the soul that organises bio-matter. From a continental philosophical perspective I will argue that human existence results from a dialectical interaction between two types of texts: the language of molecular biology and the language of civilisation; the language of the genome and the language of our socio-cultural, symbolic ambiance. Whereas the former ultimately builds on the alphabets of genes and nucleotides, the latter is informed by primordial texts such as the Bible and the Quran. In applied bioethics deliberations on genomics, science is easily framed as liberating and progressive, religious world-views as conservative and restrictive (Zwart 1993). This paper focusses on the broader cultural ambiance of the debate to discern how the bi-textuality of human existence is currently undergoing a transition, as not only the physiological, but also the normative dimension is being reframed in biomolecular and terabyte terms.

  20. Genomic signatures of diet-related shifts during human origins.

    Science.gov (United States)

    Babbitt, Courtney C; Warner, Lisa R; Fedrigo, Olivier; Wall, Christine E; Wray, Gregory A

    2011-04-07

    There are numerous anthropological analyses concerning the importance of diet during human evolution. Diet is thought to have had a profound influence on the human phenotype, and dietary differences have been hypothesized to contribute to the dramatic morphological changes seen in modern humans as compared with non-human primates. Here, we attempt to integrate the results of new genomic studies within this well-developed anthropological context. We then review the current evidence for adaptation related to diet, both at the level of sequence changes and gene expression. Finally, we propose some ways in which new technologies can help identify specific genomic adaptations that have resulted in metabolic and morphological differences between humans and non-human primates.

  1. Beyond the human genome: Microbes, methaphors and what it means to be human in an interconnected post-genomic world

    NARCIS (Netherlands)

    Nerlich, B.; Hellsten, I.R.

    2009-01-01

    Four years after the completion of the Human Genome Project, the US National Institutes for Health launched the Human Microbiome Project on 19 December 2007. Using metaphor analysis, this article investigates reporting in English-language newspapers on advances in microbiomics from 2003 onwards,

  2. 78 FR 68856 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-11-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Nakamura, Ph.D., Scientific Review Officer, Scientific Review Branch, National Human Genome Research...-402-0838. [[Page 68857

  3. Stakeholder engagement in policy development: challenges and opportunities for human genomics.

    Science.gov (United States)

    Lemke, Amy A; Harris-Wai, Julie N

    2015-12-01

    Along with rapid advances in human genomics, policies governing genomic data and clinical technologies have proliferated. Stakeholder engagement is widely lauded as an important methodology for improving clinical, scientific, and public health policy decision making. The purpose of this paper is to examine how stakeholder engagement is used to develop policies in genomics research and public health areas, as well as to identify future priorities for conducting evidence-based stakeholder engagements. We focus on exemplars in biobanking and newborn screening to illustrate a variety of current stakeholder engagement in policy-making efforts. Each setting provides an important context for examining the methods of obtaining and integrating informed stakeholder voices into the policy-making process. While many organizations have an interest in engaging stakeholders with regard to genomic policy issues, there is broad divergence with respect to the stakeholders involved, the purpose of engagements, when stakeholders are engaged during policy development, methods of engagement, and the outcomes reported. Stakeholder engagement in genomics policy development is still at a nascent stage. Several challenges of using stakeholder engagement as a tool for genomics policy development remain, and little evidence regarding how to best incorporate stakeholder feedback into policy-making processes is currently available.

  4. Continued colonization of the human genome by mitochondrial DNA.

    Directory of Open Access Journals (Sweden)

    Miria Ricchetti

    2004-09-01

    Full Text Available Integration of mitochondrial DNA fragments into nuclear chromosomes (giving rise to nuclear DNA sequences of mitochondrial origin, or NUMTs is an ongoing process that shapes nuclear genomes. In yeast this process depends on double-strand-break repair. Since NUMTs lack amplification and specific integration mechanisms, they represent the prototype of exogenous insertions in the nucleus. From sequence analysis of the genome of Homo sapiens, followed by sampling humans from different ethnic backgrounds, and chimpanzees, we have identified 27 NUMTs that are specific to humans and must have colonized human chromosomes in the last 4-6 million years. Thus, we measured the fixation rate of NUMTs in the human genome. Six such NUMTs show insertion polymorphism and provide a useful set of DNA markers for human population genetics. We also found that during recent human evolution, Chromosomes 18 and Y have been more susceptible to colonization by NUMTs. Surprisingly, 23 out of 27 human-specific NUMTs are inserted in known or predicted genes, mainly in introns. Some individuals carry a NUMT insertion in a tumor-suppressor gene and in a putative angiogenesis inhibitor. Therefore in humans, but not in yeast, NUMT integrations preferentially target coding or regulatory sequences. This is indeed the case for novel insertions associated with human diseases and those driven by environmental insults. We thus propose a mutagenic phenomenon that may be responsible for a variety of genetic diseases in humans and suggest that genetic or environmental factors that increase the frequency of chromosome breaks provide the impetus for the continued colonization of the human genome by mitochondrial DNA.

  5. Microbial genome-wide association studies: lessons from human GWAS.

    Science.gov (United States)

    Power, Robert A; Parkhill, Julian; de Oliveira, Tulio

    2017-01-01

    The reduced costs of sequencing have led to whole-genome sequences for a large number of microorganisms, enabling the application of microbial genome-wide association studies (GWAS). Given the successes of human GWAS in understanding disease aetiology and identifying potential drug targets, microbial GWAS are likely to further advance our understanding of infectious diseases. These advances include insights into pressing global health problems, such as antibiotic resistance and disease transmission. In this Review, we outline the methodologies of GWAS, the current state of the field of microbial GWAS, and how lessons from human GWAS can direct the future of the field.

  6. The human Genome project and the future of oncology

    International Nuclear Information System (INIS)

    Collins, Francis S.

    1996-01-01

    The Human Genome Project is an ambitious 15-year effort to devise maps and sequence of the 3-billion base pair human genome, including all 100,000 genes. The project is running ahead of schedule and under budget. Already the effects on progress in disease gene discovery have been dramatic, especially for cancer. The most appropriate uses of susceptibility testing for breast, ovarian, and colon cancer are being investigated in research protocols, and the need to prevent genetic discrimination in employment and health insurance is becoming more urgent. In the longer term, these gene discoveries are likely to usher in a new era of therapeutic molecular medicine

  7. Characterization of noncoding regulatory DNA in the human genome.

    Science.gov (United States)

    Elkon, Ran; Agami, Reuven

    2017-08-08

    Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

  8. The zebrafish reference genome sequence and its relationship to the human genome

    Science.gov (United States)

    Howe, Kerstin; Clark, Matthew D.; Torroja, Carlos F.; Torrance, James; Berthelot, Camille; Muffato, Matthieu; Collins, John E.; Humphray, Sean; McLaren, Karen; Matthews, Lucy; McLaren, Stuart; Sealy, Ian; Caccamo, Mario; Churcher, Carol; Scott, Carol; Barrett, Jeffrey C.; Koch, Romke; Rauch, Gerd-Jörg; White, Simon; Chow, William; Kilian, Britt; Quintais, Leonor T.; Guerra-Assunção, José A.; Zhou, Yi; Gu, Yong; Yen, Jennifer; Vogel, Jan-Hinnerk; Eyre, Tina; Redmond, Seth; Banerjee, Ruby; Chi, Jianxiang; Fu, Beiyuan; Langley, Elizabeth; Maguire, Sean F.; Laird, Gavin K.; Lloyd, David; Kenyon, Emma; Donaldson, Sarah; Sehra, Harminder; Almeida-King, Jeff; Loveland, Jane; Trevanion, Stephen; Jones, Matt; Quail, Mike; Willey, Dave; Hunt, Adrienne; Burton, John; Sims, Sarah; McLay, Kirsten; Plumb, Bob; Davis, Joy; Clee, Chris; Oliver, Karen; Clark, Richard; Riddle, Clare; Eliott, David; Threadgold, Glen; Harden, Glenn; Ware, Darren; Mortimer, Beverly; Kerry, Giselle; Heath, Paul; Phillimore, Benjamin; Tracey, Alan; Corby, Nicole; Dunn, Matthew; Johnson, Christopher; Wood, Jonathan; Clark, Susan; Pelan, Sarah; Griffiths, Guy; Smith, Michelle; Glithero, Rebecca; Howden, Philip; Barker, Nicholas; Stevens, Christopher; Harley, Joanna; Holt, Karen; Panagiotidis, Georgios; Lovell, Jamieson; Beasley, Helen; Henderson, Carl; Gordon, Daria; Auger, Katherine; Wright, Deborah; Collins, Joanna; Raisen, Claire; Dyer, Lauren; Leung, Kenric; Robertson, Lauren; Ambridge, Kirsty; Leongamornlert, Daniel; McGuire, Sarah; Gilderthorp, Ruth; Griffiths, Coline; Manthravadi, Deepa; Nichol, Sarah; Barker, Gary; Whitehead, Siobhan; Kay, Michael; Brown, Jacqueline; Murnane, Clare; Gray, Emma; Humphries, Matthew; Sycamore, Neil; Barker, Darren; Saunders, David; Wallis, Justene; Babbage, Anne; Hammond, Sian; Mashreghi-Mohammadi, Maryam; Barr, Lucy; Martin, Sancha; Wray, Paul; Ellington, Andrew; Matthews, Nicholas; Ellwood, Matthew; Woodmansey, Rebecca; Clark, Graham; Cooper, James; Tromans, Anthony; Grafham, Darren; Skuce, Carl; Pandian, Richard; Andrews, Robert; Harrison, Elliot; Kimberley, Andrew; Garnett, Jane; Fosker, Nigel; Hall, Rebekah; Garner, Patrick; Kelly, Daniel; Bird, Christine; Palmer, Sophie; Gehring, Ines; Berger, Andrea; Dooley, Christopher M.; Ersan-Ürün, Zübeyde; Eser, Cigdem; Geiger, Horst; Geisler, Maria; Karotki, Lena; Kirn, Anette; Konantz, Judith; Konantz, Martina; Oberländer, Martina; Rudolph-Geiger, Silke; Teucke, Mathias; Osoegawa, Kazutoyo; Zhu, Baoli; Rapp, Amanda; Widaa, Sara; Langford, Cordelia; Yang, Fengtang; Carter, Nigel P.; Harrow, Jennifer; Ning, Zemin; Herrero, Javier; Searle, Steve M. J.; Enright, Anton; Geisler, Robert; Plasterk, Ronald H. A.; Lee, Charles; Westerfield, Monte; de Jong, Pieter J.; Zon, Leonard I.; Postlethwait, John H.; Nüsslein-Volhard, Christiane; Hubbard, Tim J. P.; Crollius, Hugues Roest; Rogers, Jane; Stemple, Derek L.

    2013-01-01

    Zebrafish have become a popular organism for the study of vertebrate gene function1,2. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease3–5. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes6, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination. PMID:23594743

  9. The zebrafish reference genome sequence and its relationship to the human genome.

    Science.gov (United States)

    Howe, Kerstin; Clark, Matthew D; Torroja, Carlos F; Torrance, James; Berthelot, Camille; Muffato, Matthieu; Collins, John E; Humphray, Sean; McLaren, Karen; Matthews, Lucy; McLaren, Stuart; Sealy, Ian; Caccamo, Mario; Churcher, Carol; Scott, Carol; Barrett, Jeffrey C; Koch, Romke; Rauch, Gerd-Jörg; White, Simon; Chow, William; Kilian, Britt; Quintais, Leonor T; Guerra-Assunção, José A; Zhou, Yi; Gu, Yong; Yen, Jennifer; Vogel, Jan-Hinnerk; Eyre, Tina; Redmond, Seth; Banerjee, Ruby; Chi, Jianxiang; Fu, Beiyuan; Langley, Elizabeth; Maguire, Sean F; Laird, Gavin K; Lloyd, David; Kenyon, Emma; Donaldson, Sarah; Sehra, Harminder; Almeida-King, Jeff; Loveland, Jane; Trevanion, Stephen; Jones, Matt; Quail, Mike; Willey, Dave; Hunt, Adrienne; Burton, John; Sims, Sarah; McLay, Kirsten; Plumb, Bob; Davis, Joy; Clee, Chris; Oliver, Karen; Clark, Richard; Riddle, Clare; Elliot, David; Eliott, David; Threadgold, Glen; Harden, Glenn; Ware, Darren; Begum, Sharmin; Mortimore, Beverley; Mortimer, Beverly; Kerry, Giselle; Heath, Paul; Phillimore, Benjamin; Tracey, Alan; Corby, Nicole; Dunn, Matthew; Johnson, Christopher; Wood, Jonathan; Clark, Susan; Pelan, Sarah; Griffiths, Guy; Smith, Michelle; Glithero, Rebecca; Howden, Philip; Barker, Nicholas; Lloyd, Christine; Stevens, Christopher; Harley, Joanna; Holt, Karen; Panagiotidis, Georgios; Lovell, Jamieson; Beasley, Helen; Henderson, Carl; Gordon, Daria; Auger, Katherine; Wright, Deborah; Collins, Joanna; Raisen, Claire; Dyer, Lauren; Leung, Kenric; Robertson, Lauren; Ambridge, Kirsty; Leongamornlert, Daniel; McGuire, Sarah; Gilderthorp, Ruth; Griffiths, Coline; Manthravadi, Deepa; Nichol, Sarah; Barker, Gary; Whitehead, Siobhan; Kay, Michael; Brown, Jacqueline; Murnane, Clare; Gray, Emma; Humphries, Matthew; Sycamore, Neil; Barker, Darren; Saunders, David; Wallis, Justene; Babbage, Anne; Hammond, Sian; Mashreghi-Mohammadi, Maryam; Barr, Lucy; Martin, Sancha; Wray, Paul; Ellington, Andrew; Matthews, Nicholas; Ellwood, Matthew; Woodmansey, Rebecca; Clark, Graham; Cooper, James D; Cooper, James; Tromans, Anthony; Grafham, Darren; Skuce, Carl; Pandian, Richard; Andrews, Robert; Harrison, Elliot; Kimberley, Andrew; Garnett, Jane; Fosker, Nigel; Hall, Rebekah; Garner, Patrick; Kelly, Daniel; Bird, Christine; Palmer, Sophie; Gehring, Ines; Berger, Andrea; Dooley, Christopher M; Ersan-Ürün, Zübeyde; Eser, Cigdem; Geiger, Horst; Geisler, Maria; Karotki, Lena; Kirn, Anette; Konantz, Judith; Konantz, Martina; Oberländer, Martina; Rudolph-Geiger, Silke; Teucke, Mathias; Lanz, Christa; Raddatz, Günter; Osoegawa, Kazutoyo; Zhu, Baoli; Rapp, Amanda; Widaa, Sara; Langford, Cordelia; Yang, Fengtang; Schuster, Stephan C; Carter, Nigel P; Harrow, Jennifer; Ning, Zemin; Herrero, Javier; Searle, Steve M J; Enright, Anton; Geisler, Robert; Plasterk, Ronald H A; Lee, Charles; Westerfield, Monte; de Jong, Pieter J; Zon, Leonard I; Postlethwait, John H; Nüsslein-Volhard, Christiane; Hubbard, Tim J P; Roest Crollius, Hugues; Rogers, Jane; Stemple, Derek L

    2013-04-25

    Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.

  10. Public Perceptions of Human Trafficking in Moldova

    Directory of Open Access Journals (Sweden)

    Jill Robinson

    2011-11-01

    Full Text Available Human trafficking is a widely studied phenomenon. Comparing public perceptions of trafficking to institutional (i.e. the academy, governmental and non-governmental organizations perceptions gives a richer understanding of the problem. The data for this study were collected in and around Chisinau, Moldova in the summer of 2004. Public discourse provides a more intimate "portraiture" of the issue, but the public also demonstrated a complex level of understanding of this social problem in this study. Its view is juxtaposed against an institutional view of human trafficking as explored through a literature review. Combining institutional and public perceptions and knowledge of a social problem is helpful in not only establishing a more thorough understanding of the social problem and guiding policy decisions, but in exploring the experiences victims may face at the community level.

  11. Genomics and the Ark: an ecocentric perspective on human history.

    Science.gov (United States)

    Zwart, Hub; Penders, Bart

    2011-01-01

    Views of ourselves in relationship to the rest of the biosphere are changing. Theocentric and anthropocentric perspectives are giving way to more ecocentric views on the history, present, and future of humankind. Novel sciences, such as genomics, have deepened and broadened our understanding of the process of anthropogenesis, the coming into being of humans. Genomics suggests that early human history must be regarded as a complex narrative of evolving ecosystems, in which human evolution both influenced and was influenced by the evolution of companion species. During the agricultural revolution, human beings designed small-scale artificial ecosystems or evolutionary "Arks," in which networks of plants, animals, and microorganisms coevolved. Currently, our attitude towards this process seems subject to a paradoxical reversal. The boundaries of the Ark have dramatically broadened, and genomics is not only being used to increase our understanding of our ecological past, but may also help us to conserve, reconstruct, or even revivify species and ecosystems to whose degradation or (near) extinction we have contributed. This article explores the role of genomics in the elaboration of a more ecocentric view of ourselves with the help of two examples, namely the renaissance of Paleolithic diets and of Pleistocene parks. It argues that an understanding of the world in ecocentric terms requires new partnerships and mutually beneficial forms of collaboration and convergence between life sciences, social sciences, and the humanities.

  12. Forces shaping the fastest evolving regions in the human genome.

    Directory of Open Access Journals (Sweden)

    Katherine S Pollard

    2006-10-01

    Full Text Available Comparative genomics allow us to search the human genome for segments that were extensively changed in the last approximately 5 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. We found 202 genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements are dramatically changed in human but not in other primates, with seven times more substitutions in human than in chimp. The accelerated elements, and in particular the top five, show a strong bias for adenine and thymine to guanine and cytosine nucleotide changes and are disproportionately located in high recombination and high guanine and cytosine content environments near telomeres, suggesting either biased gene conversion or isochore selection. In addition, there is some evidence of directional selection in the regions containing the two most accelerated regions. A combination of evolutionary forces has contributed to accelerated evolution of the fastest evolving elements in the human genome.

  13. Data mining and the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Abarbanel, Henry [The MITRE Corporation, McLean, VA (US). JASON Program Office; Callan, Curtis [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, William [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, Freeman [The MITRE Corporation, McLean, VA (US). JASON Program Office; Hwa, Terence [The MITRE Corporation, McLean, VA (US). JASON Program Office; Koonin, Steven [The MITRE Corporation, McLean, VA (US). JASON Program Office; Levine, Herbert [The MITRE Corporation, McLean, VA (US). JASON Program Office; Rothaus, Oscar [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, Roy [The MITRE Corporation, McLean, VA (US). JASON Program Office; Stubbs, Christopher [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, Peter [The MITRE Corporation, McLean, VA (US). JASON Program Office

    2000-01-07

    As genomics research moves from an era of data acquisition to one of both acquisition and interpretation, new methods are required for organizing and prioritizing the data. These methods would allow an initial level of data analysis to be carried out before committing resources to a particular genetic locus. This JASON study sought to delineate the main problems that must be faced in bioinformatics and to identify information technologies that can help to overcome those problems. While the current influx of data greatly exceeds what biologists have experienced in the past, other scientific disciplines and the commercial sector have been handling much larger datasets for many years. Powerful datamining techniques have been developed in other fields that, with appropriate modification, could be applied to the biological sciences.

  14. Non-genomic effects of vitamin D in human spermatozoa

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Dissing, Steen

    2012-01-01

    The spectrum for vitamin D (VD) mediated effects has expanded in recent years. Activated VD (1,25(OH)(2)D(3)) binds to the VD receptor (VDR) and mediates non-genomic effects through the alternative ligand binding-pocket (VDR-ap) or regulates gene transcription through the genomic binding......-pocket. VDR and VD-metabolizing enzymes are expressed in human testis, male reproductive tract and mature spermatozoa, and VD is considered important for male reproduction. Expression of the VD-inactivating enzyme CYP24A1 at the annulus of human spermatozoa distinguish normal and infertile men with high...... specificity, and CYP24A1 expression is positively correlated with all semen variables and suggested as a marker for both semen quality and VD responsiveness. Moreover, spermatozoa are transcriptionally silent and are therefore a unique model to study non-genomic effects. 1,25(OH)(2)D(3) induced a rapid...

  15. THE HUMAN GENOME PROJECT IN CLINICAL PERSPECTIVE ...

    African Journals Online (AJOL)

    Enrique

    as Huntington disease and spino- cerebellar ataxia. • skewed X-inactivation as an expla- nation for the unusual occurrence of X-linked recessive disorders in girls. All these advances, and others, partic- ularly in the field of epigenetic (non-. DNA) control of gene expression, have come in spite of, or preceded the publication ...

  16. Evolutionary forces shaping genomic islands of population differentiation in humans

    Directory of Open Access Journals (Sweden)

    Hofer Tamara

    2012-03-01

    Full Text Available Abstract Background Levels of differentiation among populations depend both on demographic and selective factors: genetic drift and local adaptation increase population differentiation, which is eroded by gene flow and balancing selection. We describe here the genomic distribution and the properties of genomic regions with unusually high and low levels of population differentiation in humans to assess the influence of selective and neutral processes on human genetic structure. Methods Individual SNPs of the Human Genome Diversity Panel (HGDP showing significantly high or low levels of population differentiation were detected under a hierarchical-island model (HIM. A Hidden Markov Model allowed us to detect genomic regions or islands of high or low population differentiation. Results Under the HIM, only 1.5% of all SNPs are significant at the 1% level, but their genomic spatial distribution is significantly non-random. We find evidence that local adaptation shaped high-differentiation islands, as they are enriched for non-synonymous SNPs and overlap with previously identified candidate regions for positive selection. Moreover there is a negative relationship between the size of islands and recombination rate, which is stronger for islands overlapping with genes. Gene ontology analysis supports the role of diet as a major selective pressure in those highly differentiated islands. Low-differentiation islands are also enriched for non-synonymous SNPs, and contain an overly high proportion of genes belonging to the 'Oncogenesis' biological process. Conclusions Even though selection seems to be acting in shaping islands of high population differentiation, neutral demographic processes might have promoted the appearance of some genomic islands since i as much as 20% of islands are in non-genic regions ii these non-genic islands are on average two times shorter than genic islands, suggesting a more rapid erosion by recombination, and iii most loci are

  17. Insights into Modern Human Prehistory Using Ancient Genomes.

    Science.gov (United States)

    Yang, Melinda A; Fu, Qiaomei

    2018-03-01

    The genetic relationship of past modern humans to today's populations and each other was largely unknown until recently, when advances in ancient DNA sequencing allowed for unprecedented analysis of the genomes of these early people. These ancient genomes reveal new insights into human prehistory not always observed studying present-day populations, including greater details on the genetic diversity, population structure, and gene flow that characterized past human populations, particularly in early Eurasia, as well as increased insight on the relationship between archaic and modern humans. Here, we review genetic studies on ∼45000- to 7500-year-old individuals associated with mainly preagricultural cultures found in Eurasia, the Americas, and Africa. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. DOE Human Genome Program contractor-grantee workshop

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-01

    This volume contains the proceedings for the DOE Human Genome Program`s Contractor-Grantee Workshop V held in Sante Fe, New Mexico January 28, February 1, 1996. Presentations were divided into sessions entitled Sequencing; Mapping; Informatics; Ethical, Legal, and Social Issues; and Infrastructure. Reports of individual projects described herein are separately indexed and abstracted for the database.

  19. Reconsidering democracy. History of the Human Genome Project.

    NARCIS (Netherlands)

    Marli Huijer

    2003-01-01

    What options are open for people—citizens, politicians, and other nonscientists—to become actively involved in and anticipate new directions in the life sciences? In addressing this question, this article focuses on the start of the Human Genome Project (1985-1990). By contrasting various models of

  20. The Human Genome Project: Biology, Computers, and Privacy.

    Science.gov (United States)

    Cutter, Mary Ann G.; Drexler, Edward; Gottesman, Kay S.; Goulding, Philip G.; McCullough, Laurence B.; McInerney, Joseph D.; Micikas, Lynda B.; Mural, Richard J.; Murray, Jeffrey C.; Zola, John

    This module, for high school teachers, is the second of two modules about the Human Genome Project (HGP) produced by the Biological Sciences Curriculum Study (BSCS). The first section of this module provides background information for teachers about the structure and objectives of the HGP, aspects of the science and technology that underlie the…

  1. The human genome; you gain some, you lose some

    NARCIS (Netherlands)

    Kriek, Marjolein

    2007-01-01

    Copy number variations (CNVs) in the human genome are inherent in both evolutionary progression as well as the etiology of disease. The introduction of this thesis will review CNVs that appear to be neutral as well as CNVs that appear to be related to a phenotypic trait. This will be followed by a

  2. Reconsidering democracy - History of the human genome project

    NARCIS (Netherlands)

    Huijer, M

    What options are open for people-citizens, politicians, and other nonscientists-to become actively involved in and anticipate new directions in the life sciences? In addressing this question, this article focuses on the start of the Human Genome Project (1985-1990). By contrasting various models of

  3. Genome-wide linkage analysis for human longevity

    DEFF Research Database (Denmark)

    Beekman, Marian; Blanché, Hélène; Perola, Markus

    2013-01-01

    Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian...

  4. Enhancing Biology Instruction with the Human Genome Project

    Science.gov (United States)

    Buxeda, Rosa J.; Moore-Russo, Deborah A.

    2003-01-01

    The Human Genome Project (HGP) is a recent scientific milestone that has received notable attention. This article shows how a biology course is using the HGP to enhance students' experiences by providing awareness of cutting edge research, with information on new emerging career options, and with opportunities to consider ethical questions raised…

  5. Templated sequence insertion polymorphisms in the human genome

    Science.gov (United States)

    Onozawa, Masahiro; Aplan, Peter

    2016-11-01

    Templated Sequence Insertion Polymorphism (TSIP) is a recently described form of polymorphism recognized in the human genome, in which a sequence that is templated from a distant genomic region is inserted into the genome, seemingly at random. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; Class 1 TSIPs show features of insertions that are mediated via the LINE-1 ORF2 protein, including 1) target-site duplication (TSD), 2) polyadenylation 10-30 nucleotides downstream of a “cryptic” polyadenylation signal, and 3) preference for insertion at a 5’-TTTT/A-3’ sequence. In contrast, class 2 TSIPs show features consistent with repair of a DNA double-strand break via insertion of a DNA “patch” that is derived from a distant genomic region. Survey of a large number of normal human volunteers demonstrates that most individuals have 25-30 TSIPs, and that these TSIPs track with specific geographic regions. Similar to other forms of human polymorphism, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases.

  6. Genome Sequence of Novel Human Parechovirus Type 17

    OpenAIRE

    B?ttcher, Sindy; Obermeier, Patrick E.; Diedrich, Sabine; Kabor?, Yolande; D?Alfonso, Rossella; Pfister, Herbert; Kaiser, Rolf; Di Cristanziano, Veronica

    2017-01-01

    ABSTRACT Human parechoviruses (HPeV) circulate worldwide, causing a broad variety of symptoms, preferentially in early childhood. We report here the nearly complete genome sequence of a novel HPeV type, consisting of 7,062 nucleotides and encoding 2,179?amino acids. M36/CI/2014 was taxonomically classified as HPeV-17 by the picornavirus study group.

  7. The human genome project and the future of medical practice ...

    African Journals Online (AJOL)

    Contrary to the scepticism that characterised the planning stages of the human genome project, the technology and sequence data resulting from the project are set to revolutionise medical practice for good. The expected benefits include: enhanced discovery of disease genes, which will lead to improved knowledge on the ...

  8. Science communication in transition: genomics hype, public engagement, education and commercialization pressures.

    Science.gov (United States)

    Bubela, T

    2006-11-01

    This essay reports on the final session of a 2-day workshop entitled 'Genetic Diversity and Science Communication', hosted by the CIHR Institute of Genetics in Toronto, April 2006. The first speaker, Timothy Caulfield, introduced the intersecting communities that promulgate a 'cycle of hype' of the timelines and expected outcomes of the Human Genome Project (HGP): scientists, the media and the public. Other actors also contribute to the overall hype, the social science and humanities communities, industry and politicians. There currently appears to be an abatement of the overblown rhetoric of the HGP. As pointed out by the second speaker, Sharon Kardia, there is broad recognition that most phenotypic traits, including disease susceptibility are multi-factorial. That said, George Davey-Smith reminded us that some direct genotype-phenotype associations may be useful for public health issues. The Mendelian randomization approach hopes to revitalize the discipline of epidemiology by strengthening causal influences about environmentally modifiable risk factors. A more realistic informational environment paves the way for greater public engagement in science policy. Two such initiatives were presented by Kardia and Jason Robert, and Peter Finegold emphasized that science education and professional development for science teachers are important components of later public engagement in science issues. However, pressures on public research institutions to commercialize and seek industry funding may have negative impacts in both encouraging scientists to inappropriately hype research and on diminishing public trust in the scientific enterprise. The latter may have a significant effect on public engagement processes, such as those proposed by Robert and Kardia.

  9. 76 FR 66076 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Call). Contact Person: Camilla E. Day, PhD, Scientific Review Officer, CIDR, National Human Genome... Assistance Program Nos. 93.172, Human Genome Research, National Institutes of Health, HHS) Dated: October 19...

  10. 77 FR 60706 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-10-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special.... Nakamura, Ph.D., Scientific Review Officer, Scientific Review Branch, National Human Genome Research...

  11. 76 FR 19780 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-04-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... E. Day, PhD, Scientific Review Officer, CIDR, National Human Genome Research Institute, National... . (Catalogue of Federal Domestic Assistance Program No. 93.172, Human Genome Research, National Institutes of...

  12. 76 FR 3917 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-01-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Branch, National Human Genome Research Institute, 5635 Fishers Lane, Suite 4076, MSC 9306, Rockville, MD...

  13. 75 FR 56115 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-09-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Federal Domestic Assistance Program Nos. 93.172, Human Genome Research, National Institutes of Health, HHS...

  14. 77 FR 2735 - National Human Genome Research Institute; Notice of Meetings

    Science.gov (United States)

    2012-01-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... personal privacy. Name of Committee: National Advisory Council for Human Genome Research. Date: February 13... Extramural Research National Human Genome Research Institute, 5635 Fishers Lane, Suite 4076, MSC 9305...

  15. 76 FR 3643 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-01-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial... . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research, National Institutes of...

  16. 78 FR 24223 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial...: To review and evaluate grant applications. Place: National Human Genome Research Institute, 3rd floor...

  17. 77 FR 2304 - National Human Genome Research Institute; Notice of Meeting

    Science.gov (United States)

    2012-01-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome....S.C. 281(d)(4)), notice is hereby given that the National Human Genome Research Institute (NHGRI... meeting of the National Advisory Council for Human Genome Research. Background materials on the proposed...

  18. 78 FR 21382 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... applications. Place: National Human Genome Research Institute, Suite 4076, 5635 Fisher's Lane, Bethesda, MD..., National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane, Suite 4075...

  19. 78 FR 20933 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-04-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... review and evaluate grant applications. Place: National Human Genome Research Institute, Room 3055, 5635...

  20. 76 FR 22112 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-04-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special....nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  1. 78 FR 31953 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-05-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... review and evaluate grant applications. Place: National Human Genome Research Institute, 3rd Floor...

  2. 75 FR 10488 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-03-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research...- 4280, [email protected]gov . Name of Committee: National Human Genome Research Institute Special...

  3. 76 FR 35224 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-06-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome...). Contact Person: Camilla E. Day, PhD, Scientific Review Officer, CIR, National Human Genome Research..., [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  4. 75 FR 8373 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-02-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  5. 77 FR 22332 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-04-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special.... Agenda: To review and evaluate grant applications. Place: National Human Genome Research Institute, 5635...

  6. 76 FR 22407 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special.... (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research, National Institutes of...

  7. 77 FR 8268 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2012-02-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... applications. Place: National Human Genome Research Institute, 5635 Fisher's Lane, Room 4076, Rockville, MD..., CIDR, National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane, Suite...

  8. 75 FR 48977 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-08-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome.... Contact Person: Camilla E. Day, PhD, Scientific Review Officer, CIDR, National Human Genome Research..., [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  9. 77 FR 74676 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-12-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane, Suite 4075, Bethesda.... 93.172, Human Genome Research, National Institutes of Health, HHS) Dated: December 11, 2012. David...

  10. 75 FR 19984 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-04-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane, Suite 4075... Nakamura, PhD, Scientific Review Officer, Scientific Review Branch, National Human Genome Research...

  11. 75 FR 26762 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-05-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial... . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research, National Institutes of...

  12. 75 FR 35821 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-06-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Person: Camilla E. Day, PhD, Scientific Review Officer, CIDR, National Human Genome Research [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  13. 76 FR 3642 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-01-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research....nih.gov . Name of Committee: National Human Genome Research Institute Special Emphasis Panel eMERGE...

  14. 78 FR 47715 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-08-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Person: Camilla E. Day, Ph.D., Scientific Review Officer, CIDR, National Human Genome Research [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  15. 77 FR 31863 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-05-30

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special..., Human Genome Research, National Institutes of Health, HHS) Dated: May 22, 2012. Jennifer S. Spaeth...

  16. 75 FR 52537 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-08-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial....nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  17. 78 FR 61851 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-10-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... a.m. to 4:00 p.m. Agenda: To review and evaluate grant applications. Place: National Human Genome...

  18. 76 FR 79199 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-12-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome.... Contact Person: Camilla E. Day, Ph.D., Scientific Review Officer, CIDR, National Human Genome Research..., [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  19. 75 FR 80509 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-12-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Call). Contact Person: Camilla E. Day, PhD, Scientific Review Officer, CIDR, National Human Genome... Assistance Program Nos. 93.172, Human Genome Research, National Institutes of Health, HHS) Dated: December 16...

  20. 76 FR 28056 - National Human Genome Research Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-05-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... clearly unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research... D. Nakamura, PhD, Scientific Review Officer, Office of Scientific Review, National Human Genome...

  1. 75 FR 2148 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-01-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Initial....nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  2. 76 FR 66731 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-27

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Program Nos. 93.172, Human Genome Research, National Institutes of Health, HHS) Dated: October 21, 2011...

  3. 76 FR 10909 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-02-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane, Suite 4076, MSC..., Human Genome Research, National Institutes of Health, HHS). Dated: February 18, 2011. Jennifer S. Spaeth...

  4. 75 FR 52538 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-08-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Person: Ken D. Nakamura, PhD, Scientific Review Officer, Scientific Review Branch, National Human Genome...

  5. 76 FR 35223 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-06-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Person: Rudy O. Pozzatti, PhD, Scientific Review Officer, Scientific Review Branch, National Human Genome...

  6. 76 FR 36930 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-06-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special..., Human Genome Research, National Institutes of Health, HHS) Dated: June 17, 2011. Jennifer S. Spaeth...

  7. 77 FR 35991 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-06-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane, Suite 4075, Bethesda.... 93.172, Human Genome Research, National Institutes of Health, HHS) Dated: June 8, 2012. Jennifer S...

  8. 77 FR 61770 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-10-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Assistance Program Nos. 93.172, Human Genome Research, National Institutes of Health, HHS) [[Page 61771...

  9. 76 FR 63932 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-10-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... Assistance Program Nos. 93.172, Human Genome Research, National Institutes of Health, HHS) Dated: October 7...

  10. 75 FR 8977 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-02-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane, Suite 4076, MSC..., Human Genome Research, National Institutes of Health, HHS) Dated: February 18, 2010. Jennifer Spaeth...

  11. 78 FR 66752 - National Human Genome Research Institute; Amended Notice of Meeting

    Science.gov (United States)

    2013-11-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... National Human Genome Research Institute Special Emphasis Panel, October 15, 2013, 01:00 p.m. to October 15, 2013, 02:30 p.m., National Human Genome Research Institute, 5635 Fishers Lane, Suite 3055, Rockville...

  12. 75 FR 32957 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-06-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... funding cycle. (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research...

  13. 78 FR 14806 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-03-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... unwarranted invasion of personal privacy. Name of Committee: National Human Genome Research Institute Special... p.m. Agenda: To review and evaluate grant applications. Place: National Human Genome Research...

  14. 75 FR 53703 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-09-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., Scientific Review Branch, National Human Genome Research Institute, National Institutes of Health, 5635.... (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research, National Institutes of...

  15. 75 FR 51828 - National Human Genome Research Institute; Notice of Meetings

    Science.gov (United States)

    2010-08-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... personal privacy. Name of Committee: National Advisory Council for Human Genome Research. Date: February 7... Research, National Human Genome Research Institute, 5635 Fishers Lane, Suite 4076, MSC 9305, Bethesda, MD...

  16. 75 FR 67380 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-11-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Review Branch, National Human Genome Research Institute, National Institutes of Health, 5635 Fishers Lane.... (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human Genome Research, National Institutes of...

  17. Human Cancer Models Initiative | Office of Cancer Genomics

    Science.gov (United States)

    The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

  18. The Complete Sequence of a Human Parainfluenzavirus 4 Genome

    Science.gov (United States)

    Yea, Carmen; Cheung, Rose; Collins, Carol; Adachi, Dena; Nishikawa, John; Tellier, Raymond

    2009-01-01

    Although the human parainfluenza virus 4 (HPIV4) has been known for a long time, its genome, alone among the human paramyxoviruses, has not been completely sequenced to date. In this study we obtained the first complete genomic sequence of HPIV4 from a clinical isolate named SKPIV4 obtained at the Hospital for Sick Children in Toronto (Ontario, Canada). The coding regions for the N, P/V, M, F and HN proteins show very high identities (95% to 97%) with previously available partial sequences for HPIV4B. The sequence for the L protein and the non-coding regions represent new information. A surprising feature of the genome is its length, more than 17 kb, making it the longest genome within the genus Rubulavirus, although the length is well within the known range of 15 kb to 19 kb for the subfamily Paramyxovirinae. The availability of a complete genomic sequence will facilitate investigations on a respiratory virus that is still not completely characterized. PMID:21994536

  19. The Complete Sequence of a Human Parainfluenzavirus 4 Genome

    Directory of Open Access Journals (Sweden)

    Carmen Yea

    2009-06-01

    Full Text Available Although the human parainfluenza virus 4 (HPIV4 has been known for a long time, its genome, alone among the human paramyxoviruses, has not been completely sequenced to date. In this study we obtained the first complete genomic sequence of HPIV4 from a clinical isolate named SKPIV4 obtained at the Hospital for Sick Children in Toronto (Ontario, Canada. The coding regions for the N, P/V, M, F and HN proteins show very high identities (95% to 97% with previously available partial sequences for HPIV4B. The sequence for the L protein and the non-coding regions represent new information. A surprising feature of the genome is its length, more than 17 kb, making it the longest genome within the genus Rubulavirus, although the length is well within the known range of 15 kb to 19 kb for the subfamily Paramyxovirinae. The availability of a complete genomic sequence will facilitate investigations on a respiratory virus that is still not completely characterized.

  20. CRISPR Genome Engineering for Human Pluripotent Stem Cell Research.

    Science.gov (United States)

    Chaterji, Somali; Ahn, Eun Hyun; Kim, Deok-Ho

    2017-01-01

    The emergence of targeted and efficient genome editing technologies, such as repurposed bacterial programmable nucleases (e.g., CRISPR-Cas systems), has abetted the development of cell engineering approaches. Lessons learned from the development of RNA-interference (RNA-i) therapies can spur the translation of genome editing, such as those enabling the translation of human pluripotent stem cell engineering. In this review, we discuss the opportunities and the challenges of repurposing bacterial nucleases for genome editing, while appreciating their roles, primarily at the epigenomic granularity. First, we discuss the evolution of high-precision, genome editing technologies, highlighting CRISPR-Cas9. They exist in the form of programmable nucleases, engineered with sequence-specific localizing domains, and with the ability to revolutionize human stem cell technologies through precision targeting with greater on-target activities. Next, we highlight the major challenges that need to be met prior to bench-to-bedside translation, often learning from the path-to-clinic of complementary technologies, such as RNA-i. Finally, we suggest potential bioinformatics developments and CRISPR delivery vehicles that can be deployed to circumvent some of the challenges confronting genome editing technologies en route to the clinic.

  1. Human genome education model project. Ethical, legal, and social implications of the human genome project: Education of interdisciplinary professionals

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, J.O. [Alliance of Genetic Support Groups, Chevy Chase, MD (United States); Lapham, E.V. [Georgetown Univ., Washington, DC (United States). Child Development Center

    1996-12-31

    This meeting was held June 10, 1996 at Georgetown University. The purpose of this meeting was to provide a multidisciplinary forum for exchange of state-of-the-art information on the human genome education model. Topics of discussion include the following: psychosocial issues; ethical issues for professionals; legislative issues and update; and education issues.

  2. On the Immortality of Television Sets: ?Function? in the Human Genome According to the Evolution-Free Gospel of ENCODE

    OpenAIRE

    Graur, Dan; Zheng, Yichen; Price, Nicholas; Azevedo, Ricardo B.R.; Zufall, Rebecca A.; Elhaik, Eran

    2013-01-01

    A recent slew of ENCyclopedia Of DNA Elements (ENCODE) Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is less than 10%. Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selec...

  3. The draft genome of the carcinogenic human liver fluke Clonorchis sinensis

    Science.gov (United States)

    2011-01-01

    Background Clonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome. Results We combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines. Conclusions This study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control. PMID:22023798

  4. Public attitudes to the promotion of genomic crop studies in Japan: correlations between genomic literacy, trust, and favourable attitude.

    Science.gov (United States)

    Ishiyama, Izumi; Tanzawa, Tetsuro; Watanabe, Maiko; Maeda, Tadahiko; Muto, Kaori; Tamakoshi, Akiko; Nagai, Akiko; Yamagata, Zentaro

    2012-05-01

    This study aimed to assess public attitudes in Japan to the promotion of genomic selection in crop studies and to examine associated factors. We analysed data from a nationwide opinion survey. A total of 4,000 people were selected from the Japanese general population by a stratified two-phase sampling method, and 2,171 people participated by post; this survey asked about the pros and cons of crop-related genomic studies promotion, examined people's scientific literacy in genomics, and investigated factors thought to be related to genomic literacy and attitude. The relationships were examined using logistic regression models stratified by gender. Survey results showed that 50.0% of respondents approved of the promotion of crop-related genomic studies, while 6.7% disapproved. No correlation was found between literacy and attitude towards promotion. Trust in experts, belief in science, an interest in genomic studies and willingness to purchase new products correlated with a positive attitude towards crop-related genomic studies.

  5. Functional Coverage of the Human Genome by Existing Structures, Structural Genomics Targets, and Homology Models.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available The bias in protein structure and function space resulting from experimental limitations and targeting of particular functional classes of proteins by structural biologists has long been recognized, but never continuously quantified. Using the Enzyme Commission and the Gene Ontology classifications as a reference frame, and integrating structure data from the Protein Data Bank (PDB, target sequences from the structural genomics projects, structure homology derived from the SUPERFAMILY database, and genome annotations from Ensembl and NCBI, we provide a quantified view, both at the domain and whole-protein levels, of the current and projected coverage of protein structure and function space relative to the human genome. Protein structures currently provide at least one domain that covers 37% of the functional classes identified in the genome; whole structure coverage exists for 25% of the genome. If all the structural genomics targets were solved (twice the current number of structures in the PDB, it is estimated that structures of one domain would cover 69% of the functional classes identified and complete structure coverage would be 44%. Homology models from existing experimental structures extend the 37% coverage to 56% of the genome as single domains and 25% to 31% for complete structures. Coverage from homology models is not evenly distributed by protein family, reflecting differing degrees of sequence and structure divergence within families. While these data provide coverage, conversely, they also systematically highlight functional classes of proteins for which structures should be determined. Current key functional families without structure representation are highlighted here; updated information on the "most wanted list" that should be solved is available on a weekly basis from http://function.rcsb.org:8080/pdb/function_distribution/index.html.

  6. Unexpected observations after mapping LongSAGE tags to the human genome

    Directory of Open Access Journals (Sweden)

    Duret Laurent

    2007-05-01

    Full Text Available Abstract Background SAGE has been used widely to study the expression of known transcripts, but much less to annotate new transcribed regions. LongSAGE produces tags that are sufficiently long to be reliably mapped to a whole-genome sequence. Here we used this property to study the position of human LongSAGE tags obtained from all public libraries. We focused mainly on tags that do not map to known transcripts. Results Using a published error rate in SAGE libraries, we first removed the tags likely to result from sequencing errors. We then observed that an unexpectedly large number of the remaining tags still did not match the genome sequence. Some of these correspond to parts of human mRNAs, such as polyA tails, junctions between two exons and polymorphic regions of transcripts. Another non-negligible proportion can be attributed to contamination by murine transcripts and to residual sequencing errors. After filtering out our data with these screens to ensure that our dataset is highly reliable, we studied the tags that map once to the genome. 31% of these tags correspond to unannotated transcripts. The others map to known transcribed regions, but many of them (nearly half are located either in antisense or in new variants of these known transcripts. Conclusion We performed a comprehensive study of all publicly available human LongSAGE tags, and carefully verified the reliability of these data. We found the potential origin of many tags that did not match the human genome sequence. The properties of the remaining tags imply that the level of sequencing error may have been under-estimated. The frequency of tags matching once the genome sequence but not in an annotated exon suggests that the human transcriptome is much more complex than shown by the current human genome annotations, with many new splicing variants and antisense transcripts. SAGE data is appropriate to map new transcripts to the genome, as demonstrated by the high rate of cross

  7. Genomic variation landscape of the human gut microbiome

    DEFF Research Database (Denmark)

    Schloissnig, Siegfried; Arumugam, Manimozhiyan; Sunagawa, Shinichi

    2013-01-01

    Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal...... polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates...

  8. A public resource facilitating clinical use of genomes.

    NARCIS (Netherlands)

    Ball, M.P.; Thakuria, J.V.; Zaranek, A.W.; Clegg, T.; Rosenbaum, A.M.; Wu, X.; Angrist, M.; Bhak, J.; Bobe, J.; Callow, M.J.; Cano, C.; Chou, M.F.; Chung, W.K.; Douglas, S.M.; Estep, P.W.; Gore, A.; Hulick, P.; Labarga, A.; Lee, J.-H.; Lunshof, J.E.; Kim, B.C.; Kim, J.L.; Li, Z.; Murray, M.F.; Nilsen, G.B.; Peters, B.A.; Raman, A.M.; Rienhoff, H.Y.; Robasky, K.; Wheeler, M.T.; Vandewege, W.; Vorhaus, D.B.; Yang, Y.L.; Yang, L.; Aach, J.; Ashley, E.A.; Drmanac, R.; Kim, S.-J.; Li, J.B.; Peshkin, L.; Seidman, S.E.; Seo, J.-S.; Zhang, K.; Rehm, H.L.; Church, G.M.

    2012-01-01

    Rapid advances in DNA sequencing promise to enable new diagnostics and individualized therapies. Achieving personalized medicine, however, will require extensive research on highly reidentifiable, integrated datasets of genomic and health information. To assist with this, participants in the

  9. Genomic characterization of large heterochromatic gaps in the human genome assembly.

    Directory of Open Access Journals (Sweden)

    Nicolas Altemose

    2014-05-01

    Full Text Available The largest gaps in the human genome assembly correspond to multi-megabase heterochromatic regions composed primarily of two related families of tandem repeats, Human Satellites 2 and 3 (HSat2,3. The abundance of repetitive DNA in these regions challenges standard mapping and assembly algorithms, and as a result, the sequence composition and potential biological functions of these regions remain largely unexplored. Furthermore, existing genomic tools designed to predict consensus-based descriptions of repeat families cannot be readily applied to complex satellite repeats such as HSat2,3, which lack a consistent repeat unit reference sequence. Here we present an alignment-free method to characterize complex satellites using whole-genome shotgun read datasets. Utilizing this approach, we classify HSat2,3 sequences into fourteen subfamilies and predict their chromosomal distributions, resulting in a comprehensive satellite reference database to further enable genomic studies of heterochromatic regions. We also identify 1.3 Mb of non-repetitive sequence interspersed with HSat2,3 across 17 unmapped assembly scaffolds, including eight annotated gene predictions. Finally, we apply our satellite reference database to high-throughput sequence data from 396 males to estimate array size variation of the predominant HSat3 array on the Y chromosome, confirming that satellite array sizes can vary between individuals over an order of magnitude (7 to 98 Mb and further demonstrating that array sizes are distributed differently within distinct Y haplogroups. In summary, we present a novel framework for generating initial reference databases for unassembled genomic regions enriched with complex satellite DNA, and we further demonstrate the utility of these reference databases for studying patterns of sequence variation within human populations.

  10. Genome-wide survey in African Americans demonstrates potential epistasis of fitness in the human genome.

    Science.gov (United States)

    Wang, Heming; Choi, Yoonha; Tayo, Bamidele; Wang, Xuefeng; Morris, Nathan; Zhang, Xiang; Broeckel, Uli; Hanis, Craig; Kardia, Sharon; Redline, Susan; Cooper, Richard S; Tang, Hua; Zhu, Xiaofeng

    2017-02-01

    The role played by epistasis between alleles at unlinked loci in shaping population fitness has been debated for many years and the existing evidence has been mainly accumulated from model organisms. In model organisms, fitness epistasis can be systematically inferred by detecting nonindependence of genotypic values between loci in a population and confirmed through examining the number of offspring produced in two-locus genotype groups. No systematic study has been conducted to detect epistasis of fitness in humans owing to experimental constraints. In this study, we developed a novel method to detect fitness epistasis by testing the correlation between local ancestries on different chromosomes in an admixed population. We inferred local ancestry across the genome in 16,252 unrelated African Americans and systematically examined the pairwise correlations between the genomic regions on different chromosomes. Our analysis revealed a pair of genomic regions on chromosomes 4 and 6 that show significant local ancestry correlation (P-value = 4.01 × 10 -8 ) that can be potentially attributed to fitness epistasis. However, we also observed substantial local ancestry correlation that cannot be explained by systemic ancestry inference bias. To our knowledge, this study is the first to systematically examine evidence of fitness epistasis across the human genome. © 2016 WILEY PERIODICALS, INC.

  11. Learning about the Human Genome. Part 2: Resources for Science Educators. ERIC Digest.

    Science.gov (United States)

    Haury, David L.

    This ERIC Digest identifies how the human genome project fits into the "National Science Education Standards" and lists Human Genome Project Web sites found on the World Wide Web. It is a resource companion to "Learning about the Human Genome. Part 1: Challenge to Science Educators" (Haury 2001). The Web resources and…

  12. Human genomic disease variants: a neutral evolutionary explanation.

    Science.gov (United States)

    Dudley, Joel T; Kim, Yuseob; Liu, Li; Markov, Glenn J; Gerold, Kristyn; Chen, Rong; Butte, Atul J; Kumar, Sudhir

    2012-08-01

    Many perspectives on the role of evolution in human health include nonempirical assumptions concerning the adaptive evolutionary origins of human diseases. Evolutionary analyses of the increasing wealth of clinical and population genomic data have begun to challenge these presumptions. In order to systematically evaluate such claims, the time has come to build a common framework for an empirical and intellectual unification of evolution and modern medicine. We review the emerging evidence and provide a supporting conceptual framework that establishes the classical neutral theory of molecular evolution (NTME) as the basis for evaluating disease- associated genomic variations in health and medicine. For over a decade, the NTME has already explained the origins and distribution of variants implicated in diseases and has illuminated the power of evolutionary thinking in genomic medicine. We suggest that a majority of disease variants in modern populations will have neutral evolutionary origins (previously neutral), with a relatively smaller fraction exhibiting adaptive evolutionary origins (previously adaptive). This pattern is expected to hold true for common as well as rare disease variants. Ultimately, a neutral evolutionary perspective will provide medicine with an informative and actionable framework that enables objective clinical assessment beyond convenient tendencies to invoke past adaptive events in human history as a root cause of human disease.

  13. Where Public Health Meets Human Rights

    Science.gov (United States)

    Kiragu, Karusa; Sawicki, Olga; Smith, Sally; Brion, Sophie; Sharma, Aditi; Mworeko, Lilian; Iovita, Alexandrina

    2017-01-01

    Abstract In 2014, the World Health Organization (WHO) initiated a process for validation of the elimination of mother-to-child transmission (EMTCT) of HIV and syphilis by countries. For the first time in such a process for the validation of disease elimination, WHO introduced norms and approaches that are grounded in human rights, gender equality, and community engagement. This human rights-based validation process can serve as a key opportunity to enhance accountability for human rights protection by evaluating EMTCT programs against human rights norms and standards, including in relation to gender equality and by ensuring the provision of discrimination-free quality services. The rights-based validation process also involves the assessment of participation of affected communities in EMTCT program development, implementation, and monitoring and evaluation. It brings awareness to the types of human rights abuses and inequalities faced by women living with, at risk of, or affected by HIV and syphilis, and commits governments to eliminate those barriers. This process demonstrates the importance and feasibility of integrating human rights, gender, and community into key public health interventions in a manner that improves health outcomes, legitimizes the participation of affected communities, and advances the human rights of women living with HIV. PMID:29302179

  14. Multi-scale structural community organisation of the human genome.

    Science.gov (United States)

    Boulos, Rasha E; Tremblay, Nicolas; Arneodo, Alain; Borgnat, Pierre; Audit, Benjamin

    2017-04-11

    Structural interaction frequency matrices between all genome loci are now experimentally achievable thanks to high-throughput chromosome conformation capture technologies. This ensues a new methodological challenge for computational biology which consists in objectively extracting from these data the structural motifs characteristic of genome organisation. We deployed the fast multi-scale community mining algorithm based on spectral graph wavelets to characterise the networks of intra-chromosomal interactions in human cell lines. We observed that there exist structural domains of all sizes up to chromosome length and demonstrated that the set of structural communities forms a hierarchy of chromosome segments. Hence, at all scales, chromosome folding predominantly involves interactions between neighbouring sites rather than the formation of links between distant loci. Multi-scale structural decomposition of human chromosomes provides an original framework to question structural organisation and its relationship to functional regulation across the scales. By construction the proposed methodology is independent of the precise assembly of the reference genome and is thus directly applicable to genomes whose assembly is not fully determined.

  15. The noncoding human genome and the future of personalised medicine.

    Science.gov (United States)

    Cowie, Philip; Hay, Elizabeth A; MacKenzie, Alasdair

    2015-01-30

    Non-coding cis-regulatory sequences act as the 'eyes' of the genome and their role is to perceive, organise and relay cellular communication information to RNA polymerase II at gene promoters. The evolution of these sequences, that include enhancers, silencers, insulators and promoters, has progressed in multicellular organisms to the extent that cis-regulatory sequences make up as much as 10% of the human genome. Parallel evidence suggests that 75% of polymorphisms associated with heritable disease occur within predicted cis-regulatory sequences that effectively alter the 'perception' of cis-regulatory sequences or render them blind to cell communication cues. Cis-regulatory sequences also act as major functional targets of epigenetic modification thus representing an important conduit through which changes in DNA-methylation affects disease susceptibility. The objectives of the current review are (1) to describe what has been learned about identifying and characterising cis-regulatory sequences since the sequencing of the human genome; (2) to discuss their role in interpreting cell signalling pathways pathways; and (3) outline how this role may be altered by polymorphisms and epigenetic changes. We argue that the importance of the cis-regulatory genome for the interpretation of cellular communication pathways cannot be overstated and understanding its role in health and disease will be critical for the future development of personalised medicine.

  16. Opening plenary speaker: Human genomics, precision medicine, and advancing human health.

    Science.gov (United States)

    Green, Eric D

    2016-08-01

    Starting with the launch of the Human Genome Project in 1990, the past quarter-century has brought spectacular achievements in genomics that dramatically empower the study of human biology and disease. The human genomics enterprise is now in the midst of an important transition, as the growing foundation of genomic knowledge is being used by researchers and clinicians to tackle increasingly complex problems in biomedicine. Of particular prominence is the use of revolutionary new DNA sequencing technologies for generating prodigious amounts of DNA sequence data to elucidate the complexities of genome structure, function, and evolution, as well as to unravel the genomic bases of rare and common diseases. Together, these developments are ushering in the era of genomic medicine. Augmenting the advances in human genomics have been innovations in technologies for measuring environmental and lifestyle information, electronic health records, and data science; together, these provide opportunities of unprecedented scale and scope for investigating the underpinnings of health and disease. To capitalize on these opportunities, U.S. President Barack Obama recently announced a major new research endeavor - the U.S. Precision Medicine Initiative. This bold effort will be framed around several key aims, which include accelerating the use of genomically informed approaches to cancer care, making important policy and regulatory changes, and establishing a large research cohort of >1 million volunteers to facilitate precision medicine research. The latter will include making the partnership with all participants a centerpiece feature in the cohort's design and development. The Precision Medicine Initiative represents a broad-based research program that will allow new approaches for individualized medical care to be rigorously tested, so as to establish a new evidence base for advancing clinical practice and, eventually, human health.

  17. Getting the Word Out on the Human Genome Project: A Course for Physicians

    Energy Technology Data Exchange (ETDEWEB)

    Sara L. Tobin

    2004-09-29

    Our project, ''Getting the Word Out on the Human Genome Project: A Course for Physicians,'' presented educational goals to convey the power and promise of the Human Genome Program to a variety of professional, educational, and public audiences. Our initial goal was to provide practicing physicians with a comprehensive multimedia tool to update their skills in the genomic era. We therefore created the multimedia courseware, ''The New Genetics: Courseware for Physicians. Molecular Concepts, Applications, and Ramifications.'' However, as the project moved forward, several unanticipated audiences found the courseware to be useful for instruction and for self-education, so an additional edition of the courseware ''The New Genetics: Medicine and the Human Genome. Molecular Concepts, Applications, and Ramifications'' was published simultaneously with the physician version. At the time that both versions of the courseware were being completed, Stanford's Office of Technology Licensing opted not to commercialize the courseware and offered a license-back agreement if the authors founded a commercial business. The authors thus became closely involved in marketing and sales, and several thousand copies of the courseware have been sold. Surprisingly, the non-physician version has turned out to be more in demand, and this has led us in several new directions, most of which involve undergraduate education. These are discussed in detail in the Report.

  18. The mobile genetic element Alu in the human genome

    Energy Technology Data Exchange (ETDEWEB)

    Novick, G.E. [Florida International Univ., Miami, FL (United States); Batzer, M.A.; Deininger, P.L. [Louisiana State Univ. Medical Center, New Orleans, LA (United States)] [and others

    1996-01-01

    Genetic material has been traditionally envisioned as relatively static with the exception of occasional, often deleterious mutations. The sequence DNA-to-RNA-to-protein represented for many years the central dogma relating gene structure and function. Recently, the field of molecular genetics has provided revolutionary information on the dynamic role of repetitive elements in the function of the genetic material and the evolution of humans and other organisms. Alu sequences represent the largest family of short interspersed repetitive elements (SINEs) in humans, being present in an excess of 500,000 copies per haploid genome. Alu elements, as well as the other repetitive elements, were once considered to be useless. Today, the biology of Alu transposable elements is being widely examined in order to determine the molecular basis of a growing number of identified diseases and to provide new directions in genome mapping and biomedical research. 66 refs., 5 figs.

  19. Targets of balancing selection in the human genome

    DEFF Research Database (Denmark)

    Andrés, Aida M; Hubisz, Melissa J; Indap, Amit

    2009-01-01

    Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant...... to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism data set......, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows enrichment...

  20. Private Appropriation, Public Dissemination and Commercial Product Development in Genomics (DOE)

    Energy Technology Data Exchange (ETDEWEB)

    Rebecca S. Eisenberg

    2003-03-19

    With DOE funding, I have conducted research on the topic of patents and technology transfer in the Human Genome Project since 1994. My research has proceeded along the following tracks: (1) research and monitoring of legal developments relating to (a) the patenting of DNA sequences and (b) the role of patents in technology transfer; (2) investigating and monitoring the strategies of different institutions in the public and private sector that are involved in DNA sequencing with respect to patenting and disseminating sequence information; (3) investigating and monitoring the impact of these strategies on those who use sequence information in research and product development. I have published commentary as my research proceeds in a variety of forums directed at scientists, lawyers, and science policy-makers.

  1. A human genome-wide library of local phylogeny predictions for whole-genome inference problems

    Directory of Open Access Journals (Sweden)

    Schwartz Russell

    2008-08-01

    Full Text Available Abstract Background Many common inference problems in computational genetics depend on inferring aspects of the evolutionary history of a data set given a set of observed modern sequences. Detailed predictions of the full phylogenies are therefore of value in improving our ability to make further inferences about population history and sources of genetic variation. Making phylogenetic predictions on the scale needed for whole-genome analysis is, however, extremely computationally demanding. Results In order to facilitate phylogeny-based predictions on a genomic scale, we develop a library of maximum parsimony phylogenies within local regions spanning all autosomal human chromosomes based on Haplotype Map variation data. We demonstrate the utility of this library for population genetic inferences by examining a tree statistic we call 'imperfection,' which measures the reuse of variant sites within a phylogeny. This statistic is significantly predictive of recombination rate, shows additional regional and population-specific conservation, and allows us to identify outlier genes likely to have experienced unusual amounts of variation in recent human history. Conclusion Recent theoretical advances in algorithms for phylogenetic tree reconstruction have made it possible to perform large-scale inferences of local maximum parsimony phylogenies from single nucleotide polymorphism (SNP data. As results from the imperfection statistic demonstrate, phylogeny predictions encode substantial information useful for detecting genomic features and population history. This data set should serve as a platform for many kinds of inferences one may wish to make about human population history and genetic variation.

  2. The human genome project and the Catholic Church (1)

    Science.gov (United States)

    Moraczewski, Albert S

    1991-12-01

    The Cathlic Church has not made any formal statements about the Human Genome Project as such. But the present Pope, John Paul II, has commented, albeit very briefly, on various aspects of genetic manipulation. Genetic interventions which are therapeutic (e.g. gene therapy), namely, directed to the correction or amelioration of a disorder are acceptable, in principle, provided they promote the personal well being of the individual being so treated. Genetic interventions which are not therapeutic for the specific individual involved but are experimental and directed primarily to improving humans as biological entities are of dubious moral probity, but are not necessarily to be totally rejected out of hand. To be morally acceptable such genetic intervention should meet certain conditions which include due respect for the given psychological nature of each individual human being. In addition, no harm should be inflicted on the process of human generation, and its fundamental design should not be altered. Any genetic manipulation which results in, or tends to, the creation of groups with different qualities such that there would result a fresh marginalization of these people must be avoided. It has been also suggested by a few that because the Son of God took on a human nature in Jesus Christ, one may not so alter the human genome that a new distinct species would be created....

  3. Widespread of horizontal gene transfer in the human genome

    OpenAIRE

    Huang, Wenze; Tsai, Lillian; Li, Yulong; Hua, Nan; Sun, Chen; Wei, Chaochun

    2017-01-01

    Background A fundamental concept in biology is that heritable material is passed from parents to offspring, a process called vertical gene transfer. An alternative mechanism of gene acquisition is through horizontal gene transfer (HGT), which involves movement of genetic materials between different species. Horizontal gene transfer has been found prevalent in prokaryotes but very rare in eukaryote. In this paper, we investigate horizontal gene transfer in the human genome. Results From the pa...

  4. Linkage Disequilibrium between STRPs and SNPs across the Human Genome

    OpenAIRE

    Payseur, Bret A.; Place, Michael; Weber, James L.

    2008-01-01

    Patterns of linkage disequilibrium (LD) reveal the action of evolutionary processes and provide crucial information for association mapping of disease genes. Although recent studies have described the landscape of LD among single nucleotide polymorphisms (SNPs) from across the human genome, associations involving other classes of molecular variation remain poorly understood. In addition to recombination and population history, mutation rate and process are expected to shape LD. To test this i...

  5. Toward a Standards-Compliant Genomic and Metagenomic Publication Record

    DEFF Research Database (Denmark)

    Garrity, GM; Field, D; Kyrpides, N

    2008-01-01

    Increasingly, we are aware as a community of the growing need to manage the avalanche of genomic and metagenomic data, in addition to related data types like ribosomal RNA and barcode sequences, in a way that tightly integrates contextual data with traditional literature in a machine-readable way...... is in the midst of a publishing revolution. This revolution is marked by a growing shift away from a traditional dichotomy between "journal articles" and "database entries" and an increasing adoption of hybrid models of collecting and disseminating scientific information. With respect to genomes and metagenomes...... or communities) such as the call by the GSC for a central repository of Standard Operating Procedures describing the genomic annotation pipelines of the major sequencing centers. We argue that such an "eJournal," published under the Open Access paradigm by the GSC, could be an attractive publishing forum...

  6. Report of the second Human Genome Diversity workshop

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-12-31

    The Second Human Genome Diversity Workshop was successfully held at Penn State University from October 29--31, 1992. The Workshop was essentially organized around 7 groups, each comprising approximately 10 participants, representing the sampling issues in different regions of the world. These groups worked independently, using a common format provided by the organizers; this was adjusted as needed by the individual groups. The Workshop began with a presentation of the mandate to the participants, and of the procedures to be followed during the workshop. Dr. Feldman presented a summary of the results from the First Workshop. He and the other organizers also presented brief comments giving their perspective on the objectives of the Second Workshop. Dr. Julia Bodmer discussed the study of European genetic diversity, especially in the context of the HLA experience there, and of plans to extend such studies in the coming years. She also discussed surveys of world HLA laboratories in regard to resources related to Human Genome Diversity. Dr. Mark Weiss discussed the relevance of nonhuman primate studies for understanding how demographic processes, such as mate exchange between local groups, affected the local dispersion of genetic variation. Primate population geneticists have some relevant experience in interpreting variation at this local level, in particular, with various DNA fingerprinting methods. This experience may be relevant to the Human Genome Diversity Project, in terms of practical and statistical issues.

  7. Linkage disequilibrium between STRPs and SNPs across the human genome.

    Science.gov (United States)

    Payseur, Bret A; Place, Michael; Weber, James L

    2008-05-01

    Patterns of linkage disequilibrium (LD) reveal the action of evolutionary processes and provide crucial information for association mapping of disease genes. Although recent studies have described the landscape of LD among single nucleotide polymorphisms (SNPs) from across the human genome, associations involving other classes of molecular variation remain poorly understood. In addition to recombination and population history, mutation rate and process are expected to shape LD. To test this idea, we measured associations between short-tandem-repeat polymorphisms (STRPs), which can mutate rapidly and recurrently, and SNPs in 721 regions across the human genome. We directly compared STRP-SNP LD with SNP-SNP LD from the same genomic regions in the human HapMap populations. The intensity of STRP-SNP LD, measured by the average of D', was reduced, consistent with the action of recurrent mutation. Nevertheless, a higher fraction of STRP-SNP pairs than SNP-SNP pairs showed significant LD, on both short (up to 50 kb) and long (cM) scales. These results reveal the substantial effects of mutational processes on LD at STRPs and provide important measures of the potential of STRPs for association mapping of disease genes.

  8. The genomic signature of human rhinoviruses A, B and C.

    Directory of Open Access Journals (Sweden)

    Spyridon Megremis

    Full Text Available Human rhinoviruses are single stranded positive sense RNA viruses that are presented in more than 50% of acute upper respiratory tract infections. Despite extensive studies on the genetic diversity of the virus, little is known about the forces driving it. In order to explain this diversity, many research groups have focused on protein sequence requirements for viable, functional and transmissible virus but have missed out an important aspect of viral evolution such as the genomic ontology of the virus. This study presents for the first time the genomic signature of 111 fully sequenced HRV strains from all three groups HRV-A, HRV-B and HRV-C. We observed an HRV genome tendency to eliminate CpG and UpA dinucleotides, coupling with over-representation of UpG and CpA. We propose a specific mechanism which describes how rapid changes in the HRV genomic sequence can take place under the strict control of conservation of the polypeptide backbone. Moreover, the distribution of the observed under- and over-represented dinucleotides along the HRV genome is presented. Distance matrice tables based on CpG and UpA odds ratios were constructed and viewed as heatmaps and distance trees. None of the suppressions can be attributed to codon usage or in RNA secondary structure requirements. Since viral recognition is dependent on RNA motifs rich in CpG and UpA, it is possible that the overall described genome evolution mechanism acts in order to protect the virus from host recognition.

  9. De novo assembly of a haplotype-resolved human genome

    DEFF Research Database (Denmark)

    Cao, Hongzhi; Wu, Honglong; Luo, Ruibang

    2015-01-01

    The human genome is diploid, and knowledge of the variants on each chromosome is important for the interpretation of genomic information. Here we report the assembly of a haplotype-resolved diploid genome without using a reference genome. Our pipeline relies on fosmid pooling together with whole-...

  10. Navigating the evidentiary turn in public health: Sensemaking strategies to integrate genomics into state-level chronic disease prevention programs.

    Science.gov (United States)

    Senier, Laura; Smollin, Leandra; Lee, Rachael; Nicoll, Lauren; Shields, Michael; Tan, Catherine

    2018-06-23

    In the past decade, healthcare delivery has faced two major disruptions: the mapping of the human genome and the rise of evidence-based practice. Sociologists have documented the paradigmatic shift towards evidence-based practice in medicine, but have yet to examine its effect on other health professions or the broader healthcare arena. This article shows how evidence-based practice is transforming public health in the United States. We present an in-depth qualitative analysis of interview, ethnographic, and archival data to show how Michigan's state public health agency has navigated the turn to evidence-based practice, as they have integrated scientific advances in genomics into their chronic disease prevention programming. Drawing on organizational theory, we demonstrate how they managed ambiguity through a combination of sensegiving and sensemaking activities. Specifically, they linked novel developments in genomics to a long-accepted public health planning model, the Core Public Health Functions. This made cutting edge advances in genomics more familiar to their peers in the state health agency. They also marshaled state-specific surveillance data to illustrate the public health burden of hereditary cancers in Michigan, and to make expert panel recommendations for genetic screening more locally relevant. Finally, they mobilized expertise to help their internal colleagues and external partners modernize conventional public health activities in chronic disease prevention. Our findings show that tools and concepts from organizational sociology can help medical sociologists understand how evidence-based practice is shaping institutions and interprofessional relations in the healthcare arena. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. [Manipulation of the human genome: ethics and law].

    Science.gov (United States)

    Goulart, Maria Carolina Vaz; Iano, Flávia Godoy; Silva, Paulo Maurício; Sales-Peres, Silvia Helena de Carvalho; Sales-Peres, Arsênio

    2010-06-01

    The molecular biology has provided the basic tool for geneticists deepening in the molecular mechanisms that influence different diseases. It should be noted the scientific and moral responsibility of the researchers, because the scientists should imagine the moral consequences of the commercial application of genetic tests, since this fact involves not only the individual and their families, but the entire population. Besides being also necessary to make a reflection on how this information from the human genome will be used, for good or bad. The objective of this review was to bring the light of knowledge, data on characteristics of the ethical application of molecular biology, linking it with the rights of human beings. After studying literature, it might be observed that the Human Genome Project has generated several possibilities, such as the identification of genes associated with diseases with synergistic properties, but sometimes modifying behavior to genetically intervene in humans, bringing benefits or social harm. The big challenge is to decide what humanity wants on this giant leap.

  12. Los Alamos Science: The Human Genome Project. Number 20, 1992

    Science.gov (United States)

    Cooper, N. G.; Shea, N. eds.

    1992-01-01

    This document provides a broad overview of the Human Genome Project, with particular emphasis on work being done at Los Alamos. It tries to emphasize the scientific aspects of the project, compared to the more speculative information presented in the popular press. There is a brief introduction to modern genetics, including a review of classic work. There is a broad overview of the Genome Project, describing what the project is, what are some of its major five-year goals, what are major technological challenges ahead of the project, and what can the field of biology, as well as society expect to see as benefits from this project. Specific results on the efforts directed at mapping chromosomes 16 and 5 are discussed. A brief introduction to DNA libraries is presented, bearing in mind that Los Alamos has housed such libraries for many years prior to the Genome Project. Information on efforts to do applied computational work related to the project are discussed, as well as experimental efforts to do rapid DNA sequencing by means of single-molecule detection using applied spectroscopic methods. The article introduces the Los Alamos staff which are working on the Genome Project, and concludes with brief discussions on ethical, legal, and social implications of this work; a brief glimpse of genetics as it may be practiced in the next century; and a glossary of relevant terms.

  13. Experimental annotation of the human genome using microarray technology.

    Science.gov (United States)

    Shoemaker, D D; Schadt, E E; Armour, C D; He, Y D; Garrett-Engele, P; McDonagh, P D; Loerch, P M; Leonardson, A; Lum, P Y; Cavet, G; Wu, L F; Altschuler, S J; Edwards, S; King, J; Tsang, J S; Schimmack, G; Schelter, J M; Koch, J; Ziman, M; Marton, M J; Li, B; Cundiff, P; Ward, T; Castle, J; Krolewski, M; Meyer, M R; Mao, M; Burchard, J; Kidd, M J; Dai, H; Phillips, J W; Linsley, P S; Stoughton, R; Scherer, S; Boguski, M S

    2001-02-15

    The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons. These methods can provide more accurate gene numbers and allow the detection of mRNA splice variants and identification of the tissue- and disease-specific conditions under which genes are expressed. We apply our technique to chromosome 22q under 69 experimental condition pairs, and to the entire human genome under two experimental conditions. We discuss implications for more comprehensive, consistent and reliable genome annotation, more efficient, full-length complementary DNA cloning strategies and application to complex diseases.

  14. Los Alamos Science: The Human Genome Project. Number 20, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, N G; Shea, N [eds.

    1992-01-01

    This article provides a broad overview of the Human Genome Project, with particular emphasis on work being done at Los Alamos. It tries to emphasize the scientific aspects of the project, compared to the more speculative information presented in the popular press. There is a brief introduction to modern genetics, including a review of classic work. There is a broad overview of the Genome Project, describing what the project is, what are some of its major five-year goals, what are major technological challenges ahead of the project, and what can the field of biology, as well as society expect to see as benefits from this project. Specific results on the efforts directed at mapping chromosomes 16 and 5 are discussed. A brief introduction to DNA libraries is presented, bearing in mind that Los Alamos has housed such libraries for many years prior to the Genome Project. Information on efforts to do applied computational work related to the project are discussed, as well as experimental efforts to do rapid DNA sequencing by means of single-molecule detection using applied spectroscopic methods. The article introduces the Los Alamos staff which are working on the Genome Project, and concludes with brief discussions on ethical, legal, and social implications of this work; a brief glimpse of genetics as it may be practiced in the next century; and a glossary of relevant terms.

  15. Chromatin structure and evolution in the human genome

    Directory of Open Access Journals (Sweden)

    Dunlop Malcolm G

    2007-05-01

    Full Text Available Abstract Background Evolutionary rates are not constant across the human genome but genes in close proximity have been shown to experience similar levels of divergence and selection. The higher-order organisation of chromosomes has often been invoked to explain such phenomena but previously there has been insufficient data on chromosome structure to investigate this rigorously. Using the results of a recent genome-wide analysis of open and closed human chromatin structures we have investigated the global association between divergence, selection and chromatin structure for the first time. Results In this study we have shown that, paradoxically, synonymous site divergence (dS at non-CpG sites is highest in regions of open chromatin, primarily as a result of an increased number of transitions, while the rates of other traditional measures of mutation (intergenic, intronic and ancient repeat divergence as well as SNP density are highest in closed regions of the genome. Analysis of human-chimpanzee divergence across intron-exon boundaries indicates that although genes in relatively open chromatin generally display little selection at their synonymous sites, those in closed regions show markedly lower divergence at their fourfold degenerate sites than in neighbouring introns and intergenic regions. Exclusion of known Exonic Splice Enhancer hexamers has little affect on the divergence observed at fourfold degenerate sites across chromatin categories; however, we show that closed chromatin is enriched with certain classes of ncRNA genes whose RNA secondary structure may be particularly important. Conclusion We conclude that, overall, non-CpG mutation rates are lowest in open regions of the genome and that regions of the genome with a closed chromatin structure have the highest background mutation rate. This might reflect lower rates of DNA damage or enhanced DNA repair processes in regions of open chromatin. Our results also indicate that dS is a poor

  16. Genome-wide association studies in Africans and African Americans: Expanding the Framework of the Genomics of Human Traits and Disease

    Science.gov (United States)

    Peprah, Emmanuel; Xu, Huichun; Tekola-Ayele, Fasil; Royal, Charmaine D.

    2014-01-01

    Genomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance, and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago, and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent-African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions. PMID:25427668

  17. Genome-wide association studies in Africans and African Americans: expanding the framework of the genomics of human traits and disease.

    Science.gov (United States)

    Peprah, Emmanuel; Xu, Huichun; Tekola-Ayele, Fasil; Royal, Charmaine D

    2015-01-01

    Genomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions.

  18. Human Genome Project discoveries: Dialectics and rhetoric in the science of genetics

    Science.gov (United States)

    Robidoux, Charlotte A.

    The Human Genome Project (HGP), a $437 million effort that began in 1990 to chart the chemical sequence of our three billion base pairs of DNA, was completed in 2003, marking the 50th anniversary that proved the definitive structure of the molecule. This study considered how dialectical and rhetorical arguments functioned in the science, political, and public forums over a 20-year period, from 1980 to 2000, to advance human genome research and to establish the official project. I argue that Aristotle's continuum of knowledge--which ranges from the probable on one end to certified or demonstrated knowledge on the other--provides useful distinctions for analyzing scientific reasoning. While contemporary scientific research seeks to discover certified knowledge, investigators generally employ the hypothetico-deductive or scientific method, which often yields probable rather than certain findings, making these dialectical in nature. Analysis of the discourse describing human genome research revealed the use of numerous rhetorical figures and topics. Persuasive and probable reasoning were necessary for scientists to characterize unknown genetic phenomena, to secure interest in and funding for large-scale human genome research, to solve scientific problems, to issue probable findings, to convince colleagues and government officials that the findings were sound and to disseminate information to the public. Both government and private venture scientists drew on these tools of reasoning to promote their methods of mapping and sequencing the genome. The debate over how to carry out sequencing was rooted in conflicting values. Scientists representing the academic tradition valued a more conservative method that would establish high quality results, and those supporting private industry valued an unconventional approach that would yield products and profits more quickly. Values in turn influenced political and public forum arguments. Agency representatives and investors sided

  19. Ethical, legal and social issues in the context of the planning stages of the Southern African Human Genome Programme.

    Science.gov (United States)

    de Vries, Jantina; Slabbert, Melodie; Pepper, Michael S

    2012-03-01

    As the focus on the origin of modern man appears to be moving from eastern to southern Africa, it is recognised that indigenous populations in southern Africa may be the most genetically diverse on the planet and hence a valuable resource for human genetic diversity studies. In order to build regional capacity for the generation, analysis and application of genomic data, the Southern African Human Genome Programme was recently launched with the aid of seed funding from the national Department of Science and Technology in South Africa. The purpose of the article is to investigate pertinent ethical, legal and social issues that have emerged during the planning stages of the Southern African Human Genome Programme. A careful consideration of key issues such as public perception of genomic research, issues relating to genetic and genomic discrimination and stigmatisation, informed consent, privacy and data protection, and the concept of genomic sovereignty, is of paramount importance in the early stages of the Programme. This article will also consider the present legal framework governing genomic research in South Africa and will conclude with proposals regarding such a framework for the future.

  20. Human genome sequencing with direct x-ray holographic imaging

    International Nuclear Information System (INIS)

    Rhodes, C.K.

    1993-01-01

    Direct holographic imaging of biological materials is widely applicable to the study of the structure, properties and action of genetic material. This particular application involves the sequencing of the human genome where prospective genomic imaging technology is composed of three subtechnologies, name an x-ray holographic camera, suitable chemistry and enzymology for the preparation of tagged DNA samples, and the illuminator in the form of an x-ray laser. We report appropriate x-ray camera, embodied by the instrument developed by MCR, is available and that suitable chemical and enzymatic procedures exist for the preparation of the necessary tagged DNA strands. Concerning the future development of the x-ray illuminator. We find that a practical small scale x-ray light source is indeed feasible. This outcome requires the use of unconventional physical processes in order to achieve the necessary power-compression in the amplifying medium. The understanding of these new physical mechanisms is developing rapidly. Importantly, although the x-ray source does not currently exist, the understanding of these new physical mechanisms is developing rapidly and the research has established the basic scaling laws that will determine the properties of the x-ray illuminator. When this x-ray source becomes available, an extremely rapid and cost effective instrument for 3-D imaging of biological materials can be applied to a wide range of biological structural assays, including the base-pair sequencing of the human genome and many questions regarding its higher levels of organization

  1. A framework for annotating human genome in disease context.

    Science.gov (United States)

    Xu, Wei; Wang, Huisong; Cheng, Wenqing; Fu, Dong; Xia, Tian; Kibbe, Warren A; Lin, Simon M

    2012-01-01

    Identification of gene-disease association is crucial to understanding disease mechanism. A rapid increase in biomedical literatures, led by advances of genome-scale technologies, poses challenge for manually-curated-based annotation databases to characterize gene-disease associations effectively and timely. We propose an automatic method-The Disease Ontology Annotation Framework (DOAF) to provide a comprehensive annotation of the human genome using the computable Disease Ontology (DO), the NCBO Annotator service and NCBI Gene Reference Into Function (GeneRIF). DOAF can keep the resulting knowledgebase current by periodically executing automatic pipeline to re-annotate the human genome using the latest DO and GeneRIF releases at any frequency such as daily or monthly. Further, DOAF provides a computable and programmable environment which enables large-scale and integrative analysis by working with external analytic software or online service platforms. A user-friendly web interface (doa.nubic.northwestern.edu) is implemented to allow users to efficiently query, download, and view disease annotations and the underlying evidences.

  2. Human Ageing Genomic Resources: new and updated databases

    Science.gov (United States)

    Tacutu, Robi; Thornton, Daniel; Johnson, Emily; Budovsky, Arie; Barardo, Diogo; Craig, Thomas; Diana, Eugene; Lehmann, Gilad; Toren, Dmitri; Wang, Jingwei; Fraifeld, Vadim E

    2018-01-01

    Abstract In spite of a growing body of research and data, human ageing remains a poorly understood process. Over 10 years ago we developed the Human Ageing Genomic Resources (HAGR), a collection of databases and tools for studying the biology and genetics of ageing. Here, we present HAGR’s main functionalities, highlighting new additions and improvements. HAGR consists of six core databases: (i) the GenAge database of ageing-related genes, in turn composed of a dataset of >300 human ageing-related genes and a dataset with >2000 genes associated with ageing or longevity in model organisms; (ii) the AnAge database of animal ageing and longevity, featuring >4000 species; (iii) the GenDR database with >200 genes associated with the life-extending effects of dietary restriction; (iv) the LongevityMap database of human genetic association studies of longevity with >500 entries; (v) the DrugAge database with >400 ageing or longevity-associated drugs or compounds; (vi) the CellAge database with >200 genes associated with cell senescence. All our databases are manually curated by experts and regularly updated to ensure a high quality data. Cross-links across our databases and to external resources help researchers locate and integrate relevant information. HAGR is freely available online (http://genomics.senescence.info/). PMID:29121237

  3. High-density rhesus macaque oligonucleotide microarray design using early-stage rhesus genome sequence information and human genome annotations

    Directory of Open Access Journals (Sweden)

    Magness Charles L

    2007-01-01

    Full Text Available Abstract Background Until recently, few genomic reagents specific for non-human primate research have been available. To address this need, we have constructed a macaque-specific high-density oligonucleotide microarray by using highly fragmented low-pass sequence contigs from the rhesus genome project together with the detailed sequence and exon structure of the human genome. Using this method, we designed oligonucleotide probes to over 17,000 distinct rhesus/human gene orthologs and increased by four-fold the number of available genes relative to our first-generation expressed sequence tag (EST-derived array. Results We constructed a database containing 248,000 exon sequences from 23,000 human RefSeq genes and compared each human exon with its best matching sequence in the January 2005 version of the rhesus genome project list of 486,000 DNA contigs. Best matching rhesus exon sequences for each of the 23,000 human genes were then concatenated in the proper order and orientation to produce a rhesus "virtual transcriptome." Microarray probes were designed, one per gene, to the region closest to the 3' untranslated region (UTR of each rhesus virtual transcript. Each probe was compared to a composite rhesus/human transcript database to test for cross-hybridization potential yielding a final probe set representing 18,296 rhesus/human gene orthologs, including transcript variants, and over 17,000 distinct genes. We hybridized mRNA from rhesus brain and spleen to both the EST- and genome-derived microarrays. Besides four-fold greater gene coverage, the genome-derived array also showed greater mean signal intensities for genes present on both arrays. Genome-derived probes showed 99.4% identity when compared to 4,767 rhesus GenBank sequence tag site (STS sequences indicating that early stage low-pass versions of complex genomes are of sufficient quality to yield valuable functional genomic information when combined with finished genome information from

  4. Predicting human height by Victorian and genomic methods.

    Science.gov (United States)

    Aulchenko, Yurii S; Struchalin, Maksim V; Belonogova, Nadezhda M; Axenovich, Tatiana I; Weedon, Michael N; Hofman, Albert; Uitterlinden, Andre G; Kayser, Manfred; Oostra, Ben A; van Duijn, Cornelia M; Janssens, A Cecile J W; Borodin, Pavel M

    2009-08-01

    In the Victorian era, Sir Francis Galton showed that 'when dealing with the transmission of stature from parents to children, the average height of the two parents, ... is all we need care to know about them' (1886). One hundred and twenty-two years after Galton's work was published, 54 loci showing strong statistical evidence for association to human height were described, providing us with potential genomic means of human height prediction. In a population-based study of 5748 people, we find that a 54-loci genomic profile explained 4-6% of the sex- and age-adjusted height variance, and had limited ability to discriminate tall/short people, as characterized by the area under the receiver-operating characteristic curve (AUC). In a family-based study of 550 people, with both parents having height measurements, we find that the Galtonian mid-parental prediction method explained 40% of the sex- and age-adjusted height variance, and showed high discriminative accuracy. We have also explored how much variance a genomic profile should explain to reach certain AUC values. For highly heritable traits such as height, we conclude that in applications in which parental phenotypic information is available (eg, medicine), the Victorian Galton's method will long stay unsurpassed, in terms of both discriminative accuracy and costs. For less heritable traits, and in situations in which parental information is not available (eg, forensics), genomic methods may provide an alternative, given that the variants determining an essential proportion of the trait's variation can be identified.

  5. 77 FR 50140 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-08-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., Human Genome Research, National Institutes of Health, HHS) Dated: August 13, 2012. Anna Snouffer, Deputy..., Bethesda, MD 20892. Contact Person: Camilla E. Day, Ph.D., Scientific Review Officer, CIDR, National Human...

  6. 77 FR 64816 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2012-10-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., Human Genome Research, National Institutes of Health, HHS) Dated: October 16, 2012. David Clary, Program... Conference Call). Contact Person: Camilla E. Day, Ph.D., Scientific Review Officer, CIDR, National Human...

  7. 76 FR 9031 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-02-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Call). Contact Person: Camilla E. Day, PhD, Scientific Review Officer, CIDR, National Human Genome...- 402-8837, [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human...

  8. 75 FR 62548 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2010-10-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Call). Contact Person: Camilla E. Day, PhD, Scientific Review Officer, CIDR, National Human Genome...- 402-8837, [email protected] . Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human...

  9. 78 FR 11898 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-02-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome....172, Human Genome Research, National Institutes of Health, HHS) Dated: February 13, 2013. David Clary... Conference Call). Contact Person: Camilla E. Day, Ph.D., Scientific Review Officer CIDR, National Human...

  10. 78 FR 77477 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-12-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome..., Human Genome Research, National Institutes of Health, HHS). Dated: December 17, 2013. David Clary... Conference Call). Contact Person: Camilla E. Day, Ph.D., Scientific Review Officer, CIDR, National Human...

  11. 76 FR 50486 - National Human Genome Research Institute; Notice of Closed Meeting

    Science.gov (United States)

    2011-08-15

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome... Conference Call). Contact Person: Camilla E. Day, PhD, Scientific Review Officer, CIDR, National Human Genome...- 402-8837, [email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.172, Human...

  12. Human potential development as a prerequisite of public policy efficiency

    Directory of Open Access Journals (Sweden)

    Polishchuk Iryna Viktorivna

    2014-12-01

    Full Text Available The article analyses the role of the public officers’ human potential for the efficiency of making public policy. It introduces features and criteria of human potential in the context of its development of civil service. The article designates some key directions for the development of human potential of public officers.

  13. Mi-DISCOVERER: A bioinformatics tool for the detection of mi-RNA in human genome.

    Science.gov (United States)

    Arshad, Saadia; Mumtaz, Asia; Ahmad, Freed; Liaquat, Sadia; Nadeem, Shahid; Mehboob, Shahid; Afzal, Muhammad

    2010-11-27

    MicroRNAs (miRNAs) are 22 nucleotides non-coding RNAs that play pivotal regulatory roles in diverse organisms including the humans and are difficult to be identified due to lack of either sequence features or robust algorithms to efficiently identify. Therefore, we made a tool that is Mi-Discoverer for the detection of miRNAs in human genome. The tools used for the development of software are Microsoft Office Access 2003, the JDK version 1.6.0, BioJava version 1.0, and the NetBeans IDE version 6.0. All already made miRNAs softwares were web based; so the advantage of our project was to make a desktop facility to the user for sequence alignment search with already identified miRNAs of human genome present in the database. The user can also insert and update the newly discovered human miRNA in the database. Mi-Discoverer, a bioinformatics tool successfully identifies human miRNAs based on multiple sequence alignment searches. It's a non redundant database containing a large collection of publicly available human miRNAs.

  14. De novo assembly and phasing of a Korean human genome.

    Science.gov (United States)

    Seo, Jeong-Sun; Rhie, Arang; Kim, Junsoo; Lee, Sangjin; Sohn, Min-Hwan; Kim, Chang-Uk; Hastie, Alex; Cao, Han; Yun, Ji-Young; Kim, Jihye; Kuk, Junho; Park, Gun Hwa; Kim, Juhyeok; Ryu, Hanna; Kim, Jongbum; Roh, Mira; Baek, Jeonghun; Hunkapiller, Michael W; Korlach, Jonas; Shin, Jong-Yeon; Kim, Changhoon

    2016-10-13

    Advances in genome assembly and phasing provide an opportunity to investigate the diploid architecture of the human genome and reveal the full range of structural variation across population groups. Here we report the de novo assembly and haplotype phasing of the Korean individual AK1 (ref. 1) using single-molecule real-time sequencing, next-generation mapping, microfluidics-based linked reads, and bacterial artificial chromosome (BAC) sequencing approaches. Single-molecule sequencing coupled with next-generation mapping generated a highly contiguous assembly, with a contig N50 size of 17.9 Mb and a scaffold N50 size of 44.8 Mb, resolving 8 chromosomal arms into single scaffolds. The de novo assembly, along with local assemblies and spanning long reads, closes 105 and extends into 72 out of 190 euchromatic gaps in the reference genome, adding 1.03 Mb of previously intractable sequence. High concordance between the assembly and paired-end sequences from 62,758 BAC clones provides strong support for the robustness of the assembly. We identify 18,210 structural variants by direct comparison of the assembly with the human reference, identifying thousands of breakpoints that, to our knowledge, have not been reported before. Many of the insertions are reflected in the transcriptome and are shared across the Asian population. We performed haplotype phasing of the assembly with short reads, long reads and linked reads from whole-genome sequencing and with short reads from 31,719 BAC clones, thereby achieving phased blocks with an N50 size of 11.6 Mb. Haplotigs assembled from single-molecule real-time reads assigned to haplotypes on phased blocks covered 89% of genes. The haplotigs accurately characterized the hypervariable major histocompatability complex region as well as demonstrating allele configuration in clinically relevant genes such as CYP2D6. This work presents the most contiguous diploid human genome assembly so far, with extensive investigation of

  15. Identification of DNA repair genes in the human genome

    International Nuclear Information System (INIS)

    Hoeijmakers, J.H.J.; van Duin, M.; Westerveld, A.; Yasui, A.; Bootsma, D.

    1986-01-01

    To identify human DNA repair genes we have transfected human genomic DNA ligated to a dominant marker to excision repair deficient xeroderma pigmentosum (XP) and CHO cells. This resulted in the cloning of a human gene, ERCC-1, that complements the defect of a UV- and mitomycin-C sensitive CHO mutant 43-3B. The ERCC-1 gene has a size of 15 kb, consists of 10 exons and is located in the region 19q13.2-q13.3. Its primary transcript is processed into two mRNAs by alternative splicing of an internal coding exon. One of these transcripts encodes a polypeptide of 297 aminoacids. A putative DNA binding protein domain and nuclear location signal could be identified. Significant AA-homology is found between ERCC-1 and the yeast excision repair gene RAD10. 58 references, 6 figures, 1 table

  16. Public data and open source tools for multi-assay genomic investigation of disease.

    Science.gov (United States)

    Kannan, Lavanya; Ramos, Marcel; Re, Angela; El-Hachem, Nehme; Safikhani, Zhaleh; Gendoo, Deena M A; Davis, Sean; Gomez-Cabrero, David; Castelo, Robert; Hansen, Kasper D; Carey, Vincent J; Morgan, Martin; Culhane, Aedín C; Haibe-Kains, Benjamin; Waldron, Levi

    2016-07-01

    Molecular interrogation of a biological sample through DNA sequencing, RNA and microRNA profiling, proteomics and other assays, has the potential to provide a systems level approach to predicting treatment response and disease progression, and to developing precision therapies. Large publicly funded projects have generated extensive and freely available multi-assay data resources; however, bioinformatic and statistical methods for the analysis of such experiments are still nascent. We review multi-assay genomic data resources in the areas of clinical oncology, pharmacogenomics and other perturbation experiments, population genomics and regulatory genomics and other areas, and tools for data acquisition. Finally, we review bioinformatic tools that are explicitly geared toward integrative genomic data visualization and analysis. This review provides starting points for accessing publicly available data and tools to support development of needed integrative methods. © The Author 2015. Published by Oxford University Press.

  17. FANTOM5 CAGE profiles of human and mouse reprocessed for GRCh38 and GRCm38 genome assemblies.

    Science.gov (United States)

    Abugessaisa, Imad; Noguchi, Shuhei; Hasegawa, Akira; Harshbarger, Jayson; Kondo, Atsushi; Lizio, Marina; Severin, Jessica; Carninci, Piero; Kawaji, Hideya; Kasukawa, Takeya

    2017-08-29

    The FANTOM5 consortium described the promoter-level expression atlas of human and mouse by using CAGE (Cap Analysis of Gene Expression) with single molecule sequencing. In the original publications, GRCh37/hg19 and NCBI37/mm9 assemblies were used as the reference genomes of human and mouse respectively; later, the Genome Reference Consortium released newer genome assemblies GRCh38/hg38 and GRCm38/mm10. To increase the utility of the atlas in forthcoming researches, we reprocessed the data to make them available on the recent genome assemblies. The data include observed frequencies of transcription starting sites (TSSs) based on the realignment of CAGE reads, and TSS peaks that are converted from those based on the previous reference. Annotations of the peak names were also updated based on the latest public databases. The reprocessed results enable us to examine frequencies of transcription initiations on the recent genome assemblies and to refer promoters with updated information across the genome assemblies consistently.

  18. Rates of genomic divergence in humans, chimpanzees and their lice.

    Science.gov (United States)

    Johnson, Kevin P; Allen, Julie M; Olds, Brett P; Mugisha, Lawrence; Reed, David L; Paige, Ken N; Pittendrigh, Barry R

    2014-02-22

    The rate of DNA mutation and divergence is highly variable across the tree of life. However, the reasons underlying this variation are not well understood. Comparing the rates of genetic changes between hosts and parasite lineages that diverged at the same time is one way to begin to understand differences in genetic mutation and substitution rates. Such studies have indicated that the rate of genetic divergence in parasites is often faster than that of their hosts when comparing single genes. However, the variation in this relative rate of molecular evolution across different genes in the genome is unknown. We compared the rate of DNA sequence divergence between humans, chimpanzees and their ectoparasitic lice for 1534 protein-coding genes across their genomes. The rate of DNA substitution in these orthologous genes was on average 14 times faster for lice than for humans and chimpanzees. In addition, these rates were positively correlated across genes. Because this correlation only occurred for substitutions that changed the amino acid, this pattern is probably produced by similar functional constraints across the same genes in humans, chimpanzees and their ectoparasites.

  19. The Human Genome Diversity (HGD) Project. Summary document

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    In 1991 a group of human geneticists and molecular biologists proposed to the scientific community that a world wide survey be undertaken of variation in the human genome. To aid their considerations, the committee therefore decided to hold a small series of international workshops to explore the major scientific issues involved. The intention was to define a framework for the project which could provide a basis for much wider and more detailed discussion and planning--it was recognized that the successful implementation of the proposed project, which has come to be known as the Human Genome Diversity (HGD) Project, would not only involve scientists but also various national and international non-scientific groups all of which should contribute to the project`s development. The international HGD workshop held in Sardinia in September 1993 was the last in the initial series of planning workshops. As such it not only explored new ground but also pulled together into a more coherent form much of the formal and informal discussion that had taken place in the preceding two years. This report presents the deliberations of the Sardinia workshop within a consideration of the overall development of the HGD Project to date.

  20. Dynamic association of NUP98 with the human genome.

    Directory of Open Access Journals (Sweden)

    Yun Liang

    Full Text Available Faithful execution of developmental gene expression programs occurs at multiple levels and involves many different components such as transcription factors, histone-modification enzymes, and mRNA processing proteins. Recent evidence suggests that nucleoporins, well known components that control nucleo-cytoplasmic trafficking, have wide-ranging functions in developmental gene regulation that potentially extend beyond their role in nuclear transport. Whether the unexpected role of nuclear pore proteins in transcription regulation, which initially has been described in fungi and flies, also applies to human cells is unknown. Here we show at a genome-wide level that the nuclear pore protein NUP98 associates with developmentally regulated genes active during human embryonic stem cell differentiation. Overexpression of a dominant negative fragment of NUP98 levels decreases expression levels of NUP98-bound genes. In addition, we identify two modes of developmental gene regulation by NUP98 that are differentiated by the spatial localization of NUP98 target genes. Genes in the initial stage of developmental induction can associate with NUP98 that is embedded in the nuclear pores at the nuclear periphery. Alternatively, genes that are highly induced can interact with NUP98 in the nuclear interior, away from the nuclear pores. This work demonstrates for the first time that NUP98 dynamically associates with the human genome during differentiation, revealing a role of a nuclear pore protein in regulating developmental gene expression programs.

  1. The Future of Whole-Genome Sequencing for Public Health and the Clinic

    OpenAIRE

    Allard, Marc W.

    2016-01-01

    An American Society for Microbiology (ASM) conference titled the Conference on Rapid Next-Generation Sequencing and Bioinformatic Pipelines for Enhanced Molecular Epidemiological Investigation of Pathogens provided a venue for discussing how technologies surrounding whole-genome sequencing (WGS) are advancing microbiology. Several applications in microbial taxonomy, microbial forensics, and genomics for public health pathogen surveillance were presented at the meeting and are reviewed. All of...

  2. An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia

    OpenAIRE

    Rasmussen, Morten; Guo, Xiaosen; Wang, Yong; Lohmueller, Kirk E.; Rasmussen, Simon; Albrechtsen, Anders; Skotte, Line; Lindgreen, Stinus; Metspalu, Mait; Jombart, Thibaut; Kivisild, Toomas; Zhai, Weiwei; Eriksson, Anders; Manica, Andrea; Orlando, Ludovic

    2011-01-01

    We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to ...

  3. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome

    NARCIS (Netherlands)

    Sharp, Andrew J.; Hansen, Sierra; Selzer, Rebecca R.; Cheng, Ze; Regan, Regina; Hurst, Jane A.; Stewart, Helen; Price, Sue M.; Blair, Edward; Hennekam, Raoul C.; Fitzpatrick, Carrie A.; Segraves, Rick; Richmond, Todd A.; Guiver, Cheryl; Albertson, Donna G.; Pinkel, Daniel; Eis, Peggy S.; Schwartz, Stuart; Knight, Samantha J. L.; Eichler, Evan E.

    2006-01-01

    Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic

  4. Telomeres and genomic damage repair. Their implication in human pathology

    International Nuclear Information System (INIS)

    Perez, Maria del R.; Dubner, Diana; Michelin, Severino; Gisone, Pablo; Carosella, Edgardo D.

    2002-01-01

    Telomeres, functional complexed that protect eukaryotic chromosome ends, participate in the regulation of cell proliferation and could play a role in the stabilization of genomic regions in response to genotoxic stress. Their significance in human pathology becomes evident in several diseases sharing genomic instability as a common trait, in which alterations of the telomere metabolism have been demonstrated. Many of them are also associated with hypersensitivity to ionizing radiation and cancer susceptibility. Besides the specific proteins belonging to the telomeric complex, other proteins involved in the DNA repair machinery, such as ATM, BRCA1, BRCA2, PARP/tankyrase system, DNA-PK and RAD50-MRE11-NBS1 complexes, are closely related with the telomere. This suggests that the telomere sequesters DNA repair proteins for its own structure maintenance, with could also be released toward damaged sites in the genomic DNA. This communication describes essential aspects of telomere structure and function and their links with homologous recombination, non-homologous end-joining (NHEJ), V(D)J system and mismatch-repair (MMR). Several pathological conditions exhibiting alterations in some of these mechanisms are also considered. The cell response to ionizing radiation and its relationship with the telomeric metabolism is particularly taken into account as a model for studying genotoxicity. (author)

  5. Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice.

    Science.gov (United States)

    Geller, Gail; Dvoskin, Rachel; Thio, Chloe L; Duggal, Priya; Lewis, Michelle H; Bailey, Theodore C; Sutherland, Andrea; Salmon, Daniel A; Kahn, Jeffrey P

    2014-01-01

    Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.

  6. A genomic atlas of human adrenal and gonad development

    Science.gov (United States)

    del Valle, Ignacio; Buonocore, Federica; Duncan, Andrew J.; Lin, Lin; Barenco, Martino; Parnaik, Rahul; Shah, Sonia; Hubank, Mike; Gerrelli, Dianne; Achermann, John C.

    2017-01-01

    Background: In humans, the adrenal glands and gonads undergo distinct biological events between 6-10 weeks post conception (wpc), such as testis determination, the onset of steroidogenesis and primordial germ cell development. However, relatively little is currently known about the genetic mechanisms underlying these processes. We therefore aimed to generate a detailed genomic atlas of adrenal and gonad development across these critical stages of human embryonic and fetal development. Methods: RNA was extracted from 53 tissue samples between 6-10 wpc (adrenal, testis, ovary and control). Affymetrix array analysis was performed and differential gene expression was analysed using Bioconductor. A mathematical model was constructed to investigate time-series changes across the dataset. Pathway analysis was performed using ClueGo and cellular localisation of novel factors confirmed using immunohistochemistry. Results: Using this approach, we have identified novel components of adrenal development (e.g. ASB4, NPR3) and confirmed the role of SRY as the main human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated with SOX9 in the testis (e.g. CITED1), which may represent components of the testis development pathway. We have shown that testicular steroidogenesis has a distinct onset at around 8 wpc and identified potential novel components in adrenal and testicular steroidogenesis (e.g. MGARP, FOXO4, MAP3K15, GRAMD1B, RMND2), as well as testis biomarkers (e.g. SCUBE1). We have also shown that the developing human ovary expresses distinct subsets of genes (e.g. OR10G9, OR4D5), but enrichment for established biological pathways is limited. Conclusion: This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders. PMID:28459107

  7. Documenting genomics: Applying archival theory to preserving the records of the Human Genome Project.

    Science.gov (United States)

    Shaw, Jennifer

    2016-02-01

    The Human Genome Archive Project (HGAP) aimed to preserve the documentary heritage of the UK's contribution to the Human Genome Project (HGP) by using archival theory to develop a suitable methodology for capturing the results of modern, collaborative science. After assessing past projects and different archival theories, the HGAP used an approach based on the theory of documentation strategy to try to capture the records of a scientific project that had an influence beyond the purely scientific sphere. The HGAP was an archival survey that ran for two years. It led to ninety scientists being contacted and has, so far, led to six collections being deposited in the Wellcome Library, with additional collections being deposited in other UK repositories. In applying documentation strategy the HGAP was attempting to move away from traditional archival approaches to science, which have generally focused on retired Nobel Prize winners. It has been partially successful in this aim, having managed to secure collections from people who are not 'big names', but who made an important contribution to the HGP. However, the attempt to redress the gender imbalance in scientific collections and to improve record-keeping in scientific organisations has continued to be difficult to achieve. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  8. Comparative Genomics Analysis of Streptococcus Isolates from the Human Small Intestine Reveals their Adaptation to a Highly Dynamic Ecosystem

    Science.gov (United States)

    Van den Bogert, Bartholomeus; Boekhorst, Jos; Herrmann, Ruth; Smid, Eddy J.; Zoetendal, Erwin G.; Kleerebezem, Michiel

    2013-01-01

    The human small-intestinal microbiota is characterised by relatively large and dynamic Streptococcus populations. In this study, genome sequences of small-intestinal streptococci from S. mitis, S. bovis, and S. salivarius species-groups were determined and compared with those from 58 Streptococcus strains in public databases. The Streptococcus pangenome consists of 12,403 orthologous groups of which 574 are shared among all sequenced streptococci and are defined as the Streptococcus core genome. Genome mining of the small-intestinal streptococci focused on functions playing an important role in the interaction of these streptococci in the small-intestinal ecosystem, including natural competence and nutrient-transport and metabolism. Analysis of the small-intestinal Streptococcus genomes predicts a high capacity to synthesize amino acids and various vitamins as well as substantial divergence in their carbohydrate transport and metabolic capacities, which is in agreement with observed physiological differences between these Streptococcus strains. Gene-specific PCR-strategies enabled evaluation of conservation of Streptococcus populations in intestinal samples from different human individuals, revealing that the S. salivarius strains were frequently detected in the small-intestine microbiota, supporting the representative value of the genomes provided in this study. Finally, the Streptococcus genomes allow prediction of the effect of dietary substances on Streptococcus population dynamics in the human small-intestine. PMID:24386196

  9. BIOETHICS METHODS IN THE ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS OF THE HUMAN GENOME PROJECT LITERATURE

    Science.gov (United States)

    Walker, Rebecca; Morrissey, Clair

    2013-01-01

    While bioethics as a field has concerned itself with methodological issues since the early years, there has been no systematic examination of how ethics is incorporated into research on the Ethical, Legal and Social Implications (ELSI) of the Human Genome Project. Yet ELSI research may bear a particular burden of investigating and substantiating its methods given public funding, an explicitly cross-disciplinary approach, and the perceived significance of adequate responsiveness to advances in genomics. We undertook a qualitative content analysis of a sample of ELSI publications appearing between 2003-2008 with the aim of better understanding the methods, aims, and approaches to ethics that ELSI researchers employ. We found that the aims of ethics within ELSI are largely prescriptive and address multiple groups. We also found that the bioethics methods used in the ELSI literature are both diverse between publications and multiple within publications, but are usually not themselves discussed or employed as suggested by bioethics method proponents. Ethics in ELSI is also sometimes undistinguished from related inquiries (such as social, legal, or political investigations). PMID:23796275

  10. Linkage disequilibrium of evolutionarily conserved regions in the human genome

    Directory of Open Access Journals (Sweden)

    Johnson Todd A

    2006-12-01

    Full Text Available Abstract Background The strong linkage disequilibrium (LD recently found in genic or exonic regions of the human genome demonstrated that LD can be increased by evolutionary mechanisms that select for functionally important loci. This suggests that LD might be stronger in regions conserved among species than in non-conserved regions, since regions exposed to natural selection tend to be conserved. To assess this hypothesis, we used genome-wide polymorphism data from the HapMap project and investigated LD within DNA sequences conserved between the human and mouse genomes. Results Unexpectedly, we observed that LD was significantly weaker in conserved regions than in non-conserved regions. To investigate why, we examined sequence features that may distort the relationship between LD and conserved regions. We found that interspersed repeats, and not other sequence features, were associated with the weak LD tendency in conserved regions. To appropriately understand the relationship between LD and conserved regions, we removed the effect of repetitive elements and found that the high degree of sequence conservation was strongly associated with strong LD in coding regions but not with that in non-coding regions. Conclusion Our work demonstrates that the degree of sequence conservation does not simply increase LD as predicted by the hypothesis. Rather, it implies that purifying selection changes the polymorphic patterns of coding sequences but has little influence on the patterns of functional units such as regulatory elements present in non-coding regions, since the former are generally restricted by the constraint of maintaining a functional protein product across multiple exons while the latter may exist more as individually isolated units.

  11. The UK Human Genome Mapping Project online computing service.

    Science.gov (United States)

    Rysavy, F R; Bishop, M J; Gibbs, G P; Williams, G W

    1992-04-01

    This paper presents an overview of computing and networking facilities developed by the Medical Research Council to provide online computing support to the Human Genome Mapping Project (HGMP) in the UK. The facility is connected to a number of other computing facilities in various centres of genetics and molecular biology research excellence, either directly via high-speed links or through national and international wide-area networks. The paper describes the design and implementation of the current system, a 'client/server' network of Sun, IBM, DEC and Apple servers, gateways and workstations. A short outline of online computing services currently delivered by this system to the UK human genetics research community is also provided. More information about the services and their availability could be obtained by a direct approach to the UK HGMP-RC.

  12. An Aboriginal Australian genome reveals separate human dispersals into Asia.

    Science.gov (United States)

    Rasmussen, Morten; Guo, Xiaosen; Wang, Yong; Lohmueller, Kirk E; Rasmussen, Simon; Albrechtsen, Anders; Skotte, Line; Lindgreen, Stinus; Metspalu, Mait; Jombart, Thibaut; Kivisild, Toomas; Zhai, Weiwei; Eriksson, Anders; Manica, Andrea; Orlando, Ludovic; De La Vega, Francisco M; Tridico, Silvana; Metspalu, Ene; Nielsen, Kasper; Ávila-Arcos, María C; Moreno-Mayar, J Víctor; Muller, Craig; Dortch, Joe; Gilbert, M Thomas P; Lund, Ole; Wesolowska, Agata; Karmin, Monika; Weinert, Lucy A; Wang, Bo; Li, Jun; Tai, Shuaishuai; Xiao, Fei; Hanihara, Tsunehiko; van Driem, George; Jha, Aashish R; Ricaut, François-Xavier; de Knijff, Peter; Migliano, Andrea B; Gallego Romero, Irene; Kristiansen, Karsten; Lambert, David M; Brunak, Søren; Forster, Peter; Brinkmann, Bernd; Nehlich, Olaf; Bunce, Michael; Richards, Michael; Gupta, Ramneek; Bustamante, Carlos D; Krogh, Anders; Foley, Robert A; Lahr, Marta M; Balloux, Francois; Sicheritz-Pontén, Thomas; Villems, Richard; Nielsen, Rasmus; Wang, Jun; Willerslev, Eske

    2011-10-07

    We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa.

  13. Molecular biologists backing effort to map entire human genome

    International Nuclear Information System (INIS)

    Zurer, P.S.

    1988-01-01

    This article discusses how the program to map and sequence the human genome will be managed. The National Research Council (NRC) recommends that a 15-year $200-million-a-year effort to map all human genes should begin immediately. However, some people have balked at the idea, saying it is a ploy to raise money. Part of the skeptic's uneasiness stems from the involvement of the Department of Energy (DOE), an agency not often linked with biological research. The DOE's interest arises from its commitment to understanding the biological effects of nuclear radiation. Critics say it is a budget-boosting tactic. This article explains some of the arguments for and against the project and explains exactly what it would involve

  14. PROBING GENOME MAINTENANCE FUNCTIONS OF HUMAN RECQ1

    Directory of Open Access Journals (Sweden)

    Furqan Sami

    2013-03-01

    Full Text Available The RecQ helicases are a highly conserved family of DNA-unwinding enzymes that play key roles in protecting the genome stability in all kingdoms of life.'Human RecQ homologs include RECQ1, BLM, WRN, RECQ4, and RECQ5β.'Although the individual RecQ-related diseases are characterized by a variety of clinical features encompassing growth defects (Bloom Syndrome and Rothmund Thomson Syndrome to premature aging (Werner Syndrome, all these patients have a high risk of cancer predisposition.'Here, we present an overview of recent progress towards elucidating functions of RECQ1 helicase, the most abundant but poorly characterized RecQ homolog in humans.'Consistent with a conserved role in genome stability maintenance, deficiency of RECQ1 results in elevated frequency of spontaneous sister chromatid exchanges, chromosomal instability, increased DNA damage and greater sensitivity to certain genotoxic stress.'Delineating what aspects of RECQ1 catalytic functions contribute to the observed cellular phenotypes, and how this is regulated is critical to establish its biological functions in DNA metabolism.'Recent studies have identified functional specialization of RECQ1 in DNA repair; however, identification of fundamental similarities will be just as critical in developing a unifying theme for RecQ actions, allowing the functions revealed from studying one homolog to be extrapolated and generalized to other RecQ homologs.

  15. An Aboriginal Australian Genome Reveals Separate Human Dispersals into Asia

    DEFF Research Database (Denmark)

    Rasmussen, Morten; Guo, Xiaosen; Wang, Yong

    2011-01-01

    We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show that Abori......We present an Aboriginal Australian genomic sequence obtained from a 100-year-old lock of hair donated by an Aboriginal man from southern Western Australia in the early 20th century. We detect no evidence of European admixture and estimate contamination levels to be below 0.5%. We show...... that Aboriginal Australians are descendants of an early human dispersal into eastern Asia, possibly 62,000 to 75,000 years ago. This dispersal is separate from the one that gave rise to modern Asians 25,000 to 38,000 years ago. We also find evidence of gene flow between populations of the two dispersal waves...... prior to the divergence of Native Americans from modern Asian ancestors. Our findings support the hypothesis that present-day Aboriginal Australians descend from the earliest humans to occupy Australia, likely representing one of the oldest continuous populations outside Africa....

  16. Retrocopy contributions to the evolution of the human genome

    Directory of Open Access Journals (Sweden)

    Haussler David

    2008-10-01

    Full Text Available Abstract Background Evolution via point mutations is a relatively slow process and is unlikely to completely explain the differences between primates and other mammals. By contrast, 45% of the human genome is composed of retroposed elements, many of which were inserted in the primate lineage. A subset of retroposed mRNAs (retrocopies shows strong evidence of expression in primates, often yielding functional retrogenes. Results To identify and analyze the relatively recently evolved retrogenes, we carried out BLASTZ alignments of all human mRNAs against the human genome and scored a set of features indicative of retroposition. Of over 12,000 putative retrocopy-derived genes that arose mainly in the primate lineage, 726 with strong evidence of transcript expression were examined in detail. These mRNA retroposition events fall into three categories: I 34 retrocopies and antisense retrocopies that added potential protein coding space and UTRs to existing genes; II 682 complete retrocopy duplications inserted into new loci; and III an unexpected set of 13 retrocopies that contributed out-of-frame, or antisense sequences in combination with other types of transposed elements (SINEs, LINEs, LTRs, even unannotated sequence to form potentially novel genes with no homologs outside primates. In addition to their presence in human, several of the gene candidates also had potentially viable ORFs in chimpanzee, orangutan, and rhesus macaque, underscoring their potential of function. Conclusion mRNA-derived retrocopies provide raw material for the evolution of genes in a wide variety of ways, duplicating and amending the protein coding region of existing genes as well as generating the potential for new protein coding space, or non-protein coding RNAs, by unexpected contributions out of frame, in reverse orientation, or from previously non-protein coding sequence.

  17. NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genome.

    Science.gov (United States)

    Chandrani, P; Kulkarni, V; Iyer, P; Upadhyay, P; Chaubal, R; Das, P; Mulherkar, R; Singh, R; Dutt, A

    2015-06-09

    Human papilloma virus (HPV) accounts for the most common cause of all virus-associated human cancers. Here, we describe the first graphic user interface (GUI)-based automated tool 'HPVDetector', for non-computational biologists, exclusively for detection and annotation of the HPV genome based on next-generation sequencing data sets. We developed a custom-made reference genome that comprises of human chromosomes along with annotated genome of 143 HPV types as pseudochromosomes. The tool runs on a dual mode as defined by the user: a 'quick mode' to identify presence of HPV types and an 'integration mode' to determine genomic location for the site of integration. The input data can be a paired-end whole-exome, whole-genome or whole-transcriptome data set. The HPVDetector is available in public domain for download: http://www.actrec.gov.in/pi-webpages/AmitDutt/HPVdetector/HPVDetector.html. On the basis of our evaluation of 116 whole-exome, 23 whole-transcriptome and 2 whole-genome data, we were able to identify presence of HPV in 20 exomes and 4 transcriptomes of cervical and head and neck cancer tumour samples. Using the inbuilt annotation module of HPVDetector, we found predominant integration of viral gene E7, a known oncogene, at known 17q21, 3q27, 7q35, Xq28 and novel sites of integration in the human genome. Furthermore, co-infection with high-risk HPVs such as 16 and 31 were found to be mutually exclusive compared with low-risk HPV71. HPVDetector is a simple yet precise and robust tool for detecting HPV from tumour samples using variety of next-generation sequencing platforms including whole genome, whole exome and transcriptome. Two different modes (quick detection and integration mode) along with a GUI widen the usability of HPVDetector for biologists and clinicians with minimal computational knowledge.

  18. 77 FR 67385 - National Human Genome Research Institute; Amended Notice of Meeting

    Science.gov (United States)

    2012-11-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome Research Institute; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Human Genome Research Institute Special Emphasis Panel, October 29, 2012, 8:00 a.m. to October 30...

  19. 78 FR 65342 - National Human Genome Research Institute; Amended Notice of Meeting

    Science.gov (United States)

    2013-10-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome Research Institute; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Human Genome Research Institute Special Emphasis Panel, October 17, 2013, 08:00 a.m. to October 17...

  20. 76 FR 65738 - National Human Genome Research Institute; Amended Notice of Meeting

    Science.gov (United States)

    2011-10-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome Research Institute; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Human Genome Research Institute Special Emphasis Panel, November 29, 2011, 8 a.m. to November 29...

  1. 77 FR 55853 - National Human Genome Research Institute; Amended Notice of Meeting

    Science.gov (United States)

    2012-09-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome Research Institute; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Advisory Council for Human Genome Research, September 10, 2012, 8:30 a.m. to September 11, 2012, 5...

  2. 77 FR 27471 - National Human Genome Research Institute Amended Notice of Meeting

    Science.gov (United States)

    2012-05-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome Research Institute Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Advisory Council for Human Genome Research, May 21, 2012, 8:30 a.m. to May 22, 2012, 5:00 p.m...

  3. 76 FR 71581 - National Human Genome Research Institute; Amended Notice of Meeting

    Science.gov (United States)

    2011-11-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Human Genome Research Institute; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Human Genome Research Institute Special Emphasis Panel, November 22, 2011, 12 p.m. to November 22...

  4. Comparative genomics of human and non-human Listeria monocytogenes sequence type 121 strains.

    Directory of Open Access Journals (Sweden)

    Kathrin Rychli

    Full Text Available The food-borne pathogen Listeria (L. monocytogenes is able to survive for months and even years in food production environments. Strains belonging to sequence type (ST121 are particularly found to be abundant and to persist in food and food production environments. To elucidate genetic determinants characteristic for L. monocytogenes ST121, we sequenced the genomes of 14 ST121 strains and compared them with currently available L. monocytogenes ST121 genomes. In total, we analyzed 70 ST121 genomes deriving from 16 different countries, different years of isolation, and different origins-including food, animal and human ST121 isolates. All ST121 genomes show a high degree of conservation sharing at least 99.7% average nucleotide identity. The main differences between the strains were found in prophage content and prophage conservation. We also detected distinct highly conserved subtypes of prophages inserted at the same genomic locus. While some of the prophages showed more than 99.9% similarity between strains from different sources and years, other prophages showed a higher level of diversity. 81.4% of the strains harbored virtually identical plasmids. 97.1% of the ST121 strains contain a truncated internalin A (inlA gene. Only one of the seven human ST121 isolates encodes a full-length inlA gene, illustrating the need of better understanding their survival and virulence mechanisms.

  5. A scored human protein-protein interaction network to catalyze genomic interpretation

    DEFF Research Database (Denmark)

    Li, Taibo; Wernersson, Rasmus; Hansen, Rasmus B

    2017-01-01

    Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (InWeb_InBioMap,......Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (In...

  6. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes

    DEFF Research Database (Denmark)

    Parker, Brian John; Moltke, Ida; Roth, Adam

    2011-01-01

    a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein...

  7. Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human

    NARCIS (Netherlands)

    S.L. Macrae (Sheila L.); Q. Zhang (Quanwei); C. Lemetre (Christophe); I. Seim (Inge); R.B. Calder (Robert B.); J.H.J. Hoeijmakers (Jan); Y. Suh (Yousin); V.N. Gladyshev (Vadim N.); A. Seluanov (Andrei); V. Gorbunova (Vera); J. Vijg (Jan); Z.D. Zhang (Zhengdong D.)

    2015-01-01

    textabstractGenome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM

  8. Coverage of genomic medicine: information gap between lay public and scientists.

    Science.gov (United States)

    Sugawara, Yuya; Narimatsu, Hiroto; Fukao, Akira

    2012-01-01

    The sharing of information between the lay public and medical professionals is crucial to the conduct of personalized medicine using genomic information in the near future. Mass media, such as newspapers, can play an important role in disseminating scientific information. However, studies on the role of newspaper coverage of genome-related articles are highly limited. We investigated the coverage of genomic medicine in five major Japanese newspapers (Asahi, Mainichi, Yomiuri, Sankei, and Nikkei) using Nikkei Telecom and articles in scientific journals in PubMed from 1995 to 2009. The number of genome-related articles in all five newspapers temporarily increased in 2000, and began continuously decreasing thereafter from 2001 to 2009. Conversely, there was a continuous increasing trend in the number of genome-related articles in PubMed during this period. The numbers of genome-related articles among the five major newspapers from 1995 to 2009 were significantly different (P = 0.002). Commentaries, research articles, and articles about companies were the most frequent in 2001 and 2003, when the number of genome-related articles transiently increased in the five newspapers. This study highlights the significant gap between newspaper coverage and scientific articles in scientific journals.

  9. Ascertainment bias in studies of human genome-wide polymorphism

    DEFF Research Database (Denmark)

    Clark, Andrew G.; Hubisz, Melissa J.; Bustamente, Carlos D.

    2005-01-01

    of the SNPs that are found are influenced by the discovery sampling effort. The International HapMap project relied on nearly any piece of information available to identify SNPs-including BAC end sequences, shotgun reads, and differences between public and private sequences-and even made use of chimpanzee...... was a resequencing-by-hybridization effort using the 24 people of diverse origin in the Polymorphism Discovery Resource. Here we take these two data sets and contrast two basic summary statistics, heterozygosity and FST, as well as the site frequency spectra, for 500-kb windows spanning the genome. The magnitude...... of disparity between these samples in these measures of variability indicates that population genetic analysis on the raw genotype data is ill advised. Given the knowledge of the discovery samples, we perform an ascertainment correction and show how the post-correction data are more consistent across...

  10. Human Papillomavirus Genome Integration and Head and Neck Cancer.

    Science.gov (United States)

    Pinatti, L M; Walline, H M; Carey, T E

    2018-06-01

    We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens. Studies of large numbers of early cervical lesions revealed frequent viral integration into gene-poor regions of the host genome with comparatively rare integration into cellular genes, suggesting that integration is a stochastic event and that site of integration may be largely a function of chance. However, more recent studies of head and neck squamous cell carcinomas (HNSCCs) suggest that integration may represent an additional oncogenic mechanism through direct effects on cancer-related gene expression and generation of hybrid viral-host fusion transcripts. In HNSCC cell lines as well as primary tumors, integration into cancer-related genes leading to gene disruption has been reported. The studies have shown that integration-induced altered gene expression may be associated with tumor recurrence. Evidence from several studies indicates that viral integration into genic regions is accompanied by local amplification, increased expression in some cases, interruption of gene expression, and likely additional oncogenic effects. Similarly, reported examples of viral integration near microRNAs suggest that altered expression of these regulatory molecules may also contribute to oncogenesis. Future work is indicated to identify the mechanisms of these events on cancer cell behavior.

  11. Human genome and philosophy: what ethical challenge will human genome studies bring to the medical practices in the 21st century?

    Science.gov (United States)

    Renzong, Q

    2001-12-01

    A human being or person cannot be reduced to a set of human genes, or human genome. Genetic essentialism is wrong, because as a person the entity should have self-conscious and social interaction capacity which is grown in an interpersonal relationship. Genetic determinism is wrong too, the relationship between a gene and a trait is not a linear model of causation, but rather a non-linear one. Human genome is a complexity system and functions in a complexity system of human body and a complexity of systems of natural/social environment. Genetic determinism also caused the issue of how much responsibility an agent should take for her/his action, and how much degrees of freedom will a human being have. Human genome research caused several conceptual issues. Can we call a gene 'good' or 'bad', 'superior' of 'inferior'? Is a boy who is detected to have the gene of Huntington's chorea or Alzheimer disease a patient? What should the term 'eugenics' mean? What do the terms such as 'gene therapy', 'treatment' and 'enhancement' and 'human cloning' mean etc.? The research of human genome and its application caused and will cause ethical issues. Can human genome research and its application be used for eugenics, or only for the treatment and prevention of diseases? Must the principle of informed consent/choice be insisted in human genome research and its application? How to protecting gene privacy and combating the discrimination on the basis of genes? How to promote the quality between persons, harmony between ethnic groups and peace between countries? How to establish a fair, just, equal and equitable relationship between developing and developed countries in regarding to human genome research and its application?

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

    Directory of Open Access Journals (Sweden)

    Mangion Jonathan

    2009-10-01

    Full Text Available Abstract 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

  13. Genome-Wide Association Studies of the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Emily R Davenport

    Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

  14. Site-Specific Genome Engineering in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Merkert, Sylvia; Martin, Ulrich

    2016-06-24

    The possibility to generate patient-specific induced pluripotent stem cells (iPSCs) offers an unprecedented potential of applications in clinical therapy and medical research. Human iPSCs and their differentiated derivatives are tools for diseases modelling, drug discovery, safety pharmacology, and toxicology. Moreover, they allow for the engineering of bioartificial tissue and are promising candidates for cellular therapies. For many of these applications, the ability to genetically modify pluripotent stem cells (PSCs) is indispensable, but efficient site-specific and safe technologies for genetic engineering of PSCs were developed only recently. By now, customized engineered nucleases provide excellent tools for targeted genome editing, opening new perspectives for biomedical research and cellular therapies.

  15. The impact of the human genome project on risk assessment

    International Nuclear Information System (INIS)

    Katarzyna Doerffer; Paul Unrau.

    1996-01-01

    The radiation protection approach to risk assessment assumes that cancer induction following radiation exposure is purely random. Present risk assessment methods derive risk from cancer incidence frequencies in exposed populations and associate disease outcomes totally with the level of exposure to ionizing red aeon. Exposure defines a risk factor that affects the probability of the disease outcome. But cancer risk can be affected by other risk factors such as underlying genetic factors (predisposition) of the exposed organism. These genetic risk factors are now becoming available for incorporation into ionizing radiation risk assessment Progress in the Human Genome Project (HOP) will lead to direct assays to measure the effects of genetic risk determinants in disease outcomes. When all genetic risk determinants are known and incorporated into risk assessment it will be possible to reevaluate the role of ionizing radiation in the causation of cancer. (author)

  16. Life Sciences Division and Center for Human Genome Studies 1994

    Energy Technology Data Exchange (ETDEWEB)

    Cram, L.S.; Stafford, C. [comp.

    1995-09-01

    This report summarizes the research and development activities of the Los Alamos National Laboratory`s Life Sciences Division and the biological aspects of the Center for Human Genome Studies for the calendar year 1994. The technical portion of the report is divided into two parts, (1) selected research highlights and (2) research projects and accomplishments. The research highlights provide a more detailed description of a select set of projects. A technical description of all projects is presented in sufficient detail so that the informed reader will be able to assess the scope and significance of each project. Summaries useful to the casual reader desiring general information have been prepared by the group leaders and appear in each group overview. Investigators on the staff of the Life Sciences Division will be pleased to provide further information.

  17. Complete Genome Sequence of Treponema paraluiscuniculi, Strain Cuniculi A: The Loss of Infectivity to Humans Is Associated with Genome Decay

    Science.gov (United States)

    Šmajs, David; Zobaníková, Marie; Strouhal, Michal; Čejková, Darina; Dugan-Rocha, Shannon; Pospíšilová, Petra; Norris, Steven J.; Albert, Tom; Qin, Xiang; Hallsworth-Pepin, Kym; Buhay, Christian; Muzny, Donna M.; Chen, Lei; Gibbs, Richard A.; Weinstock, George M.

    2011-01-01

    Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84) affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9%) of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits) during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies. PMID:21655244

  18. Complete genome sequence of Treponema paraluiscuniculi, strain Cuniculi A: the loss of infectivity to humans is associated with genome decay.

    Directory of Open Access Journals (Sweden)

    David Šmajs

    Full Text Available Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp, arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51. In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84 affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9% of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies.

  19. Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples

    Directory of Open Access Journals (Sweden)

    Maley Carlo C

    2008-10-01

    Full Text Available Abstract Background Genomes store information for building and maintaining organisms. Complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes. Results We have analyzed aspects of the information content of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli (K-12 genomes. Virtually all possible (> 98% 12 bp oligomers appear in vertebrate genomes while 98% to D. melanogaster (12–17 bp, C. elegans (11–17 bp, A. thaliana (11–17 bp, S. cerevisiae (10–16 bp and E. coli (9–15 bp. Frequencies of unique oligomers in the genomes follow similar patterns. We identified a set of 2.6 M 15-mers that are more than 1 nucleotide different from all 15-mers in the human genome and so could be used as probes to detect microbes in human samples. In a human sample, these probes would detect 100% of the 433 currently fully sequenced prokaryotes and 75% of the 3065 fully sequenced viruses. The human genome is significantly more compact in sequence space than a random genome. We identified the most frequent 5- to 20-mers in the human genome, which may prove useful as PCR primers. We also identified a bacterium, Anaeromyxobacter dehalogenans, which has an exceptionally low diversity of oligomers given the size of its genome and its GC content. The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes. However chromosomes 1, 2, 9, 12 and 14 have a relatively high proportion of coding DNA without high entropy, and chromosome 20 is the opposite with a low frequency of coding regions but relatively high entropy. Conclusion Measures of the frequency of oligomers are useful for designing PCR assays and for identifying chromosomes and organisms with hidden structure that had not been previously recognized. This information may be used to detect

  20. Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples

    Science.gov (United States)

    Liu, Zhandong; Venkatesh, Santosh S; Maley, Carlo C

    2008-01-01

    Background Genomes store information for building and maintaining organisms. Complete sequencing of many genomes provides the opportunity to study and compare global information properties of those genomes. Results We have analyzed aspects of the information content of Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Saccharomyces cerevisiae, and Escherichia coli (K-12) genomes. Virtually all possible (> 98%) 12 bp oligomers appear in vertebrate genomes while 98% to < 2% of possible oligomers in D. melanogaster (12–17 bp), C. elegans (11–17 bp), A. thaliana (11–17 bp), S. cerevisiae (10–16 bp) and E. coli (9–15 bp). Frequencies of unique oligomers in the genomes follow similar patterns. We identified a set of 2.6 M 15-mers that are more than 1 nucleotide different from all 15-mers in the human genome and so could be used as probes to detect microbes in human samples. In a human sample, these probes would detect 100% of the 433 currently fully sequenced prokaryotes and 75% of the 3065 fully sequenced viruses. The human genome is significantly more compact in sequence space than a random genome. We identified the most frequent 5- to 20-mers in the human genome, which may prove useful as PCR primers. We also identified a bacterium, Anaeromyxobacter dehalogenans, which has an exceptionally low diversity of oligomers given the size of its genome and its GC content. The entropy of coding regions in the human genome is significantly higher than non-coding regions and chromosomes. However chromosomes 1, 2, 9, 12 and 14 have a relatively high proportion of coding DNA without high entropy, and chromosome 20 is the opposite with a low frequency of coding regions but relatively high entropy. Conclusion Measures of the frequency of oligomers are useful for designing PCR assays and for identifying chromosomes and organisms with hidden structure that had not been previously recognized. This information may be used to

  1. Stakeholder consultation insights on the future of genomics at the clinical-public health interface.

    Science.gov (United States)

    Modell, Stephen M; Kardia, Sharon L R; Citrin, Toby

    2014-05-01

    In summer 2011, the Centers for Disease Control and Prevention Office of Public Health Genomics conducted a stakeholder consultation, administered by the University of Michigan Center for Public Health and Community Genomics, and Genetic Alliance, to recommend priorities for public health genomics from 2012 through 2017. Sixty-two responses from health professionals, administrators, and members of the public were pooled with 2 sets of key informant interviews and 3 discussion groups. NVivo 9 and manual methods were used to organize themes. This review offers an interim analysis of progress with respect to the final recommendations, which demonstrated a strong interest in moving genomic discoveries toward implementation and comparative effectiveness (T3/T4) translational research. A translational research continuum exists with familial breast and ovarian cancer at one end and prostate cancer at the other. Cascade screening for inherited arrhythmia syndromes and hypercholesterolemia lags stakeholder recommendations in the United States but not in Europe; implementation of health service-based screening for Lynch syndrome, and integration into electronic health information systems, is on pace with the recommended timeline. A number of options exist to address deficits in the funding of translational research, particularly for oncogenomic gene expression profiling. The goal of personalized risk assessment necessitates both research progress (eg, in whole genome sequencing, as well as provider education in the differentiation of low- vs high-risk status. The public health approach supports an emphasis on genetic test validation while endorsing clinical translation research inclusion of an environmental and population-based perspective. Copyright © 2014 Mosby, Inc. All rights reserved.

  2. Genome-Wide Prediction and Analysis of 3D-Domain Swapped Proteins in the Human Genome from Sequence Information.

    Science.gov (United States)

    Upadhyay, Atul Kumar; Sowdhamini, Ramanathan

    2016-01-01

    3D-domain swapping is one of the mechanisms of protein oligomerization and the proteins exhibiting this phenomenon have many biological functions. These proteins, which undergo domain swapping, have acquired much attention owing to their involvement in human diseases, such as conformational diseases, amyloidosis, serpinopathies, proteionopathies etc. Early realisation of proteins in the whole human genome that retain tendency to domain swap will enable many aspects of disease control management. Predictive models were developed by using machine learning approaches with an average accuracy of 78% (85.6% of sensitivity, 87.5% of specificity and an MCC value of 0.72) to predict putative domain swapping in protein sequences. These models were applied to many complete genomes with special emphasis on the human genome. Nearly 44% of the protein sequences in the human genome were predicted positive for domain swapping. Enrichment analysis was performed on the positively predicted sequences from human genome for their domain distribution, disease association and functional importance based on Gene Ontology (GO). Enrichment analysis was also performed to infer a better understanding of the functional importance of these sequences. Finally, we developed hinge region prediction, in the given putative domain swapped sequence, by using important physicochemical properties of amino acids.

  3. A map of human genome variation from population-scale sequencing.

    Science.gov (United States)

    Abecasis, Gonçalo R; Altshuler, David; Auton, Adam; Brooks, Lisa D; Durbin, Richard M; Gibbs, Richard A; Hurles, Matt E; McVean, Gil A

    2010-10-28

    The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.

  4. Cognitive genomics: Linking genes to behavior in the human brain

    Directory of Open Access Journals (Sweden)

    Genevieve Konopka

    2017-02-01

    Full Text Available Correlations of genetic variation in DNA with functional brain activity have already provided a starting point for delving into human cognitive mechanisms. However, these analyses do not provide the specific genes driving the associations, which are complicated by intergenic localization as well as tissue-specific epigenetics and expression. The use of brain-derived expression datasets could build upon the foundation of these initial genetic insights and yield genes and molecular pathways for testing new hypotheses regarding the molecular bases of human brain development, cognition, and disease. Thus, coupling these human brain gene expression data with measurements of brain activity may provide genes with critical roles in brain function. However, these brain gene expression datasets have their own set of caveats, most notably a reliance on postmortem tissue. In this perspective, I summarize and examine the progress that has been made in this realm to date, and discuss the various frontiers remaining, such as the inclusion of cell-type-specific information, additional physiological measurements, and genomic data from patient cohorts.

  5. In-silico human genomics with GeneCards

    Directory of Open Access Journals (Sweden)

    Stelzer Gil

    2011-10-01

    Full Text Available Abstract Since 1998, the bioinformatics, systems biology, genomics and medical communities have enjoyed a synergistic relationship with the GeneCards database of human genes (http://www.genecards.org. This human gene compendium was created to help to introduce order into the increasing chaos of information flow. As a consequence of viewing details and deep links related to specific genes, users have often requested enhanced capabilities, such that, over time, GeneCards has blossomed into a suite of tools (including GeneDecks, GeneALaCart, GeneLoc, GeneNote and GeneAnnot for a variety of analyses of both single human genes and sets thereof. In this paper, we focus on inhouse and external research activities which have been enabled, enhanced, complemented and, in some cases, motivated by GeneCards. In turn, such interactions have often inspired and propelled improvements in GeneCards. We describe here the evolution and architecture of this project, including examples of synergistic applications in diverse areas such as synthetic lethality in cancer, the annotation of genetic variations in disease, omics integration in a systems biology approach to kidney disease, and bioinformatics tools.

  6. Medicina genómica aplicada a la salud pública An overview in genomic medicine and public health

    Directory of Open Access Journals (Sweden)

    Ana Burguete

    2009-01-01

    Full Text Available La genómica, visualizada como una disciplina científica encargada del mapeo, secuenciación y análisis de los genomas, ha facilitado la identificación y comprensión de las formas de organización y función de los genes de los organismos, lo cual ha generado un amplio conocimiento de la estructura y la función de los genomas. La influencia de la genómica en la medicina ha creado una nueva visión acerca de la forma de percibir los episodios patológicos y fisiológicos, tras conocer la influencia de las variaciones genéticas sobre la susceptibilidad a la enfermedad. En la salud pública, mediante la epidemiología genética, el conocimiento genético ha promovido acciones individuales y poblacionales para evaluar el efecto de la distribución de los determinantes genéticos y su interacción con factores ambientales en la etiología de las enfermedades humanas. De modo adicional, la medicina genómica propone nuevos sistemas de diagnóstico, relaciones genéticas y alteraciones alimenticias, respuesta específica a diversos medicamentos y diseño de nuevos fármacos para grupos susceptibles. Sin embargo, los grandes avances de la medicina genómica en el campo de la salud aún son sólo promisorios.Genomics, as a scientific discipline responsible for genome maps, sequencing and functional analysis of genomes, allows for continually expanding knowledge of the structure and function of genomes. The influence of genomics on medicine generates a new perspective for how we perceive health and disease, knowing the influence of genetic variations on susceptibility to disease. In the area of public health, genetic epidemiology translates genetic knowledge into individual and public actions, evaluating the effect of the distribution of genetic determinants and their interaction with environmental factors involved in the etiology of human diseases. In addition, genomic medicine suggests new diagnostic systems, genetic associations and nutritional

  7. Viral dark matter and virus–host interactions resolved from publicly available microbial genomes

    Science.gov (United States)

    Roux, Simon; Hallam, Steven J; Woyke, Tanja; Sullivan, Matthew B

    2015-01-01

    The ecological importance of viruses is now widely recognized, yet our limited knowledge of viral sequence space and virus–host interactions precludes accurate prediction of their roles and impacts. In this study, we mined publicly available bacterial and archaeal genomic data sets to identify 12,498 high-confidence viral genomes linked to their microbial hosts. These data augment public data sets 10-fold, provide first viral sequences for 13 new bacterial phyla including ecologically abundant phyla, and help taxonomically identify 7–38% of ‘unknown’ sequence space in viromes. Genome- and network-based classification was largely consistent with accepted viral taxonomy and suggested that (i) 264 new viral genera were identified (doubling known genera) and (ii) cross-taxon genomic recombination is limited. Further analyses provided empirical data on extrachromosomal prophages and coinfection prevalences, as well as evaluation of in silico virus–host linkage predictions. Together these findings illustrate the value of mining viral signal from microbial genomes. DOI: http://dx.doi.org/10.7554/eLife.08490.001 PMID:26200428

  8. A genomic point-of-view on environmental factors influencing the human brain methylome.

    Science.gov (United States)

    LaSalle, Janine M

    2011-07-01

    The etiologic paradigm of complex human disorders such as autism is that genetic and environmental risk factors are independent and additive, but the interactive effects at the epigenetic interface are largely ignored. Genomic technologies have radically changed perspective on the human genome and how the epigenetic interface may impact complex human disorders. Here, I review recent genomic, environmental, and epigenetic findings that suggest a new paradigm of "integrative genomics" in which genetic variation in genomic size may be impacted by dietary and environmental factors that influence the genomic saturation of DNA methylation. Human genomes are highly repetitive, but the interface of large-scale genomic differences with environmental factors that alter the DNA methylome such as dietary folate is under-explored. In addition to obvious direct effects of some environmental toxins on the genome by causing chromosomal breaks, non-mutagenic toxin exposures correlate with DNA hypomethylation that can lead to rearrangements between repeats or increased retrotransposition. Since human neurodevelopment appears to be particularly sensitive to alterations in epigenetic pathways, a further focus will be on how developing neurons may be particularly impacted by even subtle alterations to DNA methylation and proposing new directions towards understanding the quixotic etiology of autism by integrative genomic approaches.

  9. A BAC clone fingerprinting approach to the detection of human genome rearrangements

    Science.gov (United States)

    Krzywinski, Martin; Bosdet, Ian; Mathewson, Carrie; Wye, Natasja; Brebner, Jay; Chiu, Readman; Corbett, Richard; Field, Matthew; Lee, Darlene; Pugh, Trevor; Volik, Stas; Siddiqui, Asim; Jones, Steven; Schein, Jacquie; Collins, Collin; Marra, Marco

    2007-01-01

    We present a method, called fingerprint profiling (FPP), that uses restriction digest fingerprints of bacterial artificial chromosome clones to detect and classify rearrangements in the human genome. The approach uses alignment of experimental fingerprint patterns to in silico digests of the sequence assembly and is capable of detecting micro-deletions (1-5 kb) and balanced rearrangements. Our method has compelling potential for use as a whole-genome method for the identification and characterization of human genome rearrangements. PMID:17953769

  10. Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases.

    Science.gov (United States)

    Gundogdu, Aycan; Nalbantoglu, Ufuk

    2017-04-01

    A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome-human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis.

  11. A Genomics-Based Classification of Human Lung Tumors

    NARCIS (Netherlands)

    Seidel, Danila; Zander, Thomas; Heukamp, Lukas C.; Peifer, Martin; Bos, Marc; Fernandez-Cuesta, Lynnette; Leenders, Frauke; Lu, Xin; Ansen, Sascha; Gardizi, Masyar; Nguyen, Chau; Berg, Johannes; Russell, Prudence; Wainer, Zoe; Schildhaus, Hans-Ulrich; Rogers, Toni-Maree; Solomon, Benjamin; Pao, William; Carter, Scott L.; Getz, Gad; Hayes, D. Neil; Wilkerson, Matthew D.; Thunnissen, Erik; Travis, William D.; Perner, Sven; Wright, Gavin; Brambilla, Elisabeth; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman; Gabler, Franziska; Wilkening, Ines; Mueller, Christian; Dahmen, Ilona; Menon, Roopika; Koenig, Katharina; Albus, Kerstin; Merkelbach-Bruse, Sabine; Fassunke, Jana; Schmitz, Katja; Kuenstlinger, Helen; Kleine, Michaela; Binot, Elke; Querings, Silvia; Altmueller, Janine; Boessmann, Ingelore; Nuemberg, Peter; Schneider, Peter; Groen, Harry; Timens, Wim

    2013-01-01

    We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic

  12. Understanding the Human Genome Project: Using Stations to Provide a Comprehensive Overview

    Science.gov (United States)

    Soto, Julio G.

    2005-01-01

    A lesson was designed for lower division general education, non-major biology lecture-only course that included the historical and scientific context, some of the skills used to study the human genome, results, conclusions and ethical consideration. Students learn to examine and compare the published Human Genome maps, and employ the strategies…

  13. Whole genome analysis of Klebsiella pneumoniae T2-1-1 from human oral cavity

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2016-03-01

    Full Text Available Klebsiella pneumoniae T2-1-1 was isolated from the human tongue debris and subjected to whole genome sequencing on HiSeq platform and annotated on RAST. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession JAQL00000000. Keywords: Human tongue surface, Oral cavity, Oral bacteria, Virulence

  14. Human-specific protein isoforms produced by novel splice sites in the human genome after the human-chimpanzee divergence

    Directory of Open Access Journals (Sweden)

    Kim Dong Seon

    2012-11-01

    Full Text Available Abstract Background Evolution of splice sites is a well-known phenomenon that results in transcript diversity during human evolution. Many novel splice sites are derived from repetitive elements and may not contribute to protein products. Here, we analyzed annotated human protein-coding exons and identified human-specific splice sites that arose after the human-chimpanzee divergence. Results We analyzed multiple alignments of the annotated human protein-coding exons and their respective orthologous mammalian genome sequences to identify 85 novel splice sites (50 splice acceptors and 35 donors in the human genome. The novel protein-coding exons, which are expressed either constitutively or alternatively, produce novel protein isoforms by insertion, deletion, or frameshift. We found three cases in which the human-specific isoform conferred novel molecular function in the human cells: the human-specific IMUP protein isoform induces apoptosis of the trophoblast and is implicated in pre-eclampsia; the intronization of a part of SMOX gene exon produces inactive spermine oxidase; the human-specific NUB1 isoform shows reduced interaction with ubiquitin-like proteins, possibly affecting ubiquitin pathways. Conclusions Although the generation of novel protein isoforms does not equate to adaptive evolution, we propose that these cases are useful candidates for a molecular functional study to identify proteomic changes that might bring about novel phenotypes during human evolution.

  15. Functional assessment of human enhancer activities using whole-genome STARR-sequencing.

    Science.gov (United States)

    Liu, Yuwen; Yu, Shan; Dhiman, Vineet K; Brunetti, Tonya; Eckart, Heather; White, Kevin P

    2017-11-20

    Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome.  In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity. This approach builds upon previously developed STARR-seq in the fly genome and CapSTARR-seq techniques in targeted human genomic regions. With an improved library preparation strategy, our approach greatly increases the library complexity per unit of starting material, which makes it feasible and cost-effective to explore the landscape of regulatory activity in the much larger human genome. In addition to our ability to identify active, accessible enhancers located in open chromatin regions, we can also detect sequences with the potential for enhancer activity that are located in inaccessible, closed chromatin regions. When treated with the histone deacetylase inhibitor, Trichostatin A, genes nearby this latter class of enhancers are up-regulated, demonstrating the potential for endogenous functionality of these regulatory elements. WHG-STARR-seq provides an improved approach to current pipelines for analysis of high complexity genomes to gain a better understanding of the intricacies of transcriptional regulation.

  16. Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Le Zhan

    Full Text Available Farnesoid X receptor (FXR, NR1H4 is a ligand-activated transcription factor, belonging to the nuclear receptor superfamily. FXR is highly expressed in the liver and is essential in regulating bile acid homeostasis. FXR deficiency is implicated in numerous liver diseases and mice with modulation of FXR have been used as animal models to study liver physiology and pathology. We have reported genome-wide binding of FXR in mice by chromatin immunoprecipitation - deep sequencing (ChIP-seq, with results indicating that FXR may be involved in regulating diverse pathways in liver. However, limited information exists for the functions of human FXR and the suitability of using murine models to study human FXR functions.In the current study, we performed ChIP-seq in primary human hepatocytes (PHHs treated with a synthetic FXR agonist, GW4064 or DMSO control. In parallel, RNA deep sequencing (RNA-seq and RNA microarray were performed for GW4064 or control treated PHHs and wild type mouse livers, respectively.ChIP-seq showed similar profiles of genome-wide FXR binding in humans and mice in terms of motif analysis and pathway prediction. However, RNA-seq and microarray showed more different transcriptome profiles between PHHs and mouse livers upon GW4064 treatment.In summary, we have established genome-wide human FXR binding and transcriptome profiles. These results will aid in determining the human FXR functions, as well as judging to what level the mouse models could be used to study human FXR functions.

  17. The complete genome sequence and analysis of the human pathogen Campylobacter lari

    DEFF Research Database (Denmark)

    Miller, WG; Wang, G; Binnewies, Tim Terence

    2008-01-01

    Campylobacter lari is a member of the epsilon subdivision of the Proteobacteria and is part of the thermotolerant Campylobacter group, a clade that includes the human pathogen C. jejuni. Here we present the complete genome sequence of the human clinical isolate, C. lari RM2100. The genome of strain...... RM2100 is approximately 1.53 Mb and includes the 46 kb megaplasmid pCL2100. Also present within the strain RM2100 genome is a 36 kb putative prophage, termed CLIE1, which is similar to CJIE4, a putative prophage present within the C. jejuni RM1221 genome. Nearly all (90%) of the gene content...... in strain RM2100 is similar to genes present in the genomes of other characterized thermotolerant campylobacters. However, several genes involved in amino acid biosynthesis and energy metabolism, identified previously in other Campylobacter genomes, are absent from the C. lari RM2100 genome. Therefore, C...

  18. Meiotic gene-conversion rate and tract length variation in the human genome.

    Science.gov (United States)

    Padhukasahasram, Badri; Rannala, Bruce

    2013-02-27

    Meiotic recombination occurs in the form of two different mechanisms called crossing-over and gene-conversion and both processes have an important role in shaping genetic variation in populations. Although variation in crossing-over rates has been studied extensively using sperm-typing experiments, pedigree studies and population genetic approaches, our knowledge of variation in gene-conversion parameters (ie, rates and mean tract lengths) remains far from complete. To explore variability in population gene-conversion rates and its relationship to crossing-over rate variation patterns, we have developed and validated using coalescent simulations a comprehensive Bayesian full-likelihood method that can jointly infer crossing-over and gene-conversion rates as well as tract lengths from population genomic data under general variable rate models with recombination hotspots. Here, we apply this new method to SNP data from multiple human populations and attempt to characterize for the first time the fine-scale variation in gene-conversion parameters along the human genome. We find that the estimated ratio of gene-conversion to crossing-over rates varies considerably across genomic regions as well as between populations. However, there is a great degree of uncertainty associated with such estimates. We also find substantial evidence for variation in the mean conversion tract length. The estimated tract lengths did not show any negative relationship with the local heterozygosity levels in our analysis.European Journal of Human Genetics advance online publication, 27 February 2013; doi:10.1038/ejhg.2013.30.

  19. 137 ancient human genomes from across the Eurasian steppes.

    Science.gov (United States)

    Damgaard, Peter de Barros; Marchi, Nina; Rasmussen, Simon; Peyrot, Michaël; Renaud, Gabriel; Korneliussen, Thorfinn; Moreno-Mayar, J Víctor; Pedersen, Mikkel Winther; Goldberg, Amy; Usmanova, Emma; Baimukhanov, Nurbol; Loman, Valeriy; Hedeager, Lotte; Pedersen, Anders Gorm; Nielsen, Kasper; Afanasiev, Gennady; Akmatov, Kunbolot; Aldashev, Almaz; Alpaslan, Ashyk; Baimbetov, Gabit; Bazaliiskii, Vladimir I; Beisenov, Arman; Boldbaatar, Bazartseren; Boldgiv, Bazartseren; Dorzhu, Choduraa; Ellingvag, Sturla; Erdenebaatar, Diimaajav; Dajani, Rana; Dmitriev, Evgeniy; Evdokimov, Valeriy; Frei, Karin M; Gromov, Andrey; Goryachev, Alexander; Hakonarson, Hakon; Hegay, Tatyana; Khachatryan, Zaruhi; Khaskhanov, Ruslan; Kitov, Egor; Kolbina, Alina; Kubatbek, Tabaldiev; Kukushkin, Alexey; Kukushkin, Igor; Lau, Nina; Margaryan, Ashot; Merkyte, Inga; Mertz, Ilya V; Mertz, Viktor K; Mijiddorj, Enkhbayar; Moiyesev, Vyacheslav; Mukhtarova, Gulmira; Nurmukhanbetov, Bekmukhanbet; Orozbekova, Z; Panyushkina, Irina; Pieta, Karol; Smrčka, Václav; Shevnina, Irina; Logvin, Andrey; Sjögren, Karl-Göran; Štolcová, Tereza; Tashbaeva, Kadicha; Tkachev, Alexander; Tulegenov, Turaly; Voyakin, Dmitriy; Yepiskoposyan, Levon; Undrakhbold, Sainbileg; Varfolomeev, Victor; Weber, Andrzej; Kradin, Nikolay; Allentoft, Morten E; Orlando, Ludovic; Nielsen, Rasmus; Sikora, Martin; Heyer, Evelyne; Kristiansen, Kristian; Willerslev, Eske

    2018-05-09

    For thousands of years the Eurasian steppes have been a centre of human migrations and cultural change. Here we sequence the genomes of 137 ancient humans (about 1× average coverage), covering a period of 4,000 years, to understand the population history of the Eurasian steppes after the Bronze Age migrations. We find that the genetics of the Scythian groups that dominated the Eurasian steppes throughout the Iron Age were highly structured, with diverse origins comprising Late Bronze Age herders, European farmers and southern Siberian hunter-gatherers. Later, Scythians admixed with the eastern steppe nomads who formed the Xiongnu confederations, and moved westward in about the second or third century BC, forming the Hun traditions in the fourth-fifth century AD, and carrying with them plague that was basal to the Justinian plague. These nomads were further admixed with East Asian groups during several short-term khanates in the Medieval period. These historical events transformed the Eurasian steppes from being inhabited by Indo-European speakers of largely West Eurasian ancestry to the mostly Turkic-speaking groups of the present day, who are primarily of East Asian ancestry.

  20. Meta genome-wide network from functional linkages of genes in human gut microbial ecosystems.

    Science.gov (United States)

    Ji, Yan; Shi, Yixiang; Wang, Chuan; Dai, Jianliang; Li, Yixue

    2013-03-01

    The human gut microbial ecosystem (HGME) exerts an important influence on the human health. In recent researches, meta-genomics provided deep insights into the HGME in terms of gene contents, metabolic processes and genome constitutions of meta-genome. Here we present a novel methodology to investigate the HGME on the basis of a set of functionally coupled genes regardless of their genome origins when considering the co-evolution properties of genes. By analyzing these coupled genes, we showed some basic properties of HGME significantly associated with each other, and further constructed a protein interaction map of human gut meta-genome to discover some functional modules that may relate with essential metabolic processes. Compared with other studies, our method provides a new idea to extract basic function elements from meta-genome systems and investigate complex microbial environment by associating its biological traits with co-evolutionary fingerprints encoded in it.

  1. Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.

    Directory of Open Access Journals (Sweden)

    Christopher A Desjardins

    2011-10-01

    Full Text Available Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18 and one strain of Paracoccidioides lutzii (Pb01. These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic

  2. Integrated Public Education, Fertility and Human Capital

    Science.gov (United States)

    Azarnert, Leonid V.

    2014-01-01

    This paper analyzes the consequences of integration in public education. I show that the flight from the integrated multicultural public schools to private education increases private educational expenditures and, as a result, decreases fertility among more affluent parents whose children flee. In contrast, among less prosperous parents…

  3. A map to a new treasure island: the human genome and the concept of common heritage.

    Science.gov (United States)

    Byk, C

    1998-06-01

    While the 1970's have been called the environmental years, the 1990's could be seen as the genome years. As the challenge to map and to sequence the human genome mobilized the scientific community, risks and benefits of information and uses that would derive from this project have also raised ethical issues at the international level. The particular interest of the 1997 UNESCO Declaration relies on the fact that it emphasizes both the scientific importance of genetics and the appropriate reinforcement of human rights in this area. It considers the human genome, at least symbolically, as the common heritage of humanity.

  4. Influencing governance of a public-private partnership in plant genomics: The societal interface group as a new instrument for public involvement.

    Science.gov (United States)

    Hanssen, Lucien; Gremmen, Bart

    2013-08-01

    The Centre for BioSystems Genomics (CBSG) is a Dutch public-private partnership in plant genomics active in potato and tomato research and exploitation. Its Societal Interface Group (SIG) has been developed to inform its communication strategy and governance practice. This new instrument identifies and discusses early signals from society by bringing together people from different societal backgrounds with members of CBSG management. This interactive learning process facilitates the inclusion of public concerns and needs in scientific developments in the field of plant genomics, and simultaneously enables genomics scientists to search for more societal aims, meanings, and starting points for their research agenda. Analysis of the SIG sessions revealed that the input of public expertise is not threatening or irrational, but provides the opportunity to harness the creative potential of future users highly relevant for the development of societal practices in which plant genomics plays a role.

  5. Public Participation in Times of Privatisation: A Human Rights Analysis

    OpenAIRE

    Temperman, Jeroen

    2011-01-01

    markdownabstract__Abstract__ Privatisation may not only affect the enjoyment of the right to public participation itself, but might also impact other substantive rights. This article charts some of the ramifications of privatisation in relation to individual human rights as enshrined in international human rights conventions, with a particular focus on the impact privatisation has on the right to public participation. The right to public participation can be seen as both an example of a funda...

  6. On the immortality of television sets: "function" in the human genome according to the evolution-free gospel of ENCODE.

    Science.gov (United States)

    Graur, Dan; Zheng, Yichen; Price, Nicholas; Azevedo, Ricardo B R; Zufall, Rebecca A; Elhaik, Eran

    2013-01-01

    A recent slew of ENCyclopedia Of DNA Elements (ENCODE) Consortium publications, specifically the article signed by all Consortium members, put forward the idea that more than 80% of the human genome is functional. This claim flies in the face of current estimates according to which the fraction of the genome that is evolutionarily conserved through purifying selection is less than 10%. Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 - 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these "functional" regions or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means, chiefly by employing the seldom used "causal role" definition of biological function and then applying it inconsistently to different biochemical properties, by committing a logical fallacy known as "affirming the consequent," by failing to appreciate the crucial difference between "junk DNA" and "garbage DNA," by using analytical methods that yield biased errors and inflate estimates of functionality, by favoring statistical sensitivity over specificity, and by emphasizing statistical significance rather than the magnitude of the effect. Here, we detail the many logical and methodological transgressions involved in assigning functionality to almost every nucleotide in the human genome. The ENCODE results were predicted by one of its authors to necessitate the rewriting of textbooks. We agree, many textbooks dealing with marketing, mass-media hype, and public relations may well have to be rewritten.

  7. Genomics as public health? Community genetics and the challenge of personalised medicine in Cuba.

    Science.gov (United States)

    Gibbon, Sahra

    2009-08-01

    Making use of a comparative perspective on the emergence of 'breast cancer genetics' in the different cultural context of the UK and Cuba, this article examines the tensions between the modern promise of genomics as personalised medicine and a commitment to public health. Focusing primarily on the Cuba context and drawing on ethnographic research as part of a collaborative project working with genetic professionals and publics, the article examines the particular technologies, identities and socialities at stake in an emerging and evolving field of genetic medicine. It highlights how long-standing continuities in the commitment to the equitable provision of public health, particularly as this relates to 'family medicine', are central to understanding the scope and expansion of 'community genetics' interventions, even when at the level of local practice, public health is also now subject to the unequal dynamics of economic necessity through the working out of 'lo informal'. Illuminating the different ways agency, risk, responsibility, citizenship and activism get configured by and between publics and health professionals in Cuba, the article reveals the challenges and opportunities posed by predictive genomic medicine in relation to the dynamic and shifting terrain of public health.

  8. Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.

    Directory of Open Access Journals (Sweden)

    Shinya Akatsuka

    Full Text Available Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.

  9. Genome sequences and comparative genomics of two Lactobacillus ruminis strains from the bovine and human intestinal tracts

    LENUS (Irish Health Repository)

    2011-08-30

    Abstract Background The genus Lactobacillus is characterized by an extraordinary degree of phenotypic and genotypic diversity, which recent genomic analyses have further highlighted. However, the choice of species for sequencing has been non-random and unequal in distribution, with only a single representative genome from the L. salivarius clade available to date. Furthermore, there is no data to facilitate a functional genomic analysis of motility in the lactobacilli, a trait that is restricted to the L. salivarius clade. Results The 2.06 Mb genome of the bovine isolate Lactobacillus ruminis ATCC 27782 comprises a single circular chromosome, and has a G+C content of 44.4%. In silico analysis identified 1901 coding sequences, including genes for a pediocin-like bacteriocin, a single large exopolysaccharide-related cluster, two sortase enzymes, two CRISPR loci and numerous IS elements and pseudogenes. A cluster of genes related to a putative pilin was identified, and shown to be transcribed in vitro. A high quality draft assembly of the genome of a second L. ruminis strain, ATCC 25644 isolated from humans, suggested a slightly larger genome of 2.138 Mb, that exhibited a high degree of synteny with the ATCC 27782 genome. In contrast, comparative analysis of L. ruminis and L. salivarius identified a lack of long-range synteny between these closely related species. Comparison of the L. salivarius clade core proteins with those of nine other Lactobacillus species distributed across 4 major phylogenetic groups identified the set of shared proteins, and proteins unique to each group. Conclusions The genome of L. ruminis provides a comparative tool for directing functional analyses of other members of the L. salivarius clade, and it increases understanding of the divergence of this distinct Lactobacillus lineage from other commensal lactobacilli. The genome sequence provides a definitive resource to facilitate investigation of the genetics, biochemistry and host

  10. Genome-wide identification of coding and non-coding conserved sequence tags in human and mouse genomes

    Directory of Open Access Journals (Sweden)

    Maggi Giorgio P

    2008-06-01

    Full Text Available Abstract Background The accurate detection of genes and the identification of functional regions is still an open issue in the annotation of genomic sequences. This problem affects new genomes but also those of very well studied organisms such as human and mouse where, despite the great efforts, the inventory of genes and regulatory regions is far from complete. Comparative genomics is an effective approach to address this problem. Unfortunately it is limited by the computational requirements needed to perform genome-wide comparisons and by the problem of discriminating between conserved coding and non-coding sequences. This discrimination is often based (thus dependent on the availability of annotated proteins. Results In this paper we present the results of a comprehensive comparison of human and mouse genomes performed with a new high throughput grid-based system which allows the rapid detection of conserved sequences and accurate assessment of their coding potential. By detecting clusters of coding conserved sequences the system is also suitable to accurately identify potential gene loci. Following this analysis we created a collection of human-mouse conserved sequence tags and carefully compared our results to reliable annotations in order to benchmark the reliability of our classifications. Strikingly we were able to detect several potential gene loci supported by EST sequences but not corresponding to as yet annotated genes. Conclusion Here we present a new system which allows comprehensive comparison of genomes to detect conserved coding and non-coding sequences and the identification of potential gene loci. Our system does not require the availability of any annotated sequence thus is suitable for the analysis of new or poorly annotated genomes.

  11. Clinical Implications of Human Population Differences in Genome-wide Rates of Functional Genotypes

    Directory of Open Access Journals (Sweden)

    Ali eTorkamani

    2012-11-01

    Full Text Available There have been a number of recent successes in the use of whole genome sequencing and sophisticated bioinformatics techniques to identify pathogenic DNA sequence variants responsible for individual idiopathic congenital conditions. However, the success of this identification process is heavily influenced by the ancestry or genetic background of a patient with an idiopathic condition. This is so because potential pathogenic variants in a patient’s genome must be contrasted with variants in a reference set of genomes made up of other individuals’ genomes of the same ancestry as the patient. We explored the effect of ignoring the ancestries of both an individual patient and the individuals used to construct reference genomes. We pursued this exploration in two major steps. We first considered variation in the per-genome number and rates likely functional derived (i.e., non-ancestral, based on the chimp genome single nucleotide variants and small indels in 52 individual whole human genomes sampled from 10 different global populations. We took advantage of a suite of computational and bioinformatics techniques to predict the functional effect of over 24 million genomic variants, both coding and non-coding, across these genomes. We found that the typical human genome harbors ~5.5-6.1 million total derived variants, of which ~12,000 are likely to have a functional effect (~5000 coding and ~7000 non-coding. We also found that the rates of functional genotypes per the total number of genotypes in individual whole genomes differ dramatically between human populations. We then created tables showing how the use of comparator or reference genome panels comprised of genomes from individuals that do not have the same ancestral background as a patient can negatively impact pathogenic variant identification. Our results have important implications for clinical sequencing initiatives.

  12. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

    2012-01-01

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  13. Human Ageing Genomic Resources: Integrated databases and tools for the biology and genetics of ageing

    Science.gov (United States)

    Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E.; de Magalhães, João Pedro

    2013-01-01

    The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology. PMID:23193293

  14. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng

    2012-03-23

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  15. Influencing governance of a public-private partnership in plant genomics: The societal interface group as a new instrument for public involvement

    NARCIS (Netherlands)

    Hanssen, L.; Gremmen, B.

    2013-01-01

    The Centre for BioSystems Genomics (CBSG) is a Dutch public-private partnership in plant genomics active in potato and tomato research and exploitation. Its Societal Interface Group (SIG) has been developed to inform its communication strategy and governance practice. This new instrument identifies

  16. ELSI Bibliography: Ethical, legal and social implications of the Human Genome Project. 1994 Supplement

    Energy Technology Data Exchange (ETDEWEB)

    Yesley, M.S.; Ossorio, P.N. [comps.

    1994-09-01

    This report updates and expands the second edition of the ELSI Bibliography, published in 1993. The Bibliography and Supplement provides a comprehensive resource for identifying publications on the major topics related to the ethical, legal and social issues (ELSI) of the Human Genome Project. The Bibliography and Supplement are extracted from a database compiled at Los Alamos National Laboratory with the support of the Office of Energy Research, US Department of Energy. The second edition of the ELSI Bibliography was dated May 1993 but included publications added to the database until fall 1993. This Supplement reflects approximately 1,000 entries added to the database during the past year, bringing the total to approximately 7,000 entries. More than half of the new entries were published in the last year, and the remainder are earlier publications not previously included in the database. Most of the new entries were published in the academic and professional literature. The remainder are press reports from newspapers of record and scientific journals. The topical listing of the second edition has been followed in the Supplement, with a few changes. The topics of Cystic Fibrosis, Huntington`s Disease, and Sickle Cell Anemia have been combined in a single topic, Disorders. Also, all the entries published in the past year are included in a new topic, Publications: September 1993--September 1994, which provides a comprehensive view of recent reporting and commentary on the science and ELSI of genetics.

  17. A map of recent positive selection in the human genome.

    Directory of Open Access Journals (Sweden)

    Benjamin F Voight

    2006-03-01

    Full Text Available The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest approximately 250 signals of recent selection in each population.

  18. The genomic structure of the human UFO receptor.

    Science.gov (United States)

    Schulz, A S; Schleithoff, L; Faust, M; Bartram, C R; Janssen, J W

    1993-02-01

    Using a DNA transfection-tumorigenicity assay we have recently identified the UFO oncogene. It encodes a tyrosine kinase receptor characterized by the juxtaposition of two immunoglobulin-like and two fibronectin type III repeats in its extracellular domain. Here we describe the genomic organization of the human UFO locus. The UFO receptor is encoded by 20 exons that are distributed over a region of 44 kb. Different isoforms of UFO mRNA are generated by alternative splicing of exon 10 and differential usage of two imperfect polyadenylation sites resulting in the presence or absence of 1.5-kb 3' untranslated sequences. Primer extension and S1 nuclease analyses revealed multiple transcriptional initiation sites including a major site 169 bp upstream of the translation start site. The promoter region is GC rich, lacks TATA and CAAT boxes, but contains potential recognition sites for a variety of trans-acting factors, including Sp1, AP-2 and the cyclic AMP response element-binding protein. Proto-UFO and its oncogenic counterpart exhibit identical cDNA and promoter regions sequences. Possible modes of UFO activation are discussed.

  19. [Efficient genome editing in human pluripotent stem cells through CRISPR/Cas9].

    Science.gov (United States)

    Liu, Gai-gai; Li, Shuang; Wei, Yu-da; Zhang, Yong-xian; Ding, Qiu-rong

    2015-11-01

    The RNA-guided CRISPR (clustered regularly interspaced short palindromic repeat)-associated Cas9 nuclease has offered a new platform for genome editing with high efficiency. Here, we report the use of CRISPR/Cas9 technology to target a specific genomic region in human pluripotent stem cells. We show that CRISPR/Cas9 can be used to disrupt a gene by introducing frameshift mutations to gene coding region; to knock in specific sequences (e.g. FLAG tag DNA sequence) to targeted genomic locus via homology directed repair; to induce large genomic deletion through dual-guide multiplex. Our results demonstrate the versatile application of CRISPR/Cas9 in stem cell genome editing, which can be widely utilized for functional studies of genes or genome loci in human pluripotent stem cells.

  20. Public trust and 'ethics review' as a commodity: the case of Genomics England Limited and the UK's 100,000 genomes project.

    Science.gov (United States)

    Samuel, Gabrielle Natalie; Farsides, Bobbie

    2018-06-01

    The UK Chief Medical Officer's 2016 Annual Report, Generation Genome, focused on a vision to fully integrate genomics into all aspects of the UK's National Health Service (NHS). This process of integration, which has now already begun, raises a wide range of social and ethical concerns, many of which were discussed in the final Chapter of the report. This paper explores how the UK's 100,000 Genomes Project (100 kGP)-the catalyst for Generation Genome, and for bringing genomics into the NHS-is negotiating these ethical concerns. The UK's 100 kGP, promoted and delivered by Genomics England Limited (GEL), is an innovative venture aiming to sequence 100,000 genomes from NHS patients who have a rare disease, cancer, or an infectious disease. GEL has emphasised the importance of ethical governance and decision-making. However, some sociological critique argues that biomedical/technological organisations presenting themselves as 'ethical' entities do not necessarily reflect a space within which moral thinking occurs. Rather, the 'ethical work' conducted (and displayed) by organisations is more strategic, relating to the politics of the organisation and the need to build public confidence. We set out to explore whether GEL's ethical framework was reflective of this critique, and what this tells us more broadly about how genomics is being integrated into the NHS in response to the ethical and social concerns raised in Generation Genome. We do this by drawing on a series of 20 interviews with individuals associated with or working at GEL.

  1. Genome-wide analysis of the human Alu Yb-lineage

    Directory of Open Access Journals (Sweden)

    Carter Anthony B

    2004-03-01

    Full Text Available Abstract The Alu Yb-lineage is a 'young' primarily human-specific group of short interspersed element (SINE subfamilies that have integrated throughout the human genome. In this study, we have computationally screened the draft sequence of the human genome for Alu Yb-lineage subfamily members present on autosomal chromosomes. A total of 1,733 Yb Alu subfamily members have integrated into human autosomes. The average ages of Yb-lineage subfamilies, Yb7, Yb8 and Yb9, are estimated as 4.81, 2.39 and 2.32 million years, respectively. In order to determine the contribution of the Alu Yb-lineage to human genomic diversity, 1,202 loci were analysed using polymerase chain reaction (PCR-based assays, which amplify the genomic regions containing individual Yb-lineage subfamily members. Approximately 20 per cent of the Yb-lineage Alu elements are polymorphic for insertion presence/absence in the human genome. Fewer than 0.5 per cent of the Yb loci also demonstrate insertions at orthologous positions in non-human primate genomes. Genomic sequencing of these unusual loci demonstrates that each of the orthologous loci from non-human primate genomes contains older Y, Sg and Sx Alu family members that have been altered, through various mechanisms, into Yb8 sequences. These data suggest that Alu Yb-lineage subfamily members are largely restricted to the human genome. The high copy number, level of insertion polymorphism and estimated age indicate that members of the Alu Yb elements will be useful in a wide range of genetic analyses.

  2. De novo assembly of human genomes with massively parallel short read sequencing

    DEFF Research Database (Denmark)

    Li, Ruiqiang; Zhu, Hongmei; Ruan, Jue

    2010-01-01

    genomes from short read sequences. We successfully assembled both the Asian and African human genome sequences, achieving an N50 contig size of 7.4 and 5.9 kilobases (kb) and scaffold of 446.3 and 61.9 kb, respectively. The development of this de novo short read assembly method creates new opportunities...... for building reference sequences and carrying out accurate analyses of unexplored genomes in a cost-effective way....

  3. Efficient assembly of de novo human artificial chromosomes from large genomic loci

    Directory of Open Access Journals (Sweden)

    Stromberg Gregory

    2005-07-01

    Full Text Available Abstract Background Human Artificial Chromosomes (HACs are potentially useful vectors for gene transfer studies and for functional annotation of the genome because of their suitability for cloning, manipulating and transferring large segments of the genome. However, development of HACs for the transfer of large genomic loci into mammalian cells has been limited by difficulties in manipulating high-molecular weight DNA, as well as by the low overall frequencies of de novo HAC formation. Indeed, to date, only a small number of large (>100 kb genomic loci have been reported to be successfully packaged into de novo HACs. Results We have developed novel methodologies to enable efficient assembly of HAC vectors containing any genomic locus of interest. We report here the creation of a novel, bimolecular system based on bacterial artificial chromosomes (BACs for the construction of HACs incorporating any defined genomic region. We have utilized this vector system to rapidly design, construct and validate multiple de novo HACs containing large (100–200 kb genomic loci including therapeutically significant genes for human growth hormone (HGH, polycystic kidney disease (PKD1 and ß-globin. We report significant differences in the ability of different genomic loci to support de novo HAC formation, suggesting possible effects of cis-acting genomic elements. Finally, as a proof of principle, we have observed sustained ß-globin gene expression from HACs incorporating the entire 200 kb ß-globin genomic locus for over 90 days in the absence of selection. Conclusion Taken together, these results are significant for the development of HAC vector technology, as they enable high-throughput assembly and functional validation of HACs containing any large genomic locus. We have evaluated the impact of different genomic loci on the frequency of HAC formation and identified segments of genomic DNA that appear to facilitate de novo HAC formation. These genomic loci

  4. Cross-comparison of the genome sequences from human, chimpanzee, Neanderthal and a Denisovan hominin identifies novel potentially compensated mutations

    Directory of Open Access Journals (Sweden)

    Zhang Guojie

    2011-07-01

    Full Text Available Abstract The recent publication of the draft genome sequences of the Neanderthal and a ~50,000-year-old archaic hominin from Denisova Cave in southern Siberia has ushered in a new age in molecular archaeology. We previously cross-compared the human, chimpanzee and Neanderthal genome sequences with respect to a set of disease-causing/disease-associated missense and regulatory mutations (Human Gene Mutation Database and succeeded in identifying genetic variants which, although apparently pathogenic in humans, may represent a 'compensated' wild-type state in at least one of the other two species. Here, in an attempt to identify further 'potentially compensated mutations' (PCMs of interest, we have compared our dataset of disease-causing/disease-associated mutations with their corresponding nucleotide positions in the Denisovan hominin, Neanderthal and chimpanzee genomes. Of the 15 human putatively disease-causing mutations that were found to be compensated in chimpanzee, Denisovan or Neanderthal, only a solitary F5 variant (Val1736Met was specific to the Denisovan. In humans, this missense mutation is associated with activated protein C resistance and an increased risk of thromboembolism and recurrent miscarriage. It is unclear at this juncture whether this variant was indeed a PCM in the Denisovan or whether it could instead have been associated with disease in this ancient hominin.

  5. Germs, genomics and global public health: How can advances in genomic sciences be integrated into public health in the developing world to deal with infectious diseases?

    Science.gov (United States)

    Pang, T

    2009-12-01

    Scientific and technological advances derived from the genomics revolution have a central role to play in dealing with continuing infectious disease threats in the developing world caused by emerging and re-emerging pathogens. These techniques, coupled with increasing knowledge of host-pathogen interactions, can assist in the early identification and containment of outbreaks as well as in the development of preventive vaccination and therapeutic interventions, including the urgent need for new antibiotics. However, the effective application of genomics technologies faces key barriers and challenges which occur at three stages: from the research to the products, from the products to individual patients, and, finally, from patients to entire populations. There needs to be an emphasis on research in areas of greatest need, in facilitating the translation of research into interventions and, finally, the effective delivery of such interventions to those in greatest need. Ultimate success will depend on bringing together science, society and policy to develop effective public health implementation strategies to provide health security and health equity for all peoples.

  6. The Human Genome Project: applications in the diagnosis and treatment of neurologic disease.

    Science.gov (United States)

    Evans, G A

    1998-10-01

    The Human Genome Project (HGP), an international program to decode the entire DNA sequence of the human genome in 15 years, represents the largest biological experiment ever conducted. This set of information will contain the blueprint for the construction and operation of a human being. While the primary driving force behind the genome project is the potential to vastly expand the amount of genetic information available for biomedical research, the ramifications for other fields of study in biological research, the biotechnology and pharmaceutical industry, our understanding of evolution, effects on agriculture, and implications for bioethics are likely to be profound.

  7. The polydeoxyadenylate tract of Alu repetitive elements is polymorphic in the human genome

    International Nuclear Information System (INIS)

    Economou, E.P.; Bergen, A.W.; Warren, A.C.; Antonarakis, S.E.

    1990-01-01

    To identify DNA polymorphisms that are abundant in the human genome and are detectable by polymerase chain reaction amplification of genomic DNA, the authors hypothesize that the polydeoxyadenylate tract of the Alu family of repetitive elements is polymorphic among human chromosomes. Analysis of the 3' ends of three specific Alu sequences showed two occurrences, one in the adenosine deaminase gene and other in the β-globin pseudogene, were polymorphic. This novel class of polymorphism, termed AluVpA [Alu variable poly(A)] may represent one of the most useful and informative group of DNA markers in the human genome

  8. Expanding probe repertoire and improving reproducibility in human genomic hybridization

    Science.gov (United States)

    Dorman, Stephanie N.; Shirley, Ben C.; Knoll, Joan H. M.; Rogan, Peter K.

    2013-01-01

    Diagnostic DNA hybridization relies on probes composed of single copy (sc) genomic sequences. Sc sequences in probe design ensure high specificity and avoid cross-hybridization to other regions of the genome, which could lead to ambiguous results that are difficult to interpret. We examine how the distribution and composition of repetitive sequences in the genome affects sc probe performance. A divide and conquer algorithm was implemented to design sc probes. With this approach, sc probes can include divergent repetitive elements, which hybridize to unique genomic targets under higher stringency experimental conditions. Genome-wide custom probe sets were created for fluorescent in situ hybridization (FISH) and microarray genomic hybridization. The scFISH probes were developed for detection of copy number changes within small tumour suppressor genes and oncogenes. The microarrays demonstrated increased reproducibility by eliminating cross-hybridization to repetitive sequences adjacent to probe targets. The genome-wide microarrays exhibited lower median coefficients of variation (17.8%) for two HapMap family trios. The coefficients of variations of commercial probes within 300 nt of a repetitive element were 48.3% higher than the nearest custom probe. Furthermore, the custom microarray called a chromosome 15q11.2q13 deletion more consistently. This method for sc probe design increases probe coverage for FISH and lowers variability in genomic microarrays. PMID:23376933

  9. Whitehead Policy Symposium. The Human Genome Project: Science, law, and social change in the 21st century

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, E.K.

    2000-02-17

    Advances in the biomedical sciences, especially in human genomics, will dramatically influence law, medicine, public health, and many other sectors of our society in the decades ahead. The public already senses the revolutionary nature of genomic knowledge. In the US and Europe, we have seen widespread discussions about genetic discrimination in health insurance; privacy issues raised by the proliferation of DNA data banks; the challenge of interpreting new DNA diagnostic tests; changing definitions of what it means to be healthy; and the science and ethics of cloning animals and human beings. The primary goal of the Whitehead/ASLME Policy Symposium was to provide a bridge between the research community and professionals, who were just beginning to grasp the potential impact of new genetic technologies on their fields. The ''Human Genome Project: Science, Law, and Social Change in the 21st Century'' initially was designed as a forum for 300-500 physicians, lawyers, consumers, ethicists, and scientists to explore the impact of new genetic technologies and prepare for the challenges ahead.

  10. Ethical issues in human genome epidemiology: a case study based on the Japanese American Family Study in Seattle, Washington.

    Science.gov (United States)

    Austin, Melissa A

    2002-04-01

    Recent completion of the draft sequence of the human genome has been greeted with both excitement and skepticism, and the potential of this accomplishment for advancing public health has been tempered by ethical concerns about the protection of human subjects. This commentary explores ethical issues arising in human genome epidemiology by using a case study approach based on the ongoing Japanese American Family Study at the University of Washington in Seattle (1994-2003). Ethical issues encountered in designing the study, collecting the data, and reporting the study results are considered. When developing studies, investigators must consider whether to restrict the study to specific racial or ethnic groups and whether community involvement is appropriate. Once the study design is in place, further ethical issues emerge, including obtaining informed consent for DNA banking and protecting the privacy and confidentiality of family members. Finally, investigators must carefully consider whether to report genotype results to study participants and whether pedigrees illustrating the results of the study will be published. Overall, the promise of genomics for improving public health must be pursued based on the fundamental ethical principles of respect for persons, beneficence, and justice.

  11. Identification and classification of conserved RNA secondary structures in the human genome

    DEFF Research Database (Denmark)

    Pedersen, Jakob Skou; Bejerano, Gill; Siepel, Adam

    2006-01-01

    The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars...... for identifying functional RNAs encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose threshold for acceptance, this search resulted in a set......, the results nevertheless provide evidence for many new human functional RNAs and present specific predictions to facilitate their further characterization....

  12. Chromosomal locations of members of a family of novel endogenous human retroviral genomes

    International Nuclear Information System (INIS)

    Horn, T.M.; Huebner, K.; Croce, C.; Callahan, R.

    1986-01-01

    Human cellular DNA contains two distinguishable families of retroviral related sequences. One family shares extensive nucleotide sequence homology with infectious mammalian type C retroviral genomes. The other family contains major regions of homology with the pol genes of infectious type A and B and avian type C and D retroviral genomes. Analysis of the human recombinant clone HLM-2 has shown that the pol gene in the latter family is located within an endogenous proviral genome. The authors show that the proviral genome in HLM-2 and the related recombinant clone HLM-25 are located, respectively, on human chromosomes 1 and 5. Other related proviral genomes are located on chromosomes 7, 8, 11, 14, and 17

  13. Genome-to-genome analysis highlights the impact of the human innate and adaptive immune systems on the hepatitis C virus

    Science.gov (United States)

    Ip, Camilla; Magri, Andrea; Von Delft, Annette; Bonsall, David; Chaturvedi, Nimisha; Bartha, Istvan; Smith, David; Nicholson, George; McVean, Gilean; Trebes, Amy; Piazza, Paolo; Fellay, Jacques; Cooke, Graham; Foster, Graham R; Hudson, Emma; McLauchlan, John; Simmonds, Peter; Bowden, Rory; Klenerman, Paul; Barnes, Eleanor; Spencer, Chris C. A.

    2018-01-01

    Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. We use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals chronically infected with HCV, predominately genotype 3. We show that both HLA alleles and interferon lambda innate immune system genes drive viral genome polymorphism, and that IFNL4 genotypes determine HCV viral load through a mechanism that is dependent on a specific polymorphism in the HCV polyprotein. We highlight the interplay between innate immune responses and the viral genome in HCV control. PMID:28394351

  14. A geographically-diverse collection of 418 human gut microbiome pathway genome databases

    KAUST Repository

    Hahn, Aria S.

    2017-04-11

    Advances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GutCyc, a compendium of environmental pathway genome databases (ePGDBs) constructed from 418 assembled human microbiome datasets using MetaPathways, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GutCyc data products are searchable online, or may be downloaded and explored locally using MetaPathways and Pathway Tools.

  15. Comparative genomics of pathogenic Leptospira interrogans serovar Canicola isolated from swine and human in Brazil

    Directory of Open Access Journals (Sweden)

    Luisa Z Moreno

    Full Text Available Leptospira interrogans serovar Canicola is one of the most important pathogenic serovars for the maintenance of urban leptospirosis. Even though it is considered highly adapted to dogs, serovar Canicola infection has already been described in other animals and even a few human cases. Here, we present the genomic characterisation of two Brazilian L. interrogans serovar Canicola strains isolated from slaughtered sows (L0-3 and L0-4 and their comparison with human strain Fiocruz LV133. It was observed that the porcine serovar Canicola strains present the genetic machinery to cause human infection and, therefore, represent a higher risk to public health. Both human and porcine serovar Canicola isolates also presented sequences with high identity to the Chinese serovar Canicola published plasmids pGui1 and pGui2. The plasmids identification in the Brazilian and Chinese serovar Canicola strains suggest that extra-chromosomal elements are one more feature of this serovar that was previously unnoticed.

  16. A compact view of isochores in the draft human genome sequence

    Czech Academy of Sciences Publication Activity Database

    Pavlíček, Adam; Pačes, Jan; Clay, O.; Bernardi, G.

    2002-01-01

    Roč. 511, 1-3 (2002), s. 165-169 ISSN 0014-5793 R&D Projects: GA MŠk LN00A079 Keywords : genome organisation * mammalian DNA * human genome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.912, year: 2002

  17. New Regions of the Human Genome Linked to Skin Color Variation in Some African Populations

    Science.gov (United States)

    In the first study of its kind, an international team of genomics researchers has identified new regions of the human genome that are associated with skin color variation in some African populations, opening new avenues for research on skin diseases and cancer in all populations.

  18. Complete genome sequence of Bifidobacterium breve CECT 7263, a strain isolated from human milk.

    Science.gov (United States)

    Jiménez, Esther; Villar-Tajadura, M Antonia; Marín, María; Fontecha, Javier; Requena, Teresa; Arroyo, Rebeca; Fernández, Leónides; Rodríguez, Juan M

    2012-07-01

    Bifidobacterium breve is an actinobacterium frequently isolated from colonic microbiota of breastfeeding babies. Here, we report the complete and annotated genome sequence of a B. breve strain isolated from human milk, B. breve CECT 7263. The genome sequence will provide new insights into the biology of this potential probiotic organism and will allow the characterization of genes related to beneficial properties.

  19. An integrated map of genetic variation from 1.092 human genomes

    DEFF Research Database (Denmark)

    Abecasis, Goncalo R.; Auton, Adam; Brooks, Lisa D.

    2012-01-01

    By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination ...

  20. New bioinformatic tool for quick identification of functionally relevant endogenous retroviral inserts in human genome.

    Science.gov (United States)

    Garazha, Andrew; Ivanova, Alena; Suntsova, Maria; Malakhova, Galina; Roumiantsev, Sergey; Zhavoronkov, Alex; Buzdin, Anton

    2015-01-01

    Endogenous retroviruses (ERVs) and LTR retrotransposons (LRs) occupy ∼8% of human genome. Deep sequencing technologies provide clues to understanding of functional relevance of individual ERVs/LRs by enabling direct identification of transcription factor binding sites (TFBS) and other landmarks of functional genomic elements. Here, we performed the genome-wide identification of human ERVs/LRs containing TFBS according to the ENCODE project. We created the first interactive ERV/LRs database that groups the individual inserts according to their familial nomenclature, number of mapped TFBS and divergence from their consensus sequence. Information on any particular element can be easily extracted by the user. We also created a genome browser tool, which enables quick mapping of any ERV/LR insert according to genomic coordinates, known human genes and TFBS. These tools can be used to easily explore functionally relevant individual ERV/LRs, and for studying their impact on the regulation of human genes. Overall, we identified ∼110,000 ERV/LR genomic elements having TFBS. We propose a hypothesis of "domestication" of ERV/LR TFBS by the genome milieu including subsequent stages of initial epigenetic repression, partial functional release, and further mutation-driven reshaping of TFBS in tight coevolution with the enclosing genomic loci.

  1. Segmenting the human genome based on states of neutral genetic divergence.

    Science.gov (United States)

    Kuruppumullage Don, Prabhani; Ananda, Guruprasad; Chiaromonte, Francesca; Makova, Kateryna D

    2013-09-03

    Many studies have demonstrated that divergence levels generated by different mutation types vary and covary across the human genome. To improve our still-incomplete understanding of the mechanistic basis of this phenomenon, we analyze several mutation types simultaneously, anchoring their variation to specific regions of the genome. Using hidden Markov models on insertion, deletion, nucleotide substitution, and microsatellite divergence estimates inferred from human-orangutan alignments of neutrally evolving genomic sequences, we segment the human genome into regions corresponding to different divergence states--each uniquely characterized by specific combinations of divergence levels. We then parsed the mutagenic contributions of various biochemical processes associating divergence states with a broad range of genomic landscape features. We find that high divergence states inhabit guanine- and cytosine (GC)-rich, highly recombining subtelomeric regions; low divergence states cover inner parts of autosomes; chromosome X forms its own state with lowest divergence; and a state of elevated microsatellite mutability is interspersed across the genome. These general trends are mirrored in human diversity data from the 1000 Genomes Project, and departures from them highlight the evolutionary history of primate chromosomes. We also find that genes and noncoding functional marks [annotations from the Encyclopedia of DNA Elements (ENCODE)] are concentrated in high divergence states. Our results provide a powerful tool for biomedical data analysis: segmentations can be used to screen personal genome variants--including those associated with cancer and other diseases--and to improve computational predictions of noncoding functional elements.

  2. The first complete genome sequences of clinical isolates of human coronavirus 229E

    NARCIS (Netherlands)

    Farsani, Seyed Mohammad Jazaeri; Dijkman, Ronald; Jebbink, Maarten F.; Goossens, Herman; Ieven, Margareta; Deijs, Martin; Molenkamp, Richard; van der Hoek, Lia

    2012-01-01

    Human coronavirus 229E has been identified in the mid-1960s, yet still only one full-genome sequence is available. This full-length sequence has been determined from the cDNA-clone Inf-1 that is based on the lab-adapted strain VR-740. Lab-adaptation might have resulted in genomic changes, due to

  3. Building local capacity for genomics research in Africa: recommendations from analysis of publications in Sub-Saharan Africa from 2004 to 2013.

    Science.gov (United States)

    Adedokun, Babatunde O; Olopade, Christopher O; Olopade, Olufunmilayo I

    2016-01-01

    The poor genomics research capacity of Sub-Saharan Africa (SSA) could prevent maximal benefits from the applications of genomics in the practice of medicine and research. The objective of this study is to examine the author affiliations of genomic epidemiology publications in order to make recommendations for building local genomics research capacity in SSA. SSA genomic epidemiology articles published between 2004 and 2013 were extracted from the Human Genome Epidemiology (HuGE) database. Data on authorship details, country of population studied, and phenotype or disease were extracted. Factors associated with the first author, who has an SSA institution affiliation (AIAFA), were determined using a Chi-square test and multiple logistic regression analysis. The most commonly studied population was South Africa, accounting for 31.1%, followed by Ghana (10.6%) and Kenya (7.5%). About one-tenth of the papers were related to non-communicable diseases (NCDs) such as cancer (6.1%) and cardiovascular diseases (CVDs) (4.3%). Fewer than half of the first authors (46.9%) were affiliated with an African institution. Among the 238 articles with an African first author, over three-quarters (79.8%) belonged to a university or medical school, 16.8% were affiliated with a research institute, and 3.4% had affiliations with other institutions. Significant disparities currently exist among SSA countries in genomics research capacity. South Africa has the highest genomics research output, which is reflected in the investments made in its genomics and biotechnology sector. These findings underscore the need to focus on developing local capacity, especially among those affiliated with SSA universities where there are more opportunities for teaching and research.

  4. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome

    DEFF Research Database (Denmark)

    Pedersen, Jakob Skou; Valen, Eivind; Velazquez, Amhed Missael Vargas

    2014-01-01

    Epigenetic information is available from contemporary organisms, but is difficult to track back in evolutionary time. Here, we show that genome-wide epigenetic information can be gathered directly from next-generation sequence reads of DNA isolated from ancient remains. Using the genome sequence...... data generated from hair shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate the first ancient nucleosome map coupled with a genome-wide survey of cytosine methylation levels. The validity of both nucleosome map and methylation levels were confirmed by the recovery...

  5. Global Intersection of Long Non-Coding RNAs with Processed and Unprocessed Pseudogenes in the Human Genome

    Directory of Open Access Journals (Sweden)

    Michael John Milligan

    2016-03-01

    Full Text Available Pseudogenes are abundant in the human genome and had long been thought of purely as nonfunctional gene fossils. Recent observations point to a role for pseudogenes in regulating genes transcriptionally and post-transcriptionally in human cells. To computationally interrogate the network space of integrated pseudogene and long non-coding RNA regulation in the human transcriptome, we developed and implemented an algorithm to identify all long non-coding RNA (lncRNA transcripts that overlap the genomic spans, and specifically the exons, of any human pseudogenes in either sense or antisense orientation. As inputs to our algorithm, we imported three public repositories of pseudogenes: GENCODE v17 (processed and unprocessed, Ensembl 72; Retroposed Pseudogenes V5 (processed only and Yale Pseudo60 (processed and unprocessed, Ensembl 60; two public lncRNA catalogs: Broad Institute, GENCODE v17; NCBI annotated piRNAs; and NHGRI clinical variants. The data sets were retrieved from the UCSC Genome Database using the UCSC Table Browser. We identified 2277 loci containing exon-to-exon overlaps between pseudogenes, both processed and unprocessed, and long non-coding RNA genes. Of these loci we identified 1167 with Genbank EST and full-length cDNA support providing direct evidence of transcription on one or both strands with exon-to-exon overlaps. The analysis converged on 313 pseudogene-lncRNA exon-to-exon overlaps that were bidirectionally supported by both full-length cDNAs and ESTs. In the process of identifying transcribed pseudogenes, we generated a comprehensive, positionally non-redundant encyclopedia of human pseudogenes, drawing upon multiple, and formerly disparate public pseudogene repositories. Collectively, these observations suggest that pseudogenes are pervasively transcribed on both strands and are common drivers of gene regulation.

  6. Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases

    Science.gov (United States)

    Nalbantoglu, Ufuk

    2017-01-01

    A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome–human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis. PMID:28785422

  7. Improving the Status of Human and Material Resources in Public ...

    African Journals Online (AJOL)

    Improving the Status of Human and Material Resources in Public Primary School in Oyo States ... the Millennium Development Goals project in the State. ... libraries, well-equipped first aid centres, adequate electronically projected instructional ...

  8. Impact of UV Radiation on Genome Stability and Human Health.

    Science.gov (United States)

    Roy, Sujit

    2017-01-01

    Gradual depletion of the atmospheric ozone layer during the past few years has increased the incidence of solar UV radiation specifically the UV-C on earth's surface is one of the major environmental concerns because of the harmful effects of this radiation in all forms of life. The solar UV radiation including the harmful wavelength range of UV-B (280-320 nm) represents a significant climatic stress for both animals and plants, causing damage to the fundamental biomolecules such as DNA, proteins and lipids, thus activating genotoxic stress and induces genome instability. When DNA absorbs UV-B light, energy from the photon causes covalent linkages to form between adjacent pyrimidine bases, creating photoproducts, primarily cyclobutane pyrimidine dimers (CPDs) and pyrimidine-6,4-pyrimidinone photoproduct (6,4PPs). Pyrimidine dimers create distortions in the DNA strands and therefore can inhibit DNA replication as well transcription. Lack of efficient repair of UV-induced DNA damage may induce the formation of DNA double stand breaks (DSBs), one of the serious forms of damage in DNA double helix, as well as oxidative damage. Unrepaired DSBs in the actively dividing somatic cells severely affect cell growth and development, finally results in loss of cell viability and development of various diseases, such as cancer in man.This chapter mainly highlights the incidence of solar UV-radiation on earth's surface along with the formation of major types of UV-induced DNA damage and the associated repair mechanisms as well as methods of detecting DNA damage and finally our present understanding on the impact on solar UV radiation on human health.

  9. The genome of herpesvirus papio 2 is closely related to the genomes of human herpes simplex viruses.

    Science.gov (United States)

    Bigger, John E; Martin, David W

    2003-06-01

    Infection of baboons (Papio species) with herpesvirus papio 2 (HVP-2) produces a disease that is clinically similar to herpes simplex virus (HSV-1 and HSV-2) infection of humans. The development of a primate model of simplexvirus infection based on HVP-2 would provide a powerful resource to study virus biology and test vaccine strategies. In order to characterize the molecular biology of HVP-2 and justify further development of this model system we have constructed a physical map of the HVP-2 genome. The results of these studies have identified the presence of 26 reading frames that closely resemble HSV homologues. Furthermore, the HVP-2 genome shares a collinear arrangement with the genome of HSV. These studies further validate the development of the HVP-2 model as a surrogate system to study the biology of HSV infections.

  10. CRISPR/Cas9 for Human Genome Engineering and Disease Research.

    Science.gov (United States)

    Xiong, Xin; Chen, Meng; Lim, Wendell A; Zhao, Dehua; Qi, Lei S

    2016-08-31

    The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, a versatile RNA-guided DNA targeting platform, has been revolutionizing our ability to modify, manipulate, and visualize the human genome, which greatly advances both biological research and therapeutics development. Here, we review the current development of CRISPR/Cas9 technologies for gene editing, transcription regulation, genome imaging, and epigenetic modification. We discuss the broad application of this system to the study of functional genomics, especially genome-wide genetic screening, and to therapeutics development, including establishing disease models, correcting defective genetic mutations, and treating diseases.

  11. Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome

    NARCIS (Netherlands)

    Collins, Ryan L; Brand, Harrison; Redin, Claire E.; Hanscom, Carrie; Antolik, Caroline; Stone, Matthew R; Glessner, Joseph T.; Mason, Tamara; Pregno, Giulia; Dorrani, Naghmeh; Mandrile, Giorgia; Giachino, Daniela; Perrin, Danielle; Walsh, Cole; Cipicchio, Michelle; Costello, Maura; Stortchevoi, Alexei; An, Joon Yong; Currall, Benjamin B; Seabra, Catarina M; Ragavendran, Ashok; Margolin, Lauren; Martinez-Agosto, Julian A.; Lucente, Diane; Levy, Brynn; Sanders, Jan-Stephan; Wapner, Ronald J.; Quintero-Rivera, Fabiola; Kloosterman, Wigard; Talkowski, Michael E.

    2017-01-01

    Background: Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. Results: We sequenced 689 participants with autism spectrum disorder (ASD) and other

  12. Human Genome Teacher Networking Project, Final Report, April 1, 1992 - March 31, 1998

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Debra

    1999-10-01

    Project to provide education regarding ethical legal and social implications of Human Genome Project to high school science teachers through two consecutive summer workshops, in class activities, and peer teaching workshops.

  13. Understanding the Human Genome Project — A Fact Sheet | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... The Human Genome Project spurred a revolution in biotechnology innovation around the world and played a key ... the U.S. the global leader in the new biotechnology sector. In April 2003, researchers successfully completed the ...

  14. Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors

    Science.gov (United States)

    Huang, Mi Ni; Yu, Willie; Teoh, Wei Wei; Ardin, Maude; Jusakul, Apinya; Ng, Alvin Wei Tian; Boot, Arnoud; Abedi-Ardekani, Behnoush; Villar, Stephanie; Myint, Swe Swe; Othman, Rashidah; Poon, Song Ling; Heguy, Adriana; Olivier, Magali; Hollstein, Monica; Tan, Patrick; Teh, Bin Tean; Sabapathy, Kanaga; Zavadil, Jiri; Rozen, Steven G.

    2017-01-01

    Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here, we present the first whole-genome data on the mutational signatures of AFB1 exposure from a total of >40,000 mutations in four experimental systems: two different human cell lines, in liver tumors in wild-type mice, and in mice that carried a hepatitis B surface antigen transgene—this to model the multiplicative effects of aflatoxin exposure and hepatitis B in causing HCC. AFB1 mutational signatures from all four experimental systems were remarkably similar. We integrated the experimental mutational signatures with data from newly sequenced HCCs from Qidong County, China, a region of well-studied aflatoxin exposure. This indicated that COSMIC mutational signature 24, previously hypothesized to stem from aflatoxin exposure, indeed likely represents AFB1 exposure, possibly combined with other exposures. Among published somatic mutation data, we found evidence of AFB1 exposure in 0.7% of HCCs treated in North America, 1% of HCCs from Japan, but 16% of HCCs from Hong Kong. Thus, aflatoxin exposure apparently remains a substantial public health issue in some areas. This aspect of our study exemplifies the promise of future widespread resequencing of tumor genomes in providing new insights into the contribution of mutagenic exposures to cancer incidence. PMID:28739859

  15. Public health genomics and personalized prevention: lessons from the COGS project.

    Science.gov (United States)

    Pashayan, N; Hall, A; Chowdhury, S; Dent, T; Pharoah, P D P; Burton, H

    2013-11-01

    Using the principles of public health genomics, we examined the opportunities and challenges of implementing personalized prevention programmes for cancer at the population level. Our model-based estimates indicate that polygenic risk stratification can potentially improve the effectiveness and cost-effectiveness of screening programmes. However, compared with 'one-size-fits-all' screening programmes, personalized screening adds further layers of complexity to the organization of screening services and raises ethical, legal and social challenges. Before polygenic inheritance is translated into population screening strategy, evidence from empirical research and engagement with and education of the public and the health professionals are needed. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  16. Capturing human movement patterns in public spaces

    DEFF Research Database (Denmark)

    Nielsen, Søren Zebitz; Gade, Rikke

    2014-01-01

    Non-intrusive and non-privacy violating tracking of people by the use of thermal cameras and Computer Vision The video shows examples of data collection of pedestrian tracks in an urban plaza using a thermal camera. The data is used in my PhD project on Human Movement Patterns in Smart Cities....... The recording and analysis of the thermal videos has been made in collaboration with Rikke Gade from the Visual Analytics of People Lab at Aalborg University....

  17. Human rights and public health : towards a balanced relationship

    NARCIS (Netherlands)

    Toebes, Brigit

    This contribution attempts to scope the multiple and complex relationships between measures to protect health and the protection of human rights. The article begins with a discussion of the meaning and current understandings of the notion of ‘public health’, after which it explores how ‘public

  18. Complete genome sequence of a commensal bacterium, Hafnia alvei CBA7124, isolated from human feces.

    Science.gov (United States)

    Song, Hye Seon; Kim, Joon Yong; Kim, Yeon Bee; Jeong, Myeong Seon; Kang, Jisu; Rhee, Jin-Kyu; Kwon, Joseph; Kim, Ju Suk; Choi, Jong-Soon; Choi, Hak-Jong; Nam, Young-Do; Roh, Seong Woon

    2017-01-01

    Members of the genus Hafnia have been isolated from the feces of mammals, birds, reptiles, and fish, as well as from soil, water, sewage, and foods. Hafnia alvei is an opportunistic pathogen that has been implicated in intestinal and extraintestinal infections in humans. However, its pathogenicity is still unclear. In this study, we isolated H. alvei from human feces and performed sequencing as well as comparative genomic analysis to better understand its pathogenicity. The genome of H. alvei CBA7124 comprised a single circular chromosome with 4,585,298 bp and a GC content of 48.8%. The genome contained 25 rRNA genes (9 5S rRNA genes, 8 16S rRNA genes, and 8 23S rRNA genes), 88 tRNA genes, and 4043 protein-coding genes. Using comparative genomic analysis, the genome of this strain was found to have 72 strain-specific singletons. The genome also contained genes for antibiotic and antimicrobial resistance, as well as toxin-antitoxin systems. We revealed the complete genome sequence of the opportunistic gut pathogen, H. alvei CBA7124. We also performed comparative genomic analysis of the sequences in the genome of H. alvei CBA7124, and found that it contained strain-specific singletons, antibiotic resistance genes, and toxin-antitoxin systems. These results could improve our understanding of the pathogenicity and the mechanism behind the antibiotic resistance of H. alvei strains.

  19. MutSpec: a Galaxy toolbox for streamlined analyses of somatic mutation spectra in human and mouse cancer genomes.

    Science.gov (United States)

    Ardin, Maude; Cahais, Vincent; Castells, Xavier; Bouaoun, Liacine; Byrnes, Graham; Herceg, Zdenko; Zavadil, Jiri; Olivier, Magali

    2016-04-18

    The nature of somatic mutations observed in human tumors at single gene or genome-wide levels can reveal information on past carcinogenic exposures and mutational processes contributing to tumor development. While large amounts of sequencing data are being generated, the associated analysis and interpretation of mutation patterns that may reveal clues about the natural history of cancer present complex and challenging tasks that require advanced bioinformatics skills. To make such analyses accessible to a wider community of researchers with no programming expertise, we have developed within the web-based user-friendly platform Galaxy a first-of-its-kind package called MutSpec. MutSpec includes a set of tools that perform variant annotation and use advanced statistics for the identification of mutation signatures present in cancer genomes and for comparing the obtained signatures with those published in the COSMIC database and other sources. MutSpec offers an accessible framework for building reproducible analysis pipelines, integrating existing methods and scripts developed in-house with publicly available R packages. MutSpec may be used to analyse data from whole-exome, whole-genome or targeted sequencing experiments performed on human or mouse genomes. Results are provided in various formats including rich graphical outputs. An example is presented to illustrate the package functionalities, the straightforward workflow analysis and the richness of the statistics and publication-grade graphics produced by the tool. MutSpec offers an easy-to-use graphical interface embedded in the popular Galaxy platform that can be used by researchers with limited programming or bioinformatics expertise to analyse mutation signatures present in cancer genomes. MutSpec can thus effectively assist in the discovery of complex mutational processes resulting from exogenous and endogenous carcinogenic insults.

  20. Draft genome sequence of the first human isolate of the ruminant pathogen Mycoplasma capricolum subsp. capricolum

    DEFF Research Database (Denmark)

    Seersholm, Frederik Valeur; Fischer, Anne; Heller, Martin

    2015-01-01

    Mycoplasma capricolum subsp. capricolum is a well-known pathogen of small ruminants. A recent human case of septicemia involving this agent raised the question of its potential pathogenicity to humans. We present the first draft genome sequence of a human Mycoplasma capricolum subsp. capricolum...

  1. Efficient CRISPR/Cas9-Based Genome Engineering in Human Pluripotent Stem Cells.

    Science.gov (United States)

    Kime, Cody; Mandegar, Mohammad A; Srivastava, Deepak; Yamanaka, Shinya; Conklin, Bruce R; Rand, Tim A

    2016-01-01

    Human pluripotent stem cells (hPS cells) are rapidly emerging as a powerful tool for biomedical discovery. The advent of human induced pluripotent stem cells (hiPS cells) with human embryonic stem (hES)-cell-like properties has led to hPS cells with disease-specific genetic backgrounds for in vitro disease modeling and drug discovery as well as mechanistic and developmental studies. To fully realize this potential, it will be necessary to modify the genome of hPS cells with precision and flexibility. Pioneering experiments utilizing site-specific double-strand break (DSB)-mediated genome engineering tools, including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), have paved the way to genome engineering in previously recalcitrant systems such as hPS cells. However, these methods are technically cumbersome and require significant expertise, which has limited adoption. A major recent advance involving the clustered regularly interspaced short palindromic repeats (CRISPR) endonuclease has dramatically simplified the effort required for genome engineering and will likely be adopted widely as the most rapid and flexible system for genome editing in hPS cells. In this unit, we describe commonly practiced methods for CRISPR endonuclease genomic editing of hPS cells into cell lines containing genomes altered by insertion/deletion (indel) mutagenesis or insertion of recombinant genomic DNA. Copyright © 2016 John Wiley & Sons, Inc.

  2. Genome-wide survey of allele-specific splicing in humans

    Directory of Open Access Journals (Sweden)

    Scheffler Konrad

    2008-06-01

    Full Text Available Abstract Background Accurate mRNA splicing depends on multiple regulatory signals encoded in the transcribed RNA sequence. Many examples of mutations within human splice regulatory regions that alter splicing qualitatively or quantitatively have been reported and allelic differences in mRNA splicing are likely to be a common and important source of phenotypic diversity at the molecular level, in addition to their contribution to genetic disease susceptibility. However, because the effect of a mutation on the efficiency of mRNA splicing is often difficult to predict, many mutations that cause disease through an effect on splicing are likely to remain undiscovered. Results We have combined a genome-wide scan for sequence polymorphisms likely to affect mRNA splicing with analysis of publicly available Expressed Sequence Tag (EST and exon array data. The genome-wide scan uses published tools and identified 30,977 SNPs located within donor and acceptor splice sites, branch points and exonic splicing enhancer elements. For 1,185 candidate splicing polymorphisms the difference in splicing between alternative alleles was corroborated by publicly available exon array data from 166 lymphoblastoid cell lines. We developed a novel probabilistic method to infer allele-specific splicing from EST data. The method uses SNPs and alternative mRNA isoforms mapped to EST sequences and models both regulated alternative splicing as well as allele-specific splicing. We have also estimated heritability of splicing and report that a greater proportion of genes show evidence of splicing heritability than show heritability of overall gene expression level. Our results provide an extensive resource that can be used to assess the possible effect on splicing of human polymorphisms in putative splice-regulatory sites. Conclusion We report a set of genes showing evidence of allele-specific splicing from an integrated analysis of genomic polymorphisms, EST data and exon array

  3. Human Dignity, Misthanasia, Public Health and Bioethics in Brazil

    Directory of Open Access Journals (Sweden)

    Anna Silvia Penteado Setti da Rocha

    2017-10-01

    Full Text Available This paper aims to reflect on human dignity and misthanasia in the public health system in Brazil. For this, concepts, document reviews and public data about the condition of the Brazilian population’s access to public health were all used. The indicators show the health inequalities in the country, with the north and northeast at a disadvantage both in terms of access to health and the number of available professionals. Thus, the most underserved population tends to continue to be excluded from society and impaired with respect to their human dignity.

  4. Human resource management practices in public and private ...

    African Journals Online (AJOL)

    The results, among others, showed that private schools generally better managed their human resources than the public ones. Hence, it was recommended that there should be standard guidelines for operators of schools while human resource managers in the school system should be groomed in managerial psychology.

  5. The complete nucleotide sequence, genome organization, and origin of human adenovirus type 11

    International Nuclear Information System (INIS)

    Stone, Daniel; Furthmann, Anne; Sandig, Volker; Lieber, Andre

    2003-01-01

    The complete DNA sequence and transcription map of human adenovirus type 11 are reported here. This is the first published sequence for a subgenera B human adenovirus and demonstrates a genome organization highly similar to those of other human adenoviruses. All of the genes from the early, intermediate, and late regions are present in the expected locations of the genome for a human adenovirus. The genome size is 34,794 bp in length and has a GC content of 48.9%. Sequence alignment with genomes of groups A (Ad12), C (Ad5), D (Ad17), E (Simian adenovirus 25), and F (Ad40) revealed homologies of 64, 54, 68, 75, and 52%, respectively. Detailed genomic analysis demonstrated that Ads 11 and 35 are highly conserved in all areas except the hexon hypervariable regions and fiber. Similarly, comparison of Ad11 with subgroup E SAV25 revealed poor homology between fibers but high homology in proteins encoded by all other areas of the genome. We propose an evolutionary model in which functional viruses can be reconstituted following fiber substitution from one serotype to another. According to this model either the Ad11 genome is a derivative of Ad35, from which the fiber was substituted with Ad7, or the Ad35 genome is the product of a fiber substitution from Ad21 into the Ad11 genome. This model also provides a possible explanation for the origin of group E Ads, which are evolutionarily derived from a group C fiber substitution into a group B genome

  6. The spotted gar genome illuminates vertebrate evolution and facilitates human-to-teleost comparisons

    Science.gov (United States)

    Braasch, Ingo; Gehrke, Andrew R.; Smith, Jeramiah J.; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M.; Campbell, Michael S.; Barrell, Daniel; Martin, Kyle J.; Mulley, John F.; Ravi, Vydianathan; Lee, Alison P.; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E. G.; Sun, Yi; Hertel, Jana; Beam, Michael J.; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H.; Litman, Gary W.; Litman, Ronda T.; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F.; Wang, Han; Taylor, John S.; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M. J.; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A.; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T.; Venkatesh, Byrappa; Holland, Peter W. H.; Guiguen, Yann; Bobe, Julien; Shubin, Neil H.; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H.

    2016-01-01

    To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before the teleost genome duplication (TGD). The slowly evolving gar genome conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization, and development (e.g., Hox, ParaHox, and miRNA genes). Numerous conserved non-coding elements (CNEs, often cis-regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles of such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses revealed that the sum of expression domains and levels from duplicated teleost genes often approximate patterns and levels of gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes, and the function of human regulatory sequences. PMID:26950095

  7. The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons.

    Science.gov (United States)

    Braasch, Ingo; Gehrke, Andrew R; Smith, Jeramiah J; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M; Campbell, Michael S; Barrell, Daniel; Martin, Kyle J; Mulley, John F; Ravi, Vydianathan; Lee, Alison P; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E G; Sun, Yi; Hertel, Jana; Beam, Michael J; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H; Litman, Gary W; Litman, Ronda T; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F; Wang, Han; Taylor, John S; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M J; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T; Venkatesh, Byrappa; Holland, Peter W H; Guiguen, Yann; Bobe, Julien; Shubin, Neil H; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H

    2016-04-01

    To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.

  8. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome.

    Science.gov (United States)

    Sharp, Andrew J; Hansen, Sierra; Selzer, Rebecca R; Cheng, Ze; Regan, Regina; Hurst, Jane A; Stewart, Helen; Price, Sue M; Blair, Edward; Hennekam, Raoul C; Fitzpatrick, Carrie A; Segraves, Rick; Richmond, Todd A; Guiver, Cheryl; Albertson, Donna G; Pinkel, Daniel; Eis, Peggy S; Schwartz, Stuart; Knight, Samantha J L; Eichler, Evan E

    2006-09-01

    Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders. We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in four individuals. Using oligonucleotide arrays, we refined the breakpoints of this microdeletion, defining a 478-kb critical region containing six genes that were deleted in all four individuals. We mapped the breakpoints of this deletion and of four other pathogenic rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental duplications, suggesting that these are also sites of recurrent rearrangement. In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions.

  9. Whole genome analysis of selected human and animal rotaviruses identified in Uganda from 2012 to 2014 reveals complex genome reassortment events between human, bovine, caprine and porcine strains.

    Science.gov (United States)

    Bwogi, Josephine; Jere, Khuzwayo C; Karamagi, Charles; Byarugaba, Denis K; Namuwulya, Prossy; Baliraine, Frederick N; Desselberger, Ulrich; Iturriza-Gomara, Miren

    2017-01-01

    Rotaviruses of species A (RVA) are a common cause of diarrhoea in children and the young of various other mammals and birds worldwide. To investigate possible interspecies transmission of RVAs, whole genomes of 18 human and 6 domestic animal RVA strains identified in Uganda between 2012 and 2014 were sequenced using the Illumina HiSeq platform. The backbone of the human RVA strains had either a Wa- or a DS-1-like genetic constellation. One human strain was a Wa-like mono-reassortant containing a DS-1-like VP2 gene of possible animal origin. All eleven genes of one bovine RVA strain were closely related to those of human RVAs. One caprine strain had a mixed genotype backbone, suggesting that it emerged from multiple reassortment events involving different host species. The porcine RVA strains had mixed genotype backbones with possible multiple reassortant events with strains of human and bovine origin.Overall, whole genome characterisation of rotaviruses found in domestic animals in Uganda strongly suggested the presence of human-to animal RVA transmission, with concomitant circulation of multi-reassortant strains potentially derived from complex interspecies transmission events. However, whole genome data from the human RVA strains causing moderate and severe diarrhoea in under-fives in Uganda indicated that they were primarily transmitted from person-to-person.

  10. 'Only connect': the case for public health humanities.

    Science.gov (United States)

    Saffran, Lise

    2014-12-01

    Humanities in health has until now been primarily understood to mean humanities in medicine and has generally failed to include public health. I will argue in this paper that the common justifications for the former--including increased empathy among practitioners--are at least as applicable, if not more, to the latter. Growing emphasis on the social determinants of health and cultural competency in public health require public health students and professionals to develop a nuanced understanding of the influence of social context on health behaviour and to empathise with people in difficult circumstances. Literary fiction has been demonstrated to have an impact on skills related to empathy and social intelligence. Further, translating epidemiological evidence into public policy is a core task of public health and there is a growing body of research to indicate that statistical evidence is more persuasive when combined with narrative evidence. In this article I explore similarities and differences between proposed humanities in public health and programmes in humanities in medicine and highlight research gaps and possible implications of a more expansive view of humanities in health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Human rights, public health and medicinal cannabis use

    OpenAIRE

    Bone, Melissa; Seddon, Toby

    2015-01-01

    This paper explores the interplay between the human rights and drug control frameworks, and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of ‘health’. This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medicinal cannabis use. The paper also demonstrates how a human rights lens can alleviate a core tension between the St...

  12. Evolution and Diversity in Human Herpes Simplex Virus Genomes

    Science.gov (United States)

    Gatherer, Derek; Ochoa, Alejandro; Greenbaum, Benjamin; Dolan, Aidan; Bowden, Rory J.; Enquist, Lynn W.; Legendre, Matthieu; Davison, Andrew J.

    2014-01-01

    Herpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a gene deletion and one-third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms, although the protein sequence identity between strains exceeds 90% on average. In the first genome-scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments and will aid in the selection of vaccine antigens that are invariant worldwide. PMID:24227835

  13. New sequence-based data on the relative DNA contents of chromosomes in the normal male and female human diploid genomes for radiation molecular cytogenetics

    Directory of Open Access Journals (Sweden)

    Repin Mikhail V

    2009-06-01

    Full Text Available Abstract Background The objective of this work is to obtain the correct relative DNA contents of chromosomes in the normal male and female human diploid genomes for the use at FISH analysis of radiation-induced chromosome aberrations. Results The relative DNA contents of chromosomes in the male and female human diploid genomes have been calculated from the publicly available international Human Genome Project data. New sequence-based data on the relative DNA contents of human chromosomes were compared with the data recommended by the International Atomic Energy Agency in 2001. The differences in the values of the relative DNA contents of chromosomes obtained by using different approaches for 15 human chromosomes, mainly for large chromosomes, were below 2%. For the chromosomes 13, 17, 20 and 22 the differences were above 5%. Conclusion New sequence-based data on the relative DNA contents of chromosomes in the normal male and female human diploid genomes were obtained. This approach, based on the genome sequence, can be recommended for the use in radiation molecular cytogenetics.

  14. Genomic instability in human actinic keratosis and squamous cell carcinoma

    Science.gov (United States)

    Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

    2011-01-01

    OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

  15. Long-range autocorrelations of CpG islands in the human genome.

    Directory of Open Access Journals (Sweden)

    Benjamin Koester

    Full Text Available In this paper, we use a statistical estimator developed in astrophysics to study the distribution and organization of features of the human genome. Using the human reference sequence we quantify the global distribution of CpG islands (CGI in each chromosome and demonstrate that the organization of the CGI across a chromosome is non-random, exhibits surprisingly long range correlations (10 Mb and varies significantly among chromosomes. These correlations of CGI summarize functional properties of the genome that are not captured when considering variation in any particular separate (and local feature. The demonstration of the proposed methods to quantify the organization of CGI in the human genome forms the basis of future studies. The most illuminating of these will assess the potential impact on phenotypic variation of inter-individual variation in the organization of the functional features of the genome within and among chromosomes, and among individuals for particular chromosomes.

  16. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui

    2011-01-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...

  17. Deorphanizing the human transmembrane genome: A landscape of uncharacterized membrane proteins.

    Science.gov (United States)

    Babcock, Joseph J; Li, Min

    2014-01-01

    The sequencing of the human genome has fueled the last decade of work to functionally characterize genome content. An important subset of genes encodes membrane proteins, which are the targets of many drugs. They reside in lipid bilayers, restricting their endogenous activity to a relatively specialized biochemical environment. Without a reference phenotype, the application of systematic screens to profile candidate membrane proteins is not immediately possible. Bioinformatics has begun to show its effectiveness in focusing the functional characterization of orphan proteins of a particular functional class, such as channels or receptors. Here we discuss integration of experimental and bioinformatics approaches for characterizing the orphan membrane proteome. By analyzing the human genome, a landscape reference for the human transmembrane genome is provided.

  18. Public health ethics and more-than-human solidarity.

    Science.gov (United States)

    Rock, Melanie J; Degeling, Chris

    2015-03-01

    This article contributes to the literature on One Health and public health ethics by expanding the principle of solidarity. We conceptualise solidarity to encompass not only practices intended to assist other people, but also practices intended to assist non-human others, including animals, plants, or places. To illustrate how manifestations of humanist and more-than-human solidarity may selectively complement one another, or collide, recent responses to Hendra virus in Australia and Rabies virus in Canada serve as case examples. Given that caring relationships are foundational to health promotion, people's efforts to care for non-human others are highly relevant to public health, even when these efforts conflict with edicts issued in the name of public health. In its most optimistic explication, One Health aims to attain optimal health for humans, non-human animals and their shared environments. As a field, public health ethics needs to move beyond an exclusive preoccupation with humans, so as to account for moral complexity arising from people's diverse connections with places, plants, and non-human animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Genomes

    National Research Council Canada - National Science Library

    Brown, T. A. (Terence A.)

    2002-01-01

    ... of genome expression and replication processes, and transcriptomics and proteomics. This text is richly illustrated with clear, easy-to-follow, full color diagrams, which are downloadable from the book's website...

  20. State of human genome at low-doses ecological influences

    International Nuclear Information System (INIS)

    Mel'nov, S.B.; Rytik, P.G.; Kruchinskij, N.G.; Kovalev, V.A.; Palamar, L.A.; Senyuk, O.F.

    2005-01-01

    The results of analysis of the state of genome (amounts of single strand breaks in DNA) of the persons exposed to influence of complex 'Chernobyl factor' in remote terms after a failure on ChNPP are resulted. Findings allowed to expose the increase of level of single strand breaks in DNA at the chronically irradiated persons mainly carry adaptive character and probably can be related to instability of genome. Thus at organism level growth of mutational pressure and strengthening of instability of cellular genome is related to the change of spectrum of biological characteristics, in particular individual reaction of somatic cells of victims on additional mutagens influences. The indicated changes can testify to existence of potential risk of remote genetic consequences of long-term irradiation influence in low doses

  1. The Significance of UNESCO’s Universal Declaration on the Human Genome & Human Rights

    Directory of Open Access Journals (Sweden)

    Shawn H.E. Harmon

    2005-03-01

    Full Text Available Modern medical research, particularly genetic research, is changing the nature of medicine. Concerns surrounding these changes and their potential negative impact on human rights led UNESCO to spearhead collaboration by experts in the creation of an international instrument intended to provide guidance for the promotion of bioethics and the protection of human rights in the genetic context. The result was the Universal Declaration of the Human Genome and Human Rights. This article briefly highlights the scientific and social setting into which the Declaration was injected. This is followed by a consideration of the drafting body (the IBC so as to assess whether UNESCO was the appropriate body to lead this project. The process by which the Declaration was created is also considered so as to assess whether it represents an example of ethical and democratic drafting. Finally, the substantive content of the Declaration is considered and measured against the pre-existing regime so as to assess whether it represents an intelligible and coherent response to the concerns raised capable of offering guidance now and into the future. By assessing these procedural and substantive matters, one can draw some tentative conclusions about the utility and significance of the Declaration.

  2. Shared regulatory sites are abundant in the human genome and shed light on genome evolution and disease pleiotropy.

    Science.gov (United States)

    Tong, Pin; Monahan, Jack; Prendergast, James G D

    2017-03-01

    Large-scale gene expression datasets are providing an increasing understanding of the location of cis-eQTLs in the human genome and their role in disease. However, little is currently known regarding the extent of regulatory site-sharing between genes. This is despite it having potentially wide-ranging implications, from the determination of the way in which genetic variants may shape multiple phenotypes to the understanding of the evolution of human gene order. By first identifying the location of non-redundant cis-eQTLs, we show that regulatory site-sharing is a relatively common phenomenon in the human genome, with over 10% of non-redundant regulatory variants linked to the expression of multiple nearby genes. We show that these shared, local regulatory sites are linked to high levels of chromatin looping between the regulatory sites and their associated genes. In addition, these co-regulated gene modules are found to be strongly conserved across mammalian species, suggesting that shared regulatory sites have played an important role in shaping human gene order. The association of these shared cis-eQTLs with multiple genes means they also appear to be unusually important in understanding the genetics of human phenotypes and pleiotropy, with shared regulatory sites more often linked to multiple human phenotypes than other regulatory variants. This study shows that regulatory site-sharing is likely an underappreciated aspect of gene regulation and has important implications for the understanding of various biological phenomena, including how the two and three dimensional structures of the genome have been shaped and the potential causes of disease pleiotropy outside coding regions.

  3. Evolution of the NANOG pseudogene family in the human and chimpanzee genomes

    Directory of Open Access Journals (Sweden)

    Maughan Peter J

    2006-02-01

    Full Text Available Abstract Background The NANOG gene is expressed in mammalian embryonic stem cells where it maintains cellular pluripotency. An unusually large family of pseudogenes arose from it with one unprocessed and ten processed pseudogenes in the human genome. This article compares the NANOG gene and its pseudogenes in the human and chimpanzee genomes and derives an evolutionary history of this pseudogene family. Results The NANOG gene and all pseudogenes except NANOGP8 are present at their expected orthologous chromosomal positions in the chimpanzee genome when compared to the human genome, indicating that their origins predate the human-chimpanzee divergence. Analysis of flanking DNA sequences demonstrates that NANOGP8 is absent from the chimpanzee genome. Conclusion Based on the most parsimonious ordering of inferred source-gene mutations, the deduced evolutionary origins for the NANOG pseudogene family in the human and chimpanzee genomes, in order of most ancient to most recent, are NANOGP6, NANOGP5, NANOGP3, NANOGP10, NANOGP2, NANOGP9, NANOGP7, NANOGP1, and NANOGP4. All of these pseudogenes were fixed in the genome of the human-chimpanzee common ancestor. NANOGP8 is the most recent pseudogene and it originated exclusively in the human lineage after the human-chimpanzee divergence. NANOGP1 is apparently an unprocessed pseudogene. Comparison of its sequence to the functional NANOG gene's reading frame suggests that this apparent pseudogene remained functional after duplication and, therefore, was subject to selection-driven conservation of its reading frame, and that it may retain some functionality or that its loss of function may be evolutionarily recent.

  4. Microarray Data Processing Techniques for Genome-Scale Network Inference from Large Public Repositories.

    Science.gov (United States)

    Chockalingam, Sriram; Aluru, Maneesha; Aluru, Srinivas

    2016-09-19

    Pre-processing of microarray data is a well-studied problem. Furthermore, all popular platforms come with their own recommended best practices for differential analysis of genes. However, for genome-scale network inference using microarray data collected from large public repositories, these methods filter out a considerable number of genes. This is primarily due to the effects of aggregating a diverse array of experiments with different technical and biological scenarios. Here we introduce a pre-processing pipeline suitable for inferring genome-scale gene networks from large microarray datasets. We show that partitioning of the available microarray datasets according to biological relevance into tissue- and process-specific categories significantly extends the limits of downstream network construction. We demonstrate the effectiveness of our pre-processing pipeline by inferring genome-scale networks for the model plant Arabidopsis thaliana using two different construction methods and a collection of 11,760 Affymetrix ATH1 microarray chips. Our pre-processing pipeline and the datasets used in this paper are made available at http://alurulab.cc.gatech.edu/microarray-pp.

  5. PCR-SSCP analysis and its application to human genome study

    International Nuclear Information System (INIS)

    Hayashi, Kenshi

    1994-01-01

    A large amount of DNA sequence data are now available owing to the development of the human genome project. These data are deposited in public databases, e.g. DDBJ, GebBank and EMBL, and freely accessible to scientific community. One of the major advantages of having these databases is that we can now detect sequence differences between individuals in a large scale. Using the sequence informations, we can design primer sequences, amplify various target regions of the sample DNA's by PCR and detect abnormal sequence changes from reference, or normal sequences. Detecting sequence changes, or mutations, are essential part of searching genes responsible for hereditary diseases and also DNA diagnosis of hereditary diseases or cancer. We can also measure mutation frequency of the human genome by knowing its variability. Our group has developed and been improving a method, PCR-SSCP analysis, as an extremely rapid and easy technique for detection of sequence differences between sample DNA's. Knowing the sensitivity (percentage detection of mutations) of this technique is important in evaluating usefulness of it for the purposes stated above. Considerable number of experiences on PCR-SSCP analysis of fragments shorter than 300 b.p. are accumulating. We summarize here the sensitivity of PCR-SSCP analysis for various sequence context of this size range examined in various electrophoretic conditions conducted in many laboratories. Data on mutation detection by this technique for longer fragments are limited. We also present oue effort for defining electrophoretic conditions of PCR-SSCP analysis when examining longer (350 to 600 b.p.) fragments. (author)

  6. Distinct p53 genomic binding patterns in normal and cancer-derived human cells

    Energy Technology Data Exchange (ETDEWEB)

    Botcheva K.; McCorkle S. R.; McCombie W. R.; Dunn J. J.; Anderson C. W.

    2011-12-15

    We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

  7. Human rights, public health and medicinal cannabis use.

    Science.gov (United States)

    Bone, Melissa; Seddon, Toby

    2016-01-01

    This paper explores the interplay between the human rights and drug control frameworks and critiques case law on medicinal cannabis use to demonstrate that a bona fide human rights perspective allows for a broader conception of 'health'. This broad conception, encompassing both medicalised and social constructionist definitions, can inform public health policies relating to medicinal cannabis use. The paper also demonstrates how a human rights lens can alleviate a core tension between the State and the individual within the drug policy field. The leading medicinal cannabis case in the UK highlights the judiciary's failure to engage with an individual's human right to health as they adopt an arbitrary, externalist view, focussing on the legality of cannabis to the exclusion of other concerns. Drawing on some international comparisons, the paper considers how a human rights perspective can lead to an approach to medicinal cannabis use which facilitates a holistic understanding of public health.

  8. Mapping and annotating obesity-related genes in pig and human genomes.

    Science.gov (United States)

    Martelli, Pier Luigi; Fontanesi, Luca; Piovesan, Damiano; Fariselli, Piero; Casadio, Rita

    2014-01-01

    Background. Obesity is a major health problem in both developed and emerging countries. Obesity is a complex disease whose etiology involves genetic factors in strong interplay with environmental determinants and lifestyle. The discovery of genetic factors and biological pathways underlying human obesity is hampered by the difficulty in controlling the genetic background of human cohorts. Animal models are then necessary to further dissect the genetics of obesity. Pig has emerged as one of the most attractive models, because of the similarity with humans in the mechanisms regulating the fat deposition. Results. We collected the genes related to obesity in humans and to fat deposition traits in pig. We localized them on both human and pig genomes, building a map useful to interpret comparative studies on obesity. We characterized the collected genes structurally and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein interaction network. Conclusions. The collected set consists of 361 obesity related genes in human and pig genomes. All genes were mapped on the human genome, and 54 could not be localized on the pig genome (release 2012). Only for 3 human genes there is no counterpart in pig, confirming that this animal is a good model for human obesity studies. Obesity related genes are mostly involved in regulation and signaling processes/pathways and relevant connection emerges between obesity-related genes and diseases such as cancer and infectious diseases.

  9. Shift in genomic RNA patterns of human rotaviruses isolated from ...

    African Journals Online (AJOL)

    Rotalvirus-positive specimens from 322 infants and young children submitted to private patl1ology laboratories were analysed by polyacrylamide-gel electrophoresis of the viral RNA. A predominance of long RNA profiles occurred and a temporal shift in the genomic patterns was identified. An epidemic of the classic shorter ...

  10. Targeted genome editing in human repopulating haematopoietic stem cells

    NARCIS (Netherlands)

    P. Genovese (Pietro); G. Schiroli (Giulia); G. Escobar (Giulia); T. Di Tomaso (Tiziano); C. Firrito (Claudia); A. Calabria (Andrea); D. Moi (Davide); R. Mazzieri (Roberta); C. Bonini (Chiara); M.V. Holmes (Michael); P.D. Gregory (Philip); M. van der Burg (Mirjam); B. Gentner (Bernhard); E. Montini (Eugenio); A. Lombardo (Angelo); L. Naldini (Luigi)

    2014-01-01

    textabstractTargeted genome editing by artificial nucleases has brought the goal of site-specific transgene integration and gene correction within the reach of gene therapy. However, its application to long-term repopulating haematopoietic stem cells (HSCs) has remained elusive. Here we show that

  11. Sequence Analysis and Characterization of Active Human Alu Subfamilies Based on the 1000 Genomes Pilot Project.

    Science.gov (United States)

    Konkel, Miriam K; Walker, Jerilyn A; Hotard, Ashley B; Ranck, Megan C; Fontenot, Catherine C; Storer, Jessica; Stewart, Chip; Marth, Gabor T; Batzer, Mark A

    2015-08-29

    The goal of the 1000 Genomes Consortium is to characterize human genome structural variation (SV), including forms of copy number variations such as deletions, duplications, and insertions. Mobile element insertions, particularly Alu elements, are major contributors to genomic SV among humans. During the pilot phase of the project we experimentally validated 645 (611 intergenic and 34 exon targeted) polymorphic "young" Alu insertion events, absent from the human reference genome. Here, we report high resolution sequencing of 343 (322 unique) recent Alu insertion events, along with their respective target site duplications, precise genomic breakpoint coordinates, subfamily assignment, percent divergence, and estimated A-rich tail lengths. All the sequenced Alu loci were derived from the AluY lineage with no evidence of retrotransposition activity involving older Alu families (e.g., AluJ and AluS). AluYa5 is currently the most active Alu subfamily in the human lineage, followed by AluYb8, and many others including three newly identified subfamilies we have termed AluYb7a3, AluYb8b1, and AluYa4a1. This report provides the structural details of 322 unique Alu variants from individual human genomes collectively adding about 100 kb of genomic variation. Many Alu subfamilies are currently active in human populations, including a surprising level of AluY retrotransposition. Human Alu subfamilies exhibit continuous evolution with potential drivers sprouting new Alu lineages. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  12. Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative.

    Science.gov (United States)

    Wang, Jun; Kurilshikov, Alexander; Radjabzadeh, Djawad; Turpin, Williams; Croitoru, Kenneth; Bonder, Marc Jan; Jackson, Matthew A; Medina-Gomez, Carolina; Frost, Fabian; Homuth, Georg; Rühlemann, Malte; Hughes, David; Kim, Han-Na; Spector, Tim D; Bell, Jordana T; Steves, Claire J; Timpson, Nicolas; Franke, Andre; Wijmenga, Cisca; Meyer, Katie; Kacprowski, Tim; Franke, Lude; Paterson, Andrew D; Raes, Jeroen; Kraaij, Robert; Zhernakova, Alexandra

    2018-06-08

    In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture. Here, we announce the MiBioGen consortium initiative, which has assembled 18 population-level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full-genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta-analyses of genome-wide associations. All pipeline and summary statistics results will be shared using public data repositories. We present the largest consortium to date devoted to microbiota-GWAS. We have adapted our analytical pipelines to suit multi-cohort analyses and expect to gain insight into host-microbiota cross-talk at the genome-wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.

  13. The evolution of human influenza A viruses from 1999 to 2006: A complete genome study

    Directory of Open Access Journals (Sweden)

    Fomsgaard Anders

    2008-03-01

    Full Text Available Abstract Background Knowledge about the complete genome constellation of seasonal influenza A viruses from different countries is valuable for monitoring and understanding of the evolution and migration of strains. Few complete genome sequences of influenza A viruses from Europe are publicly available at the present time and there have been few longitudinal genome studies of human influenza A viruses. We have studied the evolution of circulating human H3N2, H1N1 and H1N2 influenza A viruses from 1999 to 2006, we analysed 234 Danish human influenza A viruses and characterised 24 complete genomes. Results H3N2 was the prevalent strain in Denmark during the study period, but H1N1 dominated the 2000–2001 season. H1N2 viruses were first observed in Denmark in 2002–2003. After years of little genetic change in the H1N1 viruses the 2005–2006 season presented H1N1 of greater variability than before. This indicates that H1N1 viruses are evolving and that H1N1 soon is likely to be the prevalent strain again. Generally, the influenza A haemagglutinin (HA of H3N2 viruses formed seasonal phylogenetic clusters. Different lineages co-circulating within the same season were also observed. The evolution has been stochastic, influenced by small "jumps" in genetic distance rather than constant drift, especially with the introduction of the Fujian-like viruses in 2002–2003. Also evolutionary stasis-periods were observed which might indicate well fit viruses. The evolution of H3N2 viruses have also been influenced by gene reassortments between lineages from different seasons. None of the influenza genes were influenced by strong positive selection pressure. The antigenic site B in H3N2 HA was the preferred site for genetic change during the study period probably because the site A has been masked by glycosylations. Substitutions at CTL-epitopes in the genes coding for the neuraminidase (NA, polymerase acidic protein (PA, matrix protein 1 (M1, non

  14. The evolution of human influenza A viruses from 1999 to 2006: a complete genome study.

    Science.gov (United States)

    Bragstad, Karoline; Nielsen, Lars P; Fomsgaard, Anders

    2008-03-07

    Knowledge about the complete genome constellation of seasonal influenza A viruses from different countries is valuable for monitoring and understanding of the evolution and migration of strains. Few complete genome sequences of influenza A viruses from Europe are publicly available at the present time and there have been few longitudinal genome studies of human influenza A viruses. We have studied the evolution of circulating human H3N2, H1N1 and H1N2 influenza A viruses from 1999 to 2006, we analysed 234 Danish human influenza A viruses and characterised 24 complete genomes. H3N2 was the prevalent strain in Denmark during the study period, but H1N1 dominated the 2000-2001 season. H1N2 viruses were first observed in Denmark in 2002-2003. After years of little genetic change in the H1N1 viruses the 2005-2006 season presented H1N1 of greater variability than before. This indicates that H1N1 viruses are evolving and that H1N1 soon is likely to be the prevalent strain again. Generally, the influenza A haemagglutinin (HA) of H3N2 viruses formed seasonal phylogenetic clusters. Different lineages co-circulating within the same season were also observed. The evolution has been stochastic, influenced by small "jumps" in genetic distance rather than constant drift, especially with the introduction of the Fujian-like viruses in 2002-2003. Also evolutionary stasis-periods were observed which might indicate well fit viruses. The evolution of H3N2 viruses have also been influenced by gene reassortments between lineages from different seasons. None of the influenza genes were influenced by strong positive selection pressure. The antigenic site B in H3N2 HA was the preferred site for genetic change during the study period probably because the site A has been masked by glycosylations. Substitutions at CTL-epitopes in the genes coding for the neuraminidase (NA), polymerase acidic protein (PA), matrix protein 1 (M1), non-structural protein 1 (NS1) and especially the nucleoprotein (NP

  15. Genetic recombination pathways and their application for genome modification of human embryonic stem cells.

    Science.gov (United States)

    Nieminen, Mikko; Tuuri, Timo; Savilahti, Harri

    2010-10-01

    Human embryonic stem cells are pluripotent cells derived from early human embryo and retain a potential to differentiate into all adult cell types. They provide vast opportunities in cell replacement therapies and are expected to become significant tools in drug discovery as well as in the studies of cellular and developmental functions of human genes. The progress in applying different types of DNA recombination reactions for genome modification in a variety of eukaryotic cell types has provided means to utilize recombination-based strategies also in human embryonic stem cells. Homologous recombination-based methods, particularly those utilizing extended homologous regions and those employing zinc finger nucleases to boost genomic integration, have shown their usefulness in efficient genome modification. Site-specific recombination systems are potent genome modifiers, and they can be used to integrate DNA into loci that contain an appropriate recombination signal sequence, either naturally occurring or suitably pre-engineered. Non-homologous recombination can be used to generate random integrations in genomes relatively effortlessly, albeit with a moderate efficiency and precision. DNA transposition-based strategies offer substantially more efficient random strategies and provide means to generate single-copy insertions, thus potentiating the generation of genome-wide insertion libraries applicable in genetic screens. 2010 Elsevier Inc. All rights reserved.

  16. The post-Human Genome Project mindset: race, reliability, and health care.

    Science.gov (United States)

    Kimmelman, J

    2006-11-01

    The following essay reports on the first session of a 2-day workshop on genetic diversity and science communication, organized by the Institute of Genetics. I argue that the four talks in this session reflected two different facets of a 'post-Human Genome Project (HGP)' view of human genetics. The first is characterized by an increasing interest in genetic differences. Two speakers - Troy Duster and Jasber Singh - expressed skepticism about one aspect of this trend: an emphasis on race in medicine and genetics. The other two speakers - Kenneth Weiss and Gustavo Turecki - spoke to a second facet of the post-HGP view: a recognition of the difficulty in translating genetic discovery into medical or public health applications. Though both sets of talks were highly critical of current trends in genetic research, they pulled in opposite directions: one warned about the role of genetics in stabilizing racial categories, while the other lamented the failure of any genetic claims or categories to stabilize at all. I argue that the use of racial categories in medicine seems likely to encounter scientific, medical, and social challenges.

  17. The Human Genome Project: Information access, management, and regulation. Final report

    Energy Technology Data Exchange (ETDEWEB)

    McInerney, J.D.; Micikas, L.B.

    1996-08-31

    The Human Genome Project is a large, internationally coordinated effort in biological research directed at creating a detailed map of human DNA. This report describes the access of information, management, and regulation of the project. The project led to the development of an instructional module titled The Human Genome Project: Biology, Computers, and Privacy, designed for use in high school biology classes. The module consists of print materials and both Macintosh and Windows versions of related computer software-Appendix A contains a copy of the print materials and discs containing the two versions of the software.

  18. The Human Genome Project and the social contract: a law policy approach.

    Science.gov (United States)

    Byk, C

    1992-08-01

    For the first time in history, genetics will enable science to completely identify each human as genetically unique. Will this knowledge reinforce the trend for more individual liberties or will it create a 'brave new world'? A law policy approach to the problems raised by the human genome project shows how far our democratic institutions are from being the proper forum to discuss such issues. Because of the fears and anxiety raised in the population, and also because of its wide implications on the everyday life, the human genome analysis more than any other project needs to succeed in setting up such a social assessment.

  19. Use of genome editing tools in human stem cell-based disease modeling and precision medicine.

    Science.gov (United States)

    Wei, Yu-da; Li, Shuang; Liu, Gai-gai; Zhang, Yong-xian; Ding, Qiu-rong

    2015-10-01

    Precision medicine emerges as a new approach that takes into account individual variability. The successful conduct of precision medicine requires the use of precise disease models. Human pluripotent stem cells (hPSCs), as well as adult stem cells, can be differentiated into a variety of human somatic cell types that can be used for research and drug screening. The development of genome editing technology over the past few years, especially the CRISPR/Cas system, has made it feasible to precisely and efficiently edit the genetic background. Therefore, disease modeling by using a combination of human stem cells and genome editing technology has offered a new platform to generate " personalized " disease models, which allow the study of the contribution of individual genetic variabilities to disease progression and the development of precise treatments. In this review, recent advances in the use of genome editing in human stem cells and the generation of stem cell models for rare diseases and cancers are discussed.

  20. Genetics, health care, and public policy: an introduction to public health genetics

    National Research Council Canada - National Science Library

    Stewart, Alison

    2007-01-01

    ... initiative About this book Further reading and resources Principles of public health The emergence of public health genetics The human genome project and 'genomic medicine' Community genetics Current developments in public health genetics Genomics and global health 2 Genetic science and technology Basic molecular genetics Genes and the geno...