Human Genetics. Informational and Educational Materials, Vol. I, No. 1.
National Clearinghouse for Human Genetic Diseases (DHEW/PHS), Rockville, MD.
This catalogue, prepared by the National Clearinghouse for Human Genetic Diseases, provides educational and informational materials on the latest advances in testing, diagnosing, counseling, and treating individuals with a concern for genetic diseases. The materials include books, brochures, pamphlets, journal articles, audio cassettes,…
Insects feeding on cadavers as an alternative source of human genetic material
Directory of Open Access Journals (Sweden)
Rafał Skowronek
2015-03-01
Full Text Available In some criminal cases, the use of classical sources of human genetic material is difficult or even impossible. One solution may be the use of insects, especially blowfly larvae which feed on corpses. A recent review of case reports and experimental studies available in biomedical databases has shown that insects can be a valuable source of human mitochondrial and genomic deoxyribonucleic acid (DNA, allowing for an effective analysis of hypervariable region (HVR sequences and short tandem repeat (STR profiles, respectively. The optimal source of human DNA is the crop (a part of the gut of active third-instar blowfly larvae. Pupae and insect faeces can be also used in forensic genetic practice instead of the contents of the alimentary tract.
Source Identification of Human Biological Materials and Its Prospect in Forensic Science.
Zou, K N; Gui, C; Gao, Y; Yang, F; Zhou, H G
2016-06-01
Source identification of human biological materials in crime scene plays an important role in reconstructing the crime process. Searching specific genetic markers to identify the source of different human biological materials is the emphasis and difficulty of the research work of legal medical experts in recent years. This paper reviews the genetic markers which are used for identifying the source of human biological materials and studied widely, such as DNA methylation, mRNA, microRNA, microflora and protein, etc. By comparing the principles and methods of source identification of human biological materials using different kinds of genetic markers, different source of human biological material owns suitable marker types and can be identified by detecting single genetic marker or combined multiple genetic markers. Though there is no uniform standard and method for identifying the source of human biological materials in forensic laboratories at present, the research and development of a series of mature and reliable methods for distinguishing different human biological materials play the role as forensic evidence which will be the future development direction. Copyright© by the Editorial Department of Journal of Forensic Medicine.
Issues related to the use of genetic material and information.
Giarelli, E; Jacobs, L A
2000-04-01
To review issues regarding the use of genetic materials and information. Professional literature, regional and federal legislation. An analysis is provided of the relationship among advances in genetic technology, use of genetic material and information, and the development of laws that protect the interests of donors, researchers, and insurers. Rapid technological achievements have generated complex questions that are difficult to answer. The Human Genome Project began and the scientific discoveries were put to use before adequate professional and public debate on the ethical, legal, social, and clinical issues. The term "proper use" of genetic material and information is not defined consistently. An incomplete patchwork of protective state and federal legislation exists. Many complicated issues surround the use and potential misuse of genetic material and information. Rapidly advancing technology in genetics makes it difficult for regulations that protect individuals and families to keep pace. Oncology nurses need to recognize their role as change agents, understand genetic technology, and advocate for patients by participating in the debate on the proper use and prevention of misuse of genetic material and information.
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.
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.
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.
Evaluating human genetic diversity
National Research Council Canada - National Science Library
This book assesses the scientific value and merit of research on human genetic differences--including a collection of DNA samples that represents the whole of human genetic diversity--and the ethical...
Morphological and Genetic Diversity of Trichuris spp. recovered from Humans and Pigs
DEFF Research Database (Denmark)
Nissen, Sofie; Nejsum, Peter; Christensen, Henrik
2009-01-01
The nematodes, Trichuris suis and Trichuris trichiura are believed to be two separate but closely related species. The aim of our study was to examine the morphological and genetic diversity of Trichuris spp. recovered from pigs and humans. Sympatric worm material isolated from 10 humans and 5 pigs...... found in pig-derived worms (31% of the human-derived worms, consensus sequence 531 nucleotides long). The results indicated that the nematodes found in pigs belong to a genetically distinct species (T. suis) whereas the nematodes in humans showed considerable genetic variability either related...... to ancestral polymorphism or more recent cross-breeding between T. trichiura and T. suis....
Genetics of human hydrocephalus
Williams, Michael A.; Rigamonti, Daniele
2006-01-01
Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human
[Quality assurance in human genetic testing].
Stuhrmann-Spangenberg, Manfred
2015-02-01
Advances in technical developments of genetic diagnostics for more than 50 years, as well as the fact that human genetic testing is usually performed only once in a lifetime, with additional impact for blood relatives, are determining the extraordinary importance of quality assurance in human genetic testing. Abidance of laws, directives, and guidelines plays a major role. This article aims to present the major laws, directives, and guidelines with respect to quality assurance of human genetic testing, paying careful attention to internal and external quality assurance. The information on quality assurance of human genetic testing was obtained through a web-based search of the web pages that are referred to in this article. Further information was retrieved from publications in the German Society of Human Genetics and through a PubMed-search using term quality + assurance + genetic + diagnostics. The most important laws, directives, and guidelines for quality assurance of human genetic testing are the gene diagnostics law (GenDG), the directive of the Federal Medical Council for quality control of clinical laboratory analysis (RiliBÄK), and the S2K guideline for human genetic diagnostics and counselling. In addition, voluntary accreditation under DIN EN ISO 15189:2013 offers a most recommended contribution towards quality assurance of human genetic testing. Legal restraints on quality assurance of human genetic testing as mentioned in § 5 GenDG are fulfilled once RiliBÄK requirements are followed.
Scaling up: human genetics as a Cold War network.
Lindee, Susan
2014-09-01
In this commentary I explore how the papers here illuminate the processes of collection that have been so central to the history of human genetics since 1945. The development of human population genetics in the Cold War period produced databases and biobanks that have endured into the present, and that continue to be used and debated. In the decades after the bomb, scientists collected and transferred human biological materials and information from populations of interest, and as they moved these biological resources or biosocial resources acquired new meanings and uses. The papers here collate these practices and map their desires and ironies. They explore how a large international network of geneticists, biological anthropologists, virologists and other physicians and scientists interacted with local informants, research subjects and public officials. They also track the networks and standards that mobilized the transfer of information, genealogies, tissue and blood samples. As Joanna Radin suggests here, the massive collections of human biological materials and data were often understood to be resources for an "as-yet-unknown" future. The stories told here contain elements of surveillance, extraction, salvage and eschatology. Copyright © 2014 Elsevier Ltd. All rights reserved.
Environmental and genetic interactions in human cancer
International Nuclear Information System (INIS)
Paterson, M.C.
Humans, depending upon their genetic make-up, differ in their susceptibility to the cancer-causing effects of extrinsic agents. Clinical and laboratory studies on the hereditary disorder, ataxia telangiectasia (AT) show that persons afflicted with this are cancer-prone and unusually sensitive to conventional radiotherapy. Their skin cells, when cultured, are hypersensitive to killing by ionizing radiation, being defective in the enzymatic repair of radiation-induced damange to the genetic material, deoxyribonucleic acid (DNA). This molecular finding implicates DNA damage and its imperfect repair as an early step in the induction of human cancer by radiation and other carcinogens. The parents of AT patients are clincally normal but their cultured cells are often moderately radiosensitive. The increased radiosensitivity of cultured cells offers a means of identifying a presumed cancer-prone subpopulation that should avoid undue exposure to certain carcinogens. The radioresponse of cells from patients with other cancer-associated genetic disorders and persons suspected of being genetically predisposed to radiation-induced cancer has also been measured. Increased cell killing by γ-rays appears in the complex genetic disease, tuberous sclerosis. Cells from cancer-stricken members of a leukemia-prone family are also radiosensitive, as are cells from one patient with radiation-associated breast cancer. These radiobiological data, taken together, strongly suggest that genetic factors can interact with extrinsic agents and thereby play a greater causative role in the development of common cancers in man than previously thought. (L.L.)
Personalized medicine and human genetic diversity.
Lu, Yi-Fan; Goldstein, David B; Angrist, Misha; Cavalleri, Gianpiero
2014-07-24
Human genetic diversity has long been studied both to understand how genetic variation influences risk of disease and infer aspects of human evolutionary history. In this article, we review historical and contemporary views of human genetic diversity, the rare and common mutations implicated in human disease susceptibility, and the relevance of genetic diversity to personalized medicine. First, we describe the development of thought about diversity through the 20th century and through more modern studies including genome-wide association studies (GWAS) and next-generation sequencing. We introduce several examples, such as sickle cell anemia and Tay-Sachs disease that are caused by rare mutations and are more frequent in certain geographical populations, and common treatment responses that are caused by common variants, such as hepatitis C infection. We conclude with comments about the continued relevance of human genetic diversity in medical genetics and personalized medicine more generally. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.
Protocols in human molecular genetics
National Research Council Canada - National Science Library
Mathew, Christopher G
1991-01-01
... sequences has led to the development of DNA fingerprinting. The application of these techniques to the study of the human genome has culminated in major advances such as the cloning of the cystic fibrosis gene, the construction of genetic linkage maps of each human chromosome, the mapping of many genes responsible for human inherited disorders, genet...
Human genetics and sleep behavior.
Shi, Guangsen; Wu, David; Ptáček, Louis J; Fu, Ying-Hui
2017-06-01
Why we sleep remains one of the greatest mysteries in science. In the past few years, great advances have been made to better understand this phenomenon. Human genetics has contributed significantly to this movement, as many features of sleep have been found to be heritable. Discoveries about these genetic variations that affect human sleep will aid us in understanding the underlying mechanism of sleep. Here we summarize recent discoveries about the genetic variations affecting the timing of sleep, duration of sleep and EEG patterns. To conclude, we also discuss some of the sleep-related neurological disorders such as Autism Spectrum Disorder (ASD) and Alzheimer's Disease (AD) and the potential challenges and future directions of human genetics in sleep research. Copyright © 2017 Elsevier Ltd. All rights reserved.
Fujimura, Joan H.; Rajagopalan, Ramya
2011-01-01
This article presents findings from our ethnographic research on biomedical scientists’ studies of human genetic variation and common complex disease. We examine the socio-material work involved in genome-wide association studies (GWAS) and discuss whether, how, and when notions of race and ethnicity are or are not used. We analyze how researchers produce simultaneously different kinds of populations and population differences. Although many geneticists use race in their analyses, we find some who have invented a statistical genetics method and associated software that they use specifically to avoid using categories of race in their genetics analysis. Their method allows them to operationalize their concept of ‘genetic ancestry’ without resorting to notions of race and ethnicity. We focus on the construction and implementation of the software’s algorithms, and discuss the consequences and implications of the software technology for debates and policies around the use of race in genetics research. We also demonstrate that the production and use of their method involves a dynamic and fluid assemblage of actors in various disciplines responding to disciplinary and sociopolitical contexts and concerns. This assemblage also includes particular discourses on human history and geography as they become entangled with research on genetic markers and disease. We introduce the concept of ‘genome geography’, to analyze how some researchers studying human genetic variation ‘locate’ stretches of DNA in different places and times. The concept of genetic ancestry and the practice of genome geography rely on old discourses, but they also incorporate new technologies, infrastructures, and political and scientific commitments. Some of these new technologies provide opportunities to change some of our institutional and cultural forms and frames around notions of difference and similarity. Neverthless, we also highlight the slipperiness of genome geography and the
[Synthetic biology and rearrangements of microbial genetic material].
Liang, Quan-Feng; Wang, Qian; Qi, Qing-Sheng
2011-10-01
As an emerging discipline, synthetic biology has shown great scientific values and application prospects. Although there have been many reviews of various aspects on synthetic biology over the last years, this article, for the first time, attempted to discuss the relationship and difference between microbial genetics and synthetic biology. We summarized the recent development of synthetic biology in rearranging microbial genetic materials, including synthesis, design and reduction of genetic materials, standardization of genetic parts and modularization of genetic circuits. The relationship between synthetic biology and microbial genetic engineering was also discussed in the paper.
Genetics of Human and Canine Dilated Cardiomyopathy.
Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F N; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S
2015-01-01
Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.
Genetics 101 --The Hereditary Material of Life
... of this page please turn Javascript on. Feature: Genetics 101 Genetics 101 — The Hereditary Material of Life Past Issues / Summer 2013 Table of Contents Genetics is the study of heredity, the process in ...
Genetics of Human and Canine Dilated Cardiomyopathy
Directory of Open Access Journals (Sweden)
Siobhan Simpson
2015-01-01
Full Text Available Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.
Human genetic factors in tuberculosis: an update.
van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G
2017-09-01
Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.
Genetic Homogenization of Composite Materials
Directory of Open Access Journals (Sweden)
P. Tobola
2009-04-01
Full Text Available The paper is focused on numerical studies of electromagnetic properties of composite materials used for the construction of small airplanes. Discussions concentrate on the genetic homogenization of composite layers and composite layers with a slot. The homogenization is aimed to reduce CPU-time demands of EMC computational models of electrically large airplanes. First, a methodology of creating a 3-dimensional numerical model of a composite material in CST Microwave Studio is proposed focusing on a sufficient accuracy of the model. Second, a proper implementation of a genetic optimization in Matlab is discussed. Third, an association of the optimization script and a simplified 2-dimensional model of the homogeneous equivalent model in Comsol Multiphysics is proposed considering EMC issues. Results of computations are experimentally verified.
Archives: Egyptian Journal of Medical Human Genetics
African Journals Online (AJOL)
Items 1 - 34 of 34 ... Archives: Egyptian Journal of Medical Human Genetics. Journal Home > Archives: Egyptian Journal of Medical Human Genetics. Log in or Register to get access to full text downloads.
An overview of human genetic privacy.
Shi, Xinghua; Wu, Xintao
2017-01-01
The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. © 2016 New York Academy of Sciences.
An overview of human genetic privacy
Shi, Xinghua; Wu, Xintao
2016-01-01
The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that needs to be carefully addressed, not only for individuals but also for their families. In this paper, we present potential genetic privacy risks and relevant ethics and regulations for sharing and protecting human genomics data. We also describe the techniques for protecting human genetic privacy from three broad perspectives: controlled access, differential privacy, and cryptographic solutions. PMID:27626905
Genetics of Human and Canine Dilated Cardiomyopathy
Siobhan Simpson; Jennifer Edwards; Thomas F. N. Ferguson-Mignan; Malcolm Cobb; Nigel P. Mongan; Catrin S. Rutland
2015-01-01
Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In th...
Evaluating human genetic diversity
National Research Council Canada - National Science Library
... into human evolution and origins and serving as a springboard for important medical research. It also addresses issues of confidentiality and individual privacy for participants in genetic diversity research studies.
Genetic Testing and Its Implications: Human Genetics Researchers Grapple with Ethical Issues.
Rabino, Isaac
2003-01-01
Contributes systematic data on the attitudes of scientific experts who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. Finds that they are highly supportive of voluntary testing and the right to know one's genetic heritage. Calls for greater genetic literacy. (Contains 87 references.) (Author/NB)
Basic Genetics: A Human Approach.
Biological Sciences Curriculum Study, Colorado Springs, CO. Center for Education in Human and Medical Genetics.
This document (which has the form of a magazine) provides a variety of articles, stories, editorials, letters, interviews, and other types of magazine features (such as book reviews) which focus on human genetics. In addition to providing information about the principles of genetics, nearly all of the sections in the "magazine" address moral,…
Genetic radiation effects and natural radioactivity of human population in Brazil
International Nuclear Information System (INIS)
Freire-Maia, A.
1972-01-01
A study on areas of natural radioactivity is done, covering the genetic effects on human population. The study is done in depth dealing with aspecto such as radioactive area involved, discussion of materials and methods, errors and fallacies, influential factors, models, buildup and natural radioactivity, hypotheses, results and perspectives, etc. It covers 24 localites, 8.572 couples and 43.930 pregnancy cases [pt
Anastasiou, Evilena; Mitchell, Piers D
2013-10-01
The development of molecular tools for the extraction, analysis and interpretation of DNA from the remains of ancient organisms (paleogenetics) has revolutionised a range of disciplines as diverse as the fields of human evolution, bioarchaeology, epidemiology, microbiology, taxonomy and population genetics. The paper draws attention to some of the challenges associated with the extraction and interpretation of ancient DNA from archaeological material, and then reviews the influence of paleogenetics on the field of human evolution. It discusses the main contributions of molecular studies to reconstructing the evolutionary and phylogenetic relationships between extinct hominins (human ancestors) and anatomically modern humans. It also explores the evidence for evolutionary changes in the genetic structure of anatomically modern humans in recent millennia. This breadth of research has led to discoveries that would never have been possible using traditional approaches to human evolution. Copyright © 2013 Elsevier B.V. All rights reserved.
Genetic testing and its implications: human genetics researchers grapple with ethical issues.
Rabino, Isaac
2003-01-01
To better understand ethical issues involved in the field of human genetics and promote debate within the scientific community, the author surveyed scientists who engage in human genetics research about the pros, cons, and ethical implications of genetic testing. This study contributes systematic data on attitudes of scientific experts. The survey finds respondents are highly supportive of voluntary testing and the right to know one's genetic heritage. The majority consider in utero testing and consequent pregnancy termination acceptable for cases involving likelihood of serious disease but disapprove for genetic reasons they consider arbitrary, leaving a gray area of distinguishing between treatment of disorders and enhancement still to be resolved. While safeguarding patient confidentiality versus protecting at-risk third parties (kin, reproductive partners) presents a dilemma, preserving privacy from misuse by institutional third parties (employers, insurers) garners strong consensus for legislation against discrimination. Finally, a call is made for greater genetic literacy.
International Nuclear Information System (INIS)
1991-03-01
The present annual report describes the results of research work done by the Institute of Genetics and Toxicology of Fissionable Materials (IGT) in 1991. The following eight subjects were dealt with: genetic repair; genetic regulation; biological carcinogenesis; molecular genetics of eukaryontic genes; genetic mouse models for human illnesses; radiation toxicology of actinides; molecular and cellular environmental toxicology, and in vivo fractionation and speciation of actinides. (MG) [de
A genetic atlas of human admixture history.
Hellenthal, Garrett; Busby, George B J; Band, Gavin; Wilson, James F; Capelli, Cristian; Falush, Daniel; Myers, Simon
2014-02-14
Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed by using genetic data alone and encompassing over 100 events occurring over the past 4000 years. We identified events whose dates and participants suggest they describe genetic impacts of the Mongol empire, Arab slave trade, Bantu expansion, first millennium CE migrations in Eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations.
Governing the postmortem procurement of human body material for research.
Van Assche, Kristof; Capitaine, Laura; Pennings, Guido; Sterckx, Sigrid
2015-03-01
Human body material removed post mortem is a particularly valuable resource for research. Considering the efforts that are currently being made to study the biochemical processes and possible genetic causes that underlie cancer and cardiovascular and neurodegenerative diseases, it is likely that this type of research will continue to gain in importance. However, post mortem procurement of human body material for research raises specific ethical concerns, more in particular with regard to the consent of the research participant. In this paper, we attempt to determine which consent regime should govern the post mortem procurement of body material for research. In order to do so, we assess the various arguments that could be put forward in support of a duty to make body material available for research purposes after death. We argue that this duty does in practice not support conscription but is sufficiently strong to defend a policy of presumed rather than explicit consent.
Host genetic variation impacts microbiome composition across human body sites.
Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G
2015-09-15
The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.
Human genetic issues from scientific and Islamic perspectives | Alwi ...
African Journals Online (AJOL)
This paper aims at revealing the Human Genome Project (HGP) and human genetic issues arising from science and Islamic perspectives such as Darwin's evolutionary theory, human cloning and eugenics. Finally, issues arising from the applications of human genetic technology need to be addressed to the best possible ...
Study of human genetic diversity : inferences on population origin and history
Haber, Marc, 1980-
2013-01-01
Patterns of human genetic diversity suggest that all modern humans originated from a small population in Africa that expanded rapidly 50,000 years ago to occupy the whole world. While moving into new environments, genetic drift and natural selection affected populations differently, creating genetic structure. By understanding the genetic structure of human populations, we can reconstruct human history and understand the genetic basis of diseases. The work presented here contributes to the on...
A genetic atlas of human admixture history
Hellenthal, Garrett; Busby, George B.J.; Band, Gavin; Wilson, James F.; Capelli, Cristian
2014-01-01
Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed using genetic data alone and encompassing over 100 events occurring over the past 4,000 years. We identify events whose dates and participants suggest they describe genetic impacts of the Mongol Empire, Arab slave trade, Bantu expansion, first millennium CE migrations in eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations. PMID:24531965
Human genetics of diabetic vascular complications
Indian Academy of Sciences (India)
Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the cardiovascular system constitute a major public health problem. There is evidence demonstrating that genetic factors contribute to the risk of DVC genetic variants, structural variants, and epigenetic changes play ...
Genetic recombination between human and animal parasites creates novel strains of human pathogen.
Gibson, Wendy; Peacock, Lori; Ferris, Vanessa; Fischer, Katrin; Livingstone, Jennifer; Thomas, James; Bailey, Mick
2015-03-01
Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr) responsible for sleeping sickness (Human African Trypanosomiasis, HAT) in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.
Genetic recombination between human and animal parasites creates novel strains of human pathogen.
Directory of Open Access Journals (Sweden)
Wendy Gibson
2015-03-01
Full Text Available Genetic recombination between pathogens derived from humans and livestock has the potential to create novel pathogen strains, highlighted by the influenza pandemic H1N1/09, which was derived from a re-assortment of swine, avian and human influenza A viruses. Here we investigated whether genetic recombination between subspecies of the protozoan parasite, Trypanosoma brucei, from humans and animals can generate new strains of human pathogen, T. b. rhodesiense (Tbr responsible for sleeping sickness (Human African Trypanosomiasis, HAT in East Africa. The trait of human infectivity in Tbr is conferred by a single gene, SRA, which is potentially transferable to the animal pathogen Tbb by sexual reproduction. We tracked the inheritance of SRA in crosses of Tbr and Tbb set up by co-transmitting genetically-engineered fluorescent parental trypanosome lines through tsetse flies. SRA was readily transferred into new genetic backgrounds by sexual reproduction between Tbr and Tbb, thus creating new strains of the human pathogen, Tbr. There was no evidence of diminished growth or transmissibility of hybrid trypanosomes carrying SRA. Although expression of SRA is critical to survival of Tbr in the human host, we show that the gene exists as a single copy in a representative collection of Tbr strains. SRA was found on one homologue of chromosome IV in the majority of Tbr isolates examined, but some Ugandan Tbr had SRA on both homologues. The mobility of SRA by genetic recombination readily explains the observed genetic variability of Tbr in East Africa. We conclude that new strains of the human pathogen Tbr are being generated continuously by recombination with the much larger pool of animal-infective trypanosomes. Such novel recombinants present a risk for future outbreaks of HAT.
Behavior genetic modeling of human fertility
DEFF Research Database (Denmark)
Rodgers, J L; Kohler, H P; Kyvik, K O
2001-01-01
Behavior genetic designs and analysis can be used to address issues of central importance to demography. We use this methodology to document genetic influence on human fertility. Our data come from Danish twin pairs born from 1953 to 1959, measured on age at first attempt to get pregnant (First......Try) and number of children (NumCh). Behavior genetic models were fitted using structural equation modeling and DF analysis. A consistent medium-level additive genetic influence was found for NumCh, equal across genders; a stronger genetic influence was identified for FirstTry, greater for females than for males....... A bivariate analysis indicated significant shared genetic variance between NumCh and FirstTry....
Insights into the genetic foundations of human communication.
Graham, Sarah A; Deriziotis, Pelagia; Fisher, Simon E
2015-03-01
The human capacity to acquire sophisticated language is unmatched in the animal kingdom. Despite the discontinuity in communicative abilities between humans and other primates, language is built on ancient genetic foundations, which are being illuminated by comparative genomics. The genetic architecture of the language faculty is also being uncovered by research into neurodevelopmental disorders that disrupt the normally effortless process of language acquisition. In this article, we discuss the strategies that researchers are using to reveal genetic factors contributing to communicative abilities, and review progress in identifying the relevant genes and genetic variants. The first gene directly implicated in a speech and language disorder was FOXP2. Using this gene as a case study, we illustrate how evidence from genetics, molecular cell biology, animal models and human neuroimaging has converged to build a picture of the role of FOXP2 in neurodevelopment, providing a framework for future endeavors to bridge the gaps between genes, brains and behavior.
Human Genetic Engineering: A Survey of Student Value Stances
Wilson, Sara McCormack; And Others
1975-01-01
Assesses the values of high school and college students relative to human genetic engineering and recommends that biology educators explore instructional strategies merging human genetic information with value clarification techniques. (LS)
Genetic effects from internally deposited radionuclides
International Nuclear Information System (INIS)
Anon.
1987-01-01
It was learned in the late 1920's that ionizing radiation could produce genetic effects such as gene mutations and chromosome aberrations. However, at least until 1945, the focus on interest in radiation protection was primarily on somatic effects manifested in the individual exposed. Studies of the genetic effects of radiation using drosophila, however, refocused attention on effects transmitted to the exposed individuals offspring and concern over fallout in the 1950's resulted in efforts to estimate the genetic effects from exposure of human populations to internally deposited radionuclides. No human populations have been identified with burdens of internally deposited radioactive materials which have been shown to produce evidence of transmissible genetic damage. As a result, the research approach has been one in which macromolecular, cellular, and whole animal genetic studies have been combined to estimate genetic effects on humans following the deposition of radioactive materials in the body. The purpose of this report is to update the information available from animal and cellular experiments that relates genetic effects to deposited activity and dose from internally deposited radioactive materials
Li, Zhou Fang; Liang, Yi Min; Lau, Pui Ngan; Shen, Wei; Wang, Dai Kui; Cheung, Wing Tai; Xue, Chun Jason; Poon, Lit Man; Lam, Yun Wah
2013-01-01
Although microRNAs are commonly known to function as a component of RNA-induced silencing complexes in the cytoplasm, they have been detected in other organelles, notably the nucleus and the nucleolus, of mammalian cells. We have conducted a systematic search for miRNAs in HeLa cell nucleoli, and identified 11 abundant miRNAs with a high level of nucleolar accumulation. Through in situ hybridisation, we have localised these miRNAs, including miR-191 and miR-484, in the nucleolus of a diversity of human and rodent cell lines. The nucleolar association of these miRNAs is resistant to various cellular stresses, but highly sensitive to the presence of exogenous nucleic acids. Introduction of both single- and double-stranded DNA as well as double stranded RNA rapidly induce the redistribution of nucleolar miRNAs to the cytoplasm. A similar change in subcellular distribution is also observed in cells infected with the influenza A virus. The partition of miRNAs between the nucleolus and the cytoplasm is affected by Leptomycin B, suggesting a role of Exportin-1 in the intracellular shuttling of miRNAs. This study reveals a previously unknown aspect of miRNA biology, and suggests a possible link between these small noncoding RNAs and the cellular management of foreign genetic materials.
The concept of human dignity in the ethics of genetic research.
Chan, David K
2015-05-01
Despite criticism that dignity is a vague and slippery concept, a number of international guidelines on bioethics have cautioned against research that is contrary to human dignity, with reference specifically to genetic technology. What is the connection between genetic research and human dignity? In this article, I investigate the concept of human dignity in its various historical forms, and examine its status as a moral concept. Unlike Kant's ideal concept of human dignity, the empirical or relational concept takes human dignity as something that is affected by one's circumstances and what others do. I argue that the dignity objection to some forms of genetic research rests on a view of human nature that gives humans a special status in nature - one that is threatened by the potential of genetic research to reduce individuals to their genetic endowment. I distinguish two main philosophical accounts of human nature. One of these, the Aristotelian view, is compatible with the use of genetic technology to help humans realize their inherent potential to a fuller extent. © 2014 John Wiley & Sons Ltd.
Inauguration of the cameroonian society of human genetics.
Wonkam, Ambroise; Kenfack, Marcel Azabji; Bigoga, Jude; Nkegoum, Blaise; Muna, Wali
2009-10-20
The conjunction of "hard genetics" research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual meeting of the African Society of Human Genetics (AfSHG, 13th-15th March 2009) was an excellent opportunity to get together in synergy the entire Cameroonian "DNA/RNA scientists" . This laid to the foundation of the Cameroonian Society of Human Genetics (CSHG) that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health". The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an understanding of the state-of-knowledge of Human Origin and Genetic Diversity. Overall one opening ceremony eight session, five keynote and guest speakers, 18 invited oral communications, 13 free oral communications, 43 posters and two social events could summarize the meeting. This year's conference was graced by the presence of one Nobel Prize winner Dr Richard Roberts (Physiology and Medicine 1993). The meeting registered up to ten contributions of Cameroonian scientists from the Diaspora (currently in USA, Belgium, Gambia, Sudan and Zimbabwe). Such Diaspora participation is an opportunity to generate collaborations with home country scientists and ultimately turn the "brain drain" to "brain circulation" that could reduce the impact of the migration of health professional from Africa. Interestingly, the personal implication of the Cameroonian Ministry of Public Heath who opened the meeting in the presence of the Secretary General of the Ministry of Higher Education and a representative of the Ministry of Scientific Research and Innovation was a wonderful opportunity for advocacy of genetic issues at the decision-makers level. Beyond our expectation, a major promise of the Cameroonian government was the creation of the National Human
Human genetics in troubled times and places.
Harper, Peter S
2018-01-01
The development of human genetics world-wide during the twentieth century, especially across Europe, has occurred against a background of repeated catastrophes, including two world wars and the ideological problems and repression posed by Nazism and Communism. The published scientific literature gives few hints of these problems and there is a danger that they will be forgotten. The First World War was largely indiscriminate in its carnage, but World War 2 and the preceding years of fascism were associated with widespread migration, especially of Jewish workers expelled from Germany, and of their children, a number of whom would become major contributors to the post-war generation of human and medical geneticists in Britain and America. In Germany itself, eminent geneticists were also involved in the abuses carried out in the name of 'eugenics' and 'race biology'. However, geneticists in America, Britain and the rest of Europe were largely responsible for the ideological foundations of these abuses. In the Soviet Union, geneticists and genetics itself became the object of persecution from the 1930s till as late as the mid 1960s, with an almost complete destruction of the field during this time; this extended also to Eastern Europe and China as part of the influence of Russian communism. Most recently, at the end of the twentieth century, China saw a renewal of government sponsored eugenics programmes, now mostly discarded. During the post-world war 2 decades, human genetics research benefited greatly from recognition of the genetic dangers posed by exposure to radiation, following the atomic bomb explosions in Japan, atmospheric testing and successive accidental nuclear disasters in Russia. Documenting and remembering these traumatic events, now largely forgotten among younger workers, is essential if we are to fully understand the history of human genetics and avoid the repetition of similar disasters in the future. The power of modern human genetic and genomic
Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.
Macdonald, Lynn E; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T; Yasenchak, Jason; Frendewey, David; Valenzuela, David M; Giallourakis, Cosmas C; Alt, Frederick W; Yancopoulos, George D; Murphy, Andrew J
2014-04-08
Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.
Human population genetics and “ancestrality” business
André Langaney
2009-01-01
Following the foundation of theoretical population genetics by Wright, Fischer, Haldane and Malécot, in the first half of the 20th century, applied human population genetics developed with great success with the improvement and accumulation of new technologies to measure genetic polymorphism, first through protein polymorphisms since the 1960’s, then through DNA typing and sequencing since the 1980’s. The field of population genetics and biological anthropology was developed by a handful of d...
Inauguration of the Cameroonian Society of Human Genetics
Directory of Open Access Journals (Sweden)
Jude Bigoga
2009-10-01
Full Text Available The conjunction of “hard genetics” research centers, with well established biomedical and bioethics research groups, and the exceptional possibility to hold the 6th annual meeting of the African Society of Human Genetics (AfSHG, 13th-15th March 2009 was an excellent opportunity to get together in synergy the entire Cameroonian “DNA/RNA scientists” . This laid to the foundation of the Cameroonian Society of Human Genetics (CSHG that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health”. The AfSHG and CSHG invited leading African and international scientists in genomics and population genetics to review recent data and provide an understanding of the state-of-knowledge of Human Origin and Genetic Diversity. Overall one opening ceremony eight session, five keynote and guest speakers, 18 invited oral communications, 13 free oral communications, 43 posters and two social events could summarize the meeting. This year’s conference was graced by the presence of one Nobel Prize winner Dr Richard Roberts (Physiology and Medicine 1993. The meeting registered up to ten contributions of Cameroonian scientists from the Diaspora (currently in USA, Belgium, Gambia, Sudan and Zimbabwe. Such Diaspora participation is an opportunity to generate collaborations with home country scientists and ultimately turn the “brain drain” to “brain circulation” that could reduce the impact of the migration of health professional from Africa. Interestingly, the personal implication of the Cameroonian Ministry of Public Heath who opened the meeting in the presence of the Secretary General of the Ministry of Higher Education and a representative of the Ministry of Scientific Research and Innovation was a wonderful opportunity for advocacy of genetic issues at the decision-makers level. Beyond our expectation, a major promise of the Cameroonian government was
Energy Technology Data Exchange (ETDEWEB)
Harris, H.; Hirschhorn, K. (eds.)
1993-01-01
This book has five chapters covering peroxisomal diseases, X-linked immunodeficiencies, genetic mutations affecting human lipoproteins and their receptors and enzymes, genetic aspects of cancer, and Gaucher disease. The chapter on peroxisomes covers their discovery, structure, functions, disorders, etc. The chapter on X-linked immunodeficiencies discusses such diseases as agammaglobulinemia, severe combined immunodeficiency, Wiskott-Aldrich syndrome, animal models, linkage analysis, etc. Apolipoprotein formation, synthesis, gene regulation, proteins, etc. are the main focus of chapter 3. The chapter on cancer covers such topics as oncogene mapping and the molecular characterization of some recessive oncogenes. Gaucher disease is covered from its diagnosis, classification, and prevention, to its organ system involvement and molecular biology.
Seeking perfection: a Kantian look at human genetic engineering.
Gunderson, Martin
2007-01-01
It is tempting to argue that Kantian moral philosophy justifies prohibiting both human germ-line genetic engineering and non-therapeutic genetic engineering because they fail to respect human dignity. There are, however, good reasons for resisting this temptation. In fact, Kant's moral philosophy provides reasons that support genetic engineering-even germ-line and non-therapeutic. This is true of Kant's imperfect duties to seek one's own perfection and the happiness of others. It is also true of the categorical imperative. Kant's moral philosophy does, however, provide limits to justifiable genetic engineering.
The history and development of the Human Genetics Society of Australasia.
Sutherland, Grant R
2008-08-01
The Human Genetics Society of Australasia is a vibrant professional society with more than 900 members that promotes and regulates the practice of human and medical genetics in Australia and New Zealand. The growth of human genetics was stimulated by the development of diagnostic clinical cytogenetics laboratories in the early to mid 1960s. This coincided with the recognition by medical specialists, mainly pediatricians, that genetic disorders, especially inborn errors of metabolism and birth defects, were of clinical interest and potentially challenging areas for their skills. The organization of professionals in human genetics was slow to evolve. There was an early Western Australian Human Genetics Society, and the cytogenetics community had begun to meet annually from about 1966 but was coordinated by a mailing list rather than as a formal organization. In 1976, as part of the celebrations of the Centenary Year of the Adelaide Children's Hospital, a clinical genetics meeting involving several high profile international speakers and most of the senior medical geneticists in Australia and New Zealand along with the annual meeting of the loose-knit cytogeneticists group agreed that a small working group be charged with setting up a Human Genetics Society. The society was formally incorporated in South Australia in 1977.
Directory of Open Access Journals (Sweden)
Zhou Fang Li
Full Text Available Although microRNAs are commonly known to function as a component of RNA-induced silencing complexes in the cytoplasm, they have been detected in other organelles, notably the nucleus and the nucleolus, of mammalian cells. We have conducted a systematic search for miRNAs in HeLa cell nucleoli, and identified 11 abundant miRNAs with a high level of nucleolar accumulation. Through in situ hybridisation, we have localised these miRNAs, including miR-191 and miR-484, in the nucleolus of a diversity of human and rodent cell lines. The nucleolar association of these miRNAs is resistant to various cellular stresses, but highly sensitive to the presence of exogenous nucleic acids. Introduction of both single- and double-stranded DNA as well as double stranded RNA rapidly induce the redistribution of nucleolar miRNAs to the cytoplasm. A similar change in subcellular distribution is also observed in cells infected with the influenza A virus. The partition of miRNAs between the nucleolus and the cytoplasm is affected by Leptomycin B, suggesting a role of Exportin-1 in the intracellular shuttling of miRNAs. This study reveals a previously unknown aspect of miRNA biology, and suggests a possible link between these small noncoding RNAs and the cellular management of foreign genetic materials.
An existential analysis of genetic engineering and human rights ...
African Journals Online (AJOL)
Genetic engineering for purposes of human enhancement poses risks that justify regulation. However, this paper argues philosophically that it is inappropriate to use human rights treaties to prohibit germ-line genetic engineering whether therapeutic or for purposes of enhancement. When also looked at existentially, the ...
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)
Genetic Differences Between Humans and Great Apes -- Implications for the Evolution of Humans
Varki, Ajit
2004-06-01
At the level of individual protein sequences, humans are 97-100% identical to the great apes, our closest evolutionary relatives. The evolution of humans (and of human intelligence) from a common ancestor with the chimpanzee and bonobo involved many steps, influenced by interactions amongst factors of genetic, developmental, ecological, microbial, climatic, behavioral, cultural and social origin. The genetic factors can be approached by direct comparisons of human and great ape genomes, genes and gene products, and by elucidating biochemical and biological consequences of any differences found. We have discovered multiple genetic and biochemical differences between humans and great apes, particularly with respect to a family of cell surface molecules called sialic acids, as well as in the metabolism of thyroid hormones. The hormone differences have potential consequences for human brain development. The differences in sialic acid biology have multiple implications for the human condition, ranging from susceptibility or resistance to microbial pathogens, effects on endogenous receptors in the immune system, and potential effects on placental signaling, expression of oncofetal antigens in cancers, consequences of dietary intake of animal foods, and development of the mammalian brain.
2006-08-01
Infertility and reproductive genetic risk are both increasing in our societies because of lifestyle changes and possibly environmental factors. Owing to the magnitude of the problem, they have implications not only at the individual and family levels but also at the community level. This leads to an increasing demand for access to assisted reproduction technology (ART) and genetic services, especially when the cause of infertility may be genetic in origin. The increasing application of genetics in reproductive medicine and vice versa requires closer collaboration between the two disciplines. ART and genetics are rapidly evolving fields where new technologies are currently introduced without sufficient knowledge of their potential long-term effects. As for any medical procedures, there are possible unexpected effects which need to be envisaged to make sure that the balance between benefits and risks is clearly on the benefit side. The development of ART and genetics as scientific activities is creating an opportunity to understand the early stages of human development, which is leading to new and challenging findings/knowledge. However, there are opinions against investigating the early stages of development in humans who deserve respect and attention. For all these reasons, these two societies, European Society of Human Genetics (ESHG) and European Society of Human Reproduction and Embryology (ESHRE), have joined efforts to explore the issues at stake and to set up recommendations to maximize the benefit for the couples in need and for the community.
Human genetics: international projects and personalized medicine.
Apellaniz-Ruiz, Maria; Gallego, Cristina; Ruiz-Pinto, Sara; Carracedo, Angel; Rodríguez-Antona, Cristina
2016-03-01
In this article, we present the progress driven by the recent technological advances and new revolutionary massive sequencing technologies in the field of human genetics. We discuss this knowledge in relation with drug response prediction, from the germline genetic variation compiled in the 1000 Genomes Project or in the Genotype-Tissue Expression project, to the phenome-genome archives, the international cancer projects, such as The Cancer Genome Atlas or the International Cancer Genome Consortium, and the epigenetic variation and its influence in gene expression, including the regulation of drug metabolism. This review is based on the lectures presented by the speakers of the Symposium "Human Genetics: International Projects & New Technologies" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society, held on the 20th and 21st of April 2015.
Animal models for human genetic diseases | Sharif | African Journal ...
African Journals Online (AJOL)
The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to ...
Human genetics of infectious diseases: a unified theory
Casanova, Jean-Laurent; Abel, Laurent
2007-01-01
Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931
Genetic contributions to human brain morphology and intelligence
DEFF Research Database (Denmark)
Hulshoff Pol, HE; Schnack, HG; Posthuma, D
2006-01-01
Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...... of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images...
Genetic and environmental factors in experimental and human cancer
Energy Technology Data Exchange (ETDEWEB)
Takayama, S.; Takebe, H.; Gelboin, H.V.; MaChahon, B.; Matsushima, T.; Sugimura, T.
1980-01-01
Recently technological advances in assaying mutagenic principles have revealed that there are many mutagens in the environment, some of which might be carcinogenic to human beings. Other advances in genetics have shown that genetic factors might play an important role in the induction of cancer in human beings, e.g., the high incidence of skin cancers in patients with xeroderma pigmentosum. These proceedings deal with the relationships between genetic and environmental factors in carcinogenesis. The contributors cover mixed-function oxidases, pharmacogenetics, twin studies, DNA repair, immunology, and epidemiology.
Genetic similarity among commercial oil palm materials based on microsatellite markers
Directory of Open Access Journals (Sweden)
Diana Arias
2012-08-01
Full Text Available Microsatellite markers are used to determine genetic similarities among individuals and might be used in various applications in breeding programs. For example, knowing the genetic similarity relationships of commercial planting materials helps to better understand their responses to environmental, agronomic and plant health factors. This study assessed 17 microsatellite markers in 9 crosses (D x P of Elaeis guineensis Jacq. from various commercial companies in Malaysia, France, Costa Rica and Colombia, in order to find possible genetic differences and/or similarities. Seventy-seven alleles were obtained, with an average of 4.5 alleles per primer and a range of 2-8 amplified alleles. The results show a significant reduction of alleles, compared to the number of alleles reported for wild oil palm populations. The obtained dendrogram shows the formation of two groups based on their genetic similarity. Group A, with ~76% similarity, contains the commercial material of 3 codes of Deli x La Mé crosses produced in France and Colombia, and group B, with ~66% genetic similarity, includes all the materials produced by commercial companies in Malaysia, France, Costa Rica and Colombia
Inferences of Recent and Ancient Human Population History Using Genetic and Non-Genetic Data
Kitchen, Andrew
2008-01-01
I have adopted complementary approaches to inferring human demographic history utilizing human and non-human genetic data as well as cultural data. These complementary approaches form an interdisciplinary perspective that allows one to make inferences of human history at varying timescales, from the events that occurred tens of thousands of years…
The genetic component of human longevity
DEFF Research Database (Denmark)
Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco
2018-01-01
In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic...... pathway. We applied this approach to study the joint effect on longevity of SNPs belonging to three candidate pathways, the insulin/insulin-like growth factor signalling (IIS), DNA repair and pro/antioxidant. We analysed data from 1,058 tagging SNPs in 140 genes, collected in 1825 subjects (1......, was further found influencing longitudinal survival in nonagenarian females (p = .026). Results here presented highlight the validity of SNP-SNP interactions analyses for investigating the genetics of human longevity, confirming previously identified markers but also pointing to novel genes as central nodes...
Generation of Genetically Modified Organotypic Skin Cultures Using Devitalized Human Dermis.
Li, Jingting; Sen, George L
2015-12-14
Organotypic cultures allow the reconstitution of a 3D environment critical for cell-cell contact and cell-matrix interactions which mimics the function and physiology of their in vivo tissue counterparts. This is exemplified by organotypic skin cultures which faithfully recapitulates the epidermal differentiation and stratification program. Primary human epidermal keratinocytes are genetically manipulable through retroviruses where genes can be easily overexpressed or knocked down. These genetically modified keratinocytes can then be used to regenerate human epidermis in organotypic skin cultures providing a powerful model to study genetic pathways impacting epidermal growth, differentiation, and disease progression. The protocols presented here describe methods to prepare devitalized human dermis as well as to genetically manipulate primary human keratinocytes in order to generate organotypic skin cultures. Regenerated human skin can be used in downstream applications such as gene expression profiling, immunostaining, and chromatin immunoprecipitations followed by high throughput sequencing. Thus, generation of these genetically modified organotypic skin cultures will allow the determination of genes that are critical for maintaining skin homeostasis.
The comparative radiation genetics of humans and mice
International Nuclear Information System (INIS)
Neel, J.V.
1990-01-01
The attempt by geneticists to predict the genetic consequences for humans of exposure to ionizing radiation has arguably been one of the most serious social responsibilities they have faced in the past half century. Important for its own sake, this issue also serves as a prototype for the effort to evaluate the ultimate genetic impact on ourselves of other human perturbations of the environment in which our species functions. Recently the authors have been developing the thesis that according to the results of studies on the children of survivors of the atomic bombings, humans may not be as sensitive to the genetic effects of radiation as has been projected by various committees on the basis of data from the most commonly employed paradigm, the laboratory mouse. In this paper, the authors attempt as detailed a comparison as space permits of the findings on humans and mice, presenting the data in a fashion that will enable those who at certain critical points in the argument wish to make other assumptions, to do so. The authors argue that a reconsideration that includes all the data now available on mice brings the estimate of the doubling dose for mice into satisfactory agreement with the higher estimate based on humans
Does genetic diversity predict health in humans?
Directory of Open Access Journals (Sweden)
Hanne C Lie
2009-07-01
Full Text Available Genetic diversity, especially at genes important for immune functioning within the Major Histocompatibility Complex (MHC, has been associated with fitness-related traits, including disease resistance, in many species. Recently, genetic diversity has been associated with mate preferences in humans. Here we asked whether these preferences are adaptive in terms of obtaining healthier mates. We investigated whether genetic diversity (heterozygosity and standardized mean d(2 at MHC and nonMHC microsatellite loci, predicted health in 153 individuals. Individuals with greater allelic diversity (d(2 at nonMHC loci and at one MHC locus, linked to HLA-DRB1, reported fewer symptoms over a four-month period than individuals with lower d(2. In contrast, there were no associations between MHC or nonMHC heterozygosity and health. NonMHC-d(2 has previously been found to predict male preferences for female faces. Thus, the current findings suggest that nonMHC diversity may play a role in both natural and sexual selection acting on human populations.
Animal models for human genetic diseases
African Journals Online (AJOL)
Sharif Sons
The study of human genetic diseases can be greatly aided by animal models because of their similarity .... and gene targeting in embryonic stem cells) has been a powerful tool in .... endonucleases that are designed to make a doublestrand.
Assessment of genetic risk for human exposure to radiation. State of the art
International Nuclear Information System (INIS)
Shevchenko, V.A.
2000-01-01
Historical aspects of the conception of genetic risk of human irradiation for recent 40 years. Methodology of assessing the genetic risk of radiation exposure is based on the concept of hitting the target. To predict genetic risk of irradiation, the direct and indirect methods of assessment, extrapolation, integral and populational criteria of risk analysis is widely used. Combination of these methods permits to calculate the risk from human exposure on the basis of data obtained for mice. Method of doubling dose based on determination of the dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. Till 1972 the main model for assessing the genetic risk was the human/mouse model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period from 1972 till 1994 the mouse/mouse model was intensively elaborated in many laboratories. This model was also used in this period to analyse the genetic risk of human irradiation. Recent achievements associated with the study of molecular nature of many hereditary human diseases as well as the criticism of a fundamental principles of the mouse/mouse model for estimating the genetic risk on a new basis. Estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method [ru
An overview of human genetic privacy
Shi, Xinghua; Wu, Xintao
2016-01-01
The study of human genomics is becoming a Big Data science, owing to recent biotechnological advances leading to availability of millions of personal genome sequences, which can be combined with biometric measurements from mobile apps and fitness trackers, and of human behavior data monitored from mobile devices and social media. With increasing research opportunities for integrative genomic studies through data sharing, genetic privacy emerges as a legitimate yet challenging concern that nee...
Genetic effects on gene expression across human tissues
Battle, Alexis; Brown, Christopher D.; Engelhardt, Barbara E.; Montgomery, Stephen B.; Aguet, François; Ardlie, Kristin G.; Cummings, Beryl B.; Gelfand, Ellen T.; Getz, Gad; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Kashin, Seva; Karczewski, Konrad J.; Lek, Monkol; Li, Xiao; MacArthur, Daniel G.; Nedzel, Jared L.; Nguyen, Duyen T.; Noble, Michael S.; Segrè, Ayellet V.; Trowbridge, Casandra A.; Tukiainen, Taru; Abell, Nathan S.; Balliu, Brunilda; Barshir, Ruth; Basha, Omer; Bogu, Gireesh K.; Brown, Andrew; Castel, Stephane E.; Chen, Lin S.; Chiang, Colby; Conrad, Donald F.; Cox, Nancy J.; Damani, Farhan N.; Davis, Joe R.; Delaneau, Olivier; Dermitzakis, Emmanouil T.; Eskin, Eleazar; Ferreira, Pedro G.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gewirtz, Ariel D. H.; Gliner, Genna; Gloudemans, Michael J.; Guigo, Roderic; Hall, Ira M.; Han, Buhm; He, Yuan
2017-01-01
Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression
The genetic component of human longevity
DEFF Research Database (Denmark)
Dato, Serena; Thinggaard, Mette Sørensen; De Rango, Francesco
2018-01-01
In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic ...
Genetic Engineering and Human Mental Ecology: Interlocking Effects and Educational Considerations
Affifi, Ramsey
2017-01-01
This paper describes some likely semiotic consequences of genetic engineering on what Gregory Bateson has called ?the mental ecology? (1979) of future humans, consequences that are less often raised in discussions surrounding the safety of GMOs (genetically modified organisms). The effects are as follows: an increased 1) habituation to the presence of GMOs in the environment, 2) normalization of empirically false assumptions grounding genetic reductionism, 3) acceptance that humans are capabl...
Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease
Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.
2014-01-01
Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772
The History of Patenting Genetic Material.
Sherkow, Jacob S; Greely, Henry T
2015-01-01
The US Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics, Inc. declared, for the first time, that isolated human genes cannot be patented. Many have wondered how genes were ever the subjects of patents. The answer lies in a nuanced understanding of both legal and scientific history. Since the early twentieth century, "products of nature" were not eligible to be patented unless they were "isolated and purified" from their surrounding environment. As molecular biology advanced, and the capability to isolate genes both physically and by sequence came to fruition, researchers (and patent offices) began to apply patent-law logic to genes themselves. These patents, along with other biological patents, generated substantial social and political criticism. Myriad Genetics, a company with patents on BRCA1 and BRCA2, two genes critical to assessing early-onset breast and ovarian cancer risk, and with a particularly controversial business approach, became the antagonist in an ultimately successful campaign to overturn gene patents in court. Despite Myriad's defeat, some questions concerning the rights to monopolize genetic information remain. The history leading to that defeat may be relevant to these future issues.
130 FEMINISM AND HUMAN GENETIC ENGINEERING: A ...
African Journals Online (AJOL)
Ike Odimegwu
genetic engineering to reconstruct the life of the human person. Negatively .... height, beauty or intelligence. Apart from ... cloning and stem-cell researches, artificial insemination. ..... form of manufacturing children involving their quality control.
Morales, N M
2009-01-01
Human cloning has become one of the most controversial debates about reproduction in Western civilization. Human cloning represents asexual reproduction, but the critics of human cloning argue that the result of cloning is not a new individual who is genetically unique. There is also awareness in the scientific community, including the medical community, that human cloning and the creation of clones are inevitable. Psychology and other social sciences, together with the natural sciences, will need to find ways to help the healthcare system, to be prepared to face the new challenges introduced by the techniques of human cloning. One of those challenges is to help the healthcare system to find specific standards of behaviour that could be used to help potential parents to interact properly with cloned babies or children created through genetic manipulation. In this paper, the concepts of personality, identity and uniqueness are discussed in relationship to the contribution of twin studies in these areas. The author argues that an individual created by human cloning techniques or any other type of genetic manipulation will not show the donor's characteristics to the extent of compromising uniqueness. Therefore, claims to such an effect are needlessly alarmist.
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)
Molecular evaluation of genetic variability of wheat elite breeding material
Directory of Open Access Journals (Sweden)
Brbaklić Ljiljana
2009-01-01
Full Text Available Estimation of genetic variability of breeding material is essential for yield improvement in wheat cultivars. Modern techniques based on molecular markers application are more efficient and precise in genetic variability evaluation then conventional methods. Variability of 96 wheat cultivars and lines was analyzed using four microsatellite markers (Gwm11, Gwm428, Psp3200, Psp3071. The markers were chosen according to their potential association with important agronomical traits indicated in the literature. Total of 31 alleles were detected with maximum number of alleles (11 in Xgwm11 locus. The highest polymorphism information content (PIC value (0,831 was found in the locus Xpsp3071. The genotypes were grouped into three subpopulations based on their similarity in the analyzed loci. The results have indicated wide genetic variability of the studied material and possibility of its application in further breeding process after validation of marker-trait association. .
Assessment of genetic risk for human exposure to radiation
International Nuclear Information System (INIS)
Sevcenko, V.A.; Rubanovic, A.V.
2002-01-01
Full text: The methodology of assessing the genetic risk of radiation exposure is based on the concept of 'hitting the target' in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the U N Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolation, integral and palpitation criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Based on the reports of UNSCEAR for the period from 1958 to 2001 the paper presents a retrospective analysis of the use of direct methods and the doubling dose method for quantitative determination of the genetic risk of human exposure expressed as different hereditary diseases. As early as 1962 UNSCEAR estimated the doubling dose (a dose causing as many mutations as those occurring spontaneously during one generation) at 1 Gy for cases of exposure to ionizing radiations with low LET at a low dose rate and this value was confirmed in the next UNSCEAR reports up to now. For cases of acute irradiation the doubling dose was estimated at 0,3-0,4 Gy for the period under review. The paper considers the evolution of the concepts of human natural hereditary variability which is a basis for assessing the risk of exposure by the doubling dose method. The level of human natural genetic variability per 1 000 000 newborns is estimated at 738 000 hereditary diseases including mendelian, chromosomal and multifactorial ones. The greatest difficulties in assessing the doubling dose value were found to occur in the case of multifactorial diseases the pheno typical expression of which depends on mutational events in polygenic systems and on numerous environmental factors. The introduction in calculations of the potential recoverability correction factor (RPCF) made it possible to assess the genetic risk taking into account this class of
Formal genetic maps | Salem | Egyptian Journal of Medical Human ...
African Journals Online (AJOL)
Formal genetic maps are databases, represented as text or graphic figures, that can be collected/organized/formulated and constructed for nearly any, and every, structural or functional region of the genetic material. Though these maps are basically descriptive, their analysis can provide relevant crucial data that can be ...
Genetic & epigenetic approach to human obesity
Directory of Open Access Journals (Sweden)
K Rajender Rao
2014-01-01
Full Text Available Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D, cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12 th u0 pdate of Human Obesity Gene Map there are 253 quantity trait loci (QTL for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.
Human genetics in Johannesburg, South Africa: Past, present and ...
African Journals Online (AJOL)
Genetic screening was then initiated for the Jewish community because of their high carrier rate for Tay-Sachs disease. Educational courses in human genetics were offered at Wits Medical School, and medical as well as other health professionals began to be trained. Research, supported by national and international ...
Human fertility, molecular genetics, and natural selection in modern societies.
Directory of Open Access Journals (Sweden)
Felix C Tropf
Full Text Available Research on genetic influences on human fertility outcomes such as number of children ever born (NEB or the age at first childbirth (AFB has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758, results show significant additive genetic effects on both traits explaining 10% (SE = 5 of the variance in the NEB and 15% (SE = 4 in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02. This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.
Human genetics of infectious diseases: between proof of principle and paradigm.
Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent
2009-09-01
The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proof of principle that infectious diseases may result from various types of inborn errors of immunity, the genetic determinism of most infectious diseases in most patients remains unclear. However, in the future, studies in human genetics are likely to establish a new paradigm for infectious diseases.
Factors affecting the exchange of genetic material between Nordic and US Holstein populatons
DEFF Research Database (Denmark)
Buch, L H; Sørensen, A C; Lassen, J
2009-01-01
in the simulation study, especially the genetic correlations between traits. A more similar relative weighting of the index traits across populations did not change total genetic gain in the Nordic Holstein population. The possibility of exchanging genetic material with the US Holstein population led...
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).
Genetics and Human Agency: Comment on Dar-Nimrod and Heine (2011)
Turkheimer, Eric
2011-01-01
Dar-Nimrod and Heine (2011) decried genetic essentialism without denying the importance of genetics in the genesis of human behavior, and although I agree on both counts, a deeper issue remains unaddressed: how should we adjust our cognitions about our own behavior in light of genetic influence, or is it perhaps not necessary to take genetics into…
Resources for human genetics on the World Wide Web.
Osborne, L R; Lee, J R; Scherer, S W
1997-09-01
A little over a century ago, the HMS Beagle sailed the Pacific Ocean bringing Charles Darwin to the perfect environment in which to piece together his observations forming the theory of evolution. Now, geneticists and laypeople alike surf the equally formidable waters of the internet in search of enlightenment. Here, we attempt to help you navigate towards resources for human genetics by providing maps to three destinations: The Human Genome Project (Box 1), education (Box 2), and human genetic diseases (Box 3). For each, we highlight a few sites that we consider are the most informative and original. A more extensive list containing other useful sites has been compiled and posted on a 'jump site' at: http:/(/)www.cgdn.generes.ca/.
Kayser, Manfred
2015-09-01
Forensic DNA Phenotyping refers to the prediction of appearance traits of unknown sample donors, or unknown deceased (missing) persons, directly from biological materials found at the scene. "Biological witness" outcomes of Forensic DNA Phenotyping can provide investigative leads to trace unknown persons, who are unidentifiable with current comparative DNA profiling. This intelligence application of DNA marks a substantially different forensic use of genetic material rather than that of current DNA profiling presented in the courtroom. Currently, group-specific pigmentation traits are already predictable from DNA with reasonably high accuracies, while several other externally visible characteristics are under genetic investigation. Until individual-specific appearance becomes accurately predictable from DNA, conventional DNA profiling needs to be performed subsequent to appearance DNA prediction. Notably, and where Forensic DNA Phenotyping shows great promise, this is on a (much) smaller group of potential suspects, who match the appearance characteristics DNA-predicted from the crime scene stain or from the deceased person's remains. Provided sufficient funding being made available, future research to better understand the genetic basis of human appearance will expectedly lead to a substantially more detailed description of an unknown person's appearance from DNA, delivering increased value for police investigations in criminal and missing person cases involving unknowns. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Fine-scaled human genetic structure revealed by SNP microarrays.
Xing, Jinchuan; Watkins, W Scott; Witherspoon, David J; Zhang, Yuhua; Guthery, Stephen L; Thara, Rangaswamy; Mowry, Bryan J; Bulayeva, Kazima; Weiss, Robert B; Jorde, Lynn B
2009-05-01
We report an analysis of more than 240,000 loci genotyped using the Affymetrix SNP microarray in 554 individuals from 27 worldwide populations in Africa, Asia, and Europe. To provide a more extensive and complete sampling of human genetic variation, we have included caste and tribal samples from two states in South India, Daghestanis from eastern Europe, and the Iban from Malaysia. Consistent with observations made by Charles Darwin, our results highlight shared variation among human populations and demonstrate that much genetic variation is geographically continuous. At the same time, principal components analyses reveal discernible genetic differentiation among almost all identified populations in our sample, and in most cases, individuals can be clearly assigned to defined populations on the basis of SNP genotypes. All individuals are accurately classified into continental groups using a model-based clustering algorithm, but between closely related populations, genetic and self-classifications conflict for some individuals. The 250K data permitted high-level resolution of genetic variation among Indian caste and tribal populations and between highland and lowland Daghestani populations. In particular, upper-caste individuals from Tamil Nadu and Andhra Pradesh form one defined group, lower-caste individuals from these two states form another, and the tribal Irula samples form a third. Our results emphasize the correlation of genetic and geographic distances and highlight other elements, including social factors that have contributed to population structure.
Precision Medicine and Advancing Genetic Technologies—Disability and Human Rights Perspectives
Directory of Open Access Journals (Sweden)
Aisling de Paor
2016-08-01
Full Text Available Scientific and technological developments are propelling genetics and genetic technologies into the public sphere. Scientific and technological innovation is becoming more refined, resulting in an increase in the availability and use of genetic testing, and other cutting edge genetic technologies, including gene editing. These genetic advances not only signal a growing trend towards precision medicine, but also provoke consideration of the protection of genetic information as an emerging human rights concern. Particular ethical and legal issues arise from a disability perspective, including the potential for discrimination and privacy violations. In consideration of the intersection of genetics and disability, this article highlights the significant concerns raised as genetic science and technology advances, and the consequences for disability rights, particularly the core concepts of non-discrimination, and respect for diversity and difference. On examining international human rights perspectives, it looks particularly at the UN Convention on the Rights of Persons with Disabilities and how it may be used to guide best practice in this area. With an acknowledgement of historical abuses of genetic science, this article highlights the need to maintain caution as to the potential consequences of advancing genetic technologies on persons with disabilities and indeed on society as a whole.
The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach
Directory of Open Access Journals (Sweden)
Amr T. M. Saeb
2016-01-01
Full Text Available Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases.
DEFF Research Database (Denmark)
Tan, Qihua; De Benedictis, G; Yashin, Annatoli
2001-01-01
New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic and demographicinf......New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene–environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic...
Antigenic and genetic variability of human metapneumoviruses
S. Herfst (Sander); L. Sprong; P.A. Cane; E. Forleo-Neto; A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); R.L. de Swart (Rik); B.G. van den Hoogen (Bernadette)
2004-01-01
textabstractHuman metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For
Genetic differences between avian and human isolates of Candida dubliniensis.
LENUS (Irish Health Repository)
McManus, Brenda A
2009-09-01
When Candida dubliniensis isolates obtained from seabird excrement and from humans in Ireland were compared by using multilocus sequence typing, 13 of 14 avian isolates were genetically distinct from human isolates. The remaining avian isolate was indistinguishable from a human isolate, suggesting that transmission may occur between humans and birds.
Articulated Human Motion Tracking Using Sequential Immune Genetic Algorithm
Directory of Open Access Journals (Sweden)
Yi Li
2013-01-01
Full Text Available We formulate human motion tracking as a high-dimensional constrained optimization problem. A novel generative method is proposed for human motion tracking in the framework of evolutionary computation. The main contribution is that we introduce immune genetic algorithm (IGA for pose optimization in latent space of human motion. Firstly, we perform human motion analysis in the learnt latent space of human motion. As the latent space is low dimensional and contents the prior knowledge of human motion, it makes pose analysis more efficient and accurate. Then, in the search strategy, we apply IGA for pose optimization. Compared with genetic algorithm and other evolutionary methods, its main advantage is the ability to use the prior knowledge of human motion. We design an IGA-based method to estimate human pose from static images for initialization of motion tracking. And we propose a sequential IGA (S-IGA algorithm for motion tracking by incorporating the temporal continuity information into the traditional IGA. Experimental results on different videos of different motion types show that our IGA-based pose estimation method can be used for initialization of motion tracking. The S-IGA-based motion tracking method can achieve accurate and stable tracking of 3D human motion.
Human genetics: measuring the raw material of evolution.
Armour, John A L
2009-09-15
By direct sequencing of two Y chromosomes inherited from the same paternal ancestor, a landmark study has derived a good direct estimate for the rate of base substitution mutations on the human Y chromosome.
Understanding human genetic variation in the era of high-throughput sequencing
Knight, Julian C.
2010-01-01
The EMBO/EMBL symposium ‘Human Variation: Cause and Consequence' highlighted advances in understanding the molecular basis of human genetic variation and its myriad implications for biology, human origins and disease.
The human pain genetics database: an interview with Luda Diatchenko.
Diatchenko, Luda
2018-06-05
Luda Diatchenko, MD, PhD is a Canada Excellence Research Chair in Human Pain Genetics, Professor, Faculty of Medicine, Department of Anesthesia and Faculty of Dentistry at McGill University, Alan Edwards Centre for Research on Pain. She earned her MD and PhD in the field of molecular biology from the Russian State Medical University. She started her career in industry, she was a Leader of the RNA Expression Group at Clontech, Inc., and subsequently, Director of Gene Discovery at Attagene, Inc. During this time, she was actively involved in the development of several widely used and widely cited molecular tools for the analysis of gene expression and regulation. Her academic career started at 2000 in the Center for Neurosensory Disorders at University of North Carolina. Her research since then is focused on determining the cellular and molecular biological mechanisms by which functional genetic variations impact human pain perception and risk of development of chronic pain conditions, enabling new approaches to identify new drug targets, treatment responses to analgesics and diagnostic. Multiple collaborative activities allow the Diatchenko group to take basic genetic findings all the way from human association studies, through molecular and cellular mechanisms to animal models and ultimately to human clinical trials. In total, she has authored or co-authored over 120 peer-reviewed research papers in journals, ten book chapters and edited a book in human pain genetics. She is a member and an active officer of several national and international scientific societies, including the International Association for the Study of Pain and the American Pain Society.
A global reference for human genetic variation
DEFF Research Database (Denmark)
Auton, Adam; Abecasis, Goncalo R.; M. Altshuler, David
2015-01-01
The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals ...
Directory of Open Access Journals (Sweden)
Ruth Hershberg
2008-12-01
Full Text Available Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC. However, all human-adapted strains of MTBC have traditionally been considered to be essentially identical. We surveyed sequence diversity within a global collection of strains belonging to MTBC using seven megabase pairs of DNA sequence data. We show that the members of MTBC affecting humans are more genetically diverse than generally assumed, and that this diversity can be linked to human demographic and migratory events. We further demonstrate that these organisms are under extremely reduced purifying selection and that, as a result of increased genetic drift, much of this genetic diversity is likely to have functional consequences. Our findings suggest that the current increases in human population, urbanization, and global travel, combined with the population genetic characteristics of M. tuberculosis described here, could contribute to the emergence and spread of drug-resistant tuberculosis.
The remarkable frequency of human immunodeficiency virus type 1 genetic recombination.
Onafuwa-Nuga, Adewunmi; Telesnitsky, Alice
2009-09-01
The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination--a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates--occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.
Molecular genetic analysis of consanguineous families with primary ...
Indian Academy of Sciences (India)
MUZAMMIL AHMAD KHAN
3Institute of Human Genetics, Medical University of Graz, Graz 8010, Austria. 4Department of Cell and ... Materials and methods. Family recruitment and sample collection ..... 2014 A Drosophila genetic resource of mutats to study mechanism ...
Systematic documentation and analysis of human genetic variation using the microattribution approach
Giardine, Belinda; Borg, Joseph; Higgs, Douglas R.; Peterson, Kenneth R.; Maglott, Donna; Basak, A. Nazli; Clark, Barnaby; Faustino, Paula; Felice, Alex E.; Francina, Alain; Gallivan, Monica V. E.; Georgitsi, Marianthi; Gibbons, Richard J.; Giordano, Piero C.; Harteveld, Cornelis L.; Joly, Philippe; Kanavakis, Emmanuel; Kollia, Panagoula; Menzel, Stephan; Miller, Webb; Moradkhani, Kamran; Old, John; Papachatzopoulou, Adamantia; Papadakis, Manoussos N.; Papadopoulos, Petros; Pavlovic, Sonja; Philipsen, Sjaak; Radmilovic, Milena; Riemer, Cathy; Schrijver, Iris; Stojiljkovic, Maja; Thein, Swee Lay; Traeger-Synodinos, Jan; Tully, Ray; Wada, Takahito; Waye, John; Wiemann, Claudia; Zukic, Branka; Chui, David H. K.; Wajcman, Henri; Hardison, Ross C.; Patrinos, George P.
2013-01-01
We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to these disorders, and then implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories 1. A total of 1,941 unique genetic variants in 37 genes, encoding globins (HBA2, HBA1, HBG2, HBG1, HBD, HBB) and other erythroid proteins (ALOX5AP, AQP9, ARG2, ASS1, ATRX, BCL11A, CNTNAP2, CSNK2A1, EPAS1, ERCC2, FLT1, GATA1, GPM6B, HAO2, HBS1L, KDR, KL, KLF1, MAP2K1, MAP3K5, MAP3K7, MYB, NOS1, NOS2, NOS3, NOX3, NUP133, PDE7B, SMAD3, SMAD6, and TOX) are currently documented in these databases with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants and now provides a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The large repository of previously reported data, together with more recent data, acquired by microattribution, demonstrates how the comprehensive documentation of human variation will provide key insights into normal biological processes and how these are perturbed in human genetic disease. Using the microattribution process set out here, datasets which took decades to accumulate for the globin genes could be assembled rapidly for other genes and disease systems. The principles established here for the globin gene system will serve as a model for other systems and the analysis of other common and/or complex human genetic diseases. PMID:21423179
The genetics of human longevity: an intricacy of genes, environment, culture and microbiome.
Dato, Serena; Rose, Giuseppina; Crocco, Paolina; Monti, Daniela; Garagnani, Paolo; Franceschi, Claudio; Passarino, Giuseppe
2017-07-01
Approximately one-quarter of the variation in lifespan in developed countries can be attributed to genetic factors. However, even large population based studies investigating genetic influence on human lifespan have been disappointing, identifying only a few genes accounting for genetic susceptibility to longevity. Some environmental and lifestyle determinants associated with longevity have been identified, which interplay with genetic factors in an intricate way. The study of gene-environment and gene-gene interactions can significantly improve our chance to disentangle this complex scenario. In this review, we first describe the most recent approaches for genetic studies of longevity, from those enriched with health parameters and frailty measures to pathway-based and SNP-SNP interaction analyses. Then, we go deeper into the concept of "environmental influences" in human aging and longevity, focusing on the contribution of life style changes, social and cultural influences, as important determinants of survival differences among individuals in a population. Finally, we discuss the contribution of the microbiome in human longevity, as an example of complex interaction between organism and environment. In conclusion, evidences collected from the latest studies on human longevity provide a support for the collection of life-long genetic and environmental/lifestyle variables with beneficial or detrimental effects on health, to improve our understanding of the determinants of human lifespan. Copyright © 2017 Elsevier B.V. All rights reserved.
Genetic evidence for a Paleolithic human population expansion in Africa
Reich, David E.; Goldstein, David B.
1998-01-01
Human populations have undergone dramatic expansions in size, but other than the growth associated with agriculture, the dates and magnitudes of those expansions have never been resolved. Here, we introduce two new statistical tests for population expansion, which use variation at a number of unlinked genetic markers to study the demographic histories of natural populations. By analyzing genetic variation in various aboriginal populations from throughout the world, we show highly significant evidence for a major human population expansion in Africa, but no evidence of expansion outside of Africa. The inferred African expansion is estimated to have occurred between 49,000 and 640,000 years ago, certainly before the Neolithic expansions, and probably before the splitting of African and non-African populations. In showing a significant difference between African and non-African populations, our analysis supports the unique role of Africa in human evolutionary history, as has been suggested by most other genetic work. In addition, the missing signal in non-African populations may be the result of a population bottleneck associated with the emergence of these populations from Africa, as postulated in the “Out of Africa” model of modern human origins. PMID:9653150
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
Genetic alterations affecting cholesterol metabolism and human fertility.
DeAngelis, Anthony M; Roy-O'Reilly, Meaghan; Rodriguez, Annabelle
2014-11-01
Single nucleotide polymorphisms (SNPs) represent genetic variations among individuals in a population. In medicine, these small variations in the DNA sequence may significantly impact an individual's response to certain drugs or influence the risk of developing certain diseases. In the field of reproductive medicine, a significant amount of research has been devoted to identifying polymorphisms which may impact steroidogenesis and fertility. This review discusses current understanding of the effects of genetic variations in cholesterol metabolic pathways on human fertility that bridge novel linkages between cholesterol metabolism and reproductive health. For example, the role of the low-density lipoprotein receptor (LDLR) in cellular metabolism and human reproduction has been well studied, whereas there is now an emerging body of research on the role of the high-density lipoprotein (HDL) receptor scavenger receptor class B type I (SR-BI) in human lipid metabolism and female reproduction. Identifying and understanding how polymorphisms in the SCARB1 gene or other genes related to lipid metabolism impact human physiology is essential and will play a major role in the development of personalized medicine for improved diagnosis and treatment of infertility. © 2014 by the Society for the Study of Reproduction, Inc.
Common genetic variants influence human subcortical brain structures.
Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E
2015-04-09
The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
Ethical Concerns About Human Genetic Enhancement in the Malay Science Fiction Novels.
Isa, Noor Munirah; Hj Safian Shuri, Muhammad Fakhruddin
2018-02-01
Advancements in science and technology have not only brought hope to humankind to produce disease-free offspring, but also offer possibilities to genetically enhance the next generation's traits and capacities. Human genetic enhancement, however, raises complex ethical questions, such as to what extent should it be allowed? It has been a great challenge for humankind to develop robust ethical guidelines for human genetic enhancement that address both public concerns and needs. We believe that research about public concerns is necessary prior to developing such guidelines, yet the issues have not been thoroughly investigated in many countries, including Malaysia. Since the novel often functions as a medium for the public to express their concerns, this paper explores ethical concerns about human genetic enhancement expressed in four Malay science fiction novels namely Klon, Leksikon Ledang, Transgenesis Bisikan Rimba and Transgenik Sifar. Religion has a strong influence on the worldview of the Malays therefore some concerns such as playing God are obviously religious. Association of the negative image of scientists as well as the private research companies with the research on human genetic enhancement reflects the authors' concerns about the main motivations for conducting such research and the extent to which such research will benefit society.
Egyptian Journal of Medical Human Genetics - Vol 14, No 3 (2013)
African Journals Online (AJOL)
Egyptian Journal of Medical Human Genetics - Vol 14, No 3 (2013) ... Comparative study: Parameters of gait in Down syndrome versus matched obese and ... episodes in a Japanese child: Clinical, radiological and molecular genetic analysis ...
Genetics of Human Sexual Behavior: Where We Are, Where We Are Going.
Jannini, Emmanuele A; Burri, Andrea; Jern, Patrick; Novelli, Giuseppe
2015-04-01
One of the never-ending debates in the developing field of sexual medicine is the extent to which genetics and experiences (i.e., "nature and nurture") contribute to sexuality. The debate continues despite the fact that these two sides have different abilities to create a scientific environment to support their cause. Contemporary genetics has produced plenty of recent evidence, however, not always confirmed or sufficiently robust. On the other hand, the more traditional social theorists, frequently without direct evidence confirming their positions, criticize, sometimes with good arguments, the methods and results of the other side. The aim of this article is to critically evaluate existent evidence that used genetic approaches to understand human sexuality. An expert in sexual medicine (E.A.J.), an expert in medical genetics (G.N.), and two experts in genetic epidemiology and quantitative genetics, with particular scientific experience in female sexual dysfunction (A.B.) and in premature ejaculation (P.J.), contributed to this review. Expert opinion supported by critical review of the currently available literature. The existing literature on human sexuality provides evidence that many sexuality-related behaviors previously considered to be the result of cultural influences (such as mating strategies, attractiveness and sex appeal, propensity to fidelity or infidelity, and sexual orientation) or dysfunctions (such as premature ejaculation or female sexual dysfunction) seem to have a genetic component. Current evidence from genetic epidemiologic studies underlines the existence of biological and congenital factors regulating male and female sexuality. However, these relatively recent findings ask for replication in methodologically more elaborated studies. Clearly, increased research efforts are needed to further improve understanding the genetics of human sexuality. Jannini EA, Burri A, Jern P, and Novelli G. Genetics of human sexual behavior: Where we are, where
African Americans' opinions about human-genetics research.
Achter, Paul; Parrott, Roxanne; Silk, Kami
2004-03-01
Research on attitudes toward genetics and medicine registers skepticism among minority communities, but the reasons for this skepticism are not well known. In the past, studies linked mistrust of the medical system to historical ethics violations involving minority groups and to suspicions about ideological premise and political intent. To assess public knowledge, attitudes, and behavior regarding human-genetics research, we surveyed 858 Americans onsite in four community settings or online in a geographically nonspecific manner. Compared to participants as a whole, African Americans were significantly more likely to believe that clinical trials might be dangerous and that the federal government knowingly conducted unethical research, including studies in which risky vaccines were administered to prison populations. However, African Americans were also significantly more likely to believe that the federal government worked to prevent environmental exposure to toxicants harmful to people with genetic vulnerabilities. Our data suggest that most Americans trust government to act ethically in sponsoring and conducting research, including genetics research, but that African Americans are particularly likely to see government as powerfully protective in some settings yet selectively disingenuous in others.
Sastry, Kumara Narasimha
2007-03-01
Effective and efficient rnultiscale modeling is essential to advance both the science and synthesis in a, wide array of fields such as physics, chemistry, materials science; biology, biotechnology and pharmacology. This study investigates the efficacy and potential of rising genetic algorithms for rnultiscale materials modeling and addresses some of the challenges involved in designing competent algorithms that solve hard problems quickly, reliably and accurately. In particular, this thesis demonstrates the use of genetic algorithms (GAs) and genetic programming (GP) in multiscale modeling with the help of two non-trivial case studies in materials science and chemistry. The first case study explores the utility of genetic programming (GP) in multi-timescaling alloy kinetics simulations. In essence, GP is used to bridge molecular dynamics and kinetic Monte Carlo methods to span orders-of-magnitude in simulation time. Specifically, GP is used to regress symbolically an inline barrier function from a limited set of molecular dynamics simulations to enable kinetic Monte Carlo that simulate seconds of real time. Results on a non-trivial example of vacancy-assisted migration on a surface of a face-centered cubic (fcc) Copper-Cobalt (CuxCo 1-x) alloy show that GP predicts all barriers with 0.1% error from calculations for less than 3% of active configurations, independent of type of potentials used to obtain the learning set of barriers via molecular dynamics. The resulting method enables 2--9 orders-of-magnitude increase in real-time dynamics simulations taking 4--7 orders-of-magnitude less CPU time. The second case study presents the application of multiobjective genetic algorithms (MOGAs) in multiscaling quantum chemistry simulations. Specifically, MOGAs are used to bridge high-level quantum chemistry and semiempirical methods to provide accurate representation of complex molecular excited-state and ground-state behavior. Results on ethylene and benzene---two common
Darkness in El Dorado: human genetics on trial
Indian Academy of Sciences (India)
Unknown
Human Genetics Research Division, University of Southampton, Southampton SO16 6YD, UK. A recent ..... advice' he acknowledges in his book (p. xviii), leading to revision .... Venezuelan government, held his team back from giving medical ...
Mapping genetic influences on the corticospinal motor system in humans
DEFF Research Database (Denmark)
Cheeran, B J; Ritter, C; Rothwell, J C
2009-01-01
of the contribution of single nucleotide polymorphisms (SNP) and variable number tandem repeats. In humans, the corticospinal motor system is essential to the acquisition of fine manual motor skills which require a finely tuned coordination of activity in distal forelimb muscles. Here we review recent brain mapping......It is becoming increasingly clear that genetic variations account for a certain amount of variance in the acquisition and maintenance of different skills. Until now, several levels of genetic influences were examined, ranging from global heritability estimates down to the analysis...... studies that have begun to explore the influence of functional genetic variation as well as mutations on function and structure of the human corticospinal motor system, and also the clinical implications of these studies. Transcranial magnetic stimulation of the primary motor hand area revealed...
Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics.
Bauer, Robert C; Khetarpal, Sumeet A; Hand, Nicholas J; Rader, Daniel J
2016-04-01
Human genetics has contributed to the development of multiple drugs to treat hyperlipidemia and coronary artery disease (CAD), most recently including antibodies targeting PCSK9 to reduce LDL cholesterol. Despite these successes, a large burden of CAD remains. Genetic and epidemiological studies have suggested that circulating triglyceride (TG)-rich lipoproteins (TRLs) are a causal risk factor for CAD, presenting an opportunity for novel therapeutic strategies. We discuss recent unbiased human genetics testing, including genome-wide association studies (GWAS) and whole-genome or -exome sequencing, that have identified the lipoprotein lipase (LPL) and hepatic lipogenesis pathways as important mechanisms in the regulation of circulating TRLs. Further strengthening the causal relationship between TRLs and CAD, findings such as these may provide novel targets for much-needed potential therapeutic interventions. Copyright © 2016. Published by Elsevier Ltd.
Computational Integration of Human Genetic Data to Evaluate AOP-Specific Susceptibility
There is a need for approaches to efficiently evaluate human genetic variability and susceptibility related to environmental chemical exposure. Direct estimation of the genetic contribution to variability in susceptibility to environmental chemicals is only possible in special ca...
Analogs of human genetic skin disease in domesticated animals
Directory of Open Access Journals (Sweden)
Justin Finch, MD
2017-09-01
The genetic skin diseases we will review are pigmentary mosaicism, piebaldism, albinism, Griscelli syndrome, ectodermal dysplasias, Waardenburg syndrome, and mucinosis in both humans and domesticated animals.
Wang, Julia; Al-Ouran, Rami; Hu, Yanhui; Kim, Seon-Young; Wan, Ying-Wooi; Wangler, Michael F; Yamamoto, Shinya; Chao, Hsiao-Tuan; Comjean, Aram; Mohr, Stephanie E; Perrimon, Norbert; Liu, Zhandong; Bellen, Hugo J
2017-06-01
One major challenge encountered with interpreting human genetic variants is the limited understanding of the functional impact of genetic alterations on biological processes. Furthermore, there remains an unmet demand for an efficient survey of the wealth of information on human homologs in model organisms across numerous databases. To efficiently assess the large volume of publically available information, it is important to provide a concise summary of the most relevant information in a rapid user-friendly format. To this end, we created MARRVEL (model organism aggregated resources for rare variant exploration). MARRVEL is a publicly available website that integrates information from six human genetic databases and seven model organism databases. For any given variant or gene, MARRVEL displays information from OMIM, ExAC, ClinVar, Geno2MP, DGV, and DECIPHER. Importantly, it curates model organism-specific databases to concurrently display a concise summary regarding the human gene homologs in budding and fission yeast, worm, fly, fish, mouse, and rat on a single webpage. Experiment-based information on tissue expression, protein subcellular localization, biological process, and molecular function for the human gene and homologs in the seven model organisms are arranged into a concise output. Hence, rather than visiting multiple separate databases for variant and gene analysis, users can obtain important information by searching once through MARRVEL. Altogether, MARRVEL dramatically improves efficiency and accessibility to data collection and facilitates analysis of human genes and variants by cross-disciplinary integration of 18 million records available in public databases to facilitate clinical diagnosis and basic research. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Genetic engineering in nonhuman primates for human disease modeling.
Sato, Kenya; Sasaki, Erika
2018-02-01
Nonhuman primate (NHP) experimental models have contributed greatly to human health research by assessing the safety and efficacy of newly developed drugs, due to their physiological and anatomical similarities to humans. To generate NHP disease models, drug-inducible methods, and surgical treatment methods have been employed. Recent developments in genetic and developmental engineering in NHPs offer new options for producing genetically modified disease models. Moreover, in recent years, genome-editing technology has emerged to further promote this trend and the generation of disease model NHPs has entered a new era. In this review, we summarize the generation of conventional disease model NHPs and discuss new solutions to the problem of mosaicism in genome-editing technology.
[Leprosy, a pillar of human genetics of infectious diseases].
Gaschignard, J; Scurr, E; Alcaïs, A
2013-06-01
Despite a natural reservoir of Mycobacterium leprae limited to humans and free availability of an effective antibiotic treatment, more than 200,000 people develop leprosy each year. This disease remains a major cause of disability and social stigma worldwide. The cause of this constant incidence is currently unknown and indicates that important aspects of the complex relationship between the pathogen and its human host remain to be discovered. An important contribution of host genetics to susceptibility to leprosy has long been suggested to account for the considerable variability between individuals sustainably exposed to M. leprae. Given the inability to cultivate M. leprae in vitro and in the absence of relevant animal model, genetic epidemiology is the main strategy used to identify the genes and, consequently, the immunological pathways involved in protective immunity to M. leprae. Recent genome-wide studies have identified new pathophysiological pathways which importance is only beginning to be understood. In addition, the prism of human genetics placed leprosy at the crossroads of other common diseases such as Crohn's disease, asthma or myocardial infarction. Therefore, novel lights on the pathogenesis of many common diseases could eventually emerge from the detailed understanding of a disease of the shadows. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
The commercialization of human genetic information and related circumstances within Turkish law.
Memiş, Tekin
2011-01-01
Today, human genetic information is used for commercial purposes as well. This means, based on the case, the direct or indirect commercialization of genetic information. In this study, this specific issue is analyzed in light of the new legal regulations as to the subject in the Turkish Law. Specifically, this study focuses on the issue of whether the commercialization of genetic information is allowed under the Turkish Law. This study also attempts to clarify the issue of whether there is any limitations for the commercialization of genetic information in the Turkish Law provided that the commercialization of genetic information is permitted. Prior to this legal analysis, the problems of the legal ownership for genetic information and of whether genetic information should be considered as an organ of human body is discussed. Accordingly, relevant Turkish laws and regulations are individually analyzed within this context. In the mean time legal regulations of some countries in this respect are taken into account with a comparative approach. In the end a general evaluation and suggestions are provided to the reader.
Human genetics after the bomb: Archives, clinics, proving grounds and board rooms.
Lindee, Susan
2016-02-01
In this paper I track the history of post-1945 human genetics and genomics emphasizing the importance of ideas about risk to the scientific study and medical management of human heredity. Drawing on my own scholarship as it is refracted through important new work by other scholars both junior and senior, I explore how radiation risk and then later disease risk mattered to the development of genetics and genomics, particularly in the United States. In this context I excavate one of the central ironies of post-war human genetics: while studies of DNA as the origin and cause of diseases have been lavishly supported by public institutions and private investment around the world, the day-to-day labor of intensive clinical innovation has played a far more important role in the actual human experience of genetic disease and genetic risk for affected families. This has implications for the archival record, where clinical interactions are less readily accessible to historians. This paper then suggests that modern genomics grew out of radiation risk; that it was and remains a risk assessment science; that it is temporally embedded as a form of both prediction and historical reconstruction; and that it has become a big business focused more on risk and prediction (which can be readily marketed) than on effective clinical intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.
Human genetics and genomics a decade after the release of the draft sequence of the human genome
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
Directory of Open Access Journals (Sweden)
Carlos Eduardo de Oliveira Alban
2016-06-01
Full Text Available Following the teachings of the “Law in the Literature” movement, as well as the method of the Phemenological Hermeneutics, the present essay intends to discuss the eugenics content present in the abstract criteria for donating genetic material in Brazil. In order to present this problem clearly for the reader, the novel Brave New World, from Aldous Huxley, will be used as an example. Opportunely, it will deal with the recent situation regarding the investigation of the London Sperm Bank donators’ politics, in which important debates related to the genetic selection aiming for avoiding congenital diseases appear.
The influence of recombination on human genetic diversity.
Directory of Open Access Journals (Sweden)
Chris C A Spencer
2006-09-01
Full Text Available In humans, the rate of recombination, as measured on the megabase scale, is positively associated with the level of genetic variation, as measured at the genic scale. Despite considerable debate, it is not clear whether these factors are causally linked or, if they are, whether this is driven by the repeated action of adaptive evolution or molecular processes such as double-strand break formation and mismatch repair. We introduce three innovations to the analysis of recombination and diversity: fine-scale genetic maps estimated from genotype experiments that identify recombination hotspots at the kilobase scale, analysis of an entire human chromosome, and the use of wavelet techniques to identify correlations acting at different scales. We show that recombination influences genetic diversity only at the level of recombination hotspots. Hotspots are also associated with local increases in GC content and the relative frequency of GC-increasing mutations but have no effect on substitution rates. Broad-scale association between recombination and diversity is explained through covariance of both factors with base composition. To our knowledge, these results are the first evidence of a direct and local influence of recombination hotspots on genetic variation and the fate of individual mutations. However, that hotspots have no influence on substitution rates suggests that they are too ephemeral on an evolutionary time scale to have a strong influence on broader scale patterns of base composition and long-term molecular evolution.
Improved genetic manipulation of human embryonic stem cells.
Braam, S.R.; Denning, C.; van den Brink, S.; Kats, P.; Hochstenbach, R.; Passier, R.; Mummery, C.L.
2008-01-01
Low efficiency of transfection limits the ability to genetically manipulate human embryonic stem cells (hESCs), and differences in cell derivation and culture methods require optimization of transfection protocols. We transiently transferred multiple independent hESC lines with different growth
Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders.
Hamosh, Ada; Scott, Alan F; Amberger, Joanna S; Bocchini, Carol A; McKusick, Victor A
2005-01-01
Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative and timely knowledgebase of human genes and genetic disorders compiled to support human genetics research and education and the practice of clinical genetics. Started by Dr Victor A. McKusick as the definitive reference Mendelian Inheritance in Man, OMIM (http://www.ncbi.nlm.nih.gov/omim/) is now distributed electronically by the National Center for Biotechnology Information, where it is integrated with the Entrez suite of databases. Derived from the biomedical literature, OMIM is written and edited at Johns Hopkins University with input from scientists and physicians around the world. Each OMIM entry has a full-text summary of a genetically determined phenotype and/or gene and has numerous links to other genetic databases such as DNA and protein sequence, PubMed references, general and locus-specific mutation databases, HUGO nomenclature, MapViewer, GeneTests, patient support groups and many others. OMIM is an easy and straightforward portal to the burgeoning information in human genetics.
Directory of Open Access Journals (Sweden)
Erik Corona
2013-05-01
Full Text Available Genetic diversity across different human populations can enhance understanding of the genetic basis of disease. We calculated the genetic risk of 102 diseases in 1,043 unrelated individuals across 51 populations of the Human Genome Diversity Panel. We found that genetic risk for type 2 diabetes and pancreatic cancer decreased as humans migrated toward East Asia. In addition, biliary liver cirrhosis, alopecia areata, bladder cancer, inflammatory bowel disease, membranous nephropathy, systemic lupus erythematosus, systemic sclerosis, ulcerative colitis, and vitiligo have undergone genetic risk differentiation. This analysis represents a large-scale attempt to characterize genetic risk differentiation in the context of migration. We anticipate that our findings will enable detailed analysis pertaining to the driving forces behind genetic risk differentiation.
Common genetic variants influence human subcortical brain structures
Hibar, D.P.; Stein, J.L.; Renteria, M.E.; Arias-Vasquez, A.; Desrivières, S.; Jahanshad, N.; Toro, R.; Wittfeld, K.; Abramovic, L.; Andersson, M.; Aribisala, B.S.; Armstrong, N.J.; Bernard, M.; Bohlken, M.M.; Biks, M.P.; Bralten, J.; Brown, A.A.; Chakravarty, M.M.; Chen, Q.; Ching, C.R.K.; Cuellar-Partida, G.; den Braber, A.; Giddaluru, S.; Goldman, A.L.; Grimm, O.; Guadalupe, T.; Hass, J.; Woldehawariat, G.; Holmes, A.J.; Hoogman, M.; Janowitz, D.; Jia, T.; Kim, S.; Klein, M.; Kraemer, B.; Lee, P.H.; Olde Loohuis, L.M.; Luciano, M.; Macare, C.; Mather, K.A.; Mattheisen, M.; Milaneschi, Y.; Nho, K.; Papmeyer, M.; Ramasamy, A.; Risacher, S.L.; Roiz-Santiañez, R.; Rose, E.J.; Salami, A.; Sämann, P.G.; Schmaal, L.; Schork, A.J.; Shin, J.; Strike, L.T.; Teumer, A.; Donkelaar, M.M.J.; van Eijk, K.R.; Walters, R.K.; Westlye, L.T.; Welan, C.D.; Winkler, A.M.; Zwiers, M.P.; Alhusaini, S.; Athanasiu, L.; Ehrlich, S.; Hakobjan, M.M.H.; Hartberg, C.B.; Haukvik, U.K.; Heister, A.J.G.A.M.; Hoehn, D.; Kasperaviciute, D.; Liewald, D.C.M.; Lopez, L.M.; Makkinje, R.R.; Matarin, M.; Naber, M.A.M.; Reese McKay, D.; Needham, M.; Nugent, A.C.; Pütz, B.; Royle, N.A.; Shen, L.; Sprooten, E.; Trabzuni, D.; van der Marel, S.S.L.; van Hulzen, K.J.E.; Walton, E.; Wolf, C.; Almasy, L.; Ames, D.; Arepalli, S.; Assareh, A.A.; Bastin, M.E.; Brodaty, H.; Bulayeva, K.B.; Carless, M.A.; Cichon, S.; Corvin, A.; Curran, J.E.; Czisch, M.; de Zubicaray, G.I.; Dillman, A.; Duggirala, R.; Dyer, T.D.; Erk, S.; Fedko, I.O.; Ferrucci, L.; Foroud, T.M.; Fox, P.T.; Fukunaga, M.; Gibbs, J.R.; Göring, H.H.H.; Green, R.C.; Guelfi, S.; Hansell, N.K.; Hartman, C.A.; Hegenscheid, K.; Heinz, A.; Hernandez, D.G.; Heslenfeld, D.J.; Hoekstra, P.J.; Holsboer, F.; Homuth, G.; Hottenga, J.J.; Ikeda, M.; Jack, C.R., Jr.; Jenkinson, M.; Johnson, R.; Kanai, R.; Keil, M.; Kent, J.W. Jr.; Kochunov, P.; Kwok, J.B.; Lawrie, S.M.; Liu, X.; Longo, D.L.; McMahon, K.L.; Meisenzahl, E.; Melle, I.; Mohnke, S.; Montgomery, G.W.; Mostert, J.C.; Mühleisen, T.W.; Nalls, M.A.; Nichols, T.E.; Nilsson, L.G.; Nöthen, M.M.; Ohi, K.; Olvera, R.L.; Perez-Iglesias, R.; Pike, G.B.; Potkin, S.G.; Reinvang, I.; Reppermund, S.; Rietschel, M.; Romanczuk-Seiferth, N.; Rosen, G.D.; Rujescu, D.; Schnell, K.; Schofield, P.R.; Smith, C.; Steen, V.M.; Sussmann, J.E.; Thalamuthu, A.; Toga, A.W.; Traynor, B.J.; Troncoso, J.; Turner, J.A.; Valdés Hernández, M.C.; van t Ent, D.; van der Brug, M.; van der Wee, N.J.A.; van Tol, M.J.; Veltman, D.J.; Wassink, T.H.; Westmann, E.; Zielke, R.H.; Zonderman, A.B.; Ashbrook, D.G.; Hager, R.; Lu, L.; McMahon, F.J.; Morris, D.W.; Williams, R.W.; Brunner, H.G.; Buckner, R.L.; Buitelaar, J.K.; Cahn, W.; Calhoun, V.D.; Cavalleri, G.L.; Crespo-Facorro, B.; Dale, A.M.; Davies, G.E.; Delanty, N.; Depondt, C.; Djurovic, S.; Drevets, W.C.; Espeseth, T.; Gollub, R.L.; Ho, B.C.; Hoffmann, W.; Hosten, N.; Kahn, R.S.; Le Hellard, S.; Meyer-Lindenberg, A.; Müller-Myhsok, B.; Nauck, M.; Nyberg, L.; Pandolfo, M.; Penninx, B.W.J.H.; Roffman, J.L.; Sisodiya, SM; Smoller, J.W.; van Bokhoven, H.; van Haren, N.E.M.; Völzke, H.; Walter, H.; Weiner, M.W.; Wen, W.; White, T.; Agartz, I.; Andreassen, O.A.; Blangero, J.; Boomsma, D.I.; Brouwer, R.M.; Cannon, D.M.; Cookson, M.R.; de Geus, E.J.C.; Deary, I.J.; Donohoe, G.; Fernandez, G.; Fisher, S.E.; Francks, C.; Glahn, D.C.; Grabe, H.J.; Gruber, O.; Hardy, J.; Hashimoto, R.; Hulshoff Pol, H.E.; Jönsson, E.G.; Kloszewska, I.; Lovestone, S.; Mattay, V.S.; Mecocci, P.; McDonald, C.; McIntosh, A.M.; Ophoff, R.A.; Paus, T.; Pausova, Z.; Ryten, M.; Sachdev, P.S.; Saykin, A.J.; Simmons, A.; Singleton, A.; Soininen, H.; Wardlaw, J.M.; Weale, M.E.; Weinberger, D.R.; Adams, H.H.H.; Launer, L.J.; Seiler, S.; Schmidt, R.; Chauhan, G.; Satizabal, C.L.; Becker, J.T.; Yanek, L.; van der Lee, S.J.; Ebling, M.; Fischl, B.; Longstreth, Jr. W.T.; Greve, D.; Schmidt, H.; Nyquist, P.; Vinke, L.N.; van Duijn, C.M.; Xue, L.; Mazoyer, B.; Bis, J.C.; Gudnason, V.; Seshadri, S.; Arfan Ikram, M.; Martin, N.G.; Wright, M.J.; Schumann, G.; Franke, B.; Thompson, P.M.; Medland, S.E.
2015-01-01
The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common
Common genetic variants influence human subcortical brain structures
D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic (Lucija); M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); L.T. Strike (Lachlan); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D.J. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (Marcella); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang); N. Hosten (Norbert); R. Kahn (René); S. Le Hellard (Stephanie); A. Meyer-Lindenberg; B. Müller-Myhsok (B.); M. Nauck (Matthias); L. Nyberg (Lars); M. Pandolfo (Massimo); B.W.J.H. Penninx (Brenda); J.L. Roffman (Joshua); S.M. Sisodiya (Sanjay); J.W. Smoller; H. van Bokhoven (Hans); N.E.M. van Haren (Neeltje E.); H. Völzke (Henry); H.J. Walter (Henrik); M.W. Weiner (Michael); W. Wen (Wei); T.J.H. White (Tonya); I. Agartz (Ingrid); O.A. Andreassen (Ole); J. Blangero (John); D.I. Boomsma (Dorret); R.M. Brouwer (Rachel); D.M. Cannon (Dara); M.R. Cookson (Mark); E.J.C. de Geus (Eco); I.J. Deary (Ian J.); D.J. Donohoe (Dennis); G. Fernandez (Guillén); S.E. Fisher (Simon); C. Francks (Clyde); D.C. Glahn (David); H.J. Grabe (Hans Jörgen); O. Gruber (Oliver); J. Hardy (John); R. Hashimoto (Ryota); H.E. Hulshoff Pol (Hilleke); E.G. Jönsson (Erik); I. Kloszewska (Iwona); S. Lovestone (Simon); V.S. Mattay (Venkata S.); P. Mecocci (Patrizia); C. McDonald (Colm); A.M. McIntosh (Andrew); R.A. Ophoff (Roel); T. Paus (Tomas); Z. Pausova (Zdenka); M. Ryten (Mina); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); A. Simmons (Andrew); A. Singleton (Andrew); H. Soininen (H.); J.M. Wardlaw (J.); M.E. Weale (Michael); D.R. Weinberger (Daniel); H.H.H. Adams (Hieab); L.J. Launer (Lenore); S. Seiler (Stephan); R. Schmidt (Reinhold); G. Chauhan (Ganesh); C.L. Satizabal (Claudia L.); J.T. Becker (James); L.R. Yanek (Lisa); S.J. van der Lee (Sven); M. Ebling (Maritza); B. Fischl (Bruce); W.T. Longstreth Jr; D. Greve (Douglas); R. Schmidt (Reinhold); P. Nyquist (Paul); L.N. Vinke (Louis N.); C.M. van Duijn (Cornelia); L. Xue (Luting); B. Mazoyer (Bernard); J.C. Bis (Joshua); V. Gudnason (Vilmundur); S. Seshadri (Sudha); M.A. Ikram (Arfan); N.G. Martin (Nicholas); M.J. Wright (Margaret); G. Schumann (Gunter); B. Franke (Barbara); P.M. Thompson (Paul); S.E. Medland (Sarah Elizabeth)
2015-01-01
textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate
Inauguration of the Cameroonian Society of Human Genetics ...
African Journals Online (AJOL)
CSHG) that was privilege to hold its inaugural meeting in conjunction to the 6th annual meeting of the AfSHG. The theme was "Human Origin, Genetic Diversity and Health”. The AfSHG and CSHG invited leading African and international scientists in ...
Human genetics for non-scientists: Practical workshops for policy makers and opinion leaders
Energy Technology Data Exchange (ETDEWEB)
NONE
1995-12-31
These workshops form part of a series of workshops that the Banbury and the DNA Learning Centers of Cold Spring Harbor Laboratory have held for a number of years, introducing genetics, and the ways in which scientific research is done, to non-scientists. The purpose of the workshops as stated in the grant application was: {open_quotes}Our objective is to foster a better understanding of the societal impact of human genome research by providing basic information on genetics to non-scientists whose professions or special interests interface with genetic technology.... Participants will be chosen for their interest in human genetics and for their roles as opinion leaders in their own communities. Primary care physicians are of particular interest to us for this series of workshops.{close_quotes} Two workshops were held under this grant. The first was held in 21-24 April, 1994 and attended by 20 participants, and the second was held 16-19 November, 1995, and attended by 16 participants. In each case, there was a combination of concept lectures on the foundations of human molecular genetics; lectures by invited specialists; and laboratory experiments to introduce non-scientists to the techniques used in molecular genetics.
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 ...
Human Genetics of Diabetic Retinopathy: Current Perspectives
Directory of Open Access Journals (Sweden)
Daniel P. K. Ng
2010-01-01
Full Text Available Diabetic retinopathy (DR is a most severe microvascular complication which, if left unchecked, can be sight-threatening. With the global prevalence of diabetes being relentlessly projected to rise to 438 million subjects by 2030, DR will undoubtedly pose a major public health concern. Efforts to unravel the human genetics of DR have been undertaken using the candidate gene and linkage approaches, while GWAS efforts are still lacking. Aside from evidence for a few genes including aldose reductase and vascular endothelial growth factor, the genetics of DR remain poorly elucidated. Nevertheless, the promise of impactful scientific discoveries may be realized if concerted and collaborative efforts are mounted to identify the genes for DR. Harnessing new genetic technologies and resources such as the upcoming 1000 Genomes Project will help advance this field of research, and potentially lead to a rich harvest of insights into the biological mechanisms underlying this debilitating complication.
Livshits, G; Yakovenko, K; Ginsburg, E; Kobyliansky, E
1998-01-01
The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.
Penchaszadeh, Victor B.; Schuler-Faccini, Lavinia
2014-01-01
Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976–1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program “Reencontro”, which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind. PMID:24764764
Penchaszadeh, Victor B; Schuler-Faccini, Lavinia
2014-03-01
Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976-1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program "Reencontro", which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual) in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind.
Directory of Open Access Journals (Sweden)
Victor B. Penchaszadeh
2014-01-01
Full Text Available Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to identity. In this article, we report the use of genetics to support the right to identity in two historical circumstances. First, we report the search, localization, DNA testing and genetic identification of 110 individuals who were appropriated as babies by the Argentine military dictatorship of 1976-1983 in the context of savage repression and egregious violations of human rights, including forced disappearance and suppression of identity. Second, we report on the repair of right-to-identity violations of hundreds of individuals that occurred during the process of compulsory isolation of patients with leprosy in Brazil through the Program "Reencontro", which has led to the genetic identification of 158 pairs of individuals who previously did not have proof that they were siblings. The high value placed on genetic identification by victims of identity suppression did not counter the prevailing view that genetic factors were not more important than other factors (social, emotional, educational, cultural, spiritual in determining the complex phenomenon of personal identity. The use of genetic identification as a tool to redress and repair human rights violations is a novel application of human genetics for the benefit of mankind.
Common genetic variants influence human subcortical brain structures
Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.
2015-01-01
The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To
[Constant or break? On the relations between human genetics and eugenics in the Twentieth Century].
Germann, Pascal
2015-07-01
The history of human genetics has been a neglected topic in history of science and medicine for a long time. Only recently, have medical historians begun to pay more attention to the history of human heredity. An important research question deals with the interconnections between human genetics and eugenics. This paper addresses this question: By focusing on a Swiss case study, the investigation of the heredity of goiter, I will argue that there existed close but also ambiguous relations between heredity research and eugenics in the twentieth century. Studies on human heredity often produced evidence that challenged eugenic aims and ideas. Concurrently, however, these studies fostered visions of genetic improvement of human populations.
The impact of advances in human molecular biology on radiation genetic risk estimation in man
International Nuclear Information System (INIS)
Sankaranarayanan, K.
1996-01-01
This paper provides an overview of the conceptual framework, the data base, methods and assumptions used thus far to assess the genetic risks of exposure of human populations to ionising radiation. These are then re-examined in the contemporary context of the rapidly expanding knowledge of the molecular biology of human mendelian diseases. This re-examination reveals that (i) many of the assumptions used thus far in radiation genetic risk estimation may not be fully valid and (ii) the current genetic risk estimates are probably conservative, but provide an adequate margin of safety for radiological protection. The view is expressed that further advances in the field of genetic risk estimation will be largely driven by advances in the molecular biology of human genetic diseases. (author). 37 refs., 5 tabs
Boudreault, Patrick; Wolfson, Alicia; Berman, Barbara; Venne, Vickie L; Sinsheimer, Janet S; Palmer, Christina
2018-04-01
Health information about inherited forms of cancer and the role of family history in cancer risk for the American Sign Language (ASL) Deaf community, a linguistic and cultural community, needs improvement. Cancer genetic education materials available in English print format are not accessible for many sign language users because English is not their native or primary language. Per Center for Disease Control and Prevention recommendations, the level of literacy for printed health education materials should not be higher than 6th grade level (~ 11 to 12 years old), and even with this recommendation, printed materials are still not accessible to sign language users or other nonnative English speakers. Genetic counseling is becoming an integral part of healthcare, but often ASL users are not considered when health education materials are developed. As a result, there are few genetic counseling materials available in ASL. Online tools such as video and closed captioning offer opportunities for educators and genetic counselors to provide digital access to genetic information in ASL to the Deaf community. The Deaf Genetics Project team used a bilingual approach to develop a 37-min interactive Cancer Genetics Education Module (CGEM) video in ASL with closed captions and quizzes, and demonstrated that this approach resulted in greater cancer genetic knowledge and increased intentions to obtain counseling or testing, compared to standard English text information (Palmer et al., Disability and Health Journal, 10(1):23-32, 2017). Though visually enhanced educational materials have been developed for sign language users with multimodal/lingual approach, little is known about design features that can accommodate a diverse audience of sign language users so the material is engaging to a wide audience. The main objectives of this paper are to describe the development of the CGEM and to determine if viewer demographic characteristics are associated with two measurable aspects of
Genetic loading on human loving styles.
Emanuele, Enzo; Brondino, Natascia; Pesenti, Sara; Re, Simona; Geroldi, Diego
2007-12-01
It has been hypothesized that cerebral neurotransmitters such as dopamine and serotonin could play a role in human romantic bonding. However, no data on the genetic basis of human romantic love are currently available. To address this issue, we looked for associations between markers in neurotransmitter genes (the serotonin transporter gene, 5-HTT; the serotonin receptor 2A, 5HT2A; the dopamine D2 receptor gene, DRD2; and the dopamine D4 receptor gene, DRD4) and the six styles of love as conceptualized by Lee (Eros, Ludus, Storge, Pragma, Mania and Agape). A total of 350 healthy young adults (165 males and 185 females, mean age: 24.1+/-3.9 years, range 18-32 years) filled the 24-item Love Attitudes Scale (LAS) and were genotyped for the following six polymorphic markers: the serotonin transporter-linked polymorphic region (5-HTTLPR), the 5HT2A T102C and C516T polymorphisms, the DRD2 TaqI A and TaqI B variants, and the DRD4 exon 3 VNTR polymorphism. Statistical analysis revealed a significant association between the DRD2 TaqI A genotypes and "Eros" (a loving style characterized by a tendency to develop intense emotional experiences based on the physical attraction to the partner), as well as between the C516T 5HT2A polymorphism and "Mania" (a possessive and dependent romantic attachment, characterized by self-defeating emotions). These associations were present in both sexes and remained significant even after adjustment for potential confounders. Our data provide the first evidence of a possible genetic loading on human loving styles.
Kanthaswamy, S
2015-10-01
This review highlights the importance of domestic animal genetic evidence sources, genetic testing, markers and analytical approaches as well as the challenges this field is facing in view of the de facto 'gold standard' human DNA identification. Because of the genetic similarity between humans and domestic animals, genetic analysis of domestic animal hair, saliva, urine, blood and other biological material has generated vital investigative leads that have been admitted into a variety of court proceedings, including criminal and civil litigation. Information on validated short tandem repeat, single nucleotide polymorphism and mitochondrial DNA markers and public access to genetic databases for forensic DNA analysis is becoming readily available. Although the fundamental aspects of animal forensic genetic testing may be reliable and acceptable, animal forensic testing still lacks the standardized testing protocols that human genetic profiling requires, probably because of the absence of monetary support from government agencies and the difficulty in promoting cooperation among competing laboratories. Moreover, there is a lack in consensus about how to best present the results and expert opinion to comply with court standards and bear judicial scrutiny. This has been the single most persistent challenge ever since the earliest use of domestic animal forensic genetic testing in a criminal case in the mid-1990s. Crime laboratory accreditation ensures that genetic test results have the courts' confidence. Because accreditation requires significant commitments of effort, time and resources, the vast majority of animal forensic genetic laboratories are not accredited nor are their analysts certified forensic examiners. The relevance of domestic animal forensic genetics in the criminal justice system is undeniable. However, further improvements are needed in a wide range of supporting resources, including standardized quality assurance and control protocols for sample
Monkey-based research on human disease: the implications of genetic differences.
Bailey, Jarrod
2014-11-01
Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90-93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer's disease, Parkinson's disease and stroke. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and monkey genetic sequences is of little benefit for biomedical research. The extrapolation of biomedical data from monkeys to humans is therefore highly unreliable, and the use of monkeys must be considered of questionable value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to scientists. 2014 FRAME.
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.
Functional characterization of genetic enzyme variations in human lipoxygenases
Directory of Open Access Journals (Sweden)
Thomas Horn
2013-01-01
Full Text Available Mammalian lipoxygenases play a role in normal cell development and differentiation but they have also been implicated in the pathogenesis of cardiovascular, hyperproliferative and neurodegenerative diseases. As lipid peroxidizing enzymes they are involved in the regulation of cellular redox homeostasis since they produce lipid hydroperoxides, which serve as an efficient source for free radicals. There are various epidemiological correlation studies relating naturally occurring variations in the six human lipoxygenase genes (SNPs or rare mutations to the frequency for various diseases in these individuals, but for most of the described variations no functional data are available. Employing a combined bioinformatical and enzymological strategy, which included structural modeling and experimental site-directed mutagenesis, we systematically explored the structural and functional consequences of non-synonymous genetic variations in four different human lipoxygenase genes (ALOX5, ALOX12, ALOX15, and ALOX15B that have been identified in the human 1000 genome project. Due to a lack of a functional expression system we resigned to analyze the functionality of genetic variations in the hALOX12B and hALOXE3 gene. We found that most of the frequent non-synonymous coding SNPs are located at the enzyme surface and hardly alter the enzyme functionality. In contrast, genetic variations which affect functional important amino acid residues or lead to truncated enzyme variations (nonsense mutations are usually rare with a global allele frequency<0.1%. This data suggest that there appears to be an evolutionary pressure on the coding regions of the lipoxygenase genes preventing the accumulation of loss-of-function variations in the human population.
Swiss Federal Law on the Genetic Testing of Humans
森, 芳周
2009-01-01
To add an article against the misuse of a reproductive technology and a genetic engineering, theSwiss Federal Constitution was revised in 1992 through an initiative in 1987. On the basis of thisarticle of the constitution, the Reproductive Medicine Act and the Stem Cell Research Act wereenacted in turns; then, the Federal Law on the Genetic Testing of Humans was enacted in October2004. This paper treats a process of the revision of the constitution in 1992 and the enactment of thelaw in 2004....
Genetic human prion disease modelled in PrP transgenic Drosophila.
Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond
2017-09-20
Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).
Annotating DNA variants is the next major goal for human genetics.
Cutting, Garry R
2014-01-02
Clinical genetic testing has undergone a dramatic transformation in the past two decades. Diagnostic laboratories that previously tested for well-established disease-causing DNA variants in a handful of genes have evolved into sequencing factories identifying thousands of variants of known and unknown medical consequence. Sorting out what does and does not cause disease in our genomes is the next great challenge in making genetics a central feature of healthcare. I propose that closing the gap in our ability to interpret variation responsible for Mendelian disorders provides a grand and unprecedented opportunity for geneticists. Human geneticists are well placed to coordinate a systematic evaluation of variants in collaboration with basic scientists and clinicians. Sharing of knowledge, data, methods, and tools will aid both researchers and healthcare workers in achieving their common goal of defining the pathogenic potential of variants. Generation of variant annotations will inform genetic testing and will deepen our understanding of gene and protein function, thereby aiding the search for molecular targeted therapies. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Genetic damage from low-level and natural background radiation
International Nuclear Information System (INIS)
Oftedal, P.
1988-01-01
Relevant predictions that have been made of possible low level biological effects on man are reviewed, and the estimate of genetic damage is discussed. It is concluded that in spite of a number of attempts, no clear-cut case of effects in human populations of radiation at natural levels has been demonstrated. The stability of genetic material is dynamic, with damage, repair and selection running as continuous processes. Genetic materials are well protected and are conservative in the extreme, not least because evolution by genetic adaptation is an expensive process: Substitution of one allele A 1 by another A 2 means the death of the whole A 1 population
Genetic contributions to human brain morphology and intelligence
DEFF Research Database (Denmark)
Hulshoff Pol, HE; Schnack, HG; Posthuma, D
2006-01-01
the focal GM and WM densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin. Genes influenced individual differences in left and right superior occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum (0.82, 0.80), optic radiation (0.69, 0.......79), corticospinal tract (0.78, 0.79), medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80), superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left postcentral cortex (0.83), left posterior cingulate cortex (0.83), right parahippocampal cortex (0.69), and amygdala (0.80, 0......Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...
Colloquium paper: uniquely human evolution of sialic acid genetics and biology.
Varki, Ajit
2010-05-11
Darwinian evolution of humans from our common ancestors with nonhuman primates involved many gene-environment interactions at the population level, and the resulting human-specific genetic changes must contribute to the "Human Condition." Recent data indicate that the biology of sialic acids (which directly involves less than 60 genes) shows more than 10 uniquely human genetic changes in comparison with our closest evolutionary relatives. Known outcomes are tissue-specific changes in abundant cell-surface glycans, changes in specificity and/or expression of multiple proteins that recognize these glycans, and novel pathogen regimes. Specific events include Alu-mediated inactivation of the CMAH gene, resulting in loss of synthesis of the Sia N-glycolylneuraminic acid (Neu5Gc) and increase in expression of the precursor N-acetylneuraminic acid (Neu5Ac); increased expression of alpha2-6-linked Sias (likely because of changed expression of ST6GALI); and multiple changes in SIGLEC genes encoding Sia-recognizing Ig-like lectins (Siglecs). The last includes binding specificity changes (in Siglecs -5, -7, -9, -11, and -12); expression pattern changes (in Siglecs -1, -5, -6, and -11); gene conversion (SIGLEC11); and deletion or pseudogenization (SIGLEC13, SIGLEC14, and SIGLEC16). A nongenetic outcome of the CMAH mutation is human metabolic incorporation of foreign dietary Neu5Gc, in the face of circulating anti-Neu5Gc antibodies, generating a novel "xeno-auto-antigen" situation. Taken together, these data suggest that both the genes associated with Sia biology and the related impacts of the environment comprise a relative "hot spot" of genetic and physiological changes in human evolution, with implications for uniquely human features both in health and disease.
DEFF Research Database (Denmark)
Tan, Qihua; Jacobsen, Rune; Sørensen, Mette
2013-01-01
The analysis of age-specific genetic effects on human survival over extreme ages is confronted with a deceleration pattern in mortality that deviates from traditional survival models and sparse genetic data available. As human late life is a distinct phase of life history, exploring the genetic...... effects on extreme age survival can be of special interest to evolutionary biology and health science. We introduce a non-parametric survival analysis approach that combines population survival information with individual genotype data in assessing the genetic effects in cohort-based longitudinal studies...
Evolving hard problems: Generating human genetics datasets with a complex etiology
Directory of Open Access Journals (Sweden)
Himmelstein Daniel S
2011-07-01
Full Text Available Abstract Background A goal of human genetics is to discover genetic factors that influence individuals' susceptibility to common diseases. Most common diseases are thought to result from the joint failure of two or more interacting components instead of single component failures. This greatly complicates both the task of selecting informative genetic variants and the task of modeling interactions between them. We and others have previously developed algorithms to detect and model the relationships between these genetic factors and disease. Previously these methods have been evaluated with datasets simulated according to pre-defined genetic models. Results Here we develop and evaluate a model free evolution strategy to generate datasets which display a complex relationship between individual genotype and disease susceptibility. We show that this model free approach is capable of generating a diverse array of datasets with distinct gene-disease relationships for an arbitrary interaction order and sample size. We specifically generate eight-hundred Pareto fronts; one for each independent run of our algorithm. In each run the predictiveness of single genetic variation and pairs of genetic variants have been minimized, while the predictiveness of third, fourth, or fifth-order combinations is maximized. Two hundred runs of the algorithm are further dedicated to creating datasets with predictive four or five order interactions and minimized lower-level effects. Conclusions This method and the resulting datasets will allow the capabilities of novel methods to be tested without pre-specified genetic models. This allows researchers to evaluate which methods will succeed on human genetics problems where the model is not known in advance. We further make freely available to the community the entire Pareto-optimal front of datasets from each run so that novel methods may be rigorously evaluated. These 76,600 datasets are available from http://discovery.dartmouth.edu/model_free_data/.
Coyne, Michael J; Roelofs, Kevin G; Comstock, Laurie E
2016-01-15
Type VI secretion systems (T6SSs) are contact-dependent antagonistic systems employed by Gram negative bacteria to intoxicate other bacteria or eukaryotic cells. T6SSs were recently discovered in a few Bacteroidetes strains, thereby extending the presence of these systems beyond Proteobacteria. The present study was designed to analyze in a global nature the diversity, abundance, and properties of T6SSs in the Bacteroidales, the most predominant Gram negative bacterial order of the human gut. By performing extensive bioinformatics analyses and creating hidden Markov models for Bacteroidales Tss proteins, we identified 130 T6SS loci in 205 human gut Bacteroidales genomes. Of the 13 core T6SS proteins of Proteobacteria, human gut Bacteroidales T6SS loci encode orthologs of nine, and an additional five other core proteins not present in Proteobacterial T6SSs. The Bacteroidales T6SS loci segregate into three distinct genetic architectures with extensive DNA identity between loci of a given genetic architecture. We found that divergent DNA regions of a genetic architecture encode numerous types of effector and immunity proteins and likely include new classes of these proteins. TheT6SS loci of genetic architecture 1 are contained on highly similar integrative conjugative elements (ICEs), as are the T6SS loci of genetic architecture 2, whereas the T6SS loci of genetic architecture 3 are not and are confined to Bacteroides fragilis. Using collections of co-resident Bacteroidales strains from human subjects, we provide evidence for the transfer of genetic architecture 1 T6SS loci among co-resident Bacteroidales species in the human gut. However, we also found that established ecosystems can harbor strains with distinct T6SS of all genetic architectures. This is the first study to comprehensively analyze of the presence and diversity of T6SS loci within an order of bacteria and to analyze T6SSs of bacteria from a natural community. These studies demonstrate that more than
Genetic recombination as a major cause of mutagenesis in the human globin gene clusters.
Borg, Joseph; Georgitsi, Marianthi; Aleporou-Marinou, Vassiliki; Kollia, Panagoula; Patrinos, George P
2009-12-01
Homologous recombination is a frequent phenomenon in multigene families and as such it occurs several times in both the alpha- and beta-like globin gene families. In numerous occasions, genetic recombination has been previously implicated as a major mechanism that drives mutagenesis in the human globin gene clusters, either in the form of unequal crossover or gene conversion. Unequal crossover results in the increase or decrease of the human globin gene copies, accompanied in the majority of cases with minor phenotypic consequences, while gene conversion contributes either to maintaining sequence homogeneity or generating sequence diversity. The role of genetic recombination, particularly gene conversion in the evolution of the human globin gene families has been discussed elsewhere. Here, we summarize our current knowledge and review existing experimental evidence outlining the role of genetic recombination in the mutagenic process in the human globin gene families.
Burridge, Paul W; Sharma, Arun; Wu, Joseph C
2015-01-01
Regeneration or replacement of lost cardiomyocytes within the heart has the potential to revolutionize cardiovascular medicine. Numerous methodologies have been used to achieve this aim, including the engraftment of bone marrow- and heart-derived cells as well as the identification of modulators of adult cardiomyocyte proliferation. Recently, the conversion of human somatic cells into induced pluripotent stem cells and induced cardiomyocyte-like cells has transformed potential approaches toward this goal, and the engraftment of cardiac progenitors derived from human embryonic stem cells into patients is now feasible. Here we review recent advances in our understanding of the genetic and epigenetic control of human cardiogenesis, cardiac differentiation, and the induced reprogramming of somatic cells to cardiomyocytes. We also cover genetic programs for inducing the proliferation of endogenous cardiomyocytes and discuss the genetic state of cells used in cardiac regenerative medicine.
Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission.
Directory of Open Access Journals (Sweden)
Shuzhen Sim
Full Text Available Dengue virus (DENV infection of an individual human or mosquito host produces a dynamic population of closely-related sequences. This intra-host genetic diversity is thought to offer an advantage for arboviruses to adapt as they cycle between two very different host species, but it remains poorly characterized. To track changes in viral intra-host genetic diversity during horizontal transmission, we infected Aedes aegypti mosquitoes by allowing them to feed on DENV2-infected patients. We then performed whole-genome deep-sequencing of human- and matched mosquito-derived DENV samples on the Illumina platform and used a sensitive variant-caller to detect single nucleotide variants (SNVs within each sample. >90% of SNVs were lost upon transition from human to mosquito, as well as from mosquito abdomen to salivary glands. Levels of viral diversity were maintained, however, by the regeneration of new SNVs at each stage of transmission. We further show that SNVs maintained across transmission stages were transmitted as a unit of two at maximum, suggesting the presence of numerous variant genomes carrying only one or two SNVs each. We also present evidence for differences in selection pressures between human and mosquito hosts, particularly on the structural and NS1 genes. This analysis provides insights into how population drops during transmission shape RNA virus genetic diversity, has direct implications for virus evolution, and illustrates the value of high-coverage, whole-genome next-generation sequencing for understanding viral intra-host genetic diversity.
Genetics of human sensitivity to ultraviolet radiation
Cleaver, James E.
1994-07-01
the major human health effects of solar and artificial UV light occur from the UVB and UVC wavelength ranges and involve a variety of short-term and long-term deleterious changes to the skin and eyes. the more important initial damage to cellular macromolecules involves dimerization of adjacent pyrimidines in DNA to produce cyclobutane pyrimidine dimes, (6-4) pyrimidine- pyrimidone, and (6-4) dewar photoproducts. these photoproducts can be repaired by a genetically regulated enzyme system (nucleotide excision repair) which removes oligonucleotides 29-30 nucleotides long that contain the photoproducts, and synthesizes replacement patches. At least a dozen gene products are involved in the process of recognizing photoproducts in DNA, altering local DNA helicity and cleaving the polynucleotide chain at defined positions either side of a photoproduct. Hereditary mutations in many of these genes are recognized in the human genetic disorders xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). Several of the gene products have other functions involving the regulation of gene transcription which accounts for the complex clinical presentation of repair deficient diseases that involve sensitivity of the skin and eyes to UV light, increased solar carcinogenesis (in XP), demyelination, and ganglial calcification (in CS), hair abnormalities (in TTD), and developmental and neurological abnormalities
Using human genetics to predict the effects and side-effects of drugs
DEFF Research Database (Denmark)
Stender, Stefan; Tybjærg-Hansen, Anne
2016-01-01
PURPOSE OF REVIEW: 'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. RECENT FINDINGS: LDL cholesterol lowering variants in HMG-Coenzyme A re...
Thomaschke, Dirk
2013-01-01
The author compares the history of human genetics in the Federal Republic of Germany and Denmark from the 1950s to the 1980s. The paper combines a discourse analysis with the exploration of human genetics experts' subject forms along the lines of current considerations within cultural studies. In the 1950s and 1960s, human geneticists acted in close cooperation with other political, judicial and administrative expert groups. They monitored the 'overall genetic development' of the population and cautioned about 'genetic crises'. Laypersons were supposed to submit to 'objectively reasonable' behavioral patterns--to their own as well as society's benefit. In the 1970s, the experts turned into 'providers' of a 'precise, purely medical, diagnostic service'. The patients mainly appeared as 'de-personalized' sources of a common human demand for 'safe eugenic information'. In the 1980s, the demand and supply paradigm manifested psychological and ethical side effects. Human geneticists became aware of the social and historical interrelations of their research and practices. The results of this study contribute to a more complex understanding of the dominant 'individualization narrative' of human genetics history. In this context, the development in Germany and Denmark displays two complementary forms of a transnational discourse.
The ecological imperative and its application to ethical issues in human genetic technology
Directory of Open Access Journals (Sweden)
W. Malcolm Byrnes
2003-08-01
Full Text Available As a species, we are on the cusp of being able to alter that which makes us uniquely human, our genome. Two new genetic technologies, embryo selection and germline engineering, are either in use today or may be developed in the future. Embryo selection acts to alter the human gene pool, reducing genetic diversity, while germline engineering will have the ability to alter directly the genomes of engineered individuals. Our genome has come to be what it is through an evolutionary process extending over millions of years, a process that has involved exceedingly complex and unpredictable interactions between ourselves or our ancestors and myriad other life forms within Earth's biosphere. In this paper, the ecological imperativ e, which states that we must not alter the human genome or the collective human genetic inheritance, will be introduced. It will be argued based on ecological principles that embryo selection and germline engineering are unethical and unwise because they will diminish our survivability as a species, will disrupt our relationship with the natural world, and will destroy the very basis of that which makes us human.
DEFF Research Database (Denmark)
Wild, Thomas; Larsen, Marie Sofie Yoo; Narita, Takeo
2016-01-01
The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin......-conjugating enzymes-UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D...... depletion. Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. These results provide insights into the regulation of APC...
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.
Gitelson, Josef
Creation of closed systems that would be able to support human life outside the biosphere for extended periods of time (CES) was started after humans went into outer space. The last fifty years have seen the construction of experimental variants of the CES in Russia, USA, and Japan. The "MELISSA" project of the European Space Agency is being prepared to be launched. Much success has been achieved in closing material loops in the CES. An obstacle to constructing a fully closed ecosystem is significant imbalance in material exchange between the producing components and the decomposing ones in the CES. The spectrum of metabolites released by humans does not fully correspond to the requirements of the main producer of the CES -plants. However, this imbalance can be corrected by rather simple physicochemical processes that can be used in the CES without unclosing the system. The major disagreement that prevents further improvement of human life support systems (LSS) is that the spectrum of products of photosynthesis in the CES does not correspond to human food requirements qual-itatively, quantitatively, or in terms of diversity. In the normal, physiologically sound, human diet, this discrepancy is resolved by adding animal products. However, there are technical, technological, and hygienic obstacles to including animals in the closed human life support systems, and if higher animals are considered, there are also ethical arguments. If between the photoautotrophic link, plants, and the heterotrophic link, the human, there were one more heterotrophic link, farm animals, the energy requirements of the system would be increased by nearly an order of magnitude, decreasing its efficiency and making it heavier and bulkier. Is there another way to close loops in human life support systems? In biology, such "findings" of evolution, which open up new perspectives and offer ample opportunities for possible adapta-tions, are termed aromorphoses (Schmalhausen, 1948). In further
Mayer, René E; Reischer, Georg H; Ixenmaier, Simone K; Derx, Julia; Blaschke, Alfred Paul; Ebdon, James E; Linke, Rita; Egle, Lukas; Ahmed, Warish; Blanch, Anicet R; Byamukama, Denis; Savill, Marion; Mushi, Douglas; Cristóbal, Héctor A; Edge, Thomas A; Schade, Margit A; Aslan, Asli; Brooks, Yolanda M; Sommer, Regina; Masago, Yoshifumi; Sato, Maria I; Taylor, Huw D; Rose, Joan B; Wuertz, Stefan; Shanks, Orin C; Piringer, Harald; Mach, Robert L; Savio, Domenico; Zessner, Matthias; Farnleitner, Andreas H
2018-05-01
Numerous bacterial genetic markers are available for the molecular detection of human sources of fecal pollution in environmental waters. However, widespread application is hindered by a lack of knowledge regarding geographical stability, limiting implementation to a small number of well-characterized regions. This study investigates the geographic distribution of five human-associated genetic markers (HF183/BFDrev, HF183/BacR287, BacHum-UCD, BacH, and Lachno2) in municipal wastewaters (raw and treated) from 29 urban and rural wastewater treatment plants (750-4 400 000 population equivalents) from 13 countries spanning six continents. In addition, genetic markers were tested against 280 human and nonhuman fecal samples from domesticated, agricultural and wild animal sources. Findings revealed that all genetic markers are present in consistently high concentrations in raw (median log 10 7.2-8.0 marker equivalents (ME) 100 mL -1 ) and biologically treated wastewater samples (median log 10 4.6-6.0 ME 100 mL -1 ) regardless of location and population. The false positive rates of the various markers in nonhuman fecal samples ranged from 5% to 47%. Results suggest that several genetic markers have considerable potential for measuring human-associated contamination in polluted environmental waters. This will be helpful in water quality monitoring, pollution modeling and health risk assessment (as demonstrated by QMRAcatch) to guide target-oriented water safety management across the globe.
Biotechnology, Genetic Engineering and Society. Monograph Series: III.
Kieffer, George H.
New techniques have expanded the field of biotechnology and awarded scientists an unprecedented degree of control over the genetic constitutions of living things. The knowledge of DNA science is the basis for this burgeoning industry which may be a major force in human existence. Just as it is possible to move genetic material from one organism to…
Teachers' Conceptions About the Genetic Determinism of Human Behaviour: A Survey in 23 Countries
Castéra, Jérémy; Clément, Pierre
2014-02-01
This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed teachers' conceptions. This illustrates that innatism is present in two distinct ways: in relation to individuals (e.g. genetic determinism to justify intellectual likeness between individuals such as twins) or in relation to groups of humans (e.g. genetic determinism to justify gender differences or the superiority of some human ethnic groups). A between-factor analysis discriminates between countries, showing very significant differences. There is more innatism among teachers' conceptions in African countries and Lebanon than in European countries, Brazil and Australia. Among the other controlled parameters, only two are significantly independent of the country: the level of training and the level of knowledge of biology. A co-inertia analysis shows a strong correlation between non-citizen attitudes towards and innatist conceptions of genetic determinism regarding human groups. We discuss these findings and their implications for education.
Simpson, Siobhan; Dunning, Mark David; de Brot, Simone; Grau-Roma, Llorenç; Mongan, Nigel Patrick; Rutland, Catrin Sian
2017-10-24
Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.
The ethics of human genetic intervention: a postmodern perspective.
Dyer, A R
1997-03-01
Gene therapy for a particular disease like Parkinson's involves ethical principles worked out for other diseases. The major ethical issues for gene therapy (and the corresponding ethical principles) are safety (nonmalfeasance), efficacy (beneficence), informed consent (autonomy), and allocation of resources (justice). Yet genetic engineering (germ-line interventions or interventions to enhance human potentialities) raises emotions and fears that might cause resistance to gene therapies. Looking at these technologies in a postmodern perspective helps one to appreciate the issues at stake in social and cultural change with a new technology such as gene therapy. While "modern" technology and ethics have focused on the autonomy of the individual, we are beginning to see a lessening of such emphasis on individualism and autonomy and more emphasis on the health of the population. Such a social change could cause technologies about which society may currently be cautious (such as human genetic interventions) to become more acceptable or even expected.
Unleashing the power of human genetic variation knowledge: New Zealand stakeholder perspectives.
Gu, Yulong; Warren, James Roy; Day, Karen Jean
2011-01-01
This study aimed to characterize the challenges in using genetic information in health care and to identify opportunities for improvement. Taking a grounded theory approach, semistructured interviews were conducted with 48 participants to collect multiple stakeholder perspectives on genetic services in New Zealand. Three themes emerged from the data: (1) four service delivery models were identified in operation, including both those expected models involving genetic counselors and variations that do not route through the formal genetic service program; (2) multiple barriers to sharing and using genetic information were perceived, including technological, organizational, institutional, legal, ethical, and social issues; and (3) impediments to wider use of genetic testing technology, including variable understanding of genetic test utilities among clinicians and the limited capacity of clinical genetic services. Targeting these problems, information technologies and knowledge management tools have the potential to support key tasks in genetic services delivery, improve knowledge processes, and enhance knowledge networks. Because of the effect of issues in genetic information and knowledge management, the potential of human genetic variation knowledge to enhance health care delivery has been put on a "leash."
Anthropogenics: human influence on global and genetic homogenization of parasite populations.
Zarlenga, Dante S; Hoberg, Eric; Rosenthal, Benjamin; Mattiucci, Simonetta; Nascetti, Giuseppe
2014-12-01
The distribution, abundance, and diversity of life on Earth have been greatly shaped by human activities. This includes the geographic expansion of parasites; however, measuring the extent to which humans have influenced the dissemination and population structure of parasites has been challenging. In-depth comparisons among parasite populations extending to landscape-level processes affecting disease emergence have remained elusive. New research methods have enhanced our capacity to discern human impact, where the tools of population genetics and molecular epidemiology have begun to shed light on our historical and ongoing influence. Only since the 1990s have parasitologists coupled morphological diagnosis, long considered the basis of surveillance and biodiversity studies, with state-of-the-art tools enabling variation to be examined among, and within, parasite populations. Prior to this time, populations were characterized only by phenotypic attributes such as virulence, infectivity, host range, and geographical location. The advent of genetic/molecular methodologies (multilocus allozyme electrophoresis, polymerase chain reaction-DNA [PCR-DNA] fragments analysis, DNA sequencing, DNA microsatellites, single nucleotide polymorphisms, etc.) have transformed our abilities to reveal variation among, and within, populations at local, regional, landscape, and global scales, and thereby enhanced our understanding of the biosphere. Numerous factors can affect population structure among parasites, e.g., evolutionary and ecological history, mode of reproduction and transmission, host dispersal, and life-cycle complexity. Although such influences can vary considerably among parasite taxa, anthropogenic factors are demonstrably perturbing parasite fauna. Minimal genetic structure among many geographically distinct (isolated) populations is a hallmark of human activity, hastened by geographic introductions, environmental perturbation, and global warming. Accelerating
Human genetics in troubled times and places
Harper, Peter S.
2017-01-01
The development of human genetics world-wide during the twentieth century, especially across Europe, has occurred against a background of repeated catastrophes, including two world wars and the ideological problems and repression posed by Nazism and Communism. The published scientific literature gives few hints of these problems and there is a danger that they will be forgotten. The First World War was largely indiscriminate in its carnage, but World War 2 and the preceding years of fascism w...
Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D
1989-01-01
The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.
The ecological imperative and its application to ethical issues in human genetic technology
W. Malcolm Byrnes
2003-01-01
As a species, we are on the cusp of being able to alter that which makes us uniquely human, our genome. Two new genetic technologies, embryo selection and germline engineering, are either in use today or may be developed in the future. Embryo selection acts to alter the human gene pool, reducing genetic diversity, while germline engineering will have the ability to alter directly the genomes of engineered individuals. Our genome has come to be what it is through an evolutionary process extend...
Integrating common and rare genetic variation in diverse human populations.
Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E
2010-09-02
Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of
Privacy and Property? Multi-level Strategies for Protecting Personal Interests in Genetic Material
Laurie, Graeme
2003-01-01
The paper builds on earlier medico-legal work by Laurie on privacy in relation to genetic material. In this chapter, the author discusses not only Laurie's views as 'pro-privacy' but the limitations of privacy, particularly once information, genetic or otherwise, enters a public sphere. The article draws on cases and laws in the UK, continental Europe, and the US, to provide a comparative view in suggesting an alternative approach to privacy.
Long term human impacts on genetic structure of Italian walnut inferred by SSR markers
Paola Pollegioni; Keith Woeste; Irene Olimpieri; Danilo Marandola; Francesco Cannata; Maria E Malvolti
2011-01-01
Life history traits, historic factors, and human activities can all shape the genetic diversity of a species. In Italy, walnut (Juglans regia L.) has a long history of cultivation both for wood and edible nuts. To better understand the genetic variability of current Italian walnut resources, we analyzed the relationships among the genetic structure...
Human genetics of infectious diseases: a unified theory
Casanova, Jean-Laurent; Abel, Laurent
2007-01-01
Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predispos...
A genetic basis for mechanosensory traits in humans.
Directory of Open Access Journals (Sweden)
Henning Frenzel
Full Text Available In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A.
Routine human-competitive machine intelligence by means of genetic programming
Koza, John R.; Streeter, Matthew J.; Keane, Martin
2004-01-01
Genetic programming is a systematic method for getting computers to automatically solve a problem. Genetic programming starts from a high-level statement of what needs to be done and automatically creates a computer program to solve the problem. The paper demonstrates that genetic programming (1) now routinely delivers high-return human-competitive machine intelligence; (2) is an automated invention machine; (3) can automatically create a general solution to a problem in the form of a parameterized topology; and (4) has delivered a progression of qualitatively more substantial results in synchrony with five approximately order-of-magnitude increases in the expenditure of computer time. Recent results involving the automatic synthesis of the topology and sizing of analog electrical circuits and controllers demonstrate these points.
Cai, Pei-qiang; Tang, Xun; Lin, Yue-qiu; Martin, Oudega; Sun, Guang-yun; Xu, Lin; Yang, Yun-kang; Zhou, Tian-hua
2006-02-01
To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs) mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI). Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3 (NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot. Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot. Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.
Directory of Open Access Journals (Sweden)
Matthew T G Holden
2009-03-01
Full Text Available The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus. These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2 toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.
Genetics of the pig tapeworm in madagascar reveal a history of human dispersal and colonization.
Yanagida, Tetsuya; Carod, Jean-François; Sako, Yasuhito; Nakao, Minoru; Hoberg, Eric P; Ito, Akira
2014-01-01
An intricate history of human dispersal and geographic colonization has strongly affected the distribution of human pathogens. The pig tapeworm Taenia solium occurs throughout the world as the causative agent of cysticercosis, one of the most serious neglected tropical diseases. Discrete genetic lineages of T. solium in Asia and Africa/Latin America are geographically disjunct; only in Madagascar are they sympatric. Linguistic, archaeological and genetic evidence has indicated that the people in Madagascar have mixed ancestry from Island Southeast Asia and East Africa. Hence, anthropogenic introduction of the tapeworm from Southeast Asia and Africa had been postulated. This study shows that the major mitochondrial haplotype of T. solium in Madagascar is closely related to those from the Indian Subcontinent. Parasitological evidence presented here, and human genetics previously reported, support the hypothesis of an Indian influence on Malagasy culture coinciding with periods of early human migration onto the island. We also found evidence of nuclear-mitochondrial discordance in single tapeworms, indicating unexpected cross-fertilization between the two lineages of T. solium. Analyses of genetic and geographic populations of T. solium in Madagascar will shed light on apparently rapid evolution of this organism driven by recent (<2,000 yr) human migrations, following tens of thousands of years of geographic isolation.
Discovery and resolve: the Human Genetics Society of Australasia Oration 2011.
Pearn, John
2011-10-01
Human genetics spans every facet of biology from molecular science, through laboratory and clinical practice, to psychology and anthropology. In each of these areas, the history of human genetics has been punctuated by paradigm shifts in knowledge. Each such new concept has been received with skepticism, often with perplexity, and sometimes with frank incredulity. Such comprise the datum milestones along the path leading to our present corpus of genetic knowledge. In parallel to the personal threats to Copernicus and Galileo in the field of astronomy in the 17th century, almost all genetic discoveries of the 19th and 20th centuries were seen as challenges to the received wisdom, and sometimes the social order, of their time and place. Researchers, scientists and clinicians encountering such new and often-heretical paradigm shifts have required considerable resolve to promote and publish their work. Just as in the field of astronomy, new directions in genetics have threatened not only the reputations and sometimes the careers of scientists, but also have been challenges to fundamental religious and sociological beliefs in society more broadly. Examples followed the discovery of biological sexual dimorphism (in plants as well as animals) by Nehemiah Grew (1641-1712). Darwinian evolution, Mendel's First and Second Laws, the existence of mitochondrial genes, apoptosis and its genetic basis, and uniparental disomy are more recent examples. Many of these new revelations, which today have led to the current understanding of fundamental biology, were discovered by individuals working in relative isolation. To promote and publish findings that fundamentally challenge received wisdom continues to require considerable resolve, if not courage. Herein lies a message for all clinicians and researchers.
Penchaszadeh, Victor B.; Schuler-Faccini, Lavinia
2014-01-01
Over the past three decades, there has been an accelerated development of genetic technology, leading to its use in human genetic identification for many purposes. Additionally, it has been made explicit that identity is a fundamental human right. A number of historical circumstances have connected these developments. Personal identity is increasingly associated with the preservation and defense of human rights and is a tool to repair the violation of these rights, particularly the right to i...
Interactively human: Sharing time, constructing materiality.
Roepstorff, Andreas
2013-06-01
Predictive processing models of cognition are promising an elegant way to unite action, perception, and learning. However, in the current formulations, they are species-unspecific and have very little particularly human about them. I propose to examine how, in this framework, humans can be able to massively interact and to build shared worlds that are both material and symbolic.
Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases
Directory of Open Access Journals (Sweden)
Ivana Antonucci
2016-04-01
Full Text Available In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers “in vitro”. In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.
Human biological monitoring of occupational genotoxic exposures
DEFF Research Database (Denmark)
Knudsen, Lisbeth E.; Sorsa, M
1993-01-01
Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e......) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors...
Common genetic variants influence human subcortical brain structures
Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.
2015-01-01
The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358
Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A
2014-09-01
Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.
Hruschka, Daniel J; Hadley, Craig; Brewis, Alexandra A; Stojanowski, Christopher M
2015-01-01
Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R2 = 0.14-0.28). However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R2 = 0.50-0.74). Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.
Directory of Open Access Journals (Sweden)
Daniel J Hruschka
Full Text Available Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R2 = 0.14-0.28. However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R2 = 0.50-0.74. Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.
Weaver, Timothy D
2014-08-01
Estimates of the amount of genetic differentiation in humans among major geographic regions (e.g., Eastern Asia vs. Europe) from quantitative-genetic analyses of cranial measurements closely match those from classical- and molecular-genetic markers. Typically, among-region differences account for ∼10% of the total variation. This correspondence is generally interpreted as evidence for the importance of neutral evolutionary processes (e.g., genetic drift) in generating among-region differences in human cranial form, but it was initially surprising because human cranial diversity was frequently assumed to show a strong signature of natural selection. Is the human degree of similarity of cranial and DNA-sequence estimates of among-region genetic differentiation unusual? How do comparisons with other taxa illuminate the evolutionary processes underlying cranial diversification? Chimpanzees provide a useful starting point for placing the human results in a broader comparative context, because common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the extant species most closely related to humans. To address these questions, I used 27 cranial measurements collected on a sample of 861 humans and 263 chimpanzees to estimate the amount of genetic differentiation between pairs of groups (between regions for humans and between species or subspecies for chimpanzees). Consistent with previous results, the human cranial estimates are quite similar to published DNA-sequence estimates. In contrast, the chimpanzee cranial estimates are much smaller than published DNA-sequence estimates. It appears that cranial differentiation has been limited in chimpanzees relative to humans. © 2014 Wiley Periodicals, Inc.
Somatic retrotransposition alters the genetic landscape of the human brain
Baillie, J.K.; Barnett, M.W.; Upton, K.R.; Gerhardt, D.J.; Richmond, T.A.; De Sapio, F.; Brennan, P.; Rizzu, P.; Smith, S.; Fell, M.; Talbot, R.T.; Gustincich, S.; Freeman, T.C.; Mattick, J.S.; Hume, D.A.; Heutink, P.; Carninci, P.; Jeddeloh, J.A.; Faulkner, G.J.
2011-01-01
Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes1. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and
Pauletti, G; Godolphin, W; Press, M F; Slamon, D J
1996-07-04
Amplification and overexpression of the HER-2/neu gene occurs in 25-30% of human breast cancers. This genetic alteration is associated with a poor clinical prognosis in women with either node negative or node positive breast cancers. The initial studies testing this association were somewhat controversial and this controversy was due in large part to significant heterogeneity in both the methods and/or reagents used in testing archival material for the presence of the alteration. These methods included a number of solid matrix blotting techniques for DNA, RNA and protein as well as immunohistochemistry. Fluorescence in situ hybridization (FISH) represents the newest methodologic approach for testing for this genetic alteration. In this study, FISH is compared to Southern, Northern and Western blot analyses as well as immunohistochemistry in a large cohort of archival human breast cancer specimens. FISH was found to be superior to all other methodologies tested in assessing formalin fixed, paraffin embedded material for HER-2/neu amplification. The results from this study also confirm that overexpression of HER-2/neu rarely occurs in the absence of gene amplification in breast cancer (approximately 3% of cases). This method of analysis is rapid, reproducible and extremely reliable in detecting presence of HER-2/neu gene amplification and should have clinical utility.
The humankind genome: from genetic diversity to the origin of human diseases.
Belizário, Jose E
2013-12-01
Genome-wide association studies have failed to establish common variant risk for the majority of common human diseases. The underlying reasons for this failure are explained by recent studies of resequencing and comparison of over 1200 human genomes and 10 000 exomes, together with the delineation of DNA methylation patterns (epigenome) and full characterization of coding and noncoding RNAs (transcriptome) being transcribed. These studies have provided the most comprehensive catalogues of functional elements and genetic variants that are now available for global integrative analysis and experimental validation in prospective cohort studies. With these datasets, researchers will have unparalleled opportunities for the alignment, mining, and testing of hypotheses for the roles of specific genetic variants, including copy number variations, single nucleotide polymorphisms, and indels as the cause of specific phenotypes and diseases. Through the use of next-generation sequencing technologies for genotyping and standardized ontological annotation to systematically analyze the effects of genomic variation on humans and model organism phenotypes, we will be able to find candidate genes and new clues for disease's etiology and treatment. This article describes essential concepts in genetics and genomic technologies as well as the emerging computational framework to comprehensively search websites and platforms available for the analysis and interpretation of genomic data.
Human impacts on genetic diversity in forest ecosystems
Energy Technology Data Exchange (ETDEWEB)
Ledig, F T [Inst. of Forest Genetics, Southwest Forest and Range Experiment Station, USDA Forest Service, Berkeley (US)
1992-01-01
Humans have converted forest to agricultural and urban uses, exploited species, fragmented wildlands, changed the demographic structure of forests, altered habitat, degraded the environment with atmospheric and soil pollutants, introduced exotic pests and competitors, and domesticated favored species. None of these activities is new; perhaps with the exception of atmospheric pollution, they date back to prehistory. All have impacted genetic diversity by their influence on the evolutionary processes of extinction, selection, drift, gene flow, and mutation, sometimes increasing diversity, as int he case of domestication, but often reducing it. Even in the absence of changes in diversity, mating systems were altered, changing the genetic structure of populations. Demographic changes influenced selection by increasing the incidence of disease. Introduction of exotic diseases, insects, mammalian herbivores, and competing vegetation has had the best-documented effects on genetic diversity, reducing both species diversity and intraspecific diversity. Deforestation has operated on a vast scale to reduce diversity by direct elimination of locally-adapted populations. Atmospheric pollution and global warming will be a major threat in the near future, particularly because forests are fragmented and migration is impeded. Past impacts can be estimated with reference to expert knowledge, but hard data are often laching. Baselines are needed to quantify future impacts and provide an early warning of problems. Genetic inventories of indicator species can provide the baselines against which to measure changes in diversity. (author) (44 refs.).
Egyptian Journal of Medical Human Genetics - Vol 13, No 2 (2012)
African Journals Online (AJOL)
Egyptian Journal of Medical Human Genetics - Vol 13, No 2 (2012) ... as independent indicators for B-CLL: Correlation to response to treatment and disease ... Profile of disorders of sexual differentiation in the Northeast region of Cairo, Egypt ...
Human genetics of infectious diseases: between proof of principle and paradigm
Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent
2009-01-01
The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proo...
Multhaup, Michael L.; Seldin, Marcus; Jaffe, Andrew E.; Lei, Xia; Kirchner, Henriette; Mondal, Prosenjit; Li, Yuanyuan; Rodriguez, Varenka; Drong, Alexander; Hussain, Mehboob; Lindgren, Cecilia; McCarthy, Mark; Näslund, Erik; Zierath, Juleen R.; Wong, G. William; Feinberg, Andrew P.
2015-01-01
SUMMARY Using a functional approach to investigate the epigenetics of Type 2 Diabetes (T2D), we combine three lines of evidence – diet-induced epigenetic dysregulation in mouse, epigenetic conservation in humans, and T2D clinical risk evidence – to identify genes implicated in T2D pathogenesis through epigenetic mechanisms related to obesity. Beginning with dietary manipulation of genetically homogeneous mice, we identify differentially DNA-methylated genomic regions. We then replicate these results in adipose samples from lean and obese patients pre- and post-Roux-en-Y gastric bypass, identifying regions where both the location and direction of methylation change is conserved. These regions overlap with 27 genetic T2D risk loci, only one of which was deemed significant by GWAS alone. Functional analysis of genes associated with these regions revealed four genes with roles in insulin resistance, demonstrating the potential general utility of this approach for complementing conventional human genetic studies by integrating cross-species epigenomics and clinical genetic risk. PMID:25565211
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...
Accelerating Precision Drug Development and Drug Repurposing by Leveraging Human Genetics.
Pulley, Jill M; Shirey-Rice, Jana K; Lavieri, Robert R; Jerome, Rebecca N; Zaleski, Nicole M; Aronoff, David M; Bastarache, Lisa; Niu, Xinnan; Holroyd, Kenneth J; Roden, Dan M; Skaar, Eric P; Niswender, Colleen M; Marnett, Lawrence J; Lindsley, Craig W; Ekstrom, Leeland B; Bentley, Alan R; Bernard, Gordon R; Hong, Charles C; Denny, Joshua C
2017-04-01
The potential impact of using human genetic data linked to longitudinal electronic medical records on drug development is extraordinary; however, the practical application of these data necessitates some organizational innovations. Vanderbilt has created resources such as an easily queried database of >2.6 million de-identified electronic health records linked to BioVU, which is a DNA biobank with more than 230,000 unique samples. To ensure these data are used to maximally benefit and accelerate both de novo drug discovery and drug repurposing efforts, we created the Accelerating Drug Development and Repurposing Incubator, a multidisciplinary think tank of experts in various therapeutic areas within both basic and clinical science as well as experts in legal, business, and other operational domains. The Incubator supports a diverse pipeline of drug indication finding projects, leveraging the natural experiment of human genetics.
A CRISPR New World: Attitudes in the Public toward Innovations in Human Genetic Modification.
Weisberg, Steven M; Badgio, Daniel; Chatterjee, Anjan
2017-01-01
The potential to genetically modify human germlines has reached a critical tipping point with recent applications of CRISPR-Cas9. Even as researchers, clinicians, and ethicists weigh the scientific and ethical repercussions of these advances, we know virtually nothing about public attitudes on the topic. Understanding such attitudes will be critical to determining the degree of broad support there might be for any public policy or regulation developed for genetic modification research. To fill this gap, we gave an online survey to a large (2,493 subjects) and diverse sample of Americans. Respondents supported genetic modification research, although demographic variables influenced these attitudes-conservatives, women, African-Americans, and older respondents, while supportive, were more cautious than liberals, men, other ethnicities, and younger respondents. Support was also was slightly muted when the risks (unanticipated mutations and possibility of eugenics) were made explicit. The information about genetic modification was also presented as contrasting vignettes, using one of five frames: genetic editing, engineering, hacking, modification, or surgery. Despite the fact that the media and academic use of frames describing the technology varies, these frames did not influence people's attitudes. These data contribute a current snapshot of public attitudes to inform policy with regard to human genetic modification.
A CRISPR New World: Attitudes in the Public toward Innovations in Human Genetic Modification
Directory of Open Access Journals (Sweden)
Steven M. Weisberg
2017-05-01
Full Text Available The potential to genetically modify human germlines has reached a critical tipping point with recent applications of CRISPR-Cas9. Even as researchers, clinicians, and ethicists weigh the scientific and ethical repercussions of these advances, we know virtually nothing about public attitudes on the topic. Understanding such attitudes will be critical to determining the degree of broad support there might be for any public policy or regulation developed for genetic modification research. To fill this gap, we gave an online survey to a large (2,493 subjects and diverse sample of Americans. Respondents supported genetic modification research, although demographic variables influenced these attitudes—conservatives, women, African-Americans, and older respondents, while supportive, were more cautious than liberals, men, other ethnicities, and younger respondents. Support was also was slightly muted when the risks (unanticipated mutations and possibility of eugenics were made explicit. The information about genetic modification was also presented as contrasting vignettes, using one of five frames: genetic editing, engineering, hacking, modification, or surgery. Despite the fact that the media and academic use of frames describing the technology varies, these frames did not influence people’s attitudes. These data contribute a current snapshot of public attitudes to inform policy with regard to human genetic modification.
Egyptian Journal of Medical Human Genetics - Vol 11, No 1 (2010)
African Journals Online (AJOL)
Egyptian Journal of Medical Human Genetics - Vol 11, No 1 (2010) ... Gene polymorphisms of TNF-α and IL-10 related to rheumatic heart disease · EMAIL ... with familial Mediterranean fever · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT
Public Attitudes toward Human Genetic Manipulation: A Revitalization of Eugenics?
Veglia, Geremia; And Others
The purpose of this investigation was to measure the attitudes of college students across the United States concerning the possible use of genetic manipulation, especially in terms of enhancing human physical and intellectual characteristics. The instrument used was divided into three general areas of inquiry: the first, designed to measure the…
Directory of Open Access Journals (Sweden)
Vasiliki I. Hatzi
2006-01-01
Full Text Available Nowadays, there is a constantly increasing concern regarding the mutagenic and carcinogenic potential of a variety of harmful environmental factors to which humans are exposed in their natural and anthropogenic environment. These factors exert their hazardous potential in humans' personal (diet, smoking, pharmaceuticals, cosmetics and occupational environment that constitute part of the anthropogenic environment. It is well known that genetic damage due to these factors has dramatic implications for human health. Since most of the environmental genotoxic factors induce arrest or delay in cell cycle progression, the conventional analysis of chromosomes at metaphase may underestimate their genotoxic potential. Premature Chromosome Condensation (PCC induced either by means of cell fusion or specific chemicals, enables the microscopic visualization of interphase chromosomes whose morphology depends on the cell cycle stage, as well as the analysis of structural and numerical aberrations at the G1 and G2 phases of the cell cycle. The PCC has been successfully used in problems involving cell cycle analysis, diagnosis and prognosis of human leukaemia, assessment of interphase chromosome malformations resulting from exposure to radiation or chemicals, as well as elucidation of the mechanisms underlying the conversion of DNA damage into chromosomal damage. In this report, particular emphasis is given to the advantages of the PCC methodology used as an alternative to conventional metaphase analysis in answering questions in the fields of radiobiology, biological dosimetry, toxicogenetics, clinical cytogenetics and experimental therapeutics.
Genetic regulation of pituitary gland development in human and mouse.
Kelberman, Daniel; Rizzoti, Karine; Lovell-Badge, Robin; Robinson, Iain C A F; Dattani, Mehul T
2009-12-01
Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.
The contribution of human factors to risks from radioactive material transport
International Nuclear Information System (INIS)
Blenkin, J.J.; Ridsdale, E.; Wilkinson, H.L.
1998-01-01
The use of probabilistic risk assessment to assess the safety of radioactive material transport operations is well accepted. However, quantitative risk assessment of radioactive material transport operations have generally not explicitly considered human factors in estimating risks. Given the high profile of human factors as the root cause of many serious transport incidents omission of an explicit consideration of human factors in a risk assessment could lead to assessments losing credibility. In addition, scrutiny of radioactive material transport incident databases reveals a large number of operational incidents and minor accidents that would have been avoided if more attention had been paid to human factors aspects, and provides examples of instances where improvements have been achieved. This paper examines the areas of radioactive material transport risk assessments (both qualitative and quantitative) which could be strengthened by further examination of the impact of human errors. It is concluded that a more complete and detailed understanding of the effects of human factors on the risks from radioactive material transport operations has been obtained. Quality assurance has a key part to play in ensuring that packages are correctly manufactured and prepared for transport. Risk assessments of radioactive material transport operations can be strengthened by concentrating on the key human factors effects. (authors)
SANITY OF CORN GRAINS AS A FUNCTION OF GENETIC MATERIAL
Directory of Open Access Journals (Sweden)
L. F. Oliveira
2018-02-01
Full Text Available Diseases that occur in corn crops can cause great losses to farmers and consumers of its product and derivatives. So, was evaluated the sanity of maize grains in different genetic materials. The grains used were obtained from the crop of 2014/2015 on a farm in the city of Sorriso, State of Mato Grosso. For this, grain samples were collected from hybrids P3630H, 30F53YH, P2830H, and P3844H. The standard test ("Blotter Test" allowed noticing the incidence of Aspergillus sp., Fusarium sp. and Penicillium sp. Data were submitted to analysis of variance and Scott-Knott test at 5% probability. In treatments with the resistant genetic material the genus with the highest incidence was Penicillium sp. (82%, followed by Fusarium sp. (68.75% and Aspergillus sp. (15.25%. The hybrid with the lower incidence of Fusarium sp. was P2830H (59%. The hybrid with greater resistance to Aspergillus sp. and Penicillium sp. was P3844H (5 and 55%, respectively. The most susceptible hybrid to pathogens Aspergillus sp., Fusarium sp. and Penicillium sp. was 30F53YH (37, 79 and 94%, respectively. For the better sanitary quality of grains, based on the observed data, it is recommended to use the hybrid P2830H
Genetic Markers of Human Evolution Are Enriched in Schizophrenia
DEFF Research Database (Denmark)
Srinivasan, Saurabh; Bettella, Francesco; Mattingsdal, Morten
2016-01-01
BACKGROUND: Why schizophrenia has accompanied humans throughout our history despite its negative effect on fitness remains an evolutionary enigma. It is proposed that schizophrenia is a by-product of the complex evolution of the human brain and a compromise for humans' language, creative thinking...... and ancillary information on genetic variants. We used information from the evolutionary proxy measure called the Neanderthal selective sweep (NSS) score. RESULTS: Gene loci associated with schizophrenia are significantly (p = 7.30 × 10(-9)) more prevalent in genomic regions that are likely to have undergone...... phenotypes. The false discovery rate conditional on the evolutionary proxy points to 27 candidate schizophrenia susceptibility loci, 12 of which are associated with schizophrenia and other psychiatric disorders or linked to brain development. CONCLUSIONS: Our results suggest that there is a polygenic overlap...
The human noncoding genome defined by genetic diversity.
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.
HSP90 Shapes the Consequences of Human Genetic Variation.
Karras, Georgios I; Yi, Song; Sahni, Nidhi; Fischer, Máté; Xie, Jenny; Vidal, Marc; D'Andrea, Alan D; Whitesell, Luke; Lindquist, Susan
2017-02-23
HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.
International Nuclear Information System (INIS)
1993-03-01
In the year under report, the institute's scope of investigations comprised the seven topics surveyed in the following together with the most recent research results obtained. These were genetic repair and genetic regulation mechanisms, biologic carcinogenesis, molecular genetics of eukaryotic genes, genetic mouse models of human disorders, toxicology of radioactive and non-radioactive heavy metals as well as environmental toxicology at the molecular and cellular levels. (orig./MG) [de
Human immunodeficiency virus type-1 (HIV-1) genetic diversity and ...
African Journals Online (AJOL)
The presence of human immunodeficiency virus (HIV) type-1 diversity has an impact on vaccine efficacy and drug resistance. It is important to know the circulating genetic variants and associated drug-resistance mutations in the context of scale up of antiretroviral therapy (ART) in Nigeria. The objective of this study was to ...
Comparing ESC and iPSC?Based Models for Human Genetic Disorders
Halevy, Tomer; Urbach, Achia
2014-01-01
Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs) from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs) from patients’ somatic cells, and the ne...
Directory of Open Access Journals (Sweden)
Marina S Ascunce
Full Text Available Understanding the evolution of parasites is important to both basic and applied evolutionary biology. Knowledge of the genetic structure of parasite populations is critical for our ability to predict how an infection can spread through a host population and for the design of effective control methods. However, very little is known about the genetic structure of most human parasites, including the human louse (Pediculus humanus. This species is composed of two ecotypes: the head louse (Pediculus humanus capitis De Geer, and the clothing (body louse (Pediculus humanus humanus Linnaeus. Hundreds of millions of head louse infestations affect children every year, and this number is on the rise, in part because of increased resistance to insecticides. Clothing lice affect mostly homeless and refugee-camp populations and although they are less prevalent than head lice, the medical consequences are more severe because they vector deadly bacterial pathogens. In this study we present the first assessment of the genetic structure of human louse populations by analyzing the nuclear genetic variation at 15 newly developed microsatellite loci in 93 human lice from 11 sites in four world regions. Both ecotypes showed heterozygote deficits relative to Hardy-Weinberg equilibrium and high inbreeding values, an expected pattern given their parasitic life history. Bayesian clustering analyses assigned lice to four distinct genetic clusters that were geographically structured. The low levels of gene flow among louse populations suggested that the evolution of insecticide resistance in lice would most likely be affected by local selection pressures, underscoring the importance of tailoring control strategies to population-specific genetic makeup and evolutionary history. Our panel of microsatellite markers provides powerful data to investigate not only ecological and evolutionary processes in lice, but also those in their human hosts because of the long
Driver, John P; Chen, Yi-Guang; Mathews, Clayton E
2012-01-01
Although once widely anticipated to unlock how human type 1 diabetes (T1D) develops, extensive study of the nonobese diabetic (NOD) mouse has failed to yield effective treatments for patients with the disease. This has led many to question the usefulness of this animal model. While criticism about the differences between NOD and human T1D is legitimate, in many cases disease in both species results from perturbations modulated by the same genes or different genes that function within the same biological pathways. Like in humans, unusual polymorphisms within an MHC class II molecule contributes the most T1D risk in NOD mice. This insight supports the validity of this model and suggests the NOD has been improperly utilized to study how to cure or prevent disease in patients. Indeed, clinical trials are far from administering T1D therapeutics to humans at the same concentration ranges and pathological states that inhibit disease in NOD mice. Until these obstacles are overcome it is premature to label the NOD mouse a poor surrogate to test agents that cure or prevent T1D. An additional criticism of the NOD mouse is the past difficulty in identifying genes underlying T1D using conventional mapping studies. However, most of the few diabetogenic alleles identified to date appear relevant to the human disorder. This suggests that rather than abandoning genetic studies in NOD mice, future efforts should focus on improving the efficiency with which diabetes susceptibility genes are detected. The current review highlights why the NOD mouse remains a relevant and valuable tool to understand the genes and their interactions that promote autoimmune diabetes and therapeutics that inhibit this disease. It also describes a new range of technologies that will likely transform how the NOD mouse is used to uncover the genetic causes of T1D for years to come.
On Gene Concepts and Teaching Genetics: Episodes from Classical Genetics
Burian, Richard M.
2013-02-01
This paper addresses the teaching of advanced high school courses or undergraduate courses for non-biology majors about genetics or history of genetics. It will probably be difficult to take the approach described here in a high school science course, although the general approach could help improve such courses. It would be ideal for a college course in history of genetics or a course designed to teach non-science majors how science works or the rudiments of the genetics in a way that will help them as citizens. The approach aims to teach the processes of discovery, correction, and validation by utilizing illustrative episodes from the history of genetics. The episodes are treated in way that should foster understanding of basic questions about genes, the sorts of techniques used to answer questions about the constitution and structure of genes, how they function, and what they determine, and some of the major biological disagreements that arose in dealing with these questions. The material covered here could be connected to social and political issues raised by genetics, but these connections are not surveyed here. As it is, to cover this much territory, the article is limited to four major episodes from Mendel's paper to the beginning of World War II. A sequel will deal with the molecularization of genetics and with molecular gene concepts through the Human Genome Project.
Blue eyes in lemurs and humans: same phenotype, different genetic mechanism
DEFF Research Database (Denmark)
Bradley, Brenda J; Pedersen, Anja; Mundy, Nicholas I
2009-01-01
Almost all mammals have brown or darkly-pigmented eyes (irises), but among primates, there are some prominent blue-eyed exceptions. The blue eyes of some humans and lemurs are a striking example of convergent evolution of a rare phenotype on distant branches of the primate tree. Recent work...... on humans indicates that blue eye color is associated with, and likely caused by, a single nucleotide polymorphism (rs12913832) in an intron of the gene HERC2, which likely regulates expression of the neighboring pigmentation gene OCA2. This raises the immediate question of whether blue eyes in lemurs might...... have a similar genetic basis. We addressed this by sequencing the homologous genetic region in the blue-eyed black lemur (Eulemur macaco flavifrons; N = 4) and the closely-related black lemur (Eulemur macaco macaco; N = 4), which has brown eyes. We then compared a 166-bp segment corresponding...
Harper, Joyce C; Geraedts, Joep; Borry, Pascal; Cornel, Martina C; Dondorp, Wybo; Gianaroli, Luca; Harton, Gary; Milachich, Tanya; Kääriäinen, Helena; Liebaers, Inge; Morris, Michael; Sequeiros, Jorge; Sermon, Karen; Shenfield, Françoise; Skirton, Heather; Soini, Sirpa; Spits, Claudia; Veiga, Anna; Vermeesch, Joris Robert; Viville, Stéphane; de Wert, Guido; Macek, Milan
2013-11-01
In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide
Wild, Thomas; Larsen, Marie Sofie Yoo; Narita, Takeo; Schou, Julie; Nilsson, Jakob; Choudhary, Chunaram
2016-03-01
The anaphase-promoting complex/cyclosome (APC/C) and the spindle assembly checkpoint (SAC), which inhibits the APC/C, are essential determinants of mitotic timing and faithful division of genetic material. Activation of the APC/C is known to depend on two APC/C-interacting E2 ubiquitin-conjugating enzymes-UBE2C and UBE2S. We show that APC/C activity in human cells is tuned by the combinatorial use of three E2s, namely UBE2C, UBE2S, and UBE2D. Genetic deletion of UBE2C and UBE2S, individually or in combination, leads to discriminative reduction in APC/C function and sensitizes cells to UBE2D depletion. Reduction of APC/C activity results in loss of switch-like metaphase-to-anaphase transition and, strikingly, renders cells insensitive to chemical inhibition of MPS1 and genetic ablation of MAD2, both of which are essential for the SAC. These results provide insights into the regulation of APC/C activity and demonstrate that the essentiality of the SAC is imposed by the strength of the APC/C. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
From sexless to sexy: Why it is time for human genetics to consider and report analyses of sex.
Powers, Matthew S; Smith, Phillip H; McKee, Sherry A; Ehringer, Marissa A
2017-01-01
Science has come a long way with regard to the consideration of sex differences in clinical and preclinical research, but one field remains behind the curve: human statistical genetics. The goal of this commentary is to raise awareness and discussion about how to best consider and evaluate possible sex effects in the context of large-scale human genetic studies. Over the course of this commentary, we reinforce the importance of interpreting genetic results in the context of biological sex, establish evidence that sex differences are not being considered in human statistical genetics, and discuss how best to conduct and report such analyses. Our recommendation is to run stratified analyses by sex no matter the sample size or the result and report the findings. Summary statistics from stratified analyses are helpful for meta-analyses, and patterns of sex-dependent associations may be hidden in a combined dataset. In the age of declining sequencing costs, large consortia efforts, and a number of useful control samples, it is now time for the field of human genetics to appropriately include sex in the design, analysis, and reporting of results.
Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin.
He, Bin Z; Ludwig, Michael Z; Dickerson, Desiree A; Barse, Levi; Arun, Bharath; Vilhjálmsson, Bjarni J; Jiang, Pengyao; Park, Soo-Young; Tamarina, Natalia A; Selleck, Scott B; Wittkopp, Patricia J; Bell, Graeme I; Kreitman, Martin
2014-02-01
The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINS(C96Y)) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINS(C96Y) background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINS(C96Y)-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanism unidentified. In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease.
Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994
DEFF Research Database (Denmark)
Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo
2016-01-01
Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic...
Comparison of French and Estonian Students' Conceptions in Genetic Determinism of Human Behaviours
Castera, Jeremy; Sarapuu, Tago; Clement, Pierre
2013-01-01
Innatism is the belief that most of the human personality can be determined by genes. This ideology is dangerous, especially when it claims to be scientific. The present study investigates conceptions of 1060 students from Estonia and France related to genetic determinism of some human behaviours. Factors taken into account included students'…
Directory of Open Access Journals (Sweden)
Salvador Darío Bergel
2002-01-01
Full Text Available La evolución operada en genética humana a partir de la década de los cincuenta, actuó como disparador en múltiples campos, en especial en los referidos a la bioética y al derecho. Muchos de los avances realizados pueden rozar la dignidad del hombre, a la par que impulsan la creación de nuevos derechos humanos. En base a ello se analizan los impactos más significativos de la nueva genética sobre la sociedad: el peligro de una nueva eugenesia, la discriminación por razones genéticas, el manejo de la información genética, los problemas derivados de la investigación sobre el genoma, la apropiación del material genético humano; marcando algunos senderos a recorrer, a modo de conclusiónA evolução ocorrida em genética humana a partir da década dos cinqüenta atuou como efeito gatilho emmuitos campos do conhecimento, em especial, na bioética e no direito. Muitos dos avanços realizados podem atingir adignidade do homem, ao mesmo tempo em que incrementam a criação de novos direitos humanos.Tomando como base esses elementos, analisamse os impactos mais significativos da nova genética sobre a sociedade: o perigo de nova eugenia, discriminação por razões genéticas, manuseio da informação genética, problemas derivados da investigação genômica, apropriação de material genético humano. Em forma de conclusão, são propostos alguns caminhos a percorrerThe evolution of human genetics, from the fifties onwards, acted as a trigger for multiple fields, especially for those dealing with bioethics and law. Many of the advances accomplished may touch human dignity and, at the same time, they impel the creation of new human rights. On the basis of these premises the author analyses the most significant impacts of the new genetics upon society: the danger of a new eugenism, genetic discrimination, manipulation of genetic information, problems derived from the investigation on the genome, the appropriation of human genetic material
Genetic variation in lipid desaturases and its impact on the development of human disease.
Merino, Diana M; Ma, David W L; Mutch, David M
2010-06-18
Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.
Blood groups and human groups: collecting and calibrating genetic data after World War Two.
Bangham, Jenny
2014-09-01
Arthur Mourant's The Distribution of the Human Blood Groups (1954) was an "indispensable" reference book on the "anthropology of blood groups" containing a vast collection of human genetic data. It was based on the results of blood-grouping tests carried out on half-a-million people and drew together studies on diverse populations around the world: from rural communities, to religious exiles, to volunteer transfusion donors. This paper pieces together sequential stages in the production of a small fraction of the blood-group data in Mourant's book, to examine how he and his colleagues made genetic data from people. Using sources from several collecting projects, I follow how blood was encountered, how it was inscribed, and how it was turned into a laboratory resource. I trace Mourant's analytical and representational strategies to make blood groups both credibly 'genetic' and understood as relevant to human ancestry, race and history. In this story, 'populations' were not simply given, but were produced through public health, colonial and post-colonial institutions, and by the labour and expertise of subjects, assistants and mediators. Genetic data were not self-evidently 'biological', but were shaped by existing historical and geographical identities, by political relationships, and by notions of kinship and belonging. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.
[Genetically modified food--unnecessary controversy?].
Tchórz, Michał; Radoniewicz-Chagowska, Anna; Lewandowska-Stanek, Hanna; Szponar, Elzbieta; Szponar, Jarosław
2012-01-01
Fast development of genetic engineering and biotechnology allows use of genetically modified organisms (GMO) more and more in different branches of science and economy. Every year we can see an increase of food amount produced with the use of modification of genetic material. In our supermarkets we can find brand new types of plants, products including genetically modified ingredients or meat from animals fed with food containing GMO. This article presents general information about genetically modified organisms, it also explains the range of genetic manipulation, use of newly developed products and current field area for GMO in the world. Based on scientific data the article presents benefits from development of biotechnology in reference to modified food. It also presents the voice of skeptics who are extremely concerned about the impact of those organisms on human health and natural environment. Problems that appear or can appear as a result of an increase of GMO are very important not only from a toxicologist's or a doctor's point of view but first of all from the point of view of ordinary consumers--all of us.
Research on human genetics in Iceland. Progress report
Energy Technology Data Exchange (ETDEWEB)
None
1980-10-31
Records of the Icelandic Population are being used to investigate the possible inheritance of disabilities and diseases as well as other characters and the effect of environment on man. The progress report of research covers the period 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.
Race, genetics, and human reproductive strategies.
Rushton, J P
1996-02-01
The international literature on racial differences is reviewed, novel data are reported, and a distinct pattern is found. People of east Asian ancestry and people of African ancestry average at opposite ends of a continuum, with people of European ancestry averaging intermediately, albeit with much variability within each major race. The racial matrix emerges from measures taken of reproductive behavior, sex hormones, twinning rate, speed of physical maturation, personality, family stability, brain size, intelligence, law abidingness, and social organization. An evolutionary theory of human reproduction is proposed, familiar to biologists as the r-K scale of reproductive strategies. At one end of this scale are r-strategies, which emphasize high reproductive rates; at the other end are K-strategies, which emphasize high levels of parental investment. This scale is generally used to compare the life histories of widely disparate species, but here it is used to describe the immensely smaller variations among human races. It is hypothesized that, again on average, Mongoloid people are more K-selected than Caucasoids, who are more K-selected than Negroids. The r-K scale of reproductive strategies is also mapped on to human evolution. Genetic distances indicate that Africans emerged from the ancestral hominid line about 200,000 years ago, with an African/non-African split about 110,000 years ago, and a Caucasoid/Mongoloid split about 41,000 years ago. Such an ordering fits with and explains how and why the variables cluster.
Zhang, Chao; Gao, Yang; Liu, Jiaojiao; Xue, Zhe; Lu, Yan; Deng, Lian; Tian, Lei; Feng, Qidi; Xu, Shuhua
2018-01-04
There are a growing number of studies focusing on delineating genetic variations that are associated with complex human traits and diseases due to recent advances in next-generation sequencing technologies. However, identifying and prioritizing disease-associated causal variants relies on understanding the distribution of genetic variations within and among populations. The PGG.Population database documents 7122 genomes representing 356 global populations from 107 countries and provides essential information for researchers to understand human genomic diversity and genetic ancestry. These data and information can facilitate the design of research studies and the interpretation of results of both evolutionary and medical studies involving human populations. The database is carefully maintained and constantly updated when new data are available. We included miscellaneous functions and a user-friendly graphical interface for visualization of genomic diversity, population relationships (genetic affinity), ancestral makeup, footprints of natural selection, and population history etc. Moreover, PGG.Population provides a useful feature for users to analyze data and visualize results in a dynamic style via online illustration. The long-term ambition of the PGG.Population, together with the joint efforts from other researchers who contribute their data to our database, is to create a comprehensive depository of geographic and ethnic variation of human genome, as well as a platform bringing influence on future practitioners of medicine and clinical investigators. PGG.Population is available at https://www.pggpopulation.org. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology
International Nuclear Information System (INIS)
Lemaire, D.; Barbosa, T.; Rihet, P.
2011-01-01
Vaccine development faces major difficulties partly because of genetic variation in both infectious organisms and humans. This causes antigenic variation in infectious agents and a high interindividual variability in the human response to the vaccine. The exponential growth of genome sequence information has induced a shift from conventional culture-based to genome-based vaccinology, and allows the tackling of challenges in vaccine development due to pathogen genetic variability. Additionally, recent advances in immunogenetics and genomics should help in the understanding of the influence of genetic factors on the interindividual and interpopulation variations in immune responses to vaccines, and could be useful for developing new vaccine strategies. Accumulating results provide evidence for the existence of a number of genes involved in protective immune responses that are induced either by natural infections or vaccines. Variation in immune responses could be viewed as the result of a perturbation of gene networks; this should help in understanding how a particular polymorphism or a combination thereof could affect protective immune responses. Here we will present: i) the first genome-based vaccines that served as proof of concept, and that provided new critical insights into vaccine development strategies; ii) an overview of genetic predisposition in infectious diseases and genetic control in responses to vaccines; iii) population genetic differences that are a rationale behind group-targeted vaccines; iv) an outlook for genetic control in infectious diseases, with special emphasis on the concept of molecular networks that will provide a structure to the huge amount of genomic data
Human Genetic Disorders and Knockout Mice Deficient in Glycosaminoglycan
Directory of Open Access Journals (Sweden)
Shuji Mizumoto
2014-01-01
Full Text Available Glycosaminoglycans (GAGs are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases and sulfotransferases. The structural diversity of GAG polysaccharides, including their sulfation patterns and sequential arrangements, is essential for a wide range of biological activities such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Studies using knockout mice of enzymes responsible for the biosynthesis of the GAG side chains of proteoglycans have revealed their physiological functions. Furthermore, mutations in the human genes encoding glycosyltransferases, sulfotransferases, and related enzymes responsible for the biosynthesis of GAGs cause a number of genetic disorders including chondrodysplasia, spondyloepiphyseal dysplasia, and Ehlers-Danlos syndromes. This review focused on the increasing number of glycobiological studies on knockout mice and genetic diseases caused by disturbances in the biosynthetic enzymes for GAGs.
Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins
Energy Technology Data Exchange (ETDEWEB)
Deschavanne, P.J.; Debieu, D.; Malaise, E.P.; Fertil, B.
1986-08-01
Statistical analysis of the radiosensitivity of 204 survival curves of non-transformed human fibroblast cell strains of different genetic origins was made using the multi-target one-hit model (characterized by parameters eta and D/sub 0/), the surviving fraction for a 2 Gy dose (S/sub 2/) and the mean inactivation dose (D-bar). D-bar is found to be the parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and discrimination between groups of cell strains of differing radiosensitivity. It allows the description of a range of 'normal' radiosensitivity for control fibroblasts and classification of genetic disorders as a function of their mean radiosensitivity expressed in terms of D-bar. Nine groups of cell strains appear to exhibit radiosensitivity differing significantly from the controls: seven groups are hypersensitive (ataxia-telengiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and individuals with chromosome 13 anomalies). Since the coupled parameter eta and D/sub 0/ failed to discriminate between the radiosensitivity of the different genetic groups, the use of D-bar to make an intercomparison of intrinsic radiosensitivity of non-transformed human fibroblasts is recommended. (U.K.).
Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins
International Nuclear Information System (INIS)
Deschavanne, P.J.; Debieu, D.; Malaise, E.P.; Fertil, B.
1986-01-01
Statistical analysis of the radiosensitivity of 204 survival curves of non-transformed human fibroblast cell strains of different genetic origins was made using the multi-target one-hit model (characterized by parameters eta and D 0 ), the surviving fraction for a 2 Gy dose (S 2 ) and the mean inactivation dose (D-bar). D-bar is found to be the parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and discrimination between groups of cell strains of differing radiosensitivity. It allows the description of a range of 'normal' radiosensitivity for control fibroblasts and classification of genetic disorders as a function of their mean radiosensitivity expressed in terms of D-bar. Nine groups of cell strains appear to exhibit radiosensitivity differing significantly from the controls: seven groups are hypersensitive (ataxia-telengiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and individuals with chromosome 13 anomalies). Since the coupled parameter eta and D 0 failed to discriminate between the radiosensitivity of the different genetic groups, the use of D-bar to make an intercomparison of intrinsic radiosensitivity of non-transformed human fibroblasts is recommended. (U.K.)
Genetic analysis of human and swine influenza A viruses isolated in Northern Italy during 2010-2015.
Chiapponi, C; Ebranati, E; Pariani, E; Faccini, S; Luppi, A; Baioni, L; Manfredi, R; Carta, V; Merenda, M; Affanni, P; Colucci, M E; Veronesi, L; Zehender, G; Foni, E
2018-02-01
Influenza A virus (IAV) infection in swine plays an important role in the ecology of influenza viruses. The emergence of new IAVs comes through different mechanisms, with the genetic reassortment of genes between influenza viruses, also originating from different species, being common. We performed a genetic analysis on 179 IAV isolates from humans (n. 75) and pigs (n. 104) collected in Northern Italy between 2010 and 2015, to monitor the genetic exchange between human and swine IAVs. No cases of human infection with swine strains were noticed, but direct infections of swine with H1N1pdm09 strains were detected. Moreover, we pointed out a continuous circulation of H1N1pdm09 strains in swine populations evidenced by the introduction of internal genes of this subtype. These events contribute to generating new viral variants-possibly endowed with pandemic potential-and emphasize the importance of continuous surveillance at both animal and human level. © 2017 The Authors. Zoonoses and Public Health published by Blackwell Verlag GmbH.
Jin, Yuesheng; Zhang, Hao; Tsao, Sai Wah; Jin, Charlotte; Lv, Mei; Strömbeck, Bodil; Wiegant, Joop; Wan, Thomas Shek Kong; Yuen, Po Wing; Kwong, Yok-Lam
2004-01-01
This study aimed at identifying the genetic events involved in immortalization of ovarian epithelial cells, which might be important steps in ovarian carcinogenesis. The genetic profiles of five human ovarian surface epithelial (HOSE) cell lines immortalized by retroviral transfection of the human papillomavirus (HPV) E6/E7 genes were thoroughly characterized by chromosome banding and fluorescence in situ hybridization (FISH), at various passages pre- and post-crisis. In pre-crisis, most cells had simple, non-clonal karyotypic changes. Telomere association was the commonest aberration, suggesting that tolermase dysfunction might be an important genetic event leading to cellular crisis. After immortalization post-crisis, however, the karyotypic patterns were non-random. Loss of genetic materials was a characteristic feature. The commonest numerical aberrations were -13, -14, -16, -17, -18, and +5. Among them, loss of chromosome 13 was common change observed in all lines. The only recurrent structural aberration was homogeneously staining regions (hsr) observed in three lines. FISH and combined binary ratio labeling (COBRA)-FISH showed in two cases that the hsrs were derived from chromosome 20. Clonal evolution was observed in four of the lines. In one line, hsr was the only change shared by all subclones, suggesting that it might be a primary event in cell immortalization. The results of the present study suggested that loss of chromosome 13 and the amplification of chromosome 20 might be early genetic events involved in ovarian cell immortalization, and might be useful targets for the study of genomic aberrations in ovarian carcinogenesis.
Maintenance modeling and optimization integrating human and material resources
International Nuclear Information System (INIS)
Martorell, S.; Villamizar, M.; Carlos, S.; Sanchez, A.
2010-01-01
Maintenance planning is a subject of concern to many industrial sectors as plant safety and business depend on it. Traditionally, the maintenance planning is formulated in terms of a multi-objective optimization (MOP) problem where reliability, availability, maintainability and cost (RAM+C) act as decision criteria and maintenance strategies (i.e. maintenance tasks intervals) act as the only decision variables. However the appropriate development of each maintenance strategy depends not only on the maintenance intervals but also on the resources (human and material) available to implement such strategies. Thus, the effect of the necessary resources on RAM+C needs to be modeled and accounted for in formulating the MOP affecting the set of objectives and constraints. In this paper RAM+C models to explicitly address the effect of human resources and material resources (spare parts) on RAM+C criteria are proposed. This extended model allows accounting for explicitly how the above decision criteria depends on the basic model parameters representing the type of strategies, maintenance intervals, durations, human resources and material resources. Finally, an application case is performed to optimize the maintenance plan of a motor-driven pump equipment considering as decision variables maintenance and test intervals and human and material resources.
Maintenance modeling and optimization integrating human and material resources
Energy Technology Data Exchange (ETDEWEB)
Martorell, S., E-mail: smartore@iqn.upv.e [Dpto. Ingenieria Quimica y Nuclear, Universidad Politecnica Valencia (Spain); Villamizar, M.; Carlos, S. [Dpto. Ingenieria Quimica y Nuclear, Universidad Politecnica Valencia (Spain); Sanchez, A. [Dpto. Estadistica e Investigacion Operativa Aplicadas y Calidad, Universidad Politecnica Valencia (Spain)
2010-12-15
Maintenance planning is a subject of concern to many industrial sectors as plant safety and business depend on it. Traditionally, the maintenance planning is formulated in terms of a multi-objective optimization (MOP) problem where reliability, availability, maintainability and cost (RAM+C) act as decision criteria and maintenance strategies (i.e. maintenance tasks intervals) act as the only decision variables. However the appropriate development of each maintenance strategy depends not only on the maintenance intervals but also on the resources (human and material) available to implement such strategies. Thus, the effect of the necessary resources on RAM+C needs to be modeled and accounted for in formulating the MOP affecting the set of objectives and constraints. In this paper RAM+C models to explicitly address the effect of human resources and material resources (spare parts) on RAM+C criteria are proposed. This extended model allows accounting for explicitly how the above decision criteria depends on the basic model parameters representing the type of strategies, maintenance intervals, durations, human resources and material resources. Finally, an application case is performed to optimize the maintenance plan of a motor-driven pump equipment considering as decision variables maintenance and test intervals and human and material resources.
Egyptian Journal of Medical Human Genetics - Vol 12, No 2 (2011)
African Journals Online (AJOL)
Egyptian Journal of Medical Human Genetics - Vol 12, No 2 (2011) ... Serum interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: Correlation with autoantibodies titers · EMAIL FREE FULL TEXT EMAIL FREE FULL ... LB Salah, CB Salem, F B'Chir, K Bouraoui, F Broly, S Saguem, 183-186.
Sanou, Adama; Tarnagda, Zekiba; Kanyala, Estelle; Zingué, Dezemon; Nouctara, Moumini; Ganamé, Zakaria; Combary, Adjima; Hien, Hervé; Dembele, Mathurin; Kabore, Antoinette; Meda, Nicolas; Van de Perre, Philippe; Neveu, Dorine; Bañuls, Anne Laure; Godreuil, Sylvain
2014-10-01
In sub-Saharan Africa, bovine tuberculosis (bTB) is a potential hazard for animals and humans health. The goal of this study was to improve our understanding of bTB epidemiology in Burkina Faso and especially Mycobacterium bovis transmission within and between the bovine and human populations. Twenty six M. bovis strains were isolated from 101 cattle carcasses with suspected bTB lesions during routine meat inspections at the Bobo Dioulasso and Ouagadougou slaughterhouses. In addition, 7 M. bovis strains were isolated from 576 patients with pulmonary tuberculosis. Spoligotyping, RDAf1 deletion and MIRU-VNTR typing were used for strains genotyping. The isolation of M. bovis strains was confirmed by spoligotyping and 12 spoligotype signatures were detected. Together, the spoligotyping and MIRU-VNTR data allowed grouping the 33 M. bovis isolates in seven clusters including isolates exclusively from cattle (5) or humans (1) or from both (1). Moreover, these data (genetic analyses and phenetic tree) showed that the M. bovis isolates belonged to the African 1 (Af1) clonal complex (81.8%) and the putative African 5 (Af5) clonal complex (18.2%), in agreement with the results of RDAf1 deletion typing. This is the first detailed molecular characterization of M. bovis strains from humans and cattle in Burkina Faso. The distribution of the two Af1 and putative Af5 clonal complexes is comparable to what has been reported in neighbouring countries. Furthermore, the strain genetic profiles suggest that M. bovis circulates across the borders and that the Burkina Faso strains originate from different countries, but have a country-specific evolution. The genetic characterization suggests that, currently, M. bovis transmission occurs mainly between cattle, occasionally between cattle and humans and potentially between humans. This study emphasizes the bTB risk in cattle but also in humans and the difficulty to set up proper disease control strategies in Burkina Faso.
Destro Bisol, Giovanni; Capocasa, Marco; Anagnostou, Paolo
2012-10-01
Due to its important effects on the ecological dynamics and the genetic structure of species, biologists have long been interested in gender-biased dispersal, a condition where one gender is more prone to move from the natal site. More recently, this topic has attracted a great attention from human evolutionary geneticists. Considering the close relations between residential rules and social structure, gender-biased dispersal is, in fact, regarded as an important case study concerning the effects of socio-cultural factors on human genetic variation. It all started with the seminal paper by Mark Seielstad, Erich Minch and Luigi Luca Cavalli Sforza from Stanford University (Seielstad et al. 1998). They observed a larger differentiation for Y-chromosome than mitochondrial DNA between extant human populations, purportedly a consequence of the prevalence of long-term patrilocality in human societies. Subsequent studies, however, have highlighted the need to consider geographically close and culturally homogeneous groups, disentangle signals due to different peopling events and obtain unbiased estimates of genetic diversity. In this issue of Molecular Ecology, not only do Marks et al. (2012) adopt an experimental design which addresses these concerns, but they also take a further and important step forward by integrating the genetic analysis of two distant populations, the Basotho and Spanish, with data regarding migration rates and matrimonial distances. Using both empirical evidence and simulations, the authors show that female-biased migration due to patrilocality might shape the genetic structure of human populations only at short ranges and under substantial differences in migration rates between genders. Providing a quantitative framework for future studies of the effects of residential rules on the human genome, this study paves the way for further developments in the field. On a wider perspective, Marks et al.'s work demonstrates the power of approaches which
Human genetic basis of interindividual variability in the course of infection
Casanova, Jean-Laurent
2015-01-01
The key problem in human infectious diseases was posed at the turn of the 20th century: their pathogenesis. For almost any given virus, bacterium, fungus, or parasite, life-threatening clinical disease develops in only a small minority of infected individuals. Solving this infection enigma is important clinically, for diagnosis, prognosis, prevention, and treatment. Some microbes will inevitably remain refractory to, or escape vaccination, or chemotherapy, or both. The solution also is important biologically, because the emergence and evolution of eukaryotes alongside more rapidly evolving prokaryotes, archaea, and viruses posed immunological challenges of an ecological and evolutionary nature. We need to study these challenges in natural, as opposed to experimental, conditions, and also at the molecular and cellular levels. According to the human genetic theory of infectious diseases, inborn variants underlie life-threatening infectious diseases. Here I review the history of the field of human genetics of infectious diseases from the turn of the 19th century to the second half of the 20th century. This paper thus sets the scene, providing the background information required to understand and appreciate the more recently described monogenic forms of resistance or predisposition to specific infections discussed in a second paper in this issue. PMID:26621739
Legal protection of public health through control over genetically modified food.
Gutorova, Nataliya; Batyhina, Olena; Trotska, Maryna
2018-01-01
Introduction: Science is constantly being developed which leads to both positive and negative changes in public health and the environment. One of the results of scientific progress is introduction of food based on genetically modified organisms whose effects on human health, to date, remain scantily studied and are ambiguous. The aim: to determine how human health can be influenced by food production based on genetically modified organisms. Materials and methods: international acts, data of international organizations and conclusions of scientists have been examined and used in the study. The article also summarizes information from scientific journals and monographs from a medical and legal point of view with scientific methods. This article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. Conclusions: Genetically modified organisms are specific human-made organisms being a result of using modern biotechnology techniques. They have both positive and negative effects on human health and the environment. The main disadvantage is not sufficient study of them in various spheres of public life.
Human performance: An essential element in materials control and accountability
International Nuclear Information System (INIS)
Haber, S.B.; Allentuck, J.
1996-01-01
The importance of the role of human performance in the successful and effective operation of many activities throughout many industries has been well documented. Most closely related to the materials control and accountability area is the work in human factors that has been ongoing in the U.S. nuclear industry since the Three Mile Island Nuclear Power Plant accident in 1979. Research related to the role of human reliability, human-system interface, and organization and management influences has been and is still being conducted to identify ways to enhance the safe and effective operation of nuclear facilities. This paper will discuss these human performance areas and how they relate to the materials control and accountability area. Particular attention will be focussed on the notion of open-quotes safety cultureclose quotes and how it can be defined and measured for understanding the values and attitudes held by individuals working in the materials control area. It is widely believed that the culture of an organization, which reflects the expectations and values of the management of an organization, is a key element to the operation of that organization. The human performance element is one which has not received a great deal of consideration in the materials control and accountability area and yet it will be demonstrated that it is an essential component to ensure the success of safeguards activities
The 5-HT2A receptor binding pattern in the human brain is strongly genetically determined
DEFF Research Database (Denmark)
Pinborg, Lars H; Arfan, Haroon; Haugbol, Steven
2007-01-01
With the appropriate radiolabeled tracers, positron emission tomography (PET) enables in vivo human brain imaging of markers for neurotransmission, including neurotransmitter synthesis, receptors, and transporters. Whereas structural imaging studies have provided compelling evidence that the human...... brain anatomy is largely genetically determined, it is currently unknown to what degree neuromodulatory markers are subjected to genetic and environmental influence. Changes in serotonin 2A (5-HT(2A)) receptors have been reported to occur in various neuropsychiatric disorders and an association between...
Transboundary movements of genetically modified organisms and ...
African Journals Online (AJOL)
Biotechnology or the engineering of the genetic material of species can give way to avenues of possibilities for the benefit of people, fauna and flora but also has the potential of posing untold and undiscovered threats to human beings and other living organisms. One of the first attempts to legislate on international rules on ...
Use of Traditional and Genetically Modified Probiotics in Human Health: What Does the Future Hold?
Bermúdez-Humarán, Luis G; Langella, Philippe
2017-09-01
Probiotics are live, nonpathogenic microorganisms that confer benefits to human health when administered in adequate amounts. Among the frequent proposed health benefits attributed to probiotics, their ability to interact with the host immune system is now well demonstrated. Although history has revealed that probiotics were part of fermented foods in the past, clinicians have started to use them therapeutically in regular diets. Moreover, the use of genetically modified probiotics to deliver molecules of therapeutic interest is gaining importance as an extension of the probiotic concept. This chapter summarizes some of the recent findings and perspectives on the use of both traditional and genetically modified probiotics to treat human diseases as well as what the future may hold concerning the use of these probiotics in humans.
Trends in population-based studies of human genetics in infectious diseases.
Rowell, Jessica L; Dowling, Nicole F; Yu, Wei; Yesupriya, Ajay; Zhang, Lyna; Gwinn, Marta
2012-01-01
Pathogen genetics is already a mainstay of public health investigation and control efforts; now advances in technology make it possible to investigate the role of human genetic variation in the epidemiology of infectious diseases. To describe trends in this field, we analyzed articles that were published from 2001 through 2010 and indexed by the HuGE Navigator, a curated online database of PubMed abstracts in human genome epidemiology. We extracted the principal findings from all meta-analyses and genome-wide association studies (GWAS) with an infectious disease-related outcome. Finally, we compared the representation of diseases in HuGE Navigator with their contributions to morbidity worldwide. We identified 3,730 articles on infectious diseases, including 27 meta-analyses and 23 GWAS. The number published each year increased from 148 in 2001 to 543 in 2010 but remained a small fraction (about 7%) of all studies in human genome epidemiology. Most articles were by authors from developed countries, but the percentage by authors from resource-limited countries increased from 9% to 25% during the period studied. The most commonly studied diseases were HIV/AIDS, tuberculosis, hepatitis B infection, hepatitis C infection, sepsis, and malaria. As genomic research methods become more affordable and accessible, population-based research on infectious diseases will be able to examine the role of variation in human as well as pathogen genomes. This approach offers new opportunities for understanding infectious disease susceptibility, severity, treatment, control, and prevention.
Novel genetic loci underlying human intracranial volume identified through genome-wide association
Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Valdés Hernández, Maria C; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic JA; Van Duijn, Cornelia M; Van Haren, Neeltje EM; Van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton JM; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M
2016-01-01
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991
Genetic variation of common walnut (Juglans regia in Piedmont, Northwestern Italy
Directory of Open Access Journals (Sweden)
Ferrazzini D
2007-12-01
Full Text Available The European or common walnut is a large tree prized as a multipurpose species: it provides valuable timber and produces a high-quality edible nut. The diffusion of the species in Italy has been largely influenced by the human activity, mainly through germplasm movement, selection of genotypes most suited for wood or fruit production and adaptation induced on fruit crop reproductive materials. As a consequence, genetic variability has been reduced, so that programs aimed at its preservation appear of the utmost importance. 104 walnut plants growing in Piedmont, northwestern Italy, were investigated through genetic variation scored at RAPD loci, yielded by PCR amplification of 10 decamer primers. Among the 101 studied loci, only 53 were polymorphic, showing a low level of genetic variation within the studied material. Genetic differentiation was estimated both at individual and geographical area level. Only in few cases trees growing in the same area showed to be genetically similar, while the differentiation between areas accounted for about 10% of the total variation, according to AMOVA. No significant correlation was found between genetic and geographic distances. The results of the study showed that also in Piedmont (such as it was already demonstrated in other parts of Italy the distribution of common walnut is a direct consequence of the human activity. The selection of individual trees, to be used as basic materials for seed supply, should therefore be based mainly on phenotypic traits, rather than ecological features of the location: in species characterized by artificial diffusion, the adoption of Region of Provenance has a scarce significance and prominence should be given to the phenotype selection.
International Nuclear Information System (INIS)
Moguilnaya, T.; Suminov, Y.; Botikov, A.; Ignatov, S.; Kononenko, A.; Agibalov, A.
2017-01-01
We developed the new automatic method that combines the method of forced luminescence and stimulated Brillouin scattering. This method is used for monitoring pathogens, genetically modified products and nanostructured materials in colloidal solution. We carried out the statistical spectral analysis of pathogens, genetically modified soy and nano-particles of silver in water from different regions in order to determine the statistical errors of the method. We studied spectral characteristics of these objects in water to perform the initial identification with 95% probability. These results were used for creation of the model of the device for monitor of pathogenic organisms and working model of the device to determine the genetically modified soy in meat.
(Dis)organizing through imbrications of human and material agencies
DEFF Research Database (Denmark)
Tavella, Elena
and material agencies. However there is a lack of insight into how human and material agencies are imbricated during the emergence of (dis)order, and how different imbrications lead to (dis)order. This paper addresses this gap by presenting a content analysis of a book reporting the Battle of Stalingrad during...... World War II. Drawing on the theory of affordances, the author identifies how different materials were used by the German and Soviet armies to organize specific activities, and whether and how those activities led to order and/or disorder. The analysis suggests that soldiers used different materials...... to organize different activities within one and the same organizational context, which led to (dis)order. Whether order or disorder emerged was dependent on how human and material agencies were imbricated within the conduct of particular activities, and how they related to internal or external influencing...
Materials used to simulate physical properties of human skin.
Dąbrowska, A K; Rotaru, G-M; Derler, S; Spano, F; Camenzind, M; Annaheim, S; Stämpfli, R; Schmid, M; Rossi, R M
2016-02-01
For many applications in research, material development and testing, physical skin models are preferable to the use of human skin, because more reliable and reproducible results can be obtained. This article gives an overview of materials applied to model physical properties of human skin to encourage multidisciplinary approaches for more realistic testing and improved understanding of skin-material interactions. The literature databases Web of Science, PubMed and Google Scholar were searched using the terms 'skin model', 'skin phantom', 'skin equivalent', 'synthetic skin', 'skin substitute', 'artificial skin', 'skin replica', and 'skin model substrate.' Articles addressing material developments or measurements that include the replication of skin properties or behaviour were analysed. It was found that the most common materials used to simulate skin are liquid suspensions, gelatinous substances, elastomers, epoxy resins, metals and textiles. Nano- and micro-fillers can be incorporated in the skin models to tune their physical properties. While numerous physical skin models have been reported, most developments are research field-specific and based on trial-and-error methods. As the complexity of advanced measurement techniques increases, new interdisciplinary approaches are needed in future to achieve refined models which realistically simulate multiple properties of human skin. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus
2011-10-01
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 of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address 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. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.
Long-Distance Dispersal Shaped Patterns of Human Genetic Diversity in Eurasia.
Alves, Isabel; Arenas, Miguel; Currat, Mathias; Sramkova Hanulova, Anna; Sousa, Vitor C; Ray, Nicolas; Excoffier, Laurent
2016-04-01
Most previous attempts at reconstructing the past history of human populations did not explicitly take geography into account or considered very simple scenarios of migration and ignored environmental information. However, it is likely that the last glacial maximum (LGM) affected the demography and the range of many species, including our own. Moreover, long-distance dispersal (LDD) may have been an important component of human migrations, allowing fast colonization of new territories and preserving high levels of genetic diversity. Here, we use a high-quality microsatellite data set genotyped in 22 populations to estimate the posterior probabilities of several scenarios for the settlement of the Old World by modern humans. We considered models ranging from a simple spatial expansion to others including LDD and a LGM-induced range contraction, as well as Neolithic demographic expansions. We find that scenarios with LDD are much better supported by data than models without LDD. Nevertheless, we show evidence that LDD events to empty habitats were strongly prevented during the settlement of Eurasia. This unexpected absence of LDD ahead of the colonization wave front could have been caused by an Allee effect, either due to intrinsic causes such as an inbreeding depression built during the expansion or due to extrinsic causes such as direct competition with archaic humans. Overall, our results suggest only a relatively limited effect of the LGM contraction on current patterns of human diversity. This is in clear contrast with the major role of LDD migrations, which have potentially contributed to the intermingled genetic structure of Eurasian populations. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
A population genetic interpretation of GWAS findings for human quantitative traits
Bullaughey, Kevin; Hudson, Richard R.; Sella, Guy
2018-01-01
Human genome-wide association studies (GWASs) are revealing the genetic architecture of anthropomorphic and biomedical traits, i.e., the frequencies and effect sizes of variants that contribute to heritable variation in a trait. To interpret these findings, we need to understand how genetic architecture is shaped by basic population genetics processes—notably, by mutation, natural selection, and genetic drift. Because many quantitative traits are subject to stabilizing selection and because genetic variation that affects one trait often affects many others, we model the genetic architecture of a focal trait that arises under stabilizing selection in a multidimensional trait space. We solve the model for the phenotypic distribution and allelic dynamics at steady state and derive robust, closed-form solutions for summary statistics of the genetic architecture. Our results provide a simple interpretation for missing heritability and why it varies among traits. They predict that the distribution of variances contributed by loci identified in GWASs is well approximated by a simple functional form that depends on a single parameter: the expected contribution to genetic variance of a strongly selected site affecting the trait. We test this prediction against the results of GWASs for height and body mass index (BMI) and find that it fits the data well, allowing us to make inferences about the degree of pleiotropy and mutational target size for these traits. Our findings help to explain why the GWAS for height explains more of the heritable variance than the similarly sized GWAS for BMI and to predict the increase in explained heritability with study sample size. Considering the demographic history of European populations, in which these GWASs were performed, we further find that most of the associations they identified likely involve mutations that arose shortly before or during the Out-of-Africa bottleneck at sites with selection coefficients around s = 10−3. PMID
Gordon, Erynn S; Gordish Dressman, Heather A; Hoffman, Eric P
2005-10-01
Much of the vast diversity we see in animals and people is governed by genetic loci that have quantitative effects of phenotype (quantitative trait loci; QTLs). Here we review the current knowledge of the genetics of atrophy and hypertrophy in both animal husbandry (meat quantity and quality), and humans (muscle size and performance). The selective breeding of animals for meat has apparently led to a few genetic loci with strong effects, with different loci in different animals. In humans, muscle quantitative trait loci (QTLs) appear to be more complex, with few "major" loci identified to date, although this is likely to change in the near future. We describe how the same phenotypic traits we see as positive, greater lean muscle mass in cattle or a better exercise results in humans, can also have negative "side effects" given specific environmental challenges. We also discuss the strength and limitations of single nucleotide polymorphisms (SNP) association studies; what the reader should look for and expect in a published study. Lastly we discuss the ethical and societal implications of this genetic information. As more and more research into the genetic loci that dictate phenotypic traits become available, the ethical implications of testing for these loci become increasingly important. As a society, most accept testing for genetic diseases or susceptibility, but do we as easily accept testing to determine one's athletic potential to be an Olympic endurance runner, or quarterback on the high school football team.
Anton, Roman
2016-01-01
Advances in embryology, genetics, and regenerative medicine regularly attract attention from scientists, scholars, journalists, and policymakers, yet implications of these advances may be broader than commonly supposed. Laboratories culturing human embryos, editing human genes, and creating human-animal chimeras have been working along lines that are now becoming intertwined. Embryogenic methods are weaving traditional in vivo and in vitro distinctions into a new "in vivitro" (in life in glass) fabric. These and other methods known to be in use or thought to be in development promise soon to bring society to startling choices and discomfiting predicaments, all in a global effort to supply reliably rejuvenating stem cells, to grow immunologically non-provocative replacement organs, and to prevent, treat, cure, or even someday eradicate diseases having genetic or epigenetic mechanisms. With humanity's human-engineering era now begun, procedural prohibitions, funding restrictions, institutional controls, and transparency rules are proving ineffective, and business incentives are migrating into the most basic life-sciences inquiries, wherein lie huge biomedical potentials and bioethical risks. Rights, health, and heritage are coming into play with bioethical presumptions and formal protections urgently needing reassessment.
Directory of Open Access Journals (Sweden)
Vaibhav Mundra
Full Text Available The objective of this study was to determine the potential of human bone marrow derived mesenchymal stem cells (hBMSCs as gene carriers for improving the outcome of human islet transplantation. hBMSCs were characterized for the expression of phenotypic markers and transduced with Adv-hVEGF-hIL-1Ra to overexpress human vascular endothelial growth factor (hVEGF and human interleukin-1 receptor antagonist (hIL-1Ra. Human islets were co-cultured with hBMSCs overexpressing hVEGF and hIL-1Ra. Islet viability was determined by membrane fluorescent method and glucose stimulation test. Transduced hBMSCs and human islets were co-transplanted under the kidney capsule of NOD.Cg-Prkdc(scid Il2rg(tm1Wjl /SzJ (NSG diabetic mice and blood glucose levels were measured over time to demonstrate the efficacy of genetically modified hBMSCs. At the end of study, immunofluorescent staining of kidney section bearing islets was performed for insulin and von Willebrand Factor (vWF. hBMSCs were positive for the expression of CD73, CD90, CD105, CD146 and Stro-1 surface markers as determined by flow cytometry. Transduction of hBMSCs with adenovirus did not affect their stemness and differentiation potential as confirmed by mRNA levels of stem cell markers and adipogenic differentiation of transduced hBMSCs. hBMSCs were efficiently transduced with Adv-hVEGF-hIL-1Ra to overexpress hVEGF and hIL-1Ra. Live dead cell staining and glucose stimulation test have shown that transduced hBMSCs improved the viability of islets against cytokine cocktail. Co-transplantation of human islets with genetically modified hBMSCs improved the glycemic control of diabetic NSG mice as determined by mean blood glucose levels and intraperitoneal glucose tolerance test. Immunofluorescent staining of kidney sections was positive for human insulin and vWF. In conclusion, our results have demonstrated that hBMSCs may be used as gene carriers and nursing cells to improve the outcome of islet
Human evolution across the disciplines: spotlights on American anthropology and genetics.
Sommer, Marianne
2012-01-01
When thinking about human evolution across the disciplines, terms such as "anthropological genetics" or "genetic anthropology" that brazenly defy the existence of the two-cultures divide seem to promise important insights. They refer to the application of genetic techniques to the past of humankind and human groups, a fact emphasized most strongly by the expression "genetic history." Such daring linguistic alliances have been forming since 1962 when the name "molecular anthropology" was introduced in the American context. This was an opportune moment for biochemists and physical chemists to enter anthropology, because in the U.S. a rapprochement between the fields was aimed for. However, a belief in and a discourse of a hierarchy of disciplines structured along the lines of methodology and epistemic object worked as an obstacle to the achievement of transdisciplinarity. Especially the DNA-sequence, initially approached through the proxy of the protein, was regarded as the most informative historical document due to its distance from the environment and its amenability to rigorous scientific techniques. These notions had a particular power at a time when anthropology was confronted with its legacy of race science. For some, the perceived objectivity of the new molecular approaches and the neutrality of molecules would render anthropology more natural-scientific and by inference less culturally contaminated. Others, to the contrary, believed that this legacy demanded a holistic and ethically reflexive anthropology. The different perceptions thus went along with different understandings of such crucial terms as "anthropology" and "history." In the paper, I revisit interfaces between different anthropological fields in the U.S. context and suggest that the beliefs in a hierarchy of approaches as well as in a nature free from culture embodied in the DNA-sequence has worked as one of the primary obstacles to an integration of these fields.
Inter-chromosomal variation in the pattern of human population genetic structure
Directory of Open Access Journals (Sweden)
Baye Tesfaye M
2011-05-01
Full Text Available Abstract Emerging technologies now make it possible to genotype hundreds of thousands of genetic variations in individuals, across the genome. The study of loci at finer scales will facilitate the understanding of genetic variation at genomic and geographic levels. We examined global and chromosomal variations across HapMap populations using 3.7 million single nucleotide polymorphisms to search for the most stratified genomic regions of human populations and linked these regions to ontological annotation and functional network analysis. To achieve this, we used five complementary statistical and genetic network procedures: principal component (PC, cluster, discriminant, fixation index (FST and network/pathway analyses. At the global level, the first two PC scores were sufficient to account for major population structure; however, chromosomal level analysis detected subtle forms of population structure within continental populations, and as many as 31 PCs were required to classify individuals into homogeneous groups. Using recommended population ancestry differentiation measures, a total of 126 regions of the genome were catalogued. Gene ontology and networks analyses revealed that these regions included the genes encoding oculocutaneous albinism II (OCA2, hect domain and RLD 2 (HERC2, ectodysplasin A receptor (EDAR and solute carrier family 45, member 2 (SLC45A2. These genes are associated with melanin production, which is involved in the development of skin and hair colour, skin cancer and eye pigmentation. We also identified the genes encoding interferon-γ (IFNG and death-associated protein kinase 1 (DAPK1, which are associated with cell death, inflammatory and immunological diseases. An in-depth understanding of these genomic regions may help to explain variations in adaptation to different environments. Our approach offers a comprehensive strategy for analysing chromosome-based population structure and differentiation, and demonstrates the
Burnett, Leslie; Barlow-Stewart, Kris; Proos, Anné L; Aizenberg, Harry
2003-05-01
This article describes a generic model for access to samples and information in human genetic databases. The model utilises a "GeneTrustee", a third-party intermediary independent of the subjects and of the investigators or database custodians. The GeneTrustee model has been implemented successfully in various community genetics screening programs and has facilitated research access to genetic databases while protecting the privacy and confidentiality of research subjects. The GeneTrustee model could also be applied to various types of non-conventional genetic databases, including neonatal screening Guthrie card collections, and to forensic DNA samples.
The impact of genetic modification of human foods in the 21st century: a review.
Uzogara, S G
2000-05-01
Genetic engineering of food is the science which involves deliberate modification of the genetic material of plants or animals. It is an old agricultural practice carried on by farmers since early historical times, but recently it has been improved by technology. Many foods consumed today are either genetically modified (GM) whole foods, or contain ingredients derived from gene modification technology. Billions of dollars in U.S. food exports are realized from sales of GM seeds and crops. Despite the potential benefits of genetic engineering of foods, the technology is surrounded by controversy. Critics of GM technology include consumer and health groups, grain importers from European Union (EU) countries, organic farmers, environmentalists, concerned scientists, ethicists, religious rights groups, food advocacy groups, some politicians and trade protectionists. Some of the specific fears expressed by opponents of GM technology include alteration in nutritional quality of foods, potential toxicity, possible antibiotic resistance from GM crops, potential allergenicity and carcinogenicity from consuming GM foods. In addition, some more general concerns include environmental pollution, unintentional gene transfer to wild plants, possible creation of new viruses and toxins, limited access to seeds due to patenting of GM food plants, threat to crop genetic diversity, religious, cultural and ethical concerns, as well as fear of the unknown. Supporters of GM technology include private industries, research scientists, some consumers, U.S. farmers and regulatory agencies. Benefits presented by proponents of GM technology include improvement in fruit and vegetable shelf-life and organoleptic quality, improved nutritional quality and health benefits in foods, improved protein and carbohydrate content of foods, improved fat quality, improved quality and quantity of meat, milk and livestock. Other potential benefits are: the use of GM livestock to grow organs for transplant
Genetic Variants Contribute to Gene Expression Variability in Humans
Hulse, Amanda M.; Cai, James J.
2013-01-01
Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607
Sachse, Carola
2011-01-01
The Max Planck Institute for Molecular Genetics (MPIMG) in Berlin-Dahlem dates its establishment to 1964. Its homepage makes no mention of its predecessor institutes, the Kaiser Wilhelm Institute for Anthropology, Human Genetics and Eugenics (KWIA) and the subsequent MPI for Comparative Genetics and Hereditary Pathology (MPIVEE). This article traces the two critical phases of transition regarding the constellations of academic staff, institutional and epistemic ruptures and continuities specific to the era. Only one of the five department heads from the final war years, Hans Nachtsheim, remained a researcher within the Max Planck Society (MPG); he nevertheless continued to advocate the pre-war and wartime eugenic agenda in the life sciences and social policy. The generational change of 1959/60 became a massive struggle within the institute, in which microbial genetics (with Fritz Kaudewitz) was pitted against human genetics (with Friedrich Vogel) and managed to establish itself after a fresh change in personnel in 1964/65. For the Dahlem institute, this involved a far-reaching reorientation of its research, but for the genetically oriented life sciences in the Max Planck Society as a whole it only meant that molecular biology, which was already being pursued in the West German institutes, gained an additional facility. With this realignment of research traditions, the Society was able to draw a line under the Nazi past without having to address it head-on.
Phillips, John
1973-01-01
Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)
The genetic influences on oxycodone response characteristics in human experimental pain
DEFF Research Database (Denmark)
Olesen, Anne Estrup; Sato, Hiroe; Nielsen, Lecia M
2015-01-01
Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic respon......; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone....
Directory of Open Access Journals (Sweden)
Scott G Kitchen
Full Text Available There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR. Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.
Biomarkers of genetic damage in human populations exposed to pesticides
International Nuclear Information System (INIS)
Aiassa, Delia; Manas, Fernando; Bosch, Beatriz; Gentile, Natalia; Bernardi, Natali; Gorla, Nora
2012-01-01
The effect of pesticides on human, animal and environmental health has been cause of concern in the scientific community for a long time. Numerous studies have reported that pesticides are not harmless and that their use can lead to harmful biological effects in the medium and long term, in exposed human and animals, and their offspring. The importance of early detection of genetic damage is that it allows us to take the necessary measures to reduce or eliminate the exposure to the deleterious agent when damage is still reversible, and thus to prevent and to diminish the risk of developing tumors or other alterations. In this paper we reviewed the main concepts in the field, the usefulness of genotoxicity studies and we compiled studies performed during the last twenty years on genetic monitoring of people occupationally exposed to pesticides. we think that genotoxicity tests, including that include chromosomal aberrations, micronucleus, sister chromatid exchanges and comet assays, should be considered as essential tools in the implementation of complete medical supervision for people exposed to potential environmental pollutants, particularly for those living in the same place as others who were others have already developed some type of malignancy. This action is particularly important at early stages to prevent the occurrence of tumors, especially from environmental origins.
Regulating human genetic research in Latin America: a race to the top or a race together?
Directory of Open Access Journals (Sweden)
Rosario Isasi
2016-05-01
Full Text Available Balancing the therapeutic potential of genetic science with the adoption of policies that reflect social values has proven to be a formidable task for Latin American countries. This essay presents some reflections on human genetics research policy in Latin America and explores a path forward for policy development.
Progress report on research on human genetics in Iceland
Energy Technology Data Exchange (ETDEWEB)
None
1980-10-31
Records of the Icelandic population are being used to investigate the possible inheritance of disabilities and diseases as well as other characteristics and the effect of environment on man. The progress report of research covers the period from 1977 to 1980. The investigation was begun in 1965 by the Genetical Committee of the University of Iceland and the materials used are demographic records from the year 1840 to present and various medical information. The records are being computerized and linked together to make them effective for use in hereditary studies.
Human fecal source identification with real-time quantitative PCR
Waterborne diseases represent a significant public health risk worldwide, and can originate from contact with water contaminated with human fecal material. We describe a real-time quantitative PCR (qPCR) method that targets a Bacteroides dori human-associated genetic marker for...
Genetically modified plants and human health.
Key, Suzie; Ma, Julian K-C; Drake, Pascal Mw
2008-06-01
Genetically modified (or GM) plants have attracted a large amount of media attention in recent years and continue to do so. Despite this, the general public remains largely unaware of what a GM plant actually is or what advantages and disadvantages the technology has to offer, particularly with regard to the range of applications for which they can be used. From the first generation of GM crops, two main areas of concern have emerged, namely risk to the environment and risk to human health. As GM plants are gradually being introduced into the European Union there is likely to be increasing public concern regarding potential health issues. Although it is now commonplace for the press to adopt 'health campaigns', the information they publish is often unreliable and unrepresentative of the available scientific evidence. We consider it important that the medical profession should be aware of the state of the art, and, as they are often the first port of call for a concerned patient, be in a position to provide an informed opinion. This review will examine how GM plants may impact on human health both directly - through applications targeted at nutrition and enhancement of recombinant medicine production - but also indirectly, through potential effects on the environment. Finally, it will examine the most important opposition currently facing the worldwide adoption of this technology: public opinion.
Directory of Open Access Journals (Sweden)
Adama Sanou
2014-10-01
Full Text Available In sub-Saharan Africa, bovine tuberculosis (bTB is a potential hazard for animals and humans health. The goal of this study was to improve our understanding of bTB epidemiology in Burkina Faso and especially Mycobacterium bovis transmission within and between the bovine and human populations.Twenty six M. bovis strains were isolated from 101 cattle carcasses with suspected bTB lesions during routine meat inspections at the Bobo Dioulasso and Ouagadougou slaughterhouses. In addition, 7 M. bovis strains were isolated from 576 patients with pulmonary tuberculosis. Spoligotyping, RDAf1 deletion and MIRU-VNTR typing were used for strains genotyping. The isolation of M. bovis strains was confirmed by spoligotyping and 12 spoligotype signatures were detected. Together, the spoligotyping and MIRU-VNTR data allowed grouping the 33 M. bovis isolates in seven clusters including isolates exclusively from cattle (5 or humans (1 or from both (1. Moreover, these data (genetic analyses and phenetic tree showed that the M. bovis isolates belonged to the African 1 (Af1 clonal complex (81.8% and the putative African 5 (Af5 clonal complex (18.2%, in agreement with the results of RDAf1 deletion typing.This is the first detailed molecular characterization of M. bovis strains from humans and cattle in Burkina Faso. The distribution of the two Af1 and putative Af5 clonal complexes is comparable to what has been reported in neighbouring countries. Furthermore, the strain genetic profiles suggest that M. bovis circulates across the borders and that the Burkina Faso strains originate from different countries, but have a country-specific evolution. The genetic characterization suggests that, currently, M. bovis transmission occurs mainly between cattle, occasionally between cattle and humans and potentially between humans. This study emphasizes the bTB risk in cattle but also in humans and the difficulty to set up proper disease control strategies in Burkina Faso.
Human lipodystrophies: genetic and acquired diseases of adipose tissue
Capeau, Jacqueline; Magré, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bénédicte; Béréziat, Véronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne
2010-01-01
Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARγ. Importantly, lamin A/C mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their aetiology is generally unknown, they could be associated with signs of auto-immunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardio-vascular and hepatic complications. PMID:20551664
Chen, S H; Anderson, J E; Giblett, E R
1977-01-01
Rare genetic variants of human red cell 2,3-diphosphoglycerate mutase (DPGM) and monophosphoglycerate mutase (MPGM) were compared by starch gel electrophoresis. The isozyme patterns showed that genetic variation of the enzymes were independent from each other, thus DPGM and MPGM must be controlled by two separate loci. Images Fig. 1 PMID:195467
Genetic modification and genetic determinism
Resnik, David B; Vorhaus, Daniel B
2006-01-01
In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884
Genetic modification and genetic determinism
Directory of Open Access Journals (Sweden)
Vorhaus Daniel B
2006-06-01
Full Text Available Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.
DEFF Research Database (Denmark)
Koutnikova, Hana; Laakso, Markku; Lu, Lu
2009-01-01
complementarities of mouse and human genetic approaches, identifies the UBP1 locus as a critical blood pressure determinant. UBP1 plays a role in cholesterol and steroid metabolism via the transcriptional activation of CYP11A, the rate-limiting enzyme in pregnenolone and aldosterone biosynthesis. We suggest......Hypertension is a major health problem of largely unknown genetic origins. To identify new genes responsible for hypertension, genetic analysis of recombinant inbred strains of mice followed by human association studies might prove powerful and was exploited in our current study. Using a set of 27...... recombinant BXD strains of mice we identified a quantitative trait locus (QTL) for blood pressure (BP) on distal chromosome 9. The association analysis of markers encompassing the syntenic region on human chromosome 3 gave in an additive genetic model the strongest association for rs17030583 C/T and rs2291897...
The impact of preimplantation genetic diagnosis on human embryos
Directory of Open Access Journals (Sweden)
García-Ferreyra J.
2016-12-01
Full Text Available Chromosome abnormalities are extremely common in human oocytes and embryos and are associated with a variety of negative outcomes for both natural cycles and those using assisted reproduction techniques. Aneuploidies embryos may fail to implant in the uterus, miscarry, or lead to children with serious medical problems (e.g., Down syndrome. Preimplantation genetic diagnosis (PGD is a technique that allows the detection of aneuploidy in embryos and seeks to improve the clinical outcomes od assisted reproduction treatments, by ensuring that the embryos chosen for the transfer are chromosomally normal.
Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.
Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola
2015-08-01
The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.
G protein-coupled receptor mutations and human genetic disease.
Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C
2014-01-01
Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common
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.
Variation in clinical phenotype of human infection among genetic groups of Blastomyces dermatitidis
Meece, Jennifer K.; Anderson, Jennifer L.; Gruszka, Sarah; Sloss, Brian L.; Sullivan, Bradley; Reed, Kurt D.
2013-01-01
Background. Blastomyces dermatitidis, the etiologic agent of blastomycosis, has 2 genetic groups and shows varied clinical presentation, ranging from silent infections to fulminant respiratory disease and dissemination. The objective of this study was to determine whether clinical phenotype and outcomes vary based on the infecting organism's genetic group.Methods. We used microsatellites to genotype 227 clinical isolates of B. dermatitidis from Wisconsin patients. For each isolate, corresponding clinical disease characteristics and patient demographic information were abstracted from electronic health records and Wisconsin Division of Health reportable disease forms and questionnaires.Results. In univariate analysis, group 1 isolates were more likely to be associated with pulmonary-only infections (P 1 month (P smoking status (P = .0001) remained predictors for group 2 infections.Conclusions. This study identified previously unknown associations between clinical phenotype of human infection and genetic groups of B. dermatitidis and provides a framework for further investigations of the genetic basis for virulence in B. dermatitidis.
Opalescence of human teeth and dental esthetic restorative materials.
Lee, Yong-Keun
2016-12-01
Human tooth enamel is opalescent, which renders teeth bluish in reflected and orange in transmitted color. The aim was to review opalescent property of teeth and application and mimetic reproduction in esthetic restorations. A PubMed search for articles published in English till 2015 on the opalescence of teeth and esthetic materials revealed 29 relevant papers. Opalescence was measured with OP-RT index, which was calculated as the difference in the yellow-blue and red-green color coordinates between the reflected and transmitted colors. Mean OP-RT value of human enamel was 22.9. OP-RT values of direct resin composites changed after polymerization, and the range in these materials was 5.7-23.7. OP-RT value ranges were 1.6-6.1 and 2.0-7.1 for the core and veneer ceramics, respectively. Since the OP-RT values of esthetic materials were lower than that of enamel, it is recommended that materials that can reproduce the opalescence of enamel be further designed.
Human Cadaver Material in Preclinical Oral Surgery.
Barber, H. Dexter; And Others
1993-01-01
A University of Michigan dental school curriculum for oral surgery that uses human cadaver heads is described. Selection, preparation, and laboratory use of the materials are outlined. Faculty and students have received the sequence well and found it prepared them for clinical rotation. (MSE)
CRISPR/Cas9 genome editing in human pluripotent stem cells: Harnessing human genetics in a dish.
González, Federico
2016-07-01
Because of their extraordinary differentiation potential, human pluripotent stem cells (hPSCs) can differentiate into virtually any cell type of the human body, providing a powerful platform not only for generating relevant cell types useful for cell replacement therapies, but also for modeling human development and disease. Expanding this potential, structures resembling human organs, termed organoids, have been recently obtained from hPSCs through tissue engineering. Organoids exhibit multiple cell types self-organizing into structures recapitulating in part the physiology and the cellular interactions observed in the organ in vivo, offering unprecedented opportunities for human disease modeling. To fulfill this promise, tissue engineering in hPSCs needs to be supported by robust and scalable genome editing technologies. With the advent of the CRISPR/Cas9 technology, manipulating the genome of hPSCs has now become an easy task, allowing modifying their genome with superior precision, speed, and throughput. Here we review current and potential applications of the CRISPR/Cas9 technology in hPSCs and how they contribute to establish hPSCs as a model of choice for studying human genetics. Developmental Dynamics 245:788-806, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels
Emdin, Connor A.; Khera, Amit V.; Natarajan, Pradeep; Klarin, Derek; Won, Hong-Hee; Peloso, Gina M.; Stitziel, Nathan O.; Nomura, Akihiro; Zekavat, Seyedeh M.; Bick, Alexander G.; Gupta, Namrata; Asselta, Rosanna; Duga, Stefano; Merlini, Piera Angelica; Correa, Adolfo; Kessler, Thorsten; Wilson, James G.; Bown, Matthew J.; Hall, Alistair S.; Braund, Peter S.; Samani, Nilesh J.; Schunkert, Heribert; Marrugat, Jaume; Elosua, Roberto; McPherson, Ruth; Farrall, Martin; Watkins, Hugh; Willer, Cristen; Abecasis, Gonçalo R.; Felix, Janine F.; Vasan, Ramachandran S.; Lander, Eric; Rader, Daniel J.; Danesh, John; Ardissino, Diego; Gabriel, Stacey; Saleheen, Danish; Kathiresan, Sekar
2017-01-01
BACKGROUND Genomic analyses have suggested that the LPA gene and its associated plasma biomarker, lipoprotein(a) (Lp[a]), represent a causal risk factor for coronary heart disease (CHD). As such, lowering Lp(a) has emerged as a therapeutic strategy. Beyond target identification, human genetics may contribute to the development of new therapies by defining the full spectrum of beneficial and adverse consequences and by developing a dose-response curve of target perturbation. OBJECTIVES We attempted to establish the full phenotypic impact of LPA gene variation and to estimate a dose-response curve between genetically altered plasma Lp(a) and risk for CHD. METHODS We leveraged genetic variants at the LPA gene from 3 data sources: individual-level data from 112,338 participants in the UK Biobank; summary association results from large-scale genome-wide association studies; and LPA gene sequencing results from cases with and controls free of CHD. RESULTS One standard deviation genetically lowered Lp(a) level was associated with 29% lower risk of CHD (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.69 to 0.73), 31% lower risk of peripheral vascular disease (OR: 0.69; 95% CI: 0.59 to 0.80), 13% lower risk of stroke (OR: 0.87; 95% CI: 0.79 to 0.96), 17% lower risk of heart failure (OR: 0.83; 95% CI: 0.73 to 0.94), and 37% lower risk of aortic stenosis (OR: 0.63; 95% CI: 0.47 to 0.83). We observed no association with 31 other disorders including type 2 diabetes and cancer. Variants that led to gain of LPA gene function increased risk for CHD whereas those that led to loss of gene function reduced CHD risk. CONCLUSIONS Beyond CHD, genetically lowered Lp(a) is associated with a lower risk of peripheral vascular disease, stroke, heart failure, and aortic stenosis. As such, pharmacological lowering of plasma Lp(a) may impact a range of atherosclerosis-related diseases. PMID:28007139
Nest materials as a source of genetic data for avian ecological studies
Pearce, J.M.; Fields, R.L.; Scribner, K.T.
1997-01-01
We examined the utility of feathers and egg shell membranes, deposited in the nests of Spectacled Eiders (Somateria fischeri), as a source of DNA for genetic studies at both the population and individual level. The potential for feather DNA contamination as a result of female behavioral interactions (e.g. nest parasitism), reuse of nest sites from previous years, or other unknown occurrences was acknowledged and specifically tested. DNA was successfully extracted from both feathers and egg shell membranes and waterfowl microsatellite loci were used to construct individual genotypes. We found no difference in the genotypes obtained from nest feathers or blood of the incubating female. Detection of nest feather contamination was possible with as little as one feather when samples from multiple females were intentionally mixed. Triplicate DNA extractions from 33 nests provided a means of detecting contamination in 3 nests. Egg membranes proved a viable source of offspring DNA and can contribute valuable data to investigations of parentage when assayed jointly with maternal feather DNA. Nest materials provide an efficient, non-invasive method of genetic sampling that can be readily incorporated into field research. However, the natural history traits and mating strategies of a species must be considered during sample collection to identify the possible sources of nest materials (e.g., paternal, maternal, parasite, etc.). Specific experiments should also be designed to test sampling assumptions.
Deng, Lian; Hoh, Boon Peng; Lu, Dongsheng; Fu, Ruiqing; Phipps, Maude E; Li, Shilin; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Ismail, Endom; Mokhtar, Siti Shuhada; Jin, Li; Zilfalil, Bin Alwi; Marshall, Christian R; Scherer, Stephen W; Al-Mulla, Fahd; Xu, Shuhua
2014-09-01
Peninsular Malaysia is a strategic region which might have played an important role in the initial peopling and subsequent human migrations in Asia. However, the genetic diversity and history of human populations--especially indigenous populations--inhabiting this area remain poorly understood. Here, we conducted a genome-wide study using over 900,000 single nucleotide polymorphisms (SNPs) in four major Malaysian ethnic groups (MEGs; Malay, Proto-Malay, Senoi and Negrito), and made comparisons of 17 world-wide populations. Our data revealed that Peninsular Malaysia has greater genetic diversity corresponding to its role as a contact zone of both early and recent human migrations in Asia. However, each single Orang Asli (indigenous) group was less diverse with a smaller effective population size (N(e)) than a European or an East Asian population, indicating a substantial isolation of some duration for these groups. All four MEGs were genetically more similar to Asian populations than to other continental groups, and the divergence time between MEGs and East Asian populations (12,000--6,000 years ago) was also much shorter than that between East Asians and Europeans. Thus, Malaysian Orang Asli groups, despite their significantly different features, may share a common origin with the other Asian groups. Nevertheless, we identified traces of recent gene flow from non-Asians to MEGs. Finally, natural selection signatures were detected in a batch of genes associated with immune response, human height, skin pigmentation, hair and facial morphology and blood pressure in MEGs. Notable examples include SYN3 which is associated with human height in all Orang Asli groups, a height-related gene (PNPT1) and two blood pressure-related genes (CDH13 and PAX5) in Negritos. We conclude that a long isolation period, subsequent gene flow and local adaptations have jointly shaped the genetic architectures of MEGs, and this study provides insight into the peopling and human migration
Global and disease-associated genetic variation in the human Fanconi anemia gene family.
Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J
2014-12-20
Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Genetic Modification of the Lung Directed Toward Treatment of Human Disease.
Sondhi, Dolan; Stiles, Katie M; De, Bishnu P; Crystal, Ronald G
2017-01-01
Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (RSV) and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection, and lung injury. A variety of viral and non-viral vectors have been employed to overcome the many physical barriers to gene transfer imposed by lung anatomy and natural defenses. Beyond the treatment of lung diseases, the lung has the potential to be used as a metabolic factory for generating proteins for delivery to the circulation for treatment of systemic diseases. Although much has been learned through a myriad of experiments about the development of genetic modification of the lung, more work is still needed to improve the delivery vehicles and to overcome challenges such as entry barriers, persistent expression, specific cell targeting, and circumventing host anti-vector responses.
Alu repeats as markers for human population genetics
Energy Technology Data Exchange (ETDEWEB)
Batzer, M.A.; Alegria-Hartman, M. [Lawrence Livermore National Lab., CA (United States); Bazan, H. [Louisiana State Univ., New Orleans, LA (United States). Medical Center] [and others
1993-09-01
The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.
Sulaiman, Irshad M; Ortega, Ynes; Simpson, Steven; Kerdahi, Khalil
2014-03-01
Cyclospora cayetanensis is an apicocomplexan parasite that infects the gastrointestinal tract and causes acute diarrheal disease in humans. In recent years, this human-pathogenic parasite has led to several foodborne outbreaks in the United States and Canada, mostly associated with imported produce. Understanding the biology and epidemiology of C. cayetanensis is difficult because little is known about its origin, possible zoonotic reservoirs, and genetic relationships with other coccidian parasites. Recently, we developed a 70kDa heat shock protein (HSP70) gene based nested PCR protocol for detection of C. cayetanensis parasite and sequenced the PCR products of 16 human isolates from Nepal, Mexico, and Peru. In this study, we have characterized the regions of 18S ribosomal RNA (rRNA) gene of 17 human C. cayetanensis isolates for molecular detection, and also to ascertain the genetic diversity of this parasite. The 18S rRNA primer sets were further tested by PCR amplification followed by nucleotide sequencing of the PCR amplified products of previously characterized C. cayetanensis isolates from three endemic regions at HSP70 locus. Although no genetic polymorphism was observed at the regions of HSP70 locus characterized in our previous study, the data analysis of this study revealed a minor genetic diversity at the 18S rRNA locus among the C. cayetanensis isolates. The 18S rRNA gene-based nested PCR protocol provides a useful genetic marker for the detection of C. cayetanensis parasite and confirms it as a genetically distinct species in genus Cyclospora. The results also supported lack of geographic segregation and existence of genetically homogeneous population for the C. cayetanensis parasites both at the HSP70 as well as at the18S rRNA loci. Published by Elsevier B.V.
Genetic effects of ionizing radiation
International Nuclear Information System (INIS)
Myers, D.K.; Childs, J.D.
1980-01-01
The genetic material in living organisms is susceptible to damage from a wide variety of causes including radiation exposure. Most of this damage is repaired by the organism; the residual damage and damage which is not correctly repaired can lead to genetic changes such as mutations. In lower organisms, most offspring carry an unaltered copy of the genetic information that was present in the parental organism, most of the genetic changes which do occur are not caused by natural background radiation, and the increase in frequency of genetic changes after irradiation at low-dose rates is directly proportional to total radiation dose. The same principles appear to be valid in mammals and other higher organisms. About 105 out of every 1000 humans born suffer from some genetic or partly-genetic condition requiring medical attention at some time. It has been estimated that approximately 1 person in every 2000 born carry a deleterious genetic mutation that was caused by the continued exposure of many generations of our ancestors to natural background radiation. On the same basis, it is predicted that the incidence of genetic diseases would be increased to 106 per 1000 in the children and grandchildren of radiation workers who were exposed to 1 rem per year commencing at age 18. However, there was no detectable change in the health and fitness of mice whose male ancestors were repeatedly exposed to high radiation doses up to 900 rem per generation. (auth)
Designing shields for KeV photons with genetic algorithms
International Nuclear Information System (INIS)
Asbury, Stephen; Holloway, James P.
2011-01-01
Shielding of x-ray sources and low energy gamma rays is often accomplished with lead aprons, comprising a thin layer (0.5 mm to 1 mm) of lead or similar high-Z material. In previous work the authors used Genetic Algorithms to explore the design of a shadow shield for space applications. Now those techniques have been applied to the problem of shielding humans from low energy gamma radiation. This paper uses a simple geometry to explore layering various materials as a method to reduce mass and dose for thin gamma shields. The genetic algorithms discover layers of materials with various Z is in fact more effective than an equivalent mass of Pb alone for lower energy gammas, but as the incident radiation energy increases the efficacy of such layering diminishes. The utility of varying Z for lower energy gammas is in part due to their complementary K-edges, where one material compensates for the transmission that would occur just below the K-edge in another material. (author)
Property regime concerning genetic resources and traditional knowledge
Directory of Open Access Journals (Sweden)
Gabriel R. Nemogá Soto
2001-01-01
Full Text Available This article provides an historical account of the changes that have taken place regarding ownership, control and access over genetic resources. Once considered the common heritage of humanity, rights over genetic resources, it is argued, have undergone radical transformations. The global legal framework regarding genetic resources has shifted to legitimize and promote their appropriation and monopolization. This transformation embraced the expansion of intellectual property rights over genetic material and information, including living organisms, through the World Trade Organization´s Trade Related Aspects of Intellectual Property (TRIPs. This was coupled by the adoption of the United Nations Convention on Biological Diversity, which recognizes sovereign rights of the countries of origin over their genetic resources and, at the same time, obligates them to permit access to those resources. The Colombian Constitution of 1991 and unparalleled judicial decisions during the last decade reaffirmed sovereign rights over genetic resources in Colombia. Conversely, the genetic resources and the traditional knowledge of Indigenous peoples and local communities continue to be freely accessible resources within the current Colombian legal framework.
Genetic complexity in a Drosophila model of diabetes-associated misfolded human proinsulin.
Park, Soo-Young; Ludwig, Michael Z; Tamarina, Natalia A; He, Bin Z; Carl, Sarah H; Dickerson, Desiree A; Barse, Levi; Arun, Bharath; Williams, Calvin L; Miles, Cecelia M; Philipson, Louis H; Steiner, Donald F; Bell, Graeme I; Kreitman, Martin
2014-02-01
Drosophila melanogaster has been widely used as a model of human Mendelian disease, but its value in modeling complex disease has received little attention. Fly models of complex disease would enable high-resolution mapping of disease-modifying loci and the identification of novel targets for therapeutic intervention. Here, we describe a fly model of permanent neonatal diabetes mellitus and explore the complexity of this model. The approach involves the transgenic expression of a misfolded mutant of human preproinsulin, hINS(C96Y), which is a cause of permanent neonatal diabetes. When expressed in fly imaginal discs, hINS(C96Y) causes a reduction of adult structures, including the eye, wing, and notum. Eye imaginal discs exhibit defects in both the structure and the arrangement of ommatidia. In the wing, expression of hINS(C96Y) leads to ectopic expression of veins and mechano-sensory organs, indicating disruption of wild-type signaling processes regulating cell fates. These readily measurable "disease" phenotypes are sensitive to temperature, gene dose, and sex. Mutant (but not wild-type) proinsulin expression in the eye imaginal disc induces IRE1-mediated XBP1 alternative splicing, a signal for endoplasmic reticulum stress response activation, and produces global change in gene expression. Mutant hINS transgene tester strains, when crossed to stocks from the Drosophila Genetic Reference Panel, produce F1 adults with a continuous range of disease phenotypes and large broad-sense heritability. Surprisingly, the severity of mutant hINS-induced disease in the eye is not correlated with that in the notum in these crosses, nor with eye reduction phenotypes caused by the expression of two dominant eye mutants acting in two different eye development pathways, Drop (Dr) or Lobe (L), when crossed into the same genetic backgrounds. The tissue specificity of genetic variability for mutant hINS-induced disease has, therefore, its own distinct signature. The genetic dominance
Bai, Haihua; Guo, Xiaosen; Zhang, Dong; Narisu, Narisu; Bu, Junjie; Jirimutu, Jirimutu; Liang, Fan; Zhao, Xiang; Xing, Yanping; Wang, Dingzhu; Li, Tongda; Zhang, Yanru; Guan, Baozhu; Yang, Xukui; Yang, Zili; Shuangshan, Shuangshan; Su, Zhe; Wu, Huiguang; Li, Wenjing; Chen, Ming; Zhu, Shilin; Bayinnamula, Bayinnamula; Chang, Yuqi; Gao, Ying; Lan, Tianming; Suyalatu, Suyalatu; Huang, Hui; Su, Yan; Chen, Yujie; Li, Wenqi; Yang, Xu; Feng, Qiang; Wang, Jian; Yang, Huanming; Wang, Jun; Wu, Qizhu; Yin, Ye; Zhou, Huanmin
2014-11-05
Mongolians have played a significant role in modern human evolution, especially after the rise of Genghis Khan (1162[?]-1227). Although the social cultural impacts of Genghis Khan and the Mongolian population have been well documented, explorations of their genome structure and genetic imprints on other human populations have been lacking. We here present the genome of a Mongolian male individual. The genome was de novo assembled using a total of 130.8-fold genomic data produced from massively parallel whole-genome sequencing. We identified high-confidence variation sets, including 3.7 million single nucleotide polymorphisms (SNPs) and 756,234 short insertions and deletions. Functional SNP analysis predicted that the individual has a pathogenic risk for carnitine deficiency. We located the patrilineal inheritance of the Mongolian genome to the lineage D3a through Y haplogroup analysis and inferred that the individual has a common patrilineal ancestor with Tibeto-Burman populations and is likely to be the progeny of the earliest settlers in East Asia. We finally investigated the genetic imprints of Mongolians on other human populations using different approaches. We found varying degrees of gene flows between Mongolians and populations living in Europe, South/Central Asia, and the Indian subcontinent. The analyses demonstrate that the genetic impacts of Mongolians likely resulted from the expansion of the Mongolian Empire in the 13th century. The genome will be of great help in further explorations of modern human evolution and genetic causes of diseases/traits specific to Mongolians. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Functional modules, mutational load and human genetic disease.
Zaghloul, Norann A; Katsanis, Nicholas
2010-04-01
The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. Copyright 2010 Elsevier Ltd. All rights reserved.
Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum.
Directory of Open Access Journals (Sweden)
Christian Gieger
2008-11-01
Full Text Available The rapidly evolving field of metabolomics aims at a comprehensive measurement of ideally all endogenous metabolites in a cell or body fluid. It thereby provides a functional readout of the physiological state of the human body. Genetic variants that associate with changes in the homeostasis of key lipids, carbohydrates, or amino acids are not only expected to display much larger effect sizes due to their direct involvement in metabolite conversion modification, but should also provide access to the biochemical context of such variations, in particular when enzyme coding genes are concerned. To test this hypothesis, we conducted what is, to the best of our knowledge, the first GWA study with metabolomics based on the quantitative measurement of 363 metabolites in serum of 284 male participants of the KORA study. We found associations of frequent single nucleotide polymorphisms (SNPs with considerable differences in the metabolic homeostasis of the human body, explaining up to 12% of the observed variance. Using ratios of certain metabolite concentrations as a proxy for enzymatic activity, up to 28% of the variance can be explained (p-values 10(-16 to 10(-21. We identified four genetic variants in genes coding for enzymes (FADS1, LIPC, SCAD, MCAD where the corresponding metabolic phenotype (metabotype clearly matches the biochemical pathways in which these enzymes are active. Our results suggest that common genetic polymorphisms induce major differentiations in the metabolic make-up of the human population. This may lead to a novel approach to personalized health care based on a combination of genotyping and metabolic characterization. These genetically determined metabotypes may subscribe the risk for a certain medical phenotype, the response to a given drug treatment, or the reaction to a nutritional intervention or environmental challenge.
Khan, Asifullah; Tian, Lei; Zhang, Chao; Yuan, Kai; Xu, Shuhua
2016-01-05
The glycine amidinotransferase gene (GATM) plays a vital role in energy metabolism in muscle tissues and is associated with multiple clinically important phenotypes. However, the genetic diversity of the GATM gene remains poorly understood within and between human populations. Here we analyzed the 1,000 Genomes Project data through population genetics approaches and observed significant genetic diversity across the GATM gene among various continental human populations. We observed considerable variations in GATM allele frequencies and haplotype composition among different populations. Substantial genetic differences were observed between East Asian and European populations (FST = 0.56). In addition, the frequency of a distinct major GATM haplotype in these groups was congruent with population-wide diversity at this locus. Furthermore, we identified GATM as the top differentiated gene compared to the other statin drug response-associated genes. Composite multiple analyses identified signatures of positive selection at the GATM locus, which was estimated to have occurred around 850 generations ago in European populations. As GATM catalyzes the key step of creatine biosynthesis involved in energy metabolism, we speculate that the European prehistorical demographic transition from hunter-gatherer to farming cultures was the driving force of selection that fulfilled creatine-based metabolic requirement of the populations.
Hoehndorf, Robert
2015-06-08
Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.
Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.
2015-06-01
Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.
Genetic and molecular basis of individual differences in human umami taste perception.
Directory of Open Access Journals (Sweden)
Noriatsu Shigemura
Full Text Available Umami taste (corresponds to savory in English is elicited by L-glutamate, typically as its Na salt (monosodium glutamate: MSG, and is one of five basic taste qualities that plays a key role in intake of amino acids. A particular property of umami is the synergistic potentiation of glutamate by purine nucleotide monophosphates (IMP, GMP. A heterodimer of a G protein coupled receptor, TAS1R1 and TAS1R3, is proposed to function as its receptor. However, little is known about genetic variation of TAS1R1 and TAS1R3 and its potential links with individual differences in umami sensitivity. Here we investigated the association between recognition thresholds for umami substances and genetic variations in human TAS1R1 and TAS1R3, and the functions of TAS1R1/TAS1R3 variants using a heterologous expression system. Our study demonstrated that the TAS1R1-372T creates a more sensitive umami receptor than -372A, while TAS1R3-757C creates a less sensitive one than -757R for MSG and MSG plus IMP, and showed a strong correlation between the recognition thresholds and in vitro dose-response relationships. These results in human studies support the propositions that a TAS1R1/TAS1R3 heterodimer acts as an umami receptor, and that genetic variation in this heterodimer directly affects umami taste sensitivity.
Mouse forward genetics in the study of the peripheral nervous system and human peripheral neuropathy
Douglas, Darlene S.; Popko, Brian
2009-01-01
Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. PMID:18481175
Heitland, I; Kenemans, J L; Böcker, K B E; Baas, J M P
2014-11-01
It has long been postulated that exogenous cannabinoids have a profound effect on human cognitive functioning. These cannabinoid effects are thought to depend, at least in parts, on alterations of phase-locking of local field potential neuronal firing. The latter can be measured as activity in the theta frequency band (4-7Hz) by electroencephalogram. Theta oscillations are supposed to serve as a mechanism in neural representations of behaviorally relevant information. However, it remains unknown whether variability in endogenous cannabinoid activity is involved in theta rhythms and therefore, may serve as an individual differences index of human cognitive functioning. To clarify this issue, we recorded resting state EEG activity in 164 healthy human subjects and extracted EEG power across frequency bands (δ, θ, α, and β). To assess variability in the endocannabinoid system, two genetic polymorphisms (rs1049353, rs2180619) within the cannabinoid receptor 1 (CB1) were determined in all participants. As expected, we observed significant effects of rs1049353 on EEG power in the theta band at frontal, central and parietal electrode regions. Crucially, these effects were specific for the theta band, with no effects on activity in the other frequency bands. Rs2180619 showed no significant associations with theta power after Bonferroni correction. Taken together, we provide novel evidence in humans showing that genetic variability in the cannabinoid receptor 1 is associated with resting state EEG power in the theta frequency band. This extends prior findings of exogenous cannabinoid effects on theta power to the endogenous cannabinoid system. Copyright © 2014 Elsevier B.V. All rights reserved.
Qiu, Zilong; Li, Xiao
2017-04-01
Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.
DEFF Research Database (Denmark)
Kogelman, Lisette; Kadarmideen, Haja; Mark, Thomas
2013-01-01
Obesity is a rising worldwide public health problem. Difficulties to precisely measure various obesity traits and the genetic heterogeneity in human have been major impediments to completely disentangle genetic factors causing obesity. The pig is a relevant model for studying human obesity...... and obesity-related (OOR) traits. Using founder breeds divergent with respect to obesity traits we have created an F2 pig resource population (454 pigs), which has been intensively phenotyped for 36 OOR traits. The main rationale for our study is to characterize the genetic architecture of OOR traits in the F...... and genetic variation in the F2 population, respectively. This fulfills the purpose of creating a resource population divergent for OOR traits. Strong genetic correlations were found between weight and lean mass at dual energy x-ray absorptiometry (DXA) scanning (0.56 – 0.97). Weight and conformation also...
Moon, Robert
2012-12-24
Research into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen.
Moon, Robert; Hall, Joanna M.; Rangkuti, Farania; Ho, YungShwen; Almond, Neil M.; Mitchell, Graham Howard; Pain, Arnab; Holder, Anthony A.; Blackman, Michael J.
2012-01-01
Research into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen.
Crop Resources Ethic in Plant Genetic Engineering and Fortune Transfer Between Generations
Institute of Scientific and Technical Information of China (English)
WANG Xiaowei; DING Guangzhou; LIANG Xueqing
2006-01-01
The relation between human and crop resources belongs to the ethic of resources exploitation. The purposes of discussing the ethic of crop resources are to protect the ecology and safety of crops, to gain sustainable development, furthermore, to choose and form the production structure that is favorable to saving crop resources and protecting the ecology of crops. Plant genetic engineering is the technology of molecule breeding of rearrangement of inheritance materials at the level of molecule directionally, of improving plant properties and of breeding high quality and yield varieties of crops. The prominent effects of the technology on the crop ecological system are human subjective factors increasing as well as violating the nature and intensifying the conflict between human being and nature.Therefore, in plant genetic engineering, crop resources exploitation should follow certain ethic principles. Under the theory of ethics of natural resources, by the means of biologioal statistics, the author systematically analyzed the possible model of crop resources transfer between generations as well as the transfer mode of magnitude of real materials and magnitude of value.
Genetic mutation analysis of human gastric adenocarcinomas using ion torrent sequencing platform.
Directory of Open Access Journals (Sweden)
Zhi Xu
Full Text Available Gastric cancer is the one of the major causes of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer samples, identification and characterization of the molecular alterations underlying individual gastric adenocarcinomas is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations on an individual basis by DNA sequencing remained a daunting task. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster, and more reliable. In this study, we aim to identify genetic mutations in the genes which are targeted by drugs in clinical use or are under development in individual human gastric adenocarcinoma samples using Ion Torrent sequencing. We sequenced 737 loci from 45 cancer-related genes in 238 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. The sequencing analysis revealed a high occurrence of mutations along the TP53 locus (9.7% in our sample set. Thus, this study indicates the utility of a cost and time efficient tool such as Ion Torrent sequencing to screen cancer mutations for the development of personalized cancer therapy.
Medical Genetics and the First Studies of the Genetics of Populations in Mexico.
Barahona, Ana
2016-09-01
Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén's studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl's studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker's studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts. Copyright © 2016 by
Physiologic and genetic evidence links hemopexin to triglycerides in mice and humans.
Lawson, H A; Zayed, M; Wayhart, J P; Fabbrini, E; Love-Gregory, L; Klein, S; Semenkovich, C F
2017-04-01
Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. Hemopexin (HPX) was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F 16 advanced intercross between the LG/J and SM/J strains of mice. Hpx expression was evaluated in both the reproductive fat pads and livers of mice representing three strains, LG/J (n=25), SM/J (n=27) and C57Bl/6J (n=19), on high- and low-fat diets. The effect of altered Hpx expression on adipogenesis was studied in 3T3-L1 cells. Circulating HPX protein along with HPX expression were characterized in subcutaneous white adipose tissue samples obtained from a cohort of metabolically abnormal (n=18) and of metabolically normal (n=24) obese human subjects. We further examined the relationship between HPX and triglycerides in human atherosclerotic plaques (n=18). HPX expression in mouse adipose tissue, but not in liver, was regulated by dietary fat regardless of genetic background. HPX increased in concert with adipogenesis in 3T3-L1 cells, and disruption of its expression impaired adipocyte differentiation. RNAseq data from the adipose tissue of obese humans showed differential expression of HPX based on metabolic disease status (Ptriglycerides in these subjects (r=0.33; P=0.03). HPX was also found in an unbiased proteomic screen of human atherosclerotic plaques and shown to display differential abundance based on the extent of disease and triglyceride content (Ptriglycerides and provide a framework for understanding mechanisms underlying lipid metabolism and metabolic disease.
Roederer, Mario; Quaye, Lydia; Mangino, Massimo; Beddall, Margaret H; Mahnke, Yolanda; Chattopadhyay, Pratip; Tosi, Isabella; Napolitano, Luca; Terranova Barberio, Manuela; Menni, Cristina; Villanova, Federica; Di Meglio, Paola; Spector, Tim D; Nestle, Frank O
2015-04-09
Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.
Somatically acquired structural genetic differences
DEFF Research Database (Denmark)
Magaard Koldby, Kristina; Nygaard, Marianne; Christensen, Kaare
2016-01-01
Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested t...... with age.European Journal of Human Genetics advance online publication, 20 April 2016; doi:10.1038/ejhg.2016.34....
Genetic and immunohistochemical analysis of HSPA5 in mouse and human retinas.
Chintalapudi, Sumana R; Wang, XiaoFei; Li, Huiling; Lau, Yin H Chan; Williams, Robert W; Jablonski, Monica M
2016-01-01
Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina. Quantitative trait locus (QTL) mapping was used to map the genomic region that regulates Hspa5 in the cross between C57BL/6J X DBA/2J mice (BXD) genetic reference panel. The stepwise refinement of candidate genes was based on expression QTL mapping, gene expression correlation analyses (direct and partial), and analysis of regional sequence variants. The subcellular localization of candidate proteins and HSPA5 in mouse and human retinas was evaluated by immunohistochemistry. Differences in the localization of extracellular HSPA5 were assessed between healthy human donor and atrophic age-related macular degeneration (AMD) donor eyes. In the eyes of healthy mice, extracellular HSPA5 was confined to the area around the cone photoreceptor outer segments. Mapping variation in Hspa5 mRNA expression levels in the retina revealed a statistically significant trans -acting expression QTL (eQTL) on Chromosome 2 (Chr 2) and a suggestive locus on Chr 15. Sulf2 on Chr 2 was the strongest candidate gene based on partial correlation analysis, Pearson correlation with Hspa5 , expression levels in the retina, a missense variant in exon 14, and its reported function in the extracellular matrix and interphotoreceptor matrix. SULF2 is localized to the rod and cone photoreceptors in both human and mouse retinas. In human retinas with no pathology, extracellular HSPA5 was localized around many cones within the macular area. In contrast, fewer HSPA5-immunopositive cones were
Carretta, Marco; de Boer, Bauke; Jaques, Jenny; Antonelli, Antonella; Horton, Sarah J; Yuan, Huipin; de Bruijn, Joost D; Groen, Richard W J; Vellenga, Edo; Schuringa, Jan Jacob
2017-07-01
Recently, NOD-SCID IL2Rγ -/- (NSG) mice were implanted with human mesenchymal stromal cells (MSCs) in the presence of ceramic scaffolds or Matrigel to mimic the human bone marrow (BM) microenvironment. This approach allowed the engraftment of leukemic samples that failed to engraft in NSG mice without humanized niches and resulted in a better preservation of leukemic stem cell self-renewal properties. To further improve our humanized niche scaffold model, we genetically engineered human MSCs to secrete human interleukin-3 (IL-3) and thrombopoietin (TPO). In vitro, these IL-3- and TPO-producing MSCs were superior in expanding human cord blood (CB) CD34 + hematopoietic stem/progenitor cells. MLL-AF9-transduced CB CD34 + cells could be transformed efficiently along myeloid or lymphoid lineages on IL-3- and TPO-producing MSCs. In vivo, these genetically engineered MSCs maintained their ability to differentiate into bone, adipocytes, and other stromal components. Upon transplantation of MLL-AF9-transduced CB CD34 + cells, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) developed in engineered scaffolds, in which a significantly higher percentage of myeloid clones was observed in the mouse compartments compared with previous models. Engraftment of primary AML, B-cell ALL, and biphenotypic acute leukemia (BAL) patient samples was also evaluated, and all patient samples could engraft efficiently; the myeloid compartment of the BAL samples was better preserved in the human cytokine scaffold model. In conclusion, we show that we can genetically engineer the ectopic human BM microenvironment in a humanized scaffold xenograft model. This approach will be useful for functional study of the importance of niche factors in normal and malignant human hematopoiesis. Copyright © 2017 ISEH - International Society for Experimental Hematology. All rights reserved.
International Nuclear Information System (INIS)
Wang, L.; Gu, X.; Qu, M.; Luan, J.; Zhang, J.
2012-01-01
Zea mays ssp. mexicana, a wild relative of cultivated maize (Z. mays ssp. mays), is a useful gene resource for maize breeding. In this study, two populations were generated by conventional breeding scheme (population I) or tissue culture regime (population II), respectively, to introgress genetic material of Z. mays ssp. mexicana into maize. Karyotype analysis showed that the arm ratios of 10 pairs of chromosomes in parent maize Ye515 and derivative lines from 2 different populations with 26% and 38% chromosome variation frequencies, respectively. Alien chromatin was detected in the root tip cells of progeny plants through genomic in situ hybridization (GISH). There were 3.3 chromosomes carrying alien chromatin on average in population I and 6.5 in population II. The hybridization signals were located mainly at the terminal or sub terminal regions of the chromosomes and the sizes were notably variant among lines. Based on those results, it is concluded that the introgression of genetic material from Z. mays ssp. mexicana into cultivated maize was facilitated by tissue culture, and subsequently some excellent materials for maize breeding were created. (author)
Tribble, Leta Meole
Nowhere is the influence of genetics more extensively seen than in medicine. More precise diagnostic testing, prevention methods, and risk counseling have resulted from recent decades of genetics research, including the Human Genome Project (HGP). The expansion in genetics knowledge and related technologies will drive a major paradigm shift from diagnosis and treatment to preventive medicine. Resulting from this predicted shift are educational challenges for healthcare professionals including both physicians and nurses. The largest group of healthcare providers is registered professional nurses whose work allows a unique and holistic view of patients and families, often caring for patients throughout the life span. Nurses need to understand basic genetic concepts including the role of genes in common diseases, to identify individuals at risk through the collection of informed family histories, to provide information about genetic testing and informed consent, and to know when and how to make appropriate referrals to genetic specialists. The purpose of this study was to expand the clinical application and use of genetic principles in patient management and care. To do this, a survey of South Carolina nursing educators from twenty two nursing programs was conducted to determine the extent of genetic content in the curriculum. The second part of the study was teaching a semester course in human genetics to undergraduate nursing students, a need identified in the literature review and supported by results of the nursing programs survey. Through the use of clinical case studies, PBL activities, and "shrink wrapped" lectures, all congruent with the constructivist viewpoint of learning, student's objective post-intervention measurements indicated significant improvement in content knowledge with an effect size of 1.6 and significant improvement in their ability to analyze and draw the family history in a pedigree format. An attitudinal tool used to assess student
Genetic integrity of the human Y chromosome exposed to groundwater arsenic
Directory of Open Access Journals (Sweden)
Ali Sher
2010-08-01
Full Text Available Abstract Background Arsenic is a known human carcinogen reported to cause chromosomal deletions and genetic anomalies in cultured cells. The vast human population inhabiting the Ganges delta in West Bengal, India and Bangladesh is exposed to critical levels of arsenic present in the groundwater. The genetic and physiological mechanism of arsenic toxicity in the human body is yet to be fully established. In addition, lack of animal models has made work on this line even more challenging. Methods Human male blood samples were collected with their informed consent from 5 districts in West Bengal having groundwater arsenic level more than 50 μg/L. Isolation of genomic DNA and preparation of metaphase chromosomes was done using standard protocols. End point PCR was performed for established sequence tagged sites to ascertain the status of recombination events. Single nucleotide variants of candidate genes and amplicons were carried out using appropriate restriction enzymes. The copy number of DYZ1 array per haploid genome was calculated using real time PCR and its chromosomal localization was done by fluorescence in-situ hybridization (FISH. Results We studied effects of arsenic exposure on the human Y chromosome in males from different areas of West Bengal focusing on known recombination events (P5-P1 proximal; P5-P1 distal; gr/gr; TSPY-TSPY, b1/b3 and b2/b3, single nucleotide variants (SNVs of a few candidate Y-linked genes (DAZ, TTY4, BPY2, GOLGA2LY and the amplicons of AZFc region. Also, possible chromosomal reorganization of DYZ1 repeat arrays was analyzed. Barring a few microdeletions, no major changes were detected in blood DNA samples. SNV analysis showed a difference in some alleles. Similarly, DYZ1 arrays signals detected by FISH were found to be affected in some males. Conclusions Our Y chromosome analysis suggests that the same is protected from the effects of arsenic by some unknown mechanisms maintaining its structural and functional
[Genetically modified food--great unknown].
Cichosz, G; Wiackowski, S K
2012-08-01
Genetically modified food (GMF) creates evident threat to consumers' health. In spite of assurances of biotechnologists, DNA of transgenic plants is instable, so, synthesis of foreign, allergenic proteins is possible. Due to high trypsin inhibitor content the GMF is digested much more slowly what, alike Bt toxin presence, increases probability of alimentary canal diseases. Next threats are bound to the presence of fitoestrogens and residues of Roundup pesticide, that can diminish reproductiveness; and even lead to cancerogenic transformation through disturbance of human hormonal metabolism. In spite of food producers and distributors assurances that food made of GMF raw materials is marked, de facto consumers have no choice. Moreover, along the food law products containing less than 0.9% of GMF protein are not included into genetically modified food.
Estimating mobility using sparse data: Application to human genetic variation.
Loog, Liisa; Mirazón Lahr, Marta; Kovacevic, Mirna; Manica, Andrea; Eriksson, Anders; Thomas, Mark G
2017-11-14
Mobility is one of the most important processes shaping spatiotemporal patterns of variation in genetic, morphological, and cultural traits. However, current approaches for inferring past migration episodes in the fields of archaeology and population genetics lack either temporal resolution or formal quantification of the underlying mobility, are poorly suited to spatially and temporally sparsely sampled data, and permit only limited systematic comparison between different time periods or geographic regions. Here we present an estimator of past mobility that addresses these issues by explicitly linking trait differentiation in space and time. We demonstrate the efficacy of this estimator using spatiotemporally explicit simulations and apply it to a large set of ancient genomic data from Western Eurasia. We identify a sequence of changes in human mobility from the Late Pleistocene to the Iron Age. We find that mobility among European Holocene farmers was significantly higher than among European hunter-gatherers both pre- and postdating the Last Glacial Maximum. We also infer that this Holocene rise in mobility occurred in at least three distinct stages: the first centering on the well-known population expansion at the beginning of the Neolithic, and the second and third centering on the beginning of the Bronze Age and the late Iron Age, respectively. These findings suggest a strong link between technological change and human mobility in Holocene Western Eurasia and demonstrate the utility of this framework for exploring changes in mobility through space and time. Copyright © 2017 the Author(s). Published by PNAS.
Understanding the Basis of Auriculocondylar Syndrome: Insights From Human and Mouse Genetic Studies
Clouthier, David E.; Passos Bueno, Maria Rita; Tavares, Andre L.P.; Lyonnet, Stanislas; Amiel, Jeanne; Gordon, Christopher T.
2014-01-01
Among human birth defect syndromes, malformations affecting the face are perhaps the most striking due to cultural and psychological expectations of facial shape. One such syndrome is auriculocondylar syndrome (ACS), in which patients present with defects in ear and mandible development. Affected structures arise from cranial neural crest cells, a population of cells in the embryo that reside in the pharyngeal arches and give rise to most of the bone, cartilage and connective tissue of the face. Recent studies have found that most cases of ACS arise from defects in signaling molecules associated with the endothelin signaling pathway. Disruption of this signaling pathway in both mouse and zebrafish results in loss of identity of neural crest cells of the mandibular portion of the first pharyngeal arch and the subsequent repatterning of these cells, leading to homeosis of lower jaw structures into more maxillary-like structures. These findings illustrate the importance of endothelin signaling in normal human craniofacial development and illustrate how clinical and basic science approaches can coalesce to improve our understanding of the genetic basis of human birth syndromes. Further, understanding the genetic basis for ACS that lies outside of known endothelin signaling components may help elucidate unknown aspects critical to the establishment of neural crest cell patterning during facial morphogenesis. PMID:24123988
Egyptian Journal of Medical Human Genetics
African Journals Online (AJOL)
... and genetic counseling as well as advances in prevention and treatment of genetic disorders. ... Clinical application of genomics and next generation sequencing ... vectors and SIN channels further relieves the limitations of gene therapy ... 3 gene in Malaysian subjects with neovascular age-related macular degeneration ...
Genetic engineering: a matter that requires further refinement in Spanish secondary school textbooks
Martínez-Gracia, M. V.; Gil-Quýlez, M. J.
2003-09-01
Genetic engineering is now an integral part of many high school textbooks but little work has been done to assess whether it is being properly addressed. A checklist with 19 items was used to analyze how genetic engineering is presented in biology textbooks commonly used in Spanish high schools, including the content, its relationship with fundamental genetic principles, and how it aims to improve the genetic literacy of students. The results show that genetic engineering was normally introduced without a clear reference to the universal genetic code, protein expression or the genetic material shared by all species. In most cases it was poorly defined, without a clear explanation of all the relevant processes involved. Some procedures (such as vectors) were explained in detail without considering previous student knowledge or skills. Some books emphasized applications such as the human genome project without describing DNA sequencing. All books included possible repercussions, but in most cases only fashionable topics such as human cloning. There was an excess of information that was not always well founded and hence was unsuitable to provide a meaningful understanding of DNA technology required for citizens in the twenty-first century.
Detecting un-authorized genetically modified organisms (GMOs) and derived materials.
Holst-Jensen, Arne; Bertheau, Yves; de Loose, Marc; Grohmann, Lutz; Hamels, Sandrine; Hougs, Lotte; Morisset, Dany; Pecoraro, Sven; Pla, Maria; Van den Bulcke, Marc; Wulff, Doerte
2012-01-01
Genetically modified plants, in the following referred to as genetically modified organisms or GMOs, have been commercially grown for almost two decades. In 2010 approximately 10% of the total global crop acreage was planted with GMOs (James, 2011). More than 30 countries have been growing commercial GMOs, and many more have performed field trials. Although the majority of commercial GMOs both in terms of acreage and specific events belong to the four species: soybean, maize, cotton and rapeseed, there are another 20+ species where GMOs are commercialized or in the pipeline for commercialization. The number of GMOs cultivated in field trials or for commercial production has constantly increased during this time period. So have the number of species, the number of countries involved, the diversity of novel (added) genetic elements and the global trade. All of these factors contribute to the increasing complexity of detecting and correctly identifying GMO derived material. Many jurisdictions, including the European Union (EU), legally distinguish between authorized (and therefore legal) and un-authorized (and therefore illegal) GMOs. Information about the developments, field trials, authorizations, cultivation, trade and observations made in the official GMO control laboratories in different countries around the world is often limited, despite several attempts such as the OECD BioTrack for voluntary dissemination of data. This lack of information inevitably makes it challenging to detect and identify GMOs, especially the un-authorized GMOs. The present paper reviews the state of the art technologies and approaches in light of coverage, practicability, sensitivity and limitations. Emphasis is put on exemplifying practical detection of un-authorized GMOs. Although this paper has a European (EU) bias when examples are given, the contents have global relevance. Copyright © 2012 Elsevier Inc. All rights reserved.
Genetics of Adiposity in Large Animal Models for Human Obesity-Studies on Pigs and Dogs.
Stachowiak, M; Szczerbal, I; Switonski, M
2016-01-01
The role of domestic mammals in the development of human biomedical sciences has been widely documented. Among these model species the pig and dog are of special importance. Both are useful for studies on the etiology of human obesity. Genome sequences of both species are known and advanced genetic tools [eg, microarray SNP for genome wide association studies (GWAS), next generation sequencing (NGS), etc.] are commonly used in such studies. In the domestic pig the accumulation of adipose tissue is an important trait, which influences meat quality and fattening efficiency. Numerous quantitative trait loci (QTLs) for pig fatness traits were identified, while gene polymorphisms associated with these traits were also described. The situation is different in dog population. Generally, excessive accumulation of adipose tissue is considered, similar to humans, as a complex disease. However, research on the genetic background of canine obesity is still in its infancy. Between-breed differences in terms of adipose tissue accumulation are well known in both animal species. In this review we show recent advances of studies on adipose tissue accumulation in pigs and dogs, and their potential importance for studies on human obesity. Copyright © 2016 Elsevier Inc. All rights reserved.
International Nuclear Information System (INIS)
Welch, Danny R; Steeg, Patricia S; Rinker-Schaeffer, Carrie W
2000-01-01
The present is an overview of recent data that describes the genetic underpinnings of the suppression of cancer metastasis. Despite the explosion of new information about the genetics of cancer, only six human genes have thus far been shown to suppress metastasis functionally. Not all have been shown to be functional in breast carcinoma. Several additional genes inhibit various steps of the metastatic cascade, but do not necessarily block metastasis when tested using in vivo assays. The implications of this are discussed. Two recently discovered metastasis suppressor genes block proliferation of tumor cells at a secondary site, offering a new target for therapeutic intervention
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...
Gagnon, Kenneth B; Delpire, Eric
2013-04-15
Among the over 300 members of the solute carrier (SLC) group of integral plasma membrane transport proteins are the nine electroneutral cation-chloride cotransporters belonging to the SLC12 gene family. Seven of these transporters have been functionally described as coupling the electrically silent movement of chloride with sodium and/or potassium. Although in silico analysis has identified two additional SLC12 family members, no physiological role has been ascribed to the proteins encoded by either the SLC12A8 or the SLC12A9 genes. Evolutionary conservation of this gene family from protists to humans confirms their importance. A wealth of physiological, immunohistochemical, and biochemical studies have revealed a great deal of information regarding the importance of this gene family to human health and disease. The sequencing of the human genome has provided investigators with the capability to link several human diseases with mutations in the genes encoding these plasma membrane proteins. The availability of bacterial artificial chromosomes, recombination engineering techniques, and the mouse genome sequence has simplified the creation of targeting constructs to manipulate the expression/function of these cation-chloride cotransporters in the mouse in an attempt to recapitulate some of these human pathologies. This review will summarize the three human disorders that have been linked to the mutation/dysfunction of the Na-Cl, Na-K-2Cl, and K-Cl cotransporters (i.e., Bartter's, Gitleman's, and Andermann's syndromes), examine some additional pathologies arising from genetically modified mouse models of these cotransporters including deafness, blood pressure, hyperexcitability, and epithelial transport deficit phenotypes.
van den Wollenberg, D J M; van den Hengel, S K; Dautzenberg, I J C; Cramer, S J; Kranenburg, O; Hoeben, R C
2008-12-01
Human Orthoreovirus Type 3 Dearing is not pathogenic to humans and has been evaluated clinically as an oncolytic agent. Its transduction efficiency and the tumor cell selectivity may be enhanced by incorporating ligands for alternative receptors. However, the genetic modification of reoviruses has been difficult, and genetic targeting of reoviruses has not been reported so far. Here we describe a technique for generating genetically targeted reoviruses. The propagation of wild-type reoviruses on cells expressing a modified sigma 1-encoding segment embedded in a conventional RNA polymerase II transcript leads to substitution of the wild-type genome segment by the modified version. This technique was used for generating reoviruses that are genetically targeted to an artificial receptor expressed on U118MG cells. These cells lack the junction adhesion molecule-1 and therefore resist infection by wild-type reoviruses. The targeted reoviruses were engineered to carry the ligand for this receptor at the C terminus of the sigma 1 spike protein. This demonstrates that the C terminus of the sigma 1 protein is a suitable locale for the insertion of oligopeptide ligands and that targeting of reoviruses is feasible. The genetically targeted viruses can be propagated using the modified U118MG cells as helper cells. This technique may be applicable for the improvement of human reoviruses as oncolytic agents.
Biosafety Procedure for Safe Handling of Genetically Modified Plant Materials in Bio Design Facility
International Nuclear Information System (INIS)
Zaiton Ahmad; Shuhaimi Shamsudin; Mohamed Najli Mohamed Yasin; Affrida Abu Hassan; Mohd Zaid Hassan; Rusli Ibrahim
2015-01-01
Bio Design Facility is the specifically designed glass house for propagation, screening and analysis of high quality plant varieties developed through biotechnology or a combination of nuclear technology and biotechnology. High quality plant varieties especially genetically modified plants (GMO) require a special glass house facility for propagation and screening to isolate them from cross-pollinating with wild type varieties in surrounding ecosystem, and for carrying out evaluation of possible risks of the plants to human, animal and environment before they are proven safe for field trials or commercial release. This facility which was developed under the Ninth Malaysia Plan is classified as the Plant Containment Level 2 and is compliance with the bio safety regulations and guidance for the safe release of GMO according to Malaysian Bio safety Act 2007. Bio Design Facility is fully operational since 2010 and in 2012, it has also been certified as the glass house for post-entry quarantine by The Department of Agriculture. This paper summarizes the bio safety procedure for a safe, controlled and contained growing and evaluation of GMO in Bio Design Facility. This procedure covers the physical (containment and equipment's) and operational (including responsibility, code of practice, growing, decontamination and disposal of plant materials, emergency and contingency plan) aspects of the facility. (author)
DEFF Research Database (Denmark)
Siebner, H R; Callicott, J H; Sommer, T
2009-01-01
In recent years, an array of brain mapping techniques has been successfully employed to link individual differences in circuit function or structure in the living human brain with individual variations in the human genome. Several proof-of-principle studies provided converging evidence that brain...... imaging can establish important links between genes and behaviour. The overarching goal is to use genetically informed brain imaging to pinpoint neurobiological mechanisms that contribute to behavioural intermediate phenotypes or disease states. This special issue on "Linking Genes to Brain Function...... in Health and Disease" provides an overview over how the "imaging genetics" approach is currently applied in the various fields of systems neuroscience to reveal the genetic underpinnings of complex behaviours and brain diseases. While the rapidly emerging field of imaging genetics holds great promise...
Quantitative genetics of disease traits.
Wray, N R; Visscher, P M
2015-04-01
John James authored two key papers on the theory of risk to relatives for binary disease traits and the relationship between parameters on the observed binary scale and an unobserved scale of liability (James Annals of Human Genetics, 1971; 35: 47; Reich, James and Morris Annals of Human Genetics, 1972; 36: 163). These two papers are John James' most cited papers (198 and 328 citations, November 2014). They have been influential in human genetics and have recently gained renewed popularity because of their relevance to the estimation of quantitative genetics parameters for disease traits using SNP data. In this review, we summarize the two early papers and put them into context. We show recent extensions of the theory for ascertained case-control data and review recent applications in human genetics. © 2015 Blackwell Verlag GmbH.
Education and certification of genetic counselors.
Katsichti, L; Hadzipetros-Bardanis, M; Bartsocas, C S
1999-01-01
Genetic counseling is defined by the American Society of Human Genetics as a communication process which deals with the human problems associated with the occurrence, or risk of occurrence, of a genetic disorder in a family. The first graduate program (Master's degree) in genetic counseling started in 1969 at Sarah Lawrence College, NY, USA, while in 1979 the National Society of Genetic Counseling (NSGC) was established. Today, there are 29 programs in U.S.A. offering a Master's degree in Genetic Counseling, five programs in Canada, one in Mexico, one in England and one in S. Africa. Most of these graduate programs offer two year training, consisting of graduate courses, seminars, research and practical training. Emphasis is given in human physiology, biochemistry, clinical genetics, cytogenetics, molecular and biochemical genetics, population genetics and statistics, prenatal diagnosis, teratology and genetic counseling in relation to psychosocial and ethical issues. Certification for eligible candidates is available through the American Board of Medical Genetics (ABMG). Requirements for certification include a master's degree in human genetics, training at sites accredited by the ABMG, documentation of genetic counseling experience, evidence of continuing education and successful completion of a comprehensive ABMG certification examination. As professionals, genetic counselors should maintain expertise, should insure mechanisms for professional advancement and should always maintain the ability to approach their patients.
Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells.
Stephenson, Emma; Ogilvie, Caroline Mackie; Patel, Heema; Cornwell, Glenda; Jacquet, Laureen; Kadeva, Neli; Braude, Peter; Ilic, Dusko
2010-12-06
The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scaling-up cell expansion for that purpose. We have to be certain that the genome of the starting material is stable and normal, but the limited resolution of conventional karyotyping is unable to give us such assurance. Advanced molecular cytogenetic technologies such as array comparative genomic hybridization for identifying chromosomal imbalances, and single nucleotide polymorphism analysis for identifying ethnic background and loss of heterozygosity should be introduced as obligatory diagnostic tests for each newly derived hESC line before it is deposited in national stem cell banks. If this new quality standard becomes a requirement, as we are proposing here, it would facilitate and accelerate the banking process, since end-users would be able to select the most appropriate line for their particular application, thus improving efficiency and streamlining the route to manufacturing therapeutics. The pharmaceutical industry, which may use hESC-derived cells for drug screening, should not ignore their genomic profile as this may risk misinterpretation of results and significant waste of resources.
Genetic Modification of Human Pancreatic Progenitor Cells Through Modified mRNA.
Lu, Song; Chow, Christie C; Zhou, Junwei; Leung, Po Sing; Tsui, Stephen K; Lui, Kathy O
2016-01-01
In this chapter, we describe a highly efficient genetic modification strategy for human pancreatic progenitor cells using modified mRNA-encoding GFP and Neurogenin-3. The properties of modified mRNA offer an invaluable platform to drive protein expression, which has broad applicability in pathway regulation, directed differentiation, and lineage specification. This approach can also be used to regulate expression of other pivotal transcription factors during pancreas development and might have potential therapeutic values in regenerative medicine.
Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12
Czech Academy of Sciences Publication Activity Database
Gusareva, Elena; Havelková, Helena; Blažková, Hana; Kosařová, Marcela; Kučera, P.; Král, V.; Salyakina, D.; Mulller-Myhsok, b.; Lipoldová, Marie
2009-01-01
Roč. 61, č. 1 (2009), s. 15-25 ISSN 0093-7711 R&D Projects: GA ČR GA310/06/1745; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z50520514 Keywords : atopy * specific IgE * genetic loci * mouse-human homology * Czech population * 8q12 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.988, year: 2009
Basic concepts of medical genetics, formal genetics, Part 1
African Journals Online (AJOL)
Mohammad Saad Zaghloul Salem
2013-11-15
Nov 15, 2013 ... maps of gene loci based on information gathered, formerly, ... represented as figure or text interface data. Relevant ... The Egyptian Journal of Medical Human Genetics ... prophylactic management and genetic counseling. 17.
... Page Search Home Health Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email Facebook Twitter Genetics Home Reference provides consumer-friendly information about the effects of genetic variation on human health. Health Conditions More than 1,200 health ...
Directory of Open Access Journals (Sweden)
David G Ashbrook
2015-07-01
Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.
Directory of Open Access Journals (Sweden)
Hector Palafox-Fonseca
2013-11-01
Full Text Available Neurocysticercosis (NC is a clinically and radiologically heterogeneous parasitic disease caused by the establishment of larval Taenia solium in the human central nervous system. Host and/or parasite variations may be related to this observed heterogeneity. Genetic differences between pig and human-derived T. solium cysticerci have been reported previously. In this study, 28 cysticerci were surgically removed from 12 human NC patients, the mitochondrial gene that encodes cytochrome b was amplified from the cysticerci and genetic variations that may be related to NC heterogeneity were characterised. Nine different haplotypes (Ht, which were clustered in four haplogroups (Hg, were identified. Hg 3 and 4 exhibited a tendency to associate with age and gender, respectively. However, no significant associations were found between NC heterogeneity and the different T. solium cysticerci Ht or Hg. Parasite variants obtained from patients with similar NC clinical or radiological features were genetically closer than those found in groups of patients with a different NC profile when using the Mantel test. Overall, this study establishes the presence of genetic differences in the Cytb gene of T. solium isolated from human cysticerci and suggests that parasite variation could contribute to NC heterogeneity.
Directory of Open Access Journals (Sweden)
Liliana Rojas-Velázquez
2018-01-01
Full Text Available Blastocystis subtype 3 (ST3 is a parasitic protist found in the digestive tract of symptomatic and asymptomatic humans around the world. While this parasite exhibits a high prevalence in the human population, its true geographic distribution and global genetic diversity are still unknown. This gap in knowledge limits the understanding of the spread mechanisms, epidemiology, and impact that this parasite has on human populations. Herein, we provided new data on the geographical distribution and genetic diversity of Blastocystis ST3 from a rural human population in Mexico. To do so, we collected and targeted the SSU-rDNA region in fecal samples from this population and further compared its genetic diversity and structure with that previously observed in populations of Blastocystis ST3 from other regions of the planet. Our analyses reveled that diversity of Blastocystis ST3 showed a high haplotype diversity and genetic structure to the world level; however, they were low in the Morelos population. The haplotype network revealed a common widespread haplotype from which the others were generated recently. Finally, our results suggested a recent expansion of the diversity of Blastocystis ST3 worldwide.
Lahey, Benjamin B; Michalska, Kalina J; Liu, Chunyu; Chen, Qi; Hipwell, Alison E; Chronis-Tuscano, Andrea; Waldman, Irwin D; Decety, Jean
2012-09-06
A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor-α plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor-α gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Revolutions in energy input and material cycling in Earth history and human history
Lenton, Timothy M.; Pichler, Peter-Paul; Weisz, Helga
2016-04-01
Major revolutions in energy capture have occurred in both Earth and human history, with each transition resulting in higher energy input, altered material cycles and major consequences for the internal organization of the respective systems. In Earth history, we identify the origin of anoxygenic photosynthesis, the origin of oxygenic photosynthesis, and land colonization by eukaryotic photosynthesizers as step changes in free energy input to the biosphere. In human history we focus on the Palaeolithic use of fire, the Neolithic revolution to farming, and the Industrial revolution as step changes in free energy input to human societies. In each case we try to quantify the resulting increase in energy input, and discuss the consequences for material cycling and for biological and social organization. For most of human history, energy use by humans was but a tiny fraction of the overall energy input to the biosphere, as would be expected for any heterotrophic species. However, the industrial revolution gave humans the capacity to push energy inputs towards planetary scales and by the end of the 20th century human energy use had reached a magnitude comparable to the biosphere. By distinguishing world regions and income brackets we show the unequal distribution in energy and material use among contemporary humans. Looking ahead, a prospective sustainability revolution will require scaling up new renewable and decarbonized energy technologies and the development of much more efficient material recycling systems - thus creating a more autotrophic social metabolism. Such a transition must also anticipate a level of social organization that can implement the changes in energy input and material cycling without losing the large achievements in standard of living and individual liberation associated with industrial societies.
Exploring the relationship between lifestyles, diets and genetic adaptations in humans.
Valente, Cristina; Alvarez, Luis; Marks, Sarah J; Lopez-Parra, Ana M; Parson, Walther; Oosthuizen, Ockie; Oosthuizen, Erica; Amorim, António; Capelli, Cristian; Arroyo-Pardo, Eduardo; Gusmão, Leonor; Prata, Maria J
2015-05-28
One of the most important dietary shifts underwent by human populations began to occur in the Neolithic, during which new modes of subsistence emerged and new nutrients were introduced in diets. This change might have worked as a selective pressure over the metabolic pathways involved in the breakdown of substances extracted from food. Here we applied a candidate gene approach to investigate whether in populations with different modes of subsistence, diet-related genetic adaptations could be identified in the genes AGXT, PLRP2, MTRR, NAT2 and CYP3A5. At CYP3A5, strong signatures of positive selection were detected, though not connected to any dietary variable, but instead to an environmental factor associated with the Tropic of Cancer. Suggestive signals of adaptions that could indeed be connected with differences in dietary habits of populations were only found for PLRP2 and NAT2. Contrarily, the demographic history of human populations seemed enough to explain patterns of diversity at AGXT and MTRR, once both conformed the evolutionary expectations under selective neutrality. Accumulated evidence indicates that CYP3A5 has been under adaptive evolution during the history of human populations. PLRP2 and NAT2 also appear to have been modelled by some selective constrains, although clear support for that did not resist to a genome wide perspective. It is still necessary to clarify which were the biological mechanisms and the environmental factors involved as well as their interactions, to understand the nature and strength of the selective pressures that contributed to shape current patterns of genetic diversity at those loci.
Can mathematics explain the evolution of human language?
Witzany, Guenther
2011-09-01
Investigation into the sequence structure of the genetic code by means of an informatic approach is a real success story. The features of human language are also the object of investigation within the realm of formal language theories. They focus on the common rules of a universal grammar that lies behind all languages and determine generation of syntactic structures. This universal grammar is a depiction of material reality, i.e., the hidden logical order of things and its relations determined by natural laws. Therefore mathematics is viewed not only as an appropriate tool to investigate human language and genetic code structures through computer science-based formal language theory but is itself a depiction of material reality. This confusion between language as a scientific tool to describe observations/experiences within cognitive constructed models and formal language as a direct depiction of material reality occurs not only in current approaches but was the central focus of the philosophy of science debate in the twentieth century, with rather unexpected results. This article recalls these results and their implications for more recent mathematical approaches that also attempt to explain the evolution of human language.
Genetics of human body size and shape: body proportions and indices.
Livshits, Gregory; Roset, A; Yakovenko, K; Trofimov, S; Kobyliansky, E
2002-01-01
environmental effects were also detectable. Genetic factors substantially influence inter-individual differences in body shape and configuration in two studied samples. However, further studies are needed to clarify the extent of pleiotropy and epigenetic effects on various facets of the human physique.
PROBLEM OF GENETICALLY MODIFIED FOODS SAFETY: A TOXICOLOGIST’S VIEW
Directory of Open Access Journals (Sweden)
E. L. Levitsky
2016-02-01
Full Text Available This study aimed to analyze the published literature regarding the problem of safety of consuming food products containing genetically modified organisms. Genetically modified food products are given a brief definition, purpose and methods of their production are described, and the pro- and contra- arguments for their consumption are presented. The discussion is mostly focused on results of evaluating possible toxicity of such foods and their safety for macroorganism using traditional methods of toxicological analysis. Test results for long-term toxic effects, namely allergenicity, carcinogenicity, reproductive toxicity, and the possibility of mutagenic effects of these food products on the human body and the intestinal microflora are discussed separately. These data are based on the current understanding of the laws of the penetration and functioning of foreign genetic material outside the body, its entry and the possibility of integration into the genome during intake of foods manufactured by genetic engineering. The basic principles of the toxicological and hygienic regulation of these food products are also considered. An analysis of published experimental results allowed to draw a general conclusion about the absence of reliable scientific information indicating the presence of the toxic properties of genetically modified foods, and therefore of credible evidence of the dangers of consuming for humans and pets.
Directory of Open Access Journals (Sweden)
Rafał Patryn
2017-09-01
The presented proposition of consent with a terminal premise is to be applied eventually to legal and formal aspects of the collecting of genetic material. It is a possible solution which would clarify the issue of informed consent, and may be implemented in the regulations of the Convention as well as constitute a self-contained legislative solution to this matter. For example, Polish law in its current form, without the ratification of the Bioethical Convention, allows the collecting of material for genetic testing for determination of the risk of genetic defects in common genetic material from people who are planning to have a child.
International Nuclear Information System (INIS)
Mortensen, Holly M.; Euling, Susan Y.
2013-01-01
Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment
Evidence for genetic variation in human mate preferences for sexually dimorphic physical traits.
Directory of Open Access Journals (Sweden)
Karin J H Verweij
Full Text Available Intersexual selection has been proposed as an important force in shaping a number of morphological traits that differ between human populations and/or between the sexes. Important to these accounts is the source of mate preferences for such traits, but this has not been investigated. In a large sample of twins, we assess forced-choice, dichotomous mate preferences for height, skin colour, hair colour and length, chest hair, facial hair, and breast size. Across the traits, identical twins reported more similar preferences than nonidentical twins, suggesting genetic effects. However, the relative magnitude of estimated genetic and environmental effects differed greatly and significantly between different trait preferences, with heritability estimates ranging from zero to 57%.
Intellectual property right in genetic resources
Directory of Open Access Journals (Sweden)
Milošević Mirjana
2017-01-01
Full Text Available Plant genetic resources for food and agriculture are necessary in food production and biodiversity conservation. These are the most important natural resources, in addition to air, water and soil. Unfortunately, during the evolution large number of plant genetic resources has been lost. The biggest negative impact on loss of plant genetic resources had been made by humans through the modernization of agriculture and the creation of varieties of high genetic uniformity. FAO and its operation through international mechanisms, such as the adoption of the Convention on Biological Diversity, the first legal act which regulates all levels of biodiversity: ecosystems, species and genetic resources, biotechnology, including the Cartagena Protocol on Biosafety (regulates the transfer of genetic material across the border, contributed to the conservation of plant genetic resources for food and agriculture. In addition to the Convention on Biological Diversity, FAO has been defined by the International Treaty on Plant Genetic Resources for Food and Agriculture in more specific and detailed way, the preservation of genetic resources. The objectives of the International Treaty on Plant Genetic Resources for Food and Agriculture are the conservation and sustainable use of all plant genetic resources for food and agriculture and the fair and equitable sharing of the benefits arising out of their use. There are four basic pillars which form the substance of the Contract, Sustainable use of plant genetic resources, Farmers' Rights, the Multilateral System and the Global Information System. Two organizations, the International Biodiversity and the International Union for the Protection of New Varieties of Plants trying to solve the issues of protection of the population and old varieties as intellectual property.
Xue, Haipeng; Wu, Jianbo; Li, Shenglan; Rao, Mahendra S; Liu, Ying
2016-01-01
Genetic modification is an indispensable tool to study gene function in normal development and disease. The recent breakthrough of creating human induced pluripotent stem cells (iPSCs) by defined factors (Takahashi et al., Cell 131:861-872, 2007) provides a renewable source of patient autologous cells that not only retain identical genetic information but also give rise to many cell types of the body including neurons and glia. Meanwhile, the rapid advancement of genome modification tools such as gene targeting by homologous recombination (Capecchi, Nat Rev Genet 6:507-512, 2005) and genome editing tools such as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas (CRISPR-associated) system, TALENs (Transcription activator-like effector nucleases), and ZFNs (Zinc finger nucleases) (Wang et al., Cell 153:910-918, 2013; Mali et al., Science 339:823-826, 2013; Hwang et al., Nat Biotechnol 31:227-229, 2013; Friedland et al., Nat Methods 10(8):741-743, 2013; DiCarlo et al., Nucleic Acids Res 41:4336-4343, 2013; Cong et al., Science 339:819-823, 2013) has greatly accelerated the development of human genome manipulation at the molecular level. This chapter describes the protocols for making neural lineage reporter lines using homologous recombination and the CRISPR/Cas system-mediated genome editing, including construction of targeting vectors, guide RNAs, transfection into hPSCs, and selection and verification of successfully targeted clones. This method can be applied to various needs of hPSC genetic engineering at high efficiency and high reliability.
Genetic technologies and ethics.
Ardekani, Ali M
2009-01-01
In the past decade, the human genome has been completely sequenced and the knowledge from it has begun to influence the fields of biological and social sciences in fundamental ways. Identification of about 25000 genes in the human genome is expected to create great benefits in diagnosis and treatment of diseases in the coming years. However, Genetic technologies have also created many interesting and difficult ethical issues which can affect the human societies now and in the future. Application of genetic technologies in the areas of stem cells, cloning, gene therapy, genetic manipulation, gene selection, sex selection and preimplantation diagnosis has created a great potential for the human race to influence and change human life on earth as we know it today. Therefore, it is important for leaders of societies in the modern world to pay attention to the advances in genetic technologies and prepare themselves and those institutions under their command to face the challenges which these new technologies induce in the areas of ethics, law and social policies.
Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C
2017-09-12
Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.
Liberal or Conservative? Genetic Rhetoric, Disability, and Human Species Modification
Directory of Open Access Journals (Sweden)
Christopher F. Goodey
2016-11-01
Full Text Available A certain political rhetoric is implicit and sometimes explicit in the advocacy of human genetic modification (indicating here both the enhancement and the prevention of disability. The main claim is that it belongs to a liberal tradition. From a perspective supplied by the history and philosophy of science rather than by ethics, the content of that claim is examined to see if such a self-description is justified. The techniques are analyzed by which apparently liberal arguments get to be presented as “reasonable” in a juridical sense that draws on theories of law and rhetoric.
Lech, T
2016-05-06
Historical parchments in the form of documents, manuscripts, books, or letters, make up a large portion of cultural heritage collections. Their priceless historical value is associated with not only their content, but also the information hidden in the DNA deposited on them. Analyses of ancient DNA (aDNA) retrieved from parchments can be used in various investigations, including, but not limited to, studying their authentication, tracing the development of the culture, diplomacy, and technology, as well as obtaining information on the usage and domestication of animals. This article proposes and verifies a procedure for aDNA recovery from historical parchments and its appropriate preparation for further analyses. This study involved experimental selection of an aDNA extraction method with the highest efficiency and quality of extracted genetic material, from among the multi-stage phenol-chloroform extraction methods, and the modern, column-based techniques that use selective DNA-binding membranes. Moreover, current techniques to amplify entire genetic material were questioned, and the possibility of using mitochondrial DNA for species identification was analyzed. The usefulness of the proposed procedure was successfully confirmed in identification tests of historical parchments dating back to the 13-16th century AD.
Genetic and immunohistochemical analysis of HSPA5 in mouse and human retinas
Chintalapudi, Sumana R.; Wang, XiaoFei; Li, Huiling; Lau, Yin H. Chan; Williams, Robert W.; Jablonski, Monica M.
2016-01-01
Purpose Photoreceptor degenerative diseases are among the leading causes of vision loss. Although the causative genetic mutations are often known, mechanisms leading to photoreceptor degeneration remain poorly defined. We have previously demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is a product of the HSPA5 gene. In this study, we used systems genetic methods, statistical modeling, and immunostaining to identify and analyze candidate genes that modulate Hspa5 expression in the retina. Methods Quantitative trait locus (QTL) mapping was used to map the genomic region that regulates Hspa5 in the cross between C57BL/6J X DBA/2J mice (BXD) genetic reference panel. The stepwise refinement of candidate genes was based on expression QTL mapping, gene expression correlation analyses (direct and partial), and analysis of regional sequence variants. The subcellular localization of candidate proteins and HSPA5 in mouse and human retinas was evaluated by immunohistochemistry. Differences in the localization of extracellular HSPA5 were assessed between healthy human donor and atrophic age-related macular degeneration (AMD) donor eyes. Results In the eyes of healthy mice, extracellular HSPA5 was confined to the area around the cone photoreceptor outer segments. Mapping variation in Hspa5 mRNA expression levels in the retina revealed a statistically significant trans-acting expression QTL (eQTL) on Chromosome 2 (Chr 2) and a suggestive locus on Chr 15. Sulf2 on Chr 2 was the strongest candidate gene based on partial correlation analysis, Pearson correlation with Hspa5, expression levels in the retina, a missense variant in exon 14, and its reported function in the extracellular matrix and interphotoreceptor matrix. SULF2 is localized to the rod and cone photoreceptors in both human and mouse retinas. In human retinas with no pathology, extracellular HSPA5 was localized around many cones within the macular area. In contrast, fewer HSPA5
Benedetti, Sara; Uno, Narumi; Hoshiya, Hidetoshi; Ragazzi, Martina; Ferrari, Giulia; Kazuki, Yasuhiro; Moyle, Louise Anne; Tonlorenzi, Rossana; Lombardo, Angelo; Chaouch, Soraya; Mouly, Vincent; Moore, Marc; Popplewell, Linda; Kazuki, Kanako; Katoh, Motonobu; Naldini, Luigi; Dickson, George; Messina, Graziella; Oshimura, Mitsuo; Cossu, Giulio; Tedesco, Francesco Saverio
2018-02-01
Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation. We previously reported amelioration of the dystrophic phenotype in mice transplanted with murine muscle progenitors containing a HAC with the entire dystrophin locus (DYS-HAC). However, translation of this strategy to human muscle progenitors requires extension of their proliferative potential to withstand clonal cell expansion after HAC transfer. Here, we show that reversible cell immortalisation mediated by lentivirally delivered excisable hTERT and Bmi1 transgenes extended cell proliferation, enabling transfer of a novel DYS-HAC into DMD satellite cell-derived myoblasts and perivascular cell-derived mesoangioblasts. Genetically corrected cells maintained a stable karyotype, did not undergo tumorigenic transformation and retained their migration ability. Cells remained myogenic in vitro (spontaneously or upon MyoD induction) and engrafted murine skeletal muscle upon transplantation. Finally, we combined the aforementioned functions into a next-generation HAC capable of delivering reversible immortalisation, complete genetic correction, additional dystrophin expression, inducible differentiation and controllable cell death. This work establishes a novel platform for complex gene transfer into clinically relevant human muscle progenitors for DMD gene therapy. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.
Sex-specific genetic diversity is shaped by cultural factors in Inner Asian human populations.
Marchi, Nina; Hegay, Tatyana; Mennecier, Philippe; Georges, Myriam; Laurent, Romain; Whitten, Mark; Endicott, Philipp; Aldashev, Almaz; Dorzhu, Choduraa; Nasyrova, Firuza; Chichlo, Boris; Ségurel, Laure; Heyer, Evelyne
2017-04-01
Sex-specific genetic structures have been previously documented worldwide in humans, even though causal factors have not always clearly been identified. In this study, we investigated the impact of ethnicity, geography and social organization on the sex-specific genetic structure in Inner Asia. Furthermore, we explored the process of ethnogenesis in multiple ethnic groups. We sampled DNA in Central and Northern Asia from 39 populations of Indo-Iranian and Turkic-Mongolic native speakers. We focused on genetic data of the Y chromosome and mitochondrial DNA. First, we compared the frequencies of haplogroups to South European and East Asian populations. Then, we investigated the genetic differentiation for eight Y-STRs and the HVS1 region, and tested for the effect of geography and ethnicity on such patterns. Finally, we reconstructed the male demographic history, inferred split times and effective population sizes of different ethnic groups. Based on the haplogroup data, we observed that the Indo-Iranian- and Turkic-Mongolic-speaking populations have distinct genetic backgrounds. However, each population showed consistent mtDNA and Y chromosome haplogroups patterns. As expected in patrilocal populations, we found that the Y-STRs were more structured than the HVS1. While ethnicity strongly influenced the genetic diversity on the Y chromosome, geography better explained that of the mtDNA. Furthermore, when looking at various ethnic groups, we systematically found a genetic split time older than historical records, suggesting a cultural rather than biological process of ethnogenesis. This study highlights that, in Inner Asia, specific cultural behaviors, especially patrilineality and patrilocality, leave a detectable signature on the sex-specific genetic structure. © 2017 Wiley Periodicals, Inc.
Directory of Open Access Journals (Sweden)
Khoury Muin J
2008-04-01
Full Text Available Abstract Background Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM, a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. Results The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. Conclusion GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.
Edwards, Karen L.; Lemke, Amy A.; Trinidad, Susan B.; Lewis, Susan M.; Starks, Helene; Snapinn, Katherine W.; Griffin, Mary Quinn; Wiesner, Georgia L.; Burke, Wylie
2012-01-01
Purpose Genetic research involving human participants can pose challenging questions related to ethical and regulatory standards for research oversight. However, few empirical studies describe how genetic researchers and institutional review board (IRB) professionals conceptualize ethical issues in genetic research or where common ground might exist. Methods Parallel online surveys collected information from human genetic researchers (n = 351) and IRB professionals (n = 208) regarding their views about human participant oversight for genetic protocols. Results A range of opinions were observed within groups on most issues. In both groups, a minority thought it likely that people would be harmed by participation in genetic research or identified from coded genetic data. A majority of both groups agreed that reconsent should be required for four of the six scenarios presented. Statistically significant differences were observed between groups on some issues, with more genetic researcher respondents trusting the confidentiality of coded data, fewer expecting harms from reidentification, and fewer considering reconsent necessary in certain scenarios. Conclusions The range of views observed within and between IRB and genetic researcher groups highlights the complexity and unsettled nature of many ethical issues in genome research. Our findings also identify areas where researcher and IRB views diverge and areas of common ground. PMID:22241102
Directory of Open Access Journals (Sweden)
Jasper A. Bovenberg
2004-12-01
Full Text Available Modern biomedical research into the genetic component of common diseases calls for broad access to existing and novel collections of samples of human biological material, aka Biobanks. Groups of donors of these samples, however, increasingly claim a property right in their samples. They perceive the recognition of a personal property right in their biological material as the best means to serve two goals: to secure ongoing control over their samples after donation and to underpin their claim for a share in the proceeds that the research on their samples may yield. Given the objective of ensuring ongoing control, this property right is claimed to be inalienable. Recognition of a personal property right in ones biological material is problematic, especially where the requirement of inalienability seems at odds with the claim for a share of the profits. Yet, property rights in human biological material may be justified in a certain context, e.g. to enable subsets of patients to negotiate the terms and conditions of the research into their specific disorders. Biobanks, however, contain so many samples, which can be used for so many research purposes, that the unrestricted exercise of personal property rights by the sample donors will lead to a proliferation of rights. This proliferation is likely to deter or slow down both the creation of de novo Biobanks and the use of existing sample collections. Thus, recognising inalienable property rights in human biological material may lead to suboptimal use of these resources and create a classic anticommons property scenario. It would also undermine the current trend to simplify existing informed consent requirements which aims to facilitate broad and previously unanticipated research on de novo and existing Biobanks. In addition, the tradition of altruistic participation in research and the notion that large-scale collections of human biological material are global public goods are arguments against
DEFF Research Database (Denmark)
Tupasela, Aaro
2016-01-01
inheritance as a way to unify populations within politically and geographically bounded areas. Thus, new genetics have contributed to the development of genetic romanticisms, whereby populations (human, plant, and animal) can be delineated and mobilized through scientific and medical practices to represent...
Directory of Open Access Journals (Sweden)
Anni eRichter
2014-08-01
Full Text Available Motivational salience plays an important role in shaping human behavior, but recent studies demonstrate that human performance is not uniformly improved by motivation. Instead, action has been shown to dominate valence in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward, but the neural mechanism behind this behavioral specificity is yet unclear. In all mammals, including humans, the monoamine neurotransmitter dopamine is particularly important in the neural manifestation of appetitively motivated behavior, and the human dopamine system is subject to considerable genetic variability. The well-studied TaqIA restriction fragment length polymorphism (rs1800497 has previously been shown to affect striatal dopamine metabolism. In this study we investigated a potential effect of this genetic variation on motivated action/inhibition learning. Two independent cohorts consisting of 87 and 95 healthy participants, respectively, were tested using the previously described valenced go/no-go learning paradigm in which participants learned the reward-associated no-go condition significantly worse than all other conditions. This effect was modulated by the TaqIA polymorphism, with carriers of the A1 allele showing a diminished learning-related performance enhancement in the rewarded no-go condition compared to the A2 homozygotes. This result highlights a modulatory role for genetic variability of the dopaminergic system in individual learning differences of action-valence interaction.
Directory of Open Access Journals (Sweden)
John W. Oller
2010-03-01
Full Text Available Entropy can be defined as the antithesis of well-formed true reports that agree with each other and with the material facts accessible through the experience of one or more competent observers. The abstract convergence (strictly formal, logical agreement of true narrative representations (TNRs—ordinary valid reports of facts of experience—makes them formally more complete than fictions, errors, lies, and nonsense. A limit of absolute entropy is theoretically reached if all resemblance to a TNR is lost. As argued here, TNRs—formally defined along the lines of Peirce's exact logic—provide the necessary foundation for functional human languages and for biosemiotic systems. The theoretical concepts of pragmatic mapping—the fitting of a TNR to whatever facts it represents—and the constructive cycle of abstraction that enables a child to discover the systems underlying such mappings are introduced and illustrated from child development and then shown to apply to the human neuroarchitecture, genetics, fetal development, and our immune systems. It is also argued that biological disorders and disease conditions logically must involve corrupted (damaged, undeveloped, or otherwise incomplete representations at one or many levels.
Genetic determination of human facial morphology: links between cleft-lips and normal variation.
Boehringer, Stefan; van der Lijn, Fedde; Liu, Fan; Günther, Manuel; Sinigerova, Stella; Nowak, Stefanie; Ludwig, Kerstin U; Herberz, Ruth; Klein, Stefan; Hofman, Albert; Uitterlinden, Andre G; Niessen, Wiro J; Breteler, Monique M B; van der Lugt, Aad; Würtz, Rolf P; Nöthen, Markus M; Horsthemke, Bernhard; Wieczorek, Dagmar; Mangold, Elisabeth; Kayser, Manfred
2011-11-01
Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 × 10(-4)), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P=0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.
Genetics & sport: bioethical concerns.
Miah, Andy
2012-12-01
This paper provides an overview of the ethical issues pertaining to the use of genetic insights and techniques in sport. Initially, it considers a range of scientific findings that have stimulated debate about the ethical issues associated with genetics applied to sport. It also outlines some of the early policy responses to these discoveries from world leading sports organizations, along with knowledge about actual use of gene technologies in sport. Subsequently, it considers the challenges with distinguishing between therapeutic use and human enhancement within genetic science, which is a particularly important issue for the world of sport. Next, particular attention is given to the use of genetic information, which raises questions about the legitimacy and reliability of genetic tests, along with the potential public value of having DNA databanks to economize in health care. Finally, the ethics of gene transfer are considered, inviting questions into the values of sport and humanity. It argues that, while gene modification may seem conceptually similar to other forms of doping, the requirements upon athletes are such that new forms of enhancement become increasingly necessary to discover. Insofar as genetic science is able to create safer, more effective techniques of human modification, then it may be an appealing route through which to modify athletes to safeguard the future of elite sports as enterprises of human excellence.
Shu, Bo; Garten, Rebecca; Emery, Shannon; Balish, Amanda; Cooper, Lynn; Sessions, Wendy; Deyde, Varough; Smith, Catherine; Berman, LaShondra; Klimov, Alexander; Lindstrom, Stephen; Xu, Xiyan
2012-01-05
Swine influenza viruses (SIV) have been recognized as important pathogens for pigs and occasional human infections with swine origin influenza viruses (SOIV) have been reported. Between 1990 and 2010, a total of twenty seven human cases of SOIV infections have been identified in the United States. Six viruses isolated from 1990 to 1995 were recognized as classical SOIV (cSOIV) A(H1N1). After 1998, twenty-one SOIV recovered from human cases were characterized as triple reassortant (tr_SOIV) inheriting genes from classical swine, avian and human influenza viruses. Of those twenty-one tr_SOIV, thirteen were of A(H1N1), one of A(H1N2), and seven of A(H3N2) subtype. SOIV characterized were antigenically and genetically closely related to the subtypes of influenza viruses circulating in pigs but distinct from contemporary influenza viruses circulating in humans. The diversity of subtypes and genetic lineages in SOIV cases highlights the importance of continued surveillance at the animal-human interface. Copyright © 2011. Published by Elsevier Inc.
Teachers' Conceptions about the Genetic Determinism of Human Behaviour: A Survey in 23 Countries
Castéra, Jérémy; Clément, Pierre
2014-01-01
This work analyses the answers to a questionnaire from 8,285 in-service and pre-service teachers from 23 countries, elaborated by the Biohead-Citizen research project, to investigate teachers' conceptions related to the genetic determinism of human behaviour. A principal components analysis is used to assess the main trends in all the interviewed…
Genetic Characterization and Classification of Human and Animal Sapoviruses.
Directory of Open Access Journals (Sweden)
Tomoichiro Oka
Full Text Available Sapoviruses (SaVs are enteric caliciviruses that have been detected in multiple mammalian species, including humans, pigs, mink, dogs, sea lions, chimpanzees, and rats. They show a high level of diversity. A SaV genome commonly encodes seven nonstructural proteins (NSs, including the RNA polymerase protein NS7, and two structural proteins (VP1 and VP2. We classified human and animal SaVs into 15 genogroups (G based on available VP1 sequences, including three newly characterized genomes from this study. We sequenced the full length genomes of one new genogroup V (GV, one GVII and one GVIII porcine SaV using long range RT-PCR including newly designed forward primers located in the conserved motifs of the putative NS3, and also 5' RACE methods. We also determined the 5'- and 3'-ends of sea lion GV SaV and canine GXIII SaV. Although the complete genomic sequences of GIX-GXII, and GXV SaVs are unavailable, common features of SaV genomes include: 1 "GTG" at the 5'-end of the genome, and a short (9~14 nt 5'-untranslated region; and 2 the first five amino acids (M [A/V] S [K/R] P of the putative NS1 and the five amino acids (FEMEG surrounding the putative cleavage site between NS7 and VP1 were conserved among the chimpanzee, two of five genogroups of pig (GV and GVIII, sea lion, canine, and human SaVs. In contrast, these two amino acid motifs were clearly different in three genogroups of porcine (GIII, GVI and GVII, and bat SaVs. Our results suggest that several animal SaVs have genetic similarities to human SaVs. However, the ability of SaVs to be transmitted between humans and animals is uncertain.
Fetal magnetic resonance imaging and human genetics
International Nuclear Information System (INIS)
Hengstschlaeger, Markus
2006-01-01
The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data
Fetal magnetic resonance imaging and human genetics
Energy Technology Data Exchange (ETDEWEB)
Hengstschlaeger, Markus [Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)]. E-mail: markus.hengstschlaeger@meduniwien.ac.at
2006-02-15
The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data.
Genetics and the making of Homo sapiens.
Carroll, Sean B
2003-04-24
Understanding the genetic basis of the physical and behavioural traits that distinguish humans from other primates presents one of the great new challenges in biology. Of the millions of base-pair differences between humans and chimpanzees, which particular changes contributed to the evolution of human features after the separation of the Pan and Homo lineages 5-7 million years ago? How can we identify the 'smoking guns' of human genetic evolution from neutral ticks of the molecular evolutionary clock? The magnitude and rate of morphological evolution in hominids suggests that many independent and incremental developmental changes have occurred that, on the basis of recent findings in model animals, are expected to be polygenic and regulatory in nature. Comparative genomics, population genetics, gene-expression analyses and medical genetics have begun to make complementary inroads into the complex genetic architecture of human evolution.
Energy Technology Data Exchange (ETDEWEB)
None
1990-04-01
The Human Genome Initiative is a worldwide research effort with the goal of analyzing the structure of human DNA and determining the location of the estimated 100,000 human genes. In parallel with this effort, the DNA of a set of model organisms will be studied to provide the comparative information necessary for understanding the functioning of the human genome. The information generated by the human genome project is expected to be the source book for biomedical science in the 21st century and will by of immense benefit to the field of medicine. It will help us to understand and eventually treat many of the more than 4000 genetic diseases that affect mankind, as well as the many multifactorial diseases in which genetic predisposition plays an important role. A centrally coordinated project focused on specific objectives is believed to be the most efficient and least expensive way of obtaining this information. The basic data produced will be collected in electronic databases that will make the information readily accessible on convenient form to all who need it. This report describes the plans for the U.S. human genome project and updates those originally prepared by the Office of Technology Assessment (OTA) and the National Research Council (NRC) in 1988. In the intervening two years, improvements in technology for almost every aspect of genomics research have taken place. As a result, more specific goals can now be set for the project.
Research on metallic material defect detection based on bionic sensing of human visual properties
Zhang, Pei Jiang; Cheng, Tao
2018-05-01
Due to the fact that human visual system can quickly lock the areas of interest in complex natural environment and focus on it, this paper proposes an eye-based visual attention mechanism by simulating human visual imaging features based on human visual attention mechanism Bionic Sensing Visual Inspection Model Method to Detect Defects of Metallic Materials in the Mechanical Field. First of all, according to the biologically visually significant low-level features, the mark of defect experience marking is used as the intermediate feature of simulated visual perception. Afterwards, SVM method was used to train the advanced features of visual defects of metal material. According to the weight of each party, the biometrics detection model of metal material defect, which simulates human visual characteristics, is obtained.
Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico
Directory of Open Access Journals (Sweden)
Hilda Montero
2012-01-01
Full Text Available Human rhinovirus (HRV is a leading cause of acute respiratory infection (ARI in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not as frequently as HRV-A, which was the most frequent species. Most of the cases of the three species of HRV were in children under 2 years of age, and all species were associated with very mild and moderate ARI.
Genetic Contributions to Clinical Pain and Analgesia: Avoiding Pitfalls in Genetic Research
Kim, Hyungsuk; Clark, David; Dionne, Raymond A.
2010-01-01
Understanding the genetic basis of human variations in pain is critical to elucidating the molecular basis of pain sensitivity, variable responses to analgesic drugs, and, ultimately, to individualized treatment of pain and improved public health. With the help of recently accumulated knowledge and advanced technologies, pain researchers hope to gain insight into genetic mechanisms of pain and eventually apply this knowledge to pain treatment. Perspective We critically reviewed the published literature to examine the strength of evidence supporting genetic influences on clinical and human experimental pain. Based on this evidence and the experience of false associations that have occurred in other related disciplines, we provide recommendations for avoiding pitfalls in pain genetic research. PMID:19559388
Liao, Hanpeng; Lu, Xiaomei; Rensing, Christopher; Friman, Ville Petri; Geisen, Stefan; Chen, Zhi; Yu, Zhen; Wei, Zhong; Zhou, Shungui; Zhu, Yongguan
2018-01-01
Composting is an efficient way to convert organic waste into fertilizers. However, waste materials often contain large amounts of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) that can reduce the efficacy of antibiotic treatments when transmitted to humans. Because
Mitchell, M X
2017-05-01
In the years following World War II, and increasingly during the 1960s and 1970s, professional scientific societies developed internal sub-committees to address the social implications of their scientific expertise (Moore, Disrupting Science: Social Movements, American Scientists, and the Politics of the Military, 1945-1975. Princeton: Princeton University Press, 2008). This article explores the early years of one such committee, the American Society of Human Genetics' "Social Issues Committee," founded in 1967. Although the committee's name might suggest it was founded to increase the ASHG's public and policy engagement, exploration of the committee's early years reveals a more complicated reality. Affronted by legislators' recent unwillingness to seek the expert advice of human geneticists before adopting widespread neonatal screening programs for phenylketonuria (PKU), and feeling pressed to establish their relevance in an increasingly resource-scarce funding environment, committee members sought to increase the discipline's expert authority. Painfully aware of controversy over abortion rights and haunted by the taint of the discipline's eugenic past, however, the committee proceeded with great caution. Seeking to harness interest in and assert professional control over emerging techniques of genetic diagnosis, the committee strove to protect the society's image by relegating ethical and policy questions about their use to the individual consciences of member scientists. It was not until 1973, after the committee's modest success in organizing support for a retrospective public health study of PKU screening and following the legalization of abortion on demand, that the committee decided to take a more publicly engaged stance.
Derivation of novel genetically diverse human embryonic stem cell lines.
Stefanova, Valentina T; Grifo, James A; Hansis, Christoph
2012-06-10
Human embryonic stem cells (hESCs) have the potential to revolutionize many biomedical fields ranging from basic research to disease modeling, regenerative medicine, drug discovery, and toxicity testing. A multitude of hESC lines have been derived worldwide since the first 5 lines by Thomson et al. 13 years ago, but many of these are poorly characterized, unavailable, or do not represent desired traits, thus making them unsuitable for application purposes. In order to provide the scientific community with better options, we have derived 12 new hESC lines at New York University from discarded genetically normal and abnormal embryos using the latest techniques. We examined the genetic status of the NYUES lines in detail as well as their molecular and cellular features and DNA fingerprinting profile. Furthermore, we differentiated our hESCs into the tissues most affected by a specific condition or into clinically desired cell types. To our knowledge, a number of characteristics of our hESCs have not been previously reported, for example, mutation for alpha thalassemia X-linked mental retardation syndrome, linkage to conditions with a genetic component such as asthma or poor sperm morphology, and novel combinations of ethnic backgrounds. Importantly, all of our undifferentiated euploid female lines tested to date did not show X chromosome inactivation, believed to result in superior potency. We continue to derive new hESC lines and add them to the NIH registry and other registries. This should facilitate the use of our hESCs and lead to advancements for patient-benefitting applications.
Czech Academy of Sciences Publication Activity Database
Rodemerck, U.; Baerns, M.; Holeňa, Martin; Wolf, D.
2004-01-01
Roč. 223, - (2004), s. 168-174 ISSN 0169-4332 Institutional research plan: CEZ:AV0Z1030915 Keywords : genetic algorithm * neural network * catalytic materials Subject RIV: BA - General Mathematics Impact factor: 1.497, year: 2004
Hogan, Andrew J
2014-07-01
This paper explores evolving conceptions and depictions of the human genome among human and medical geneticists during the postwar period. Historians of science and medicine have shown significant interest in the use of informational approaches in postwar genetics, which treat the genome as an expansive digital data set composed of three billion DNA nucleotides. Since the 1950s, however, geneticists have largely interacted with the human genome at the microscopically visible level of chromosomes. Mindful of this, I examine the observational and representational approaches of postwar human and medical genetics. During the 1970s and 1980s, the genome increasingly came to be understood as, at once, a discrete part of the human anatomy and a standardised scientific object. This paper explores the role of influential medical geneticists in recasting the human genome as being a visible, tangible, and legible entity, which was highly relevant to traditional medical thinking and practice. I demonstrate how the human genome was established as an object amenable to laboratory and clinical research, and argue that the observational and representational approaches of postwar medical genetics reflect, more broadly, the interdisciplinary efforts underlying the development of contemporary biomedicine.
Genetic analysis of human parainfluenza virus type 3 obtained in Croatia, 2011-2015.
Košutić-Gulija, Tanja; Slovic, Anamarija; Ljubin-Sternak, Sunčanica; Mlinarić-Galinović, Gordana; Forčić, Dubravko
2017-04-01
This study investigated the HPIV3 circulating strains in Croatia and whether the other parts of HPIV3 genome (F gene and HN 582 nucleotides fragment) could be equally suitable for genetic and phylogenetic analysis. Clinical materials were collected in period 2011-2015 from children suffering from respiratory illnesses. In positive HPIV3 samples viral genome was partially amplified and sequenced for HN and F genes. Obtained sequences were analysed by phylogenetic analysis and genetic characterization was performed. All samples from this study belonged to subcluster C and over a short period of time, genetic lineage C3a gained prevalence over the other C genetic lineages, from 39 % in 2011 to more than 90 % in 2013 and 2014. Phylogenetic classifications of HPIV3 based on the entire HN gene, HN 582 nt fragment and entire fusion (F) gene showed identical classification results for Croatian strains and the reference strains. Molecular analysis of the F and HN glycoproteins, showed their similar nucleotide diversity (Fcds P=0.0244 and HNcds P=0.0231) and similar Ka/Ks ratios (F Ka/Ks=0.0553 and HN Ka/Ks=0.0428). Potential N-glycosylation sites, cysteine residues and antigenic sites are generally strongly conserved in HPIV3 glycoproteins from both our and the reference samples. The HPIV3 subclaster C3 (genetic lineage C3a) became the most detected circulating HPIV3 strain in Croatia. The results indicated that the HN 582 nt and the entire F gene sequences were as good for phylogenetic analysis as the entire HN gene sequence.
A Genetic Epidemiological Study of Behavioral Traits
N. Amin (Najaf)
2011-01-01
textabstractHuman behavioural genetics aims to unravel the genetic and environmental contributions to variations in human behaviour. Behaviour is a complex trait, involving multiple genes that are affected by a variety of other factors. Genetic epidemiological research of behaviour goes back to
Computational dissection of human episodic memory reveals mental process-specific genetic profiles.
Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J-F
2015-09-01
Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.
Computational dissection of human episodic memory reveals mental process-specific genetic profiles
Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G.; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J.-F.
2015-01-01
Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory. PMID:26261317
The effects of genetic polymorphism on treatment response of recombinant human growth hormone.
Chen, Shi; You, Hanxiao; Pan, Hui; Zhu, Huijuan; Yang, Hongbo; Gong, Fengying; Wang, Linjie; Jiang, Yu; Yan, Chengsheng
2017-12-06
Recombinant human growth hormone (rhGH) has been widely used in clinical treatment of growth hormone deficiency (GHD) or non GHD since 1985 and technology have achieved a great development in different long-acting formulations. Although the mathematical models for predicting the growth hormone response could help clinicians get to an individual personalized growth dose, many patients just can't reach the target height and the growth hormone responses differed.Genetic polymorphisms may play a role in the varies of individual responses in this treatment process.This article gives an overview of the genetic polymorphisms research of growth hormone in recent years, in order to give some potential suggestion and guide for the dose titration during treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Ezzelarab, Mohamed; Ezzelarab, Corin; Wilhite, Tyler; Kumar, Goutham; Hara, Hidetaka; Ayares, David; Cooper, David K C
2011-01-01
Mesenchymal stromal cells (MSC) are being investigated as immunomodulatory therapy in the field of transplantation, particularly islet transplantation. While MSC can regenerate across species barriers, the immunoregulatory influence of genetically modified pig MSC (pMSC) on the human and non-human primate T-cell responses has not been studied. Mesenchymal stromal cells from wild-type (WT), α1,3-galactosyltransferase gene knockout (GTKO) and GTKO pigs transgenic for the human complement-regulatory protein CD46 (GTKO/CD46) were isolated and tested for differentiation. Antibody binding and T-cell responses to WT and GTKO pMSC in comparison with GTKO pig aortic endothelial cells (pAEC) were investigated. The expression of swine leukocyte antigen (SLA) class II (SLA II) was tested. Costimulatory molecules CD80 and CD86 mRNA levels were measured. Human T-cell proliferation and the production of pro-inflammatory cytokines in response to GTKO and GTKO/CD46 pMSC in comparison with human MSC (hMSC) were evaluated. α1,3-galactosyltransferase gene knockout and GTKO/CD46 pMSC isolation and differentiation were achieved in vitro. Binding of human antibodies and T-cell responses were lower to GTKO than those to WT pMSC. Human and baboon (naïve and sensitized) antibody binding were significantly lower to GTKO pMSC than to GTKO pAEC. Before activation, human CD4(+) T-cell response to GTKO pMSC was significantly weaker than that to GTKO pAEC, even after pIFN-γ activation. More than 99% of GTKO/CD46 pMSC expressed hCD46. Human peripheral blood mononuclear cells and CD4(+) T-cell responses to GTKO and GTKO/CD46 pMSC were comparable with those to hMSC, and all were significantly lower than to GTKO pAEC. GTKO/CD46 pMSC downregulated human T-cell proliferation as efficiently as hMSC. The level of proinflammatory cytokines IL-2, IFN-γ, TNF-α, and sCD40L correlated with the downregulation of T-cell proliferation by all types of MSC. Genetically modified pMSC is significantly less
Difficulties in Genetics Problem Solving.
Tolman, Richard R.
1982-01-01
Examined problem-solving strategies of 30 high school students as they solved genetics problems. Proposes a new sequence of teaching genetics based on results: meiosis, sex chromosomes, sex determination, sex-linked traits, monohybrid and dihybrid crosses (humans), codominance (humans), and Mendel's pea experiments. (JN)
Genetic Diseases and Genetic Determinism Models in French Secondary School Biology Textbooks
Castera, Jeremy; Bruguiere, Catherine; Clement, Pierre
2008-01-01
The presentation of genetic diseases in French secondary school biology textbooks is analysed to determine the major conceptions taught in the field of human genetics. References to genetic diseases, and the processes by which they are explained (monogeny, polygeny, chromosomal anomaly and environmental influence) are studied in recent French…
Directory of Open Access Journals (Sweden)
V. N. Afonyushkin
2016-01-01
Full Text Available Abstract The changes in bacterial genetic material under the action of different biocidal products have been investigated. It was confirmed by PCR and genetic engineering that biocidal product Ecocid was able to remove both chromosomal and plasmid DNA, either isolated or contained within the bacterial cells. Using a disinfectant that destroys DNA on the surfaces of meat production equipment is a promising measure to prevent horizontal transfer of unwanted genetic material, such as bacterial genes associated with the resistance to antibiotics, or genes of toxin production.
Araújo, Luciano V; Malkowski, Simon; Braghetto, Kelly R; Passos-Bueno, Maria R; Zatz, Mayana; Pu, Calton; Ferreira, João E
2011-12-22
Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.
Genetic resources as initial material for developing new soft winter wheat varieties
Directory of Open Access Journals (Sweden)
В. М. Кір’ян
2016-12-01
Full Text Available Purpose. To estimate genetic resources collection of soft winter wheat plants (new collection accessions of Ustymivka Experimental Station for Plant Production and select initial material for breeding of adaptive, productive and qualitative soft winter wheat varieties. Methods. Field experiment, laboratory testing. Results. The authors pre- sented results of study of over 1000 samples of gene pool of soft winter wheat from 25 countries during 2001–2005 in Ustymivka Experimental Station for Plant Production of Plant Production Institute nd. a. V. Ya. Yuriev, NAAS of Ukraine for a complex of economic traits. More than 400 new sources with high adaptive properties were selected that combine traits of high productivity and high quality of grain, early ripening, resistance to biotic and abiotic fac- tors (the assessment of samples for 16 valuable traits is given. The selected material comes from various agro-cli- matic zones, including zones of unsustainable agriculture. Conclusions. Recommended sources of traits that have breeding value will allow to enrich high-quality assortment of wheat and considerably accelerate breeding process du- ring development of new soft winter wheat varieties.
Carter, C. O.
1973-01-01
Can genetic evolution be controlled by man in a manner which does not violate a civilized, humane, and democratic ethos? The genetics of health and illhealth and of normal variation are discussed with respect to this question. (PEB)
Directory of Open Access Journals (Sweden)
Serhiyenko Leonid Prokopovich
2011-10-01
Full Text Available The article deals with the study of correlation between blood groups system AB0 and Rh with the peculiarities of the development of human speed abilities. Complex of genetic markers is defined. It is possible to use this complex in the individual prognosis of the development of human motor abilities. With 0(I and A(II blood groups and Rh+ have a high inclination to the physical development. Better identify trends in the phenotypic expression of high-speed abilities in people with 0(I and A(II blood groups in comparison with people with the AB(IV and B(III blood group. The pattern of decreasing susceptibility to the development of high-speed abilities as follows: 0(I>A(II>B(III>AB (IV. It is established that a complex system of genetic markers AB0 and Rh blood has no gender differences.
Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens
DEFF Research Database (Denmark)
Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.
2016-01-01
The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we...... compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing ‘gold standard’ method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum....../3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox....
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 ...
Thomas, Evert; van Zonneveld, Maarten; Loo, Judy; Hodgkin, Toby; Galluzzi, Gea; van Etten, Jacob
2012-01-01
Cacao (Theobroma cacao L.) is indigenous to the Amazon basin, but is generally believed to have been domesticated in Mesoamerica for the production of chocolate beverage. However, cacao's distribution of genetic diversity in South America is also likely to reflect pre-Columbian human influences that were superimposed on natural processes of genetic differentiation. Here we present the results of a spatial analysis of the intra-specific diversity of cacao in Latin America, drawing on a dataset of 939 cacao trees genotypically characterized by means of 96 SSR markers. To assess continental diversity patterns we performed grid-based calculations of allelic richness, Shannon diversity and Nei gene diversity, and distinguished different spatially coherent genetic groups by means of cluster analysis. The highest levels of genetic diversity were observed in the Upper Amazon areas from southern Peru to the Ecuadorian Amazon and the border areas between Colombia, Peru and Brazil. On the assumption that the last glaciation (22,000-13,000 BP) had the greatest pre-human impact on the current distribution and diversity of cacao, we modeled the species' Pleistocene niche suitability and overlaid this with present-day diversity maps. The results suggest that cacao was already widely distributed in the Western Amazon before the onset of glaciation. During glaciations, cacao populations were likely to have been restricted to several refugia where they probably underwent genetic differentiation, resulting in a number of genetic clusters which are representative for, or closest related to, the original wild cacao populations. The analyses also suggested that genetic differentiation and geographical distribution of a number of other clusters seem to have been significantly affected by processes of human management and accompanying genetic bottlenecks. We discuss the implications of these results for future germplasm collection and in situ, on farm and ex situ conservation of cacao.
Human diseases with genetically altered DNA repair processes
International Nuclear Information System (INIS)
Cleaver, J.E.; Bootsma, D.; Friedberg, E.
1975-01-01
DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)
Human diseases with genetically altered DNA repair processes
International Nuclear Information System (INIS)
Cleaver, J.E.; Bootsma, D.; Friedberg, E.
1975-01-01
DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed
Random genetic drift, natural selection, and noise in human cranial evolution.
Roseman, Charles C
2016-08-01
This study assesses the extent to which relationships among groups complicate comparative studies of adaptation in recent human cranial variation and the extent to which departures from neutral additive models of evolution hinder the reconstruction of population relationships among groups using cranial morphology. Using a maximum likelihood evolutionary model fitting approach and a mixed population genomic and cranial data set, I evaluate the relative fits of several widely used models of human cranial evolution. Moreover, I compare the goodness of fit of models of cranial evolution constrained by genomic variation to test hypotheses about population specific departures from neutrality. Models from population genomics are much better fits to cranial variation than are traditional models from comparative human biology. There is not enough evolutionary information in the cranium to reconstruct much of recent human evolution but the influence of population history on cranial variation is strong enough to cause comparative studies of adaptation serious difficulties. Deviations from a model of random genetic drift along a tree-like population history show the importance of environmental effects, gene flow, and/or natural selection on human cranial variation. Moreover, there is a strong signal of the effect of natural selection or an environmental factor on a group of humans from Siberia. The evolution of the human cranium is complex and no one evolutionary process has prevailed at the expense of all others. A holistic unification of phenome, genome, and environmental context, gives us a strong point of purchase on these problems, which is unavailable to any one traditional approach alone. Am J Phys Anthropol 160:582-592, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Social justice and research using human biological material: A ...
African Journals Online (AJOL)
Social justice and research using human biological material: A response to Mahomed, Nöthling-Slabbert and Pepper. ... South African Medical Journal ... In a recent article, Mahomed, Nöthling-Slabbert and Pepper proposed that research participants should be entitled to share in the profits emanating from such research ...
Hogan, Andrew J.
2014-01-01
This paper explores evolving conceptions and depictions of the human genome among human and medical geneticists during the postwar period. Historians of science and medicine have shown significant interest in the use of informational approaches in postwar genetics, which treat the genome as an expansive digital data set composed of three billion DNA nucleotides. Since the 1950s, however, geneticists have largely interacted with the human genome at the microscopically visible level of chromosomes. Mindful of this, I examine the observational and representational approaches of postwar human and medical genetics. During the 1970s and 1980s, the genome increasingly came to be understood as, at once, a discrete part of the human anatomy and a standardised scientific object. This paper explores the role of influential medical geneticists in recasting the human genome as being a visible, tangible, and legible entity, which was highly relevant to traditional medical thinking and practice. I demonstrate how the human genome was established as an object amenable to laboratory and clinical research, and argue that the observational and representational approaches of postwar medical genetics reflect, more broadly, the interdisciplinary efforts underlying the development of contemporary biomedicine. PMID:25045177
Directory of Open Access Journals (Sweden)
Dyah Ayu Hewajuli
2012-12-01
Full Text Available Influenza A virus is a hazardous virus and harm to respiratory tract. The virus infect birds, pigs, horses, dogs, mammals and humans. Pigs are important hosts in ecology of the influenza virus because they have two receptors, namely NeuAc 2,3Gal and NeuAc 2,6Gal which make the pigs are sensitive to infection of influenza virus from birds and humans and genetic reassortment can be occurred. Classical swine influenza H1N1 viruses had been circulated in pigs in North America and other countries for 80 years. In 1998, triple reassortant H3N2 swine influenza viruses that contains genes of human influenza A virus (H3N2, swine influenza virus (H1N1 and avian influenza are reported as cause an outbreaks in pigs in North America. Furthermore, the circulation of triple reassortant H3N2 swine influenza virus resulting reassortant H1N1 swine influenza and reassortant H1N2 swine influenza viruses cause infection in humans. Humans who were infected by triple reassortant swine influenza A virus (H1N1 usually made direct contact with pigs. Although without any clinical symptoms, pigs that are infected by triple reassortant swine influenza A (H1N1 can transmit infection to the humans around them. In June 2009, WHO declared that pandemic influenza of reassortant H1N1 influenza A virus (novel H1N1 has reached phase 6. In Indonesia until 2009, there were 1005 people were infected by H1N1 influenza A and 5 of them died. Novel H1N1 and H5N1 viruses have been circulated in humans and pigs in Indonesia. H5N1 reassortant and H1N1 viruses or the seasonal flu may could arise because of genetic reassortment between avian influenza and humans influenza viruses that infect pigs together.
Directory of Open Access Journals (Sweden)
Zetterberg Henrik
2004-02-01
Full Text Available Abstract The pathogenesis of human spontaneous abortion involves a complex interaction of several genetic and environmental factors. The firm association between increased homocysteine concentration and neural tube defects (NTD has led to the hypothesis that high concentrations of homocysteine might be embryotoxic and lead to decreased fetal viability. There are several genetic polymorphisms that are associated with defects in folate- and vitamin B12-dependent homocysteine metabolism. The methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C polymorphisms cause elevated homocysteine concentration and are associated with an increased risk of NTD. Additionally, low concentration of vitamin B12 (cobalamin or transcobalamin that delivers vitamin B12 to the cells of the body leads to hyperhomocysteinemia and is associated with NTD. This effect involves the transcobalamin (TC 776C>G polymorphism. Importantly, the biochemical consequences of these polymorphisms can be modified by folate and vitamin B12 supplementation. In this review, I focus on recent studies on the role of hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human spontaneous abortion and discuss the possibility that periconceptional supplementation with folate and vitamin B12 might lower the incidence of miscarriage in women planning a pregnancy.
Density comparison of 3D printing materials and the human body
International Nuclear Information System (INIS)
Savi, M.; Silveira, L.C.; Cechinel, C.M.; Soares, F.A.P.; Potiens, M.P.A.
2017-01-01
Introduction: Phantoms are commonly used for teaching and radiation dosimetry as a simulator of the human body in order that no individual be exposed to radiation during training and research. Some are the properties that can be used as a measurement parameter in a phantom: density, energy compatibility, attenuation and scattering of the radiation, anthropomorphism, among others. 3D printing has revolutionized many areas of knowledge, including those that make use of radiations. In this context, this study aims to evaluate the density of various materials applied in 3D printing and compare found values with human body density in ICRP 110. Methods: Cubes with 2cm edges were printed on 12 materials of different compositions with internal filling of 60 %, 80% and 100%, weighed on a precision balance and measured with a caliper. Results: The densities found ranged from 0,575 g/cm³ to 2,624 g/cm³ for 60% infill, 0,686 g/cm³ to 3,091 g/cm³ for 80% and 0,794 g/cm³ to 3,572 g/cm³ for 100%. Densities related to teeth, bones, muscles, fat, among others, could be created from specific infill variations. Conclusion: All analyzed materials have the capacity to mimic the structures described in ICRP 110 when the percentage of filling are varied. However, even achieving human tissue density the materials may be not adequate for attenuation and require further experiments. (author)
Density comparison of 3D printing materials and the human body
Energy Technology Data Exchange (ETDEWEB)
Savi, M.; Silveira, L.C.; Cechinel, C.M.; Soares, F.A.P., E-mail: Matheus.savi@ifsc.edu.br [Instituo Federal de Santa Catarina (IFSC), Florianópolis (Brazil). Departamento Acadêmico de Saúde e Serviços; Potiens, M.P.A. [Instituto de Pesquisas Energéticas Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil). Lab. de Calibração de Instrumentos
2017-07-01
Introduction: Phantoms are commonly used for teaching and radiation dosimetry as a simulator of the human body in order that no individual be exposed to radiation during training and research. Some are the properties that can be used as a measurement parameter in a phantom: density, energy compatibility, attenuation and scattering of the radiation, anthropomorphism, among others. 3D printing has revolutionized many areas of knowledge, including those that make use of radiations. In this context, this study aims to evaluate the density of various materials applied in 3D printing and compare found values with human body density in ICRP 110. Methods: Cubes with 2cm edges were printed on 12 materials of different compositions with internal filling of 60 %, 80% and 100%, weighed on a precision balance and measured with a caliper. Results: The densities found ranged from 0,575 g/cm³ to 2,624 g/cm³ for 60% infill, 0,686 g/cm³ to 3,091 g/cm³ for 80% and 0,794 g/cm³ to 3,572 g/cm³ for 100%. Densities related to teeth, bones, muscles, fat, among others, could be created from specific infill variations. Conclusion: All analyzed materials have the capacity to mimic the structures described in ICRP 110 when the percentage of filling are varied. However, even achieving human tissue density the materials may be not adequate for attenuation and require further experiments. (author)
White, April F; Mazur, Marina; Sorscher, Eric J; Zinn, Kurt R; Ponnazhagan, Selvarangan
2008-12-01
Cystic fibrosis (CF) is a common genetic disease characterized by defects in the expression of the CF transmembrane conductance regulator (CFTR) gene. Gene therapy offers better hope for the treatment of CF. Adeno-associated viral (AAV) vectors are capable of stable expression with low immunogenicity. Despite their potential in CF gene therapy, gene transfer efficiency by AAV is limited because of pathophysiological barriers in these patients. Although a few AAV serotypes have shown better transduction compared with the AAV2-based vectors, gene transfer efficiency in human airway epithelium has still not reached therapeutic levels. To engineer better AAV vectors for enhanced gene delivery in human airway epithelium, we developed and characterized mutant AAV vectors by genetic capsid modification, modeling the well-characterized AAV2 serotype. We genetically incorporated putative high-affinity peptide ligands to human airway epithelium on the GH loop region of AAV2 capsid protein. Six independent mutant AAV were constructed, containing peptide ligands previously reported to bind with high affinity for known and unknown receptors on human airway epithelial cells. The vectors were tested on nonairway cells and nonpolarized and polarized human airway epithelial cells for enhanced infectivity. One of the mutant vectors, with the peptide sequence THALWHT, not only showed the highest transduction in undifferentiated human airway epithelial cells but also indicated significant transduction in polarized cells. Interestingly, this modified vector was also able to infect cells independently of the heparan sulfate proteoglycan receptor. Incorporation of this ligand on other AAV serotypes, which have shown improved gene transfer efficiency in the human airway epithelium, may enhance the application of AAV vectors in CF gene therapy.
Products used for treatment of water intended for human consumption - pyrolyzed coal material
Energy Technology Data Exchange (ETDEWEB)
NONE
2009-03-11
This European Standard is applicable to pyrolyzed coal material used for treatment of water intended for human consumption. It describes the characteristics of pyrolyzed coal material and specifies the requirements and the corresponding test methods for pyrolyzed coal material. It gives information on its use in water treatment.
Qi, Xuebin; Cui, Chaoying; Peng, Yi; Zhang, Xiaoming; Yang, Zhaohui; Zhong, Hua; Zhang, Hui; Xiang, Kun; Cao, Xiangyu; Wang, Yi; Ouzhuluobu; Basang; Ciwangsangbu; Bianba; Gonggalanzi; Wu, Tianyi; Chen, Hua; Shi, Hong; Su, Bing
2013-08-01
Tibetans live on the highest plateau in the world, their current population size is approximately 5 million, and most of them live at an altitude exceeding 3,500 m. Therefore, the Tibetan Plateau is a remarkable area for cultural and biological studies of human population history. However, the chronological profile of the Tibetan Plateau's colonization remains an unsolved question of human prehistory. To reconstruct the prehistoric colonization and demographic history of modern humans on the Tibetan Plateau, we systematically sampled 6,109 Tibetan individuals from 41 geographic populations across the entire region of the Tibetan Plateau and analyzed the phylogeographic patterns of both paternal (n = 2,354) and maternal (n = 6,109) lineages as well as genome-wide single nucleotide polymorphism markers (n = 50) in Tibetan populations. We found that there have been two distinct, major prehistoric migrations of modern humans into the Tibetan Plateau. The first migration was marked by ancient Tibetan genetic signatures dated to approximately 30,000 years ago, indicating that the initial peopling of the Tibetan Plateau by modern humans occurred during the Upper Paleolithic rather than Neolithic. We also found evidences for relatively young (only 7-10 thousand years old) shared Y chromosome and mitochondrial DNA haplotypes between Tibetans and Han Chinese, suggesting a second wave of migration during the early Neolithic. Collectively, the genetic data indicate that Tibetans have been adapted to a high altitude environment since initial colonization of the Tibetan Plateau in the early Upper Paleolithic, before the last glacial maximum, followed by a rapid population expansion that coincided with the establishment of farming and yak pastoralism on the Plateau in the early Neolithic.
Human Germline Genome Editing.
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.
Variation in human recombination rates and its genetic determinants.
Directory of Open Access Journals (Sweden)
Adi Fledel-Alon
Full Text Available Despite the fundamental role of crossing-over in the pairing and segregation of chromosomes during human meiosis, the rates and placements of events vary markedly among individuals. Characterizing this variation and identifying its determinants are essential steps in our understanding of the human recombination process and its evolution.Using three large sets of European-American pedigrees, we examined variation in five recombination phenotypes that capture distinct aspects of crossing-over patterns. We found that the mean recombination rate in males and females and the historical hotspot usage are significantly heritable and are uncorrelated with one another. We then conducted a genome-wide association study in order to identify loci that influence them. We replicated associations of RNF212 with the mean rate in males and in females as well as the association of Inversion 17q21.31 with the female mean rate. We also replicated the association of PRDM9 with historical hotspot usage, finding that it explains most of the genetic variance in this phenotype. In addition, we identified a set of new candidate regions for further validation.These findings suggest that variation at broad and fine scales is largely separable and that, beyond three known loci, there is no evidence for common variation with large effects on recombination phenotypes.
Directory of Open Access Journals (Sweden)
Vijay P Bondre
2016-01-01
Interpretation & conclusions: Our results showed that the full-length genome sequence generated from an Indian HSV-1 isolate shared close genetic relationship with the American KOS and Chinese CR38 strains which belonged to the Asian genetic lineage. Recombination analysis of Indian isolate demonstrated multiple recombination crossover points throughout the genome. This full-length genome sequence amplified from the Indian isolate would be helpful to study HSV evolution, genetic basis of differential pathogenesis, host-virus interactions and viral factors contributing towards differential clinical outcome in human infections.
van Schaik, Willem
2015-06-05
In recent decades, the emergence and spread of antibiotic resistance among bacterial pathogens has become a major threat to public health. Bacteria can acquire antibiotic resistance genes by the mobilization and transfer of resistance genes from a donor strain. The human gut contains a densely populated microbial ecosystem, termed the gut microbiota, which offers ample opportunities for the horizontal transfer of genetic material, including antibiotic resistance genes. Recent technological advances allow microbiota-wide studies into the diversity and dynamics of the antibiotic resistance genes that are harboured by the gut microbiota ('the gut resistome'). Genes conferring resistance to antibiotics are ubiquitously present among the gut microbiota of humans and most resistance genes are harboured by strictly anaerobic gut commensals. The horizontal transfer of genetic material, including antibiotic resistance genes, through conjugation and transduction is a frequent event in the gut microbiota, but mostly involves non-pathogenic gut commensals as these dominate the microbiota of healthy individuals. Resistance gene transfer from commensals to gut-dwelling opportunistic pathogens appears to be a relatively rare event but may contribute to the emergence of multi-drug resistant strains, as is illustrated by the vancomycin resistance determinants that are shared by anaerobic gut commensals and the nosocomial pathogen Enterococcus faecium.
Personalized medicine and access to genetic technologies.
den Exter, André
2010-01-01
Personalized medicine started after the Human Genome Project and is a relatively new concept that will dramatically change clinical practice. It offers clear clinical advantages by applying genetic diagnostic tests and then treating the patient with targeted medicines based on his or her genetic make-up. Its potential seems promising but there are quite a few legal concerns. One of these questions deals with the right to health care and access to genetic technologies. In this paper, the author explains the meaning of such a right to health care under international human rights law, its relevance for making genetic services eligible for public funding, how to cope with quality concerns of commercial testing, and finally, the patentability controversy and clinical access to genetic information. Apart from more traditional human rights concerns (consent, privacy, confidentiality) and genetics, States should be aware of the meaning of the equal access concept under international law and its consequences when introducing new technologies such genetic testing and services.
A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets
DEFF Research Database (Denmark)
Taneera, Jalal; Lang, Stefan; Sharma, Amitabh
2012-01-01
Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified ...
Drosophila Melanogaster as an Emerging Translational Model of Human Nephrolithiasis
Miller, Joe; Chi, Thomas; Kapahi, Pankaj; Kahn, Arnold J.; Kim, Man Su; Hirata, Taku; Romero, Michael F.; Dow, Julian A.T.; Stoller, Marshall L.
2013-01-01
Purpose The limitations imposed by human clinical studies and mammalian models of nephrolithiasis have hampered the development of effective medical treatments and preventative measures for decades. The simple but elegant Drosophila melanogaster is emerging as a powerful translational model of human disease, including nephrolithiasis and may provide important information essential to our understanding of stone formation. We present the current state of research using D. melanogaster as a model of human nephrolithiasis. Materials and Methods A comprehensive review of the English language literature was performed using PUBMED. When necessary, authoritative texts on relevant subtopics were consulted. Results The genetic composition, anatomic structure and physiologic function of Drosophila Malpighian tubules are remarkably similar to those of the human nephron. The direct effects of dietary manipulation, environmental alteration, and genetic variation on stone formation can be observed and quantified in a matter of days. Several Drosophila models of human nephrolithiasis, including genetically linked and environmentally induced stones, have been developed. A model of calcium oxalate stone formation is among the most recent fly models of human nephrolithiasis. Conclusions The ability to readily manipulate and quantify stone formation in D. melanogaster models of human nephrolithiasis presents the urologic community with a unique opportunity to increase our understanding of this enigmatic disease. PMID:23500641
Towards cultural materialism in the medical humanities: the case of blood rejuvenation
2018-01-01
This paper argues for an approach within the medical humanities that draws on the theoretical legacy of cultural materialism as a framework for reading cultural practices and their relationship to the social and economic order. It revisits the origins and development of cultural materialism in cultural studies and literary studies between the 1970s and 1990s and considers how, with adaptation, this methodology might facilitate ideological criticism focused on material formations of health, disease and the human body. I outline three key characteristics of a medicocultural materialist approach along these lines: (a) interdisciplinary work on a broad range of medical and cultural sources, including those drawn from ‘popular’ forms of culture; (b) the combination of historicist analysis with scrutiny of present-day contexts; (c) analyses that engage with political economy perspectives and/or the work of medical sociology in this area. The subsequent sections of the paper employ a medicocultural materialist approach to examine conjectural understandings of, and empirical investigations into, the capacity of transfused human blood to rejuvenate the ageing body. I trace textual faultlines that expose the structures of power which inform the movement of blood between bodies in ‘medical gothic’ fictions from the 19th-century fin de siècle, including Mary Elizabeth Braddon's ‘Good Lady Ducayne’ (1896) and Bram Stoker's Dracula (1897). I conclude with a critique of biomedical innovations in blood rejuvenation in the era of medical neoliberalism, before considering the potential applications of medicocultural materialism to other topics within the field of the medical humanities. PMID:28495908
Using Fuzzy Gaussian Inference and Genetic Programming to Classify 3D Human Motions
Khoury, Mehdi; Liu, Honghai
This research introduces and builds on the concept of Fuzzy Gaussian Inference (FGI) (Khoury and Liu in Proceedings of UKCI, 2008 and IEEE Workshop on Robotic Intelligence in Informationally Structured Space (RiiSS 2009), 2009) as a novel way to build Fuzzy Membership Functions that map to hidden Probability Distributions underlying human motions. This method is now combined with a Genetic Programming Fuzzy rule-based system in order to classify boxing moves from natural human Motion Capture data. In this experiment, FGI alone is able to recognise seven different boxing stances simultaneously with an accuracy superior to a GMM-based classifier. Results seem to indicate that adding an evolutionary Fuzzy Inference Engine on top of FGI improves the accuracy of the classifier in a consistent way.
Energy Technology Data Exchange (ETDEWEB)
Erichsen, Thomas J; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O; Mueller, Tordis M [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany); Munzel, Peter A [Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tubingen, Tubingen (Germany); Manns, Michael P [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany); Strassburg, Christian P. [Department of Gastroenterology, Hepatology and Endocrinology, Hannover, Medical School, Hannover (Germany)], E-mail: strassburg.christian@mh-hannover.de
2008-07-15
UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism.
International Nuclear Information System (INIS)
Erichsen, Thomas J.; Ehmer, Ursula; Kalthoff, Sandra; Lankisch, Tim O.; Mueller, Tordis M.; Munzel, Peter A.; Manns, Michael P.; Strassburg, Christian P.
2008-01-01
UDP glucuronosyltransferases (UGTs) play an important role for drug detoxification and toxicity. UGT function is genetically modulated by single nucleotide polymorphisms (SNPs) which lead to the expression of functionally altered protein, or altered expression levels. UGT1A4 activity includes anticonvulsants, antidepressants and environmental mutagens. In this study the induction of the human UGT1A4 gene and a potential influence of genetic variation in its promoter region were analyzed. SNPs at bp - 219 and - 163 occurred in 9% among 109 blood donors reducing UGT1A4 transcription by 40%. UGT1A4 transcription was dioxin inducible. Reporter gene experiments identified 2 xenobiotic response elements (XRE), which were functionally confirmed by mutagenesis analyses, and binding was demonstrated by electromobility shift assays. Constitutive human UGT1A4 gene expression and induction was aryl hydrocarbon receptor (AhR)-dependent, and reduced in the presence of SNPs at bp - 219 and - 163. AhR-mediated regulation of the human UGT1A4 gene by two XRE and a modulation by naturally occurring genetic variability by SNPs is demonstrated, which indicates gene-environment interaction with potential relevance for drug metabolism
International Nuclear Information System (INIS)
1991-03-01
The annual report summarizes the R+D activities of the Institute performed in the year 1990 in accordance with the Institute's R+D framework. The activities cover studies on gene repair, gene regulation, biological carcinogenesis, molecular genetics of enkaryontic genes, genetic mouse models for the study of human disease, radiotoxicology of the actinides, cellular inhalation toxicology, cellular and molecular toxicology, fractionation and speciation of actinides in vivo. There is a bibliography of publications issued by members of the Institute in 1990 and of the IGT primary reports issued in 1989 and 1990, and a list of lectures held but not available in printed form. (VHE) [de
International Nuclear Information System (INIS)
Anon.
1979-01-01
This book has as its subject the radiation dose to cells from incorporated radioactive material. According to the authors, NCRP Scientific Committee 24, the most sensitive cellular material is the genetic material of DNA and RNA in the nucleus. The biological effects of exposure are examined, since each cell line has its own sensitivities and hazards, which must be taken into account when a particular radioactive material is considered. The various kinds of radiation injury may lead to cell death, failure to mature, tumor genesis, transmutation of nuclides leading to DNA breaks, and gene mutation. Some of these injuries are no more potent when the source is external, whereas others, such as transmutation, occur only inside cells. The method for dose calculation is based upon the concern for doses coming from heterogeneously distributed beta emitters. The critical volume is the nucleus of stem cells, since injury to stem cells leads to late somatic and genetic effects. The dose at issue is that to labeled stem cells, not the whole population of stem cells. On this basis a maximum permissible intake of the material in question is calculated
Energy Technology Data Exchange (ETDEWEB)
Platonov, V.V.; Proskuryakov, V.A.; Podshibyakin, S.I.; Domogatskii, V.V.; Shvykin, A.Y.; Shavyrina, O.A.; Chilachava, K.B. [Leo Tolstoy State Pedagog University, Tula (Russian Federation)
2002-07-01
The genetic relationship of quinoline and isoquinoline compounds present in semicoking tars of Kimovsk lignites (near-Moscow fields) with the initial vegetable material is discussed. Transformation pathways of the native compounds in the course of lignite formation are suggested.
Inertial and magnetic sensing of human movement near ferromagnetic materials
Roetenberg, D.; Luinge, Hendrik J.; Veltink, Petrus H.
2003-01-01
This paper describes a Kalman filter design to estimate orientation of human body segments by fusing gyroscope, accelerometer and magnetometer signals. Ferromagnetic materials near the sensor disturb the local magnetic field and therefore the orientation estimation. The magnetic disturbance can be
Human Genetic Variation and Parkinson’s Disease
Directory of Open Access Journals (Sweden)
Sun Ju Chung
2010-05-01
Full Text Available Parkinson’s disease (PD is a chronic neurodegenerative disorder with multifactorial etiology. In the past decade, the genetic causes of monogenic forms of familial PD have been defined. However, the etiology and pathogenesis of the majority of sporadic PD cases that occur in outbred populations have yet to be clarified. The recent development of resources such as the International HapMap Project and technological advances in high-throughput genotyping have provided new basis for genetic association studies of common complex diseases, including PD. A new generation of genome-wide association studies will soon offer a potentially powerful approach for mapping causal genes and will likely change treatment and alter our perception of the genetic determinants of PD. However, the execution and analysis of such studies will require great care.
Property and Human Genetic Information
DEFF Research Database (Denmark)
Nielsen, Morten Ebbe Juul; Kongsholm, Nana Cecilie Halmsted; Schovsbo, Jens Hemmingsen
2018-01-01
Do donors (of samples from which genetic information is derived) have some sort of pre-legal (moral) or legal property right tothat information? In this paper, we address this question from both a moral philosophical and a legal point of view. We argue thatphilosophical theories about property do...
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.
Directory of Open Access Journals (Sweden)
George Maia Santos
2015-12-01
Full Text Available This article aims to demonstrate that the mandatory submission convicted of a crime committed, intentionally, with serious violence against person or heinous crime, to identify the genetic profile by DNA extraction - deoxyribonucleic acid, although by proper and painless technique is offensive to fundamental rights. For this purpose, it is part of the overall concept of the right to privacy, which is configured as a negative right or protection against unlawful state mismanagement, in order to protect a need or a basic right to the free individual self-determination. Then genetic intimacy is defined as an asset able to reveal the physical, psychological, behavioral and disease features, which, if disclosed or accessed without the consent of the accused, may generate stigmatization and discrimination of the subject involved, violating in this way, therefore, the right to privacy. In conclusion, we move towards emphasizing besides the right to privacy, compulsory provision of biological material to identify the genetic profile is offensive to fundamental rights to physical liberty or outpatient; physical integrity; to the freedom of religion or conscience; non-discrimination; the silence and non-production of evidences against himself, and in last instance, the biggest vector of all fundamental rights: the dignity of the human person.
Directory of Open Access Journals (Sweden)
Vladimir TRAJKOVSKI
1999-05-01
Full Text Available Fast development of medical genetics and it’s subdisciplines is noticed in last thirty years. Modern diagnostic methods made possible to establish human genome and its impairment. In human genetics, ethic is main principle in working. Ethic is science about biggest goodness for human or society, and its aim protecting human health.Today's conditions for leaving and science development open a wide way for ethical approaches, but also for non-ethical manipulations with human even before his conception. We must keep to attitude that without law, with our behavior will must conduct our conscience. It is best to have neutral eugenetic attitude, which allows free ethical choice of each individual, in any case, for the well being of man.
Directory of Open Access Journals (Sweden)
Shlomit Farkash-Amar
2014-03-01
Full Text Available To understand gene function, genetic analysis uses large perturbations such as gene deletion, knockdown or over-expression. Large perturbations have drawbacks: they move the cell far from its normal working point, and can thus be masked by off-target effects or compensation by other genes. Here, we offer a complementary approach, called noise genetics. We use natural cell-cell variations in protein level and localization, and correlate them to the natural variations of the phenotype of the same cells. Observing these variations is made possible by recent advances in dynamic proteomics that allow measuring proteins over time in individual living cells. Using motility of human cancer cells as a model system, and time-lapse microscopy on 566 fluorescently tagged proteins, we found 74 candidate motility genes whose level or localization strongly correlate with motility in individual cells. We recovered 30 known motility genes, and validated several novel ones by mild knockdown experiments. Noise genetics can complement standard genetics for a variety of phenotypes.
Singh, Surya; Nalwa, Hari Singh
2007-09-01
The field of nanotechnology has recently emerged as the most commercially viable technology of this century because of its wide-ranging applications in our daily lives. Man-made nanostructured materials such as fullerenes, nanoparticles, nanopowders, nanotubes, nanowires, nanorods, nanofibers, quantum dots, dendrimers, nanoclusters, nanocrystals, and nanocomposites are globally produced in large quantities due to their wide potential applications, e.g., in skincare and consumer products, healthcare, electronics, photonics, biotechnology, engineering products, pharmaceuticals, drug delivery, and agriculture. Human exposure to these nanostructured materials is inevitable, as they can enter the body through the lungs or other organs via food, drink, and medicine and affect different organs and tissues such as the brain, liver, kidney, heart, colon, spleen, bone, blood, etc., and may cause cytotoxic effects, e.g., deformation and inhibition of cell growth leading to various diseases in humans and animals. Since a very wide variety of nanostructured materials exits, their interactions with biological systems and toxicity largely depend upon their properties, such as size, concentration, solubility, chemical and biological properties, and stability. The toxicity of nanostructured materials could be reduced by chemical approaches such by surface treatment, functionalization, and composite formation. This review summarizes the sources of various nanostructured materials and their human exposure, biocompatibility in relation to potential toxicological effects, risk assessment, and safety evaluation on human and animal health as well as on the environment.
Genetics, genomes and cloning the biotechnology revolution
CERN. Geneva
1999-01-01
As this century draws to a close, spectacular advances in the fields of genomics and genetics are opening up dramatic new horizons for medicine. For much of the 20th century, genetic research has focused on rare diseases caused by mutations in a particular gene. However, more recently it has been realised that common genetic variations (polymorphisms), interacting with the environment, can influence an individual's susceptibility to diseases widely represented in our populations (e.g. mental illness and asthma), redefining the term "genetic disease". Officially starting in 1990, the Human Genome Project was a $3-billion, 15-year program to find the estimated 80,000 human genes and determine the sequence of the 3 billion DNA building blocks that underlie all of human biology and its diversity. The resulting boom in genetic information and technologies, not only from humans, but from many other organisms, means that we now have new tools to understand and treat normal and disease states. This information is bei...
Genetically Modified Organisms
Directory of Open Access Journals (Sweden)
Claro Llaguno
2001-06-01
Full Text Available Recent reports have brought to public attention concerns about Bt corn and genetically modified organisms (GMO in general. The timing, it seems, is most appropriate considering two related developments early this year: the final approval of the Cartagena Protocol on Biosafety in Montreal on January 29, 2001, and the OECD Edinburgh Conference on GM food safety last February 28- March 1, 2001. The protocol makes clear that GMOs include all living modified organisms (LMO defined as "any living organism that possesses a novel combination of genetic material obtained through the use of modern biotechnology". This includes seeds, live fish, and other organisms intentionally obtained for release to the environment. It would seem that the common understanding about GMOs as referring to farm-to-table products is perforce expanded to embrace genetically modified farm animals and aquatic resources. Being a trade agreement, the Montreal accord primarily deals with the safety issues related to the transboundary movement of LMOs around the globe. The OECD conference on the other hand, called for an international body "to address all sides of the GM debate" in response to the public outcry, particularly in Western Europe, regarding the risks the new products pose to human health and the environment. Some points of contention, which remain unresolved, include issues such as whether countries should be allowed to develop their own GM food based on their needs, and whether a global moratorium on GMOs and mandatory labeling should be enforced worldwide.
Simpson, Siobhan; Dunning, Mark D.; de Brot, Simone; Grau-Roma, Llorenc; Mongan, Nigel P.; Rutland, Catrin S.
2017-01-01
Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with th...
Global and disease-associated genetic variation in the human Fanconi anemia gene family
Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.
2014-01-01
Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population gen...
Hope, M; Bowles, J; Prociv, P; McManus, D P
1992-01-06
To test the hypothesis that the hydatid parasite infecting macropods and dingoes in Queensland is a sylvatic strain of Echinococcus granulosus, distinct from the domestic strain which produces cysts in sheep and humans. Molecular biological techniques were used to compare DNA isolated from hydatid cysts from humans, local macropods and sheep from New South Wales and the United Kingdom, as well as from adult tapeworms in dingoes. The human cysts were surgically resected from two patients seen with hydatidosis in Brisbane teaching hospitals over a one-year period. Neither patient had had previous contact with sheep farms. Macropods and dingoes were shot randomly in the localities where the patients presumably acquired their infections. Sheep liver cysts were obtained from abattoirs. Studies comprised extraction of DNA from cysts, digestion by a series of restriction endonucleases, slab gel electrophoresis. Southern blotting and then hybridisation with defined DNA probes. Polymerase chain reaction, in combination with direct DNA sequencing, was used to compare DNA from cysts and adult worms from dingoes. The restriction fragment length polymorphism (RFLP) patterns of DNA from all cysts and a defined mitochondrial DNA sequence from all sources were indistinguishable. This finding is significant as both techniques can clearly distinguish between genetically distinct, well characterised strains of E. granulosus. Hydatid cysts are prevalent in some macropod populations and adult worms are common in dingoes. Since there are relatively few sheep-rearing areas in Queensland, contact with wild animals may be the main source of human hydatid infection in this State. The strain of E. granulosus in both patients was genetically indistinguishable from that found in macropods, dingoes and sheep from New South Wales and the United Kingdom. This strongly suggests that the domestic strain of E. granulosus, or a form very close genetically, freely infects Australian wildlife, and
Martin, Michael D; Jay, Flora; Castellano, Sergi; Slatkin, Montgomery
2017-08-01
We develop and evaluate methods for inferring relatedness among individuals from low-coverage DNA sequences of their genomes, with particular emphasis on sequences obtained from fossil remains. We suggest the major factors complicating the determination of relatedness among ancient individuals are sequencing depth, the number of overlapping sites, the sequencing error rate and the presence of contamination from present-day genetic sources. We develop a theoretical model that facilitates the exploration of these factors and their relative effects, via measurement of pairwise genetic distances, without calling genotypes, and determine the power to infer relatedness under various scenarios of varying sequencing depth, present-day contamination and sequencing error. The model is validated by a simulation study as well as the analysis of aligned sequences from present-day human genomes. We then apply the method to the recently published genome sequences of ancient Europeans, developing a statistical treatment to determine confidence in assigned relatedness that is, in some cases, more precise than previously reported. As the majority of ancient specimens are from animals, this method would be applicable to investigate kinship in nonhuman remains. The developed software grups (Genetic Relatedness Using Pedigree Simulations) is implemented in Python and freely available. © 2017 John Wiley & Sons Ltd.
Human nature: neither material nor spiritually being
Directory of Open Access Journals (Sweden)
M. Alba Martínez Amorós
2017-08-01
Full Text Available The idea of «human nature» defended by Ortega y Gasset is as original as opposite to what is usually understood. We are making a mistake if the starting point is to conceive Man as one living being among others. Neither science nor philosophy, while remaining in the Eleatic tradition, can give a clear explanation. Science, because if we look at Man, as he is presented to us, it is impossible to distinguish in him materially from spiritually; his body and his psyche. Philosophy, because the concept of «human nature» is an invention of our reason, a fantasy. That nature doesn’t exist because the being of man is so strange and different from other beings that its consistency is just going to be what it never manages to be. Therefore, it is what happens, a journey, a history that is running within a circumstance. This is my life, and that of everyone.
Philosophy of race meets population genetics.
Spencer, Quayshawn
2015-08-01
In this paper, I respond to four common semantic and metaphysical objections that philosophers of race have launched at scholars who interpret recent human genetic clustering results in population genetics as evidence for biological racial realism. I call these objections 'the discreteness objection', 'the visibility objection', 'the very important objection', and 'the objectively real objection.' After motivating each objection, I show that each one stems from implausible philosophical assumptions about the relevant meaning of 'race' or the nature of biological racial realism. In order to be constructive, I end by offering some advice for how we can productively critique attempts to defend biological racial realism based on recent human genetic clustering results. I also offer a clarification of the relevant human-population genetic research. Copyright © 2015 Elsevier Ltd. All rights reserved.
Arroyo-Salgado, Bárbara; Buelvas-Montes, Yaleyvis; Villalba-Vizcaíno, Vivian; Salomón-Arzuza, Octavio
2014-01-01
Giardia intestinalis (G. Intestinalis) is a protozoan that causes diarrheal disease and malabsorption syndrome in humans and other mammals. It presents a high genetic diversity evidenced in the recognition of 7 genotypes (A-G). Genotypes A and B are commonly associated to humans and domestic animals such as dogs. The aim of this study was to conduct a preliminary genetic characterization of G. intestinalis in humans and dogs from two cities on the Caribbean coast of Colombia. Sampling areas were selected according to the highest numbers of acute diarrheal disease. Stool samples were collected from children under 7 years old, with positive medical tests for G. intestinalis. Cysts were purified by sucrose gradient and DNA samples were isolated by extraction with organic solvents. Molecular characterization was performed by amplifying the gene triose phosphate isomerase (tpi) by using a semi-nested PCR. A total of 202 samples of DNA were obtained; of these, 111 were positive in coproparasitological analysis (13 dogs and 98 children). Genotype distribution in positive samples was: 5.1% belonged to genotype A and 92.3% to genotype B. Genotype B was present in humans and animals. The most common genotype in both human and animal samples was genotype B, suggesting a zoonotic transmission cycle. Copyright © 2012 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Genetic engineered color silk: fabrication of a photonics material through a bioassisted technology.
Shimizu, Katsuhiko
2018-05-15
Silk produced by the silkworm Bombyx mori is an attractive material because of its luster, smooth and soft texture, conspicuous mechanical strength, good biocompatibility, slow biodegradation, and carbon neutral synthesis. Silkworms have been domesticated and bred for production of better quality and quantity of silk, resulting in the development of sericulture and the textile industry. Silk is generally white, so dyeing is required to obtain colored fiber. However, the dyeing process involves harsh conditions and generates a large volume of waste water, which have environmentally and economically negative impacts. Although some strains produce cocoons that contain pigments derived from the mulberry leaves that they eat, the pigments are distributed in the sericin layer and are lost during gumming. In trials for production of colored silk by feeding silkworms on diets containing dyes, only limited species of dye molecules were incorporated into the silk threads. A method for the generation of transgenic silkworm was established in conjunction with the discovery of green fluorescent protein (GFP), and silkworms carrying the GFP gene spun silk threads that formed cocoons that glowed bright green and still retained the original properties of silk. A wide range of color variation of silk threads has been obtained by replacing the GFP gene with the genes of other fluorescent proteins chosen from the fluorescent protein palette. The genetically modified silk with photonic properties can be processed to form various products including linear threads, 2D fabrics, and 3D materials. The transgenic colored silk could be economically advantageous due to addition of a new value to silk and reduction of cost for water waste, and environmentally preferable for saving water. Here, I review the literature regarding the production methods of fluorescent silk from transgenic silkworms and present examples of genetically modified color silk.
Driel, van M.A.; Cuelenaere, K.; Kemmeren, P.P.C.W.; Leunissen, J.A.M.; Brunner, H.G.
2003-01-01
To identify the gene underlying a human genetic disorder can be difficult and time-consuming. Typically, positional data delimit a chromosomal region that contains between 20 and 200 genes. The choice then lies between sequencing large numbers of genes, or setting priorities by combining positional
Feral Cat Globetrotters: genetic traces of historical human-mediated dispersal.
Koch, Katrin; Algar, Dave; Schwenk, Klaus
2016-08-01
Endemic species on islands are highly susceptible to local extinction, in particular if they are exposed to invasive species. Invasive predators, such as feral cats, have been introduced to islands around the world, causing major losses in local biodiversity. In order to control and manage invasive species successfully, information about source populations and level of gene flow is essential. Here, we investigate the origin of feral cats of Hawaiian and Australian islands to verify their European ancestry and a potential pattern of isolation by distance. We analyzed the genetic structure and diversity of feral cats from eleven islands as well as samples from Malaysia and Europe using mitochondrial DNA (ND5 and ND6 regions) and microsatellite DNA data. Our results suggest an overall European origin of Hawaiian cats with no pattern of isolation by distance between Australian, Malaysian, and Hawaiian populations. Instead, we found low levels of genetic differentiation between samples from Tasman Island, Lana'i, Kaho'olawe, Cocos (Keeling) Island, and Asia. As these populations are separated by up to 10,000 kilometers, we assume an extensive passive dispersal event along global maritime trade routes in the beginning of the 19th century, connecting Australian, Asian, and Hawaiian islands. Thus, islands populations, which are characterized by low levels of current gene flow, represent valuable sources of information on historical, human-mediated global dispersal patterns of feral cats.
Ngui, Romano; Mahdy, Mohammed A K; Chua, Kek Heng; Traub, Rebecca; Lim, Yvonne A L
2013-10-01
Ancylostoma ceylanicum is the only zoonotic hookworm species that is able to produce patent infections in humans with the majority of cases reported in South East Asia. Over the past few years, there have been an increasing number of studies investigating the prevalence of this parasitic zoonosis using molecular diagnostic tools and a single genetic locus as marker for species identification. As there can be limitations in using a single genetic locus for epidemiological studies and genetic discrimination, the complementary use of a more variable locus will provide additional evidence to support the zoonotic exchange of hookworm species between humans and animals. In the present study, the cytochrome c oxidase subunit 1 (cox 1) sequence of A. ceylanicum from positive human and animal fecal samples were determined and compared with published reference sequences. Phylogenetic analysis demonstrated that isolates of A. ceylanicum were divided into two clusters, one consisting 3 human isolates and the other comprising 19 isolates of human and animal origin from different geographical locations within Malaysia. The two groups of A. ceylanicum could be distinguished from one another through five fixed nucleotide differences at locations 891, 966, 1008, 1077 and 1083. The detection of genetically distinct groups and considerable level of genetic variation within the cox 1 sequence of A. ceylanicum might suggest potential haplotype-linked differences in zoonotic, epidemiological and pathobiological characteristics, a hypothesis that still needs further investigation. Copyright © 2013 Elsevier B.V. All rights reserved.
Liang, L.; Liao, J. S.; Gong, P.
2012-12-01
The transmission and distribution of schistomiasis, one of the most serious infectious diseases in East and Southeast Asia, tied closely to its unique intermediate snail host Oncomelania hupensis. The coevolved relationships of O. hupensis populations with its parasite Schistosoma japonisum are important in understanding the mechanism of disease spread. The genetic diversification pattern within population is supposed to influence the amount of parasite loads, and the susceptibility of snails determined the chance for human or mammals to get infected. Meanwhile, intervening environmental features had been long suggested to affect snail population dynamics and evolutionary trajectories of species. However, no comprehensive study referring to the above topics has been carried out on O.hupensis populations before. In this study, we reanalyzed published data in mainland China to evaluate whether human infection rate and genetic diversification patterns are related under natural environment. Besides that, we used an array of remotely sensed image derived environmental variables to quantify the amount of variation in population genetic structure that could be explained by those factors by landscape genetic analysis. We found that human schistosomiasis infection rate is positively correlated with intra-population genetic diversification and inter-population genetic exchange, which is contradictory with the Red Queen hypothesis. The patterns of genetic diversification are better revealed when non-Euclidean, environmentally determined distance measures or features are used in large heterogeneous landscape. The impact of stream connectivity on the snail inter-population genetic distances does not so evident unless taking wetlands into calculation, and thus control activities planned solely along river systems may be suboptimal. Climate features have a stronger impact on genetic structure of snails than topology, and precipitation seasonality dominates the highest proportion
Widespread of horizontal gene transfer in the human genome
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...
Genetic manipulation of Francisella tularensis
Directory of Open Access Journals (Sweden)
Xhavit eZogaj
2011-01-01
Full Text Available Francisella tularensis is a facultative intracellular pathogen that causes the disease tularemia. F. tularensis subsp. tularensis causes the most severe disease in humans and has been classified as a select A agent and potential bioweapon. There is currently no vaccine approved for human use, making genetic manipulation of this organism critical to unraveling the genetic basis of pathogenesis and developing countermeasures against tularemia. The development of genetic techniques applicable to F. tularensis have lagged behind those routinely used for other bacteria, primarily due to lack of research and the restricted nature of the biocontainment required for studying this pathogen. However, in recent years, genetic techniques, such as transposon mutagenesis and targeted gene disruption, have been developed, that have had a dramatic impact on our understanding of the genetic basis of F. tularensis virulence. In this review, we describe some of the methods developed for genetic manipulation of F. tularensis.
He, Qiong; Wang, Hui-Hui; Cheng, Tao; Yuan, Wei-Ping; Ma, Yu-Po; Jiang, Yong-Ping; Ren, Zhi-Hua
2017-09-27
Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay. Results The cell line bore a missense mutation in the 6 th coding exon (c.676 C>T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.
Genetic variation and effects on human eating behavior
de Krom, Mariken; Bauer, Florianne; Collier, David; Adan, R. A. H.; la Fleur, Susanne E.
2009-01-01
Feeding is a physiological process, influenced by genetic factors and the environment. In recent years, many studies have been performed to unravel the involvement of genetics in both eating behavior and its pathological forms: eating disorders and obesity. In this review, we provide a condensed
Directory of Open Access Journals (Sweden)
Anna Jurkiewicz
2014-03-01
Full Text Available Objective. The objective of the study was recognition of the opinions of adolescents completing secondary schools concerning genetically modified organisms and genetically modified food, especially the respondents’ emotional attitude towards scientific achievements in the area of live genetically modified organisms. Material and method. The study covered a group of 500 school adolescents completing secondary school at the level of maturity examination. The study was conducted by the method of a diagnostic survey using a self-designed questionnaire form. Results. Knowledge concerning the possible health effects of consumption of food containing GMO among adolescents competing secondary schools is on a relatively low level; the adolescents examined ‘know rather little’ or ‘very little know’ about this problem. In respondents’ opinions the results of reliable studies pertaining to the health effects of consumption of GMO ‘rather do not exist’. The respondents are against the cultivation of GM plants and breeding of GM animals on own farm in the future. Secondary school adolescents considered that the production of genetically modified food means primarily the enrichment of biotechnological companies, higher income for food producers, and not the elimination of hunger in the world or elimination of many diseases haunting humans.
Reproductive cloning combined with genetic modification.
Strong, C
2005-11-01
Although there is widespread opposition to reproductive cloning, some have argued that its use by infertile couples to have genetically related children would be ethically justifiable. Others have suggested that lesbian or gay couples might wish to use cloning to have genetically related children. Most of the main objections to human reproductive cloning are based on the child's lack of unique nuclear DNA. In the future, it may be possible safely to create children using cloning combined with genetic modifications, so that they have unique nuclear DNA. The genetic modifications could be aimed at giving such children genetic characteristics of both members of the couple concerned. Thus, cloning combined with genetic modification could be appealing to infertile, lesbian, or gay couples who seek genetically related children who have genetic characteristics of both members. In such scenarios, the various objections to human reproductive cloning that are based on the lack of genetic uniqueness would no longer be applicable. The author argues that it would be ethically justifiable for such couples to create children in this manner, assuming these techniques could be used safely.
Directory of Open Access Journals (Sweden)
Rami Shinnawi
2015-10-01
Full Text Available The advent of the human-induced pluripotent stem cell (hiPSC technology has transformed biomedical research, providing new tools for human disease modeling, drug development, and regenerative medicine. To fulfill its unique potential in the cardiovascular field, efficient methods should be developed for high-resolution, large-scale, long-term, and serial functional cellular phenotyping of hiPSC-derived cardiomyocytes (hiPSC-CMs. To achieve this goal, we combined the hiPSC technology with genetically encoded voltage (ArcLight and calcium (GCaMP5G fluorescent indicators. Expression of ArcLight and GCaMP5G in hiPSC-CMs permitted to reliably follow changes in transmembrane potential and intracellular calcium levels, respectively. This allowed monitoring short- and long-term changes in action-potential and calcium-handling properties and the development of arrhythmias in response to several pharmaceutical agents and in hiPSC-CMs derived from patients with different inherited arrhythmogenic syndromes. Combining genetically encoded fluorescent reporters with hiPSC-CMs may bring a unique value to the study of inherited disorders, developmental biology, and drug development and testing.
International Nuclear Information System (INIS)
Kodaira, Mieko
2002-01-01
Human minisatellite genes are composed from 0.1-30 kb with a high frequency of polymorphism. The genes exist in mammalian genomes and mice's ones are well studied after irradiation of their gonad cells by X-ray and γ-ray. Following five reports concerning the significant and/or insignificant increases of the mutation rate of the genes post A-bomb exposure, Chernobyl accident and nuclear weapons test in Semipalatinsk are reviewed and discussed on the subject number, exposed dose, problems of the control group, regions examined of loci and exposure conditions. Genetic influences of radiation examined by the author's facility are not recognized in the mutation rate (3.21% vs 4.94% in the control) of minisatellite genes in children of A-bomb survivors and their parents. The mutation rates are 4.27 vs 2.52% (positive influence) and 4.2-6.01% vs 3.5-6.34% in Chernobyl, and 4.3 (parents) and 3.8% (F 1 ) vs 2.5% (positive). Mutation of human minisatellite genes can be an important measure of genetic influences at the medical level. (K.H.)
Directory of Open Access Journals (Sweden)
Peter J. Belmont
2014-06-01
Full Text Available Effective treatment options for advanced colorectal cancer (CRC are limited, survival rates are poor and this disease continues to be a leading cause of cancer-related deaths worldwide. Despite being a highly heterogeneous disease, a large subset of individuals with sporadic CRC typically harbor relatively few established ‘driver’ lesions. Here, we describe a collection of genetically engineered mouse models (GEMMs of sporadic CRC that combine lesions frequently altered in human patients, including well-characterized tumor suppressors and activators of MAPK signaling. Primary tumors from these models were profiled, and individual GEMM tumors segregated into groups based on their genotypes. Unique allelic and genotypic expression signatures were generated from these GEMMs and applied to clinically annotated human CRC patient samples. We provide evidence that a Kras signature derived from these GEMMs is capable of distinguishing human tumors harboring KRAS mutation, and tracks with poor prognosis in two independent human patient cohorts. Furthermore, the analysis of a panel of human CRC cell lines suggests that high expression of the GEMM Kras signature correlates with sensitivity to targeted pathway inhibitors. Together, these findings implicate GEMMs as powerful preclinical tools with the capacity to recapitulate relevant human disease biology, and support the use of genetic signatures generated in these models to facilitate future drug discovery and validation efforts.
Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors
DEFF Research Database (Denmark)
von Deimling, A; Fimmers, R; Schmidt, M C
2000-01-01
Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However......, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2...... may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors....
The role of protozoa-driven selection in shaping human genetic variability.
Pozzoli, Uberto; Fumagalli, Matteo; Cagliani, Rachele; Comi, Giacomo P; Bresolin, Nereo; Clerici, Mario; Sironi, Manuela
2010-03-01
Protozoa exert a strong selective pressure in humans. The selection signatures left by these pathogens can be exploited to identify genetic modulators of infection susceptibility. We show that protozoa diversity in different geographic locations is a good measure of protozoa-driven selective pressure; protozoa diversity captured selection signatures at known malaria resistance loci and identified several selected single nucleotide polymorphisms in immune and hemolytic anemia genes. A genome-wide search enabled us to identify 5180 variants mapping to 1145 genes that are subjected to protozoa-driven selective pressure. We provide a genome-wide estimate of protozoa-driven selective pressure and identify candidate susceptibility genes for protozoa-borne diseases. Copyright 2010 Elsevier Ltd. All rights reserved.
Orth, Gérard
2010-06-01
The outcomes of infection by human papillomaviruses (HPV), both oncogenic and non oncogenic, show major interindividual variability The underlying genetic factors and mechanisms are poorly known, but their complexity is illustrated by epidermodysplasia verruciformis (EV), a rare autosomal recessive genodermatosis associated with a high risk of non melanoma skin cancer. This model disease is characterized by abnormal susceptibility to widespread betapapillomaviruses, including HPV-5, a virus associated with EV cancers. Most cases of EV are caused by a mutation that inactivates either of two related genes, EVER1 and EVER2. This inactivation likely compensates for the absence of a viral gene (E5 or E8) essential for HPV pathogenicity. Proteins E5 and E8 interfere with the interaction between EVER proteins and ZnT1, a zinc transporter EV is thus likely to represent a primary defect of intrinsic (constitutive) immunity or innate immunity to betapapillomaviruses, involving modulation of zinc homeostasis upon keratinocyte infection. It remains to be established which cellular genes are involved in intrinsic, innate or acquired immune responses to other human papillomaviruses, including oncogenic genital types.
Comparing ESC and iPSC—Based Models for Human Genetic Disorders
Directory of Open Access Journals (Sweden)
Tomer Halevy
2014-10-01
Full Text Available Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs from patients’ somatic cells, and the new technologies for genome editing of pluripotent stem cells have opened a new window of opportunities in the field of disease modeling, and enabled studying diseases that couldn’t be modeled in the past. Importantly, despite the high similarity between ESCs and iPSCs, there are several fundamental differences between these cells, which have important implications regarding disease modeling. In this review we compare ESC-based models to iPSC-based models, and highlight the advantages and disadvantages of each system. We further suggest a roadmap for how to choose the optimal strategy to model each specific disorder.
Comparing ESC and iPSC-Based Models for Human Genetic Disorders.
Halevy, Tomer; Urbach, Achia
2014-10-24
Traditionally, human disorders were studied using animal models or somatic cells taken from patients. Such studies enabled the analysis of the molecular mechanisms of numerous disorders, and led to the discovery of new treatments. Yet, these systems are limited or even irrelevant in modeling multiple genetic diseases. The isolation of human embryonic stem cells (ESCs) from diseased blastocysts, the derivation of induced pluripotent stem cells (iPSCs) from patients' somatic cells, and the new technologies for genome editing of pluripotent stem cells have opened a new window of opportunities in the field of disease modeling, and enabled studying diseases that couldn't be modeled in the past. Importantly, despite the high similarity between ESCs and iPSCs, there are several fundamental differences between these cells, which have important implications regarding disease modeling. In this review we compare ESC-based models to iPSC-based models, and highlight the advantages and disadvantages of each system. We further suggest a roadmap for how to choose the optimal strategy to model each specific disorder.
On human self-domestication, psychiatry, and eugenics
Directory of Open Access Journals (Sweden)
Brüne Martin
2007-10-01
Full Text Available Abstract The hypothesis that anatomically modern homo sapiens could have undergone changes akin to those observed in domesticated animals has been contemplated in the biological sciences for at least 150 years. The idea had already plagued philosophers such as Rousseau, who considered the civilisation of man as going against human nature, and eventually "sparked over" to the medical sciences in the late 19th and early 20th century. At that time, human "self-domestication" appealed to psychiatry, because it served as a causal explanation for the alleged degeneration of the "erbgut" (genetic material of entire populations and the presumed increase of mental disorders. Consequently, Social Darwinists emphasised preventing procreation by people of "lower genetic value" and positively selecting favourable traits in others. Both tendencies culminated in euthanasia and breeding programs ("Lebensborn" during the Nazi regime in Germany. Whether or not domestication actually plays a role in some anatomical changes since the late Pleistocene period is, from a biological standpoint, contentious, and the currently resurrected debate depends, in part, on the definitional criteria applied. However, the example of human self-domestication may illustrate that scientific ideas, especially when dealing with human biology, are prone to misuse, particularly if "is" is confused with "ought", i.e., if moral principles are deduced from biological facts. Although such naturalistic fallacies appear to be banned, modern genetics may, at least in theory, pose similar ethical problems to medicine, including psychiatry. In times during which studies into the genetics of psychiatric disorders are scientifically more valued than studies into environmental causation of disorders (which is currently the case, the prospects of genetic therapy may be tempting to alter the human genome in patients, probably at costs that no-one can foresee. In the case of "self-domestication", it
Costa, Beatriz Souza; Brito, Nathalia Bastos do Vale
2016-01-01
This article examines the United States Supreme Court’s decision that invalidated patents on human genetic material held by Myriad laboratories. It raises the question about the impact of this decision on the protection of the human genetic heritage, considering it as part of the environment, in light of bioethical considerations. The overall goal is the search for the answer to this question using, for that, the deductive-inductive logic and the bibliographic research technique. Through the...
Genetic Dissection of Behavioral Phenotypes. Lost & Found in Translation
Bruining, H.
2011-01-01
This thesis shows that the exploration of human genetic disorders and animal genetic models can bring understanding of the causes and mechanisms of common psychiatric disorders. The first part of the thesis contains studies on genetic behavioral phenotypes in boys with Klinefelter syndrome, a human
Directory of Open Access Journals (Sweden)
Nuha Elhassan
Full Text Available Human genetic variation particularly in Africa is still poorly understood. This is despite a consensus on the large African effective population size compared to populations from other continents. Based on sequencing of the mitochondrial Cytochrome C Oxidase subunit II (MT-CO2, and genome wide microsatellite data we observe evidence suggesting the effective size (Ne of humans to be larger than the current estimates, with a foci of increased genetic diversity in east Africa, and a population size of east Africans being at least 2-6 fold larger than other populations. Both phylogenetic and network analysis indicate that east Africans possess more ancestral lineages in comparison to various continental populations placing them at the root of the human evolutionary tree. Our results also affirm east Africa as the likely spot from which migration towards Asia has taken place. The study reflects the spectacular level of sequence variation within east Africans in comparison to the global sample, and appeals for further studies that may contribute towards filling the existing gaps in the database. The implication of these data to current genomic research, as well as the need to carry out defined studies of human genetic variation that includes more African populations; particularly east Africans is paramount.
Towards cultural materialism in the medical humanities: the case of blood rejuvenation.
Oakley, Catherine
2018-03-01
This paper argues for an approach within the medical humanities that draws on the theoretical legacy of cultural materialism as a framework for reading cultural practices and their relationship to the social and economic order. It revisits the origins and development of cultural materialism in cultural studies and literary studies between the 1970s and 1990s and considers how, with adaptation, this methodology might facilitate ideological criticism focused on material formations of health, disease and the human body. I outline three key characteristics of a medicocultural materialist approach along these lines: (a) interdisciplinary work on a broad range of medical and cultural sources, including those drawn from 'popular' forms of culture; (b) the combination of historicist analysis with scrutiny of present-day contexts; (c) analyses that engage with political economy perspectives and/or the work of medical sociology in this area. The subsequent sections of the paper employ a medicocultural materialist approach to examine conjectural understandings of, and empirical investigations into, the capacity of transfused human blood to rejuvenate the ageing body. I trace textual faultlines that expose the structures of power which inform the movement of blood between bodies in 'medical gothic' fictions from the 19th-century fin de siècle, including Mary Elizabeth Braddon's 'Good Lady Ducayne' (1896) and Bram Stoker's Dracula (1897). I conclude with a critique of biomedical innovations in blood rejuvenation in the era of medical neoliberalism, before considering the potential applications of medicocultural materialism to other topics within the field of the medical humanities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
The ecology of primate material culture.
Koops, Kathelijne; Visalberghi, Elisabetta; van Schaik, Carel P
2014-11-01
Tool use in extant primates may inform our understanding of the conditions that favoured the expansion of hominin technology and material culture. The 'method of exclusion' has, arguably, confirmed the presence of culture in wild animal populations by excluding ecological and genetic explanations for geographical variation in behaviour. However, this method neglects ecological influences on culture, which, ironically, may be critical for understanding technology and thus material culture. We review all the current evidence for the role of ecology in shaping material culture in three habitual tool-using non-human primates: chimpanzees, orangutans and capuchin monkeys. We show that environmental opportunity, rather than necessity, is the main driver. We argue that a better understanding of primate technology requires explicit investigation of the role of ecological conditions. We propose a model in which three sets of factors, namely environment, sociality and cognition, influence invention, transmission and retention of material culture. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
International Nuclear Information System (INIS)
Robinson, A.
1984-01-01
In recent years, practitioners of medicine have become increasingly aware of the importance of genetics in the understanding of physical and mental health and in the management of disease. The last decades have witnessed unprecedented developments in genetics that have increased our understanding of the basic processes of heredity enormously. New techniques and understanding have provided insights directly applicable to medicine. The fundamental fact of heredity may be considered the ability of living organisms to produce offspring that resemble their parents more than others. One of the basic characteristics of the human condition is the uniqueness and diversity of all individuals. This results from their genetic individuality (with the exception of identical twins) and the interaction of the genetic constitution (the genome) with the environment, which is generally unique to the individual as well. In short, the interaction of genes with the environment is what confers biologic uniqueness to all humans
Genetics for the ophthalmologist
Directory of Open Access Journals (Sweden)
Karthikeyan A Sadagopan
2012-01-01
Full Text Available The eye has played a major role in human genomics including gene therapy. It is the fourth most common organ system after integument (skin, hair and nails, nervous system, and musculoskeletal system to be involved in genetic disorders. The eye is involved in single gene disorders and those caused by multifactorial etiology. Retinoblastoma was the first human cancer gene to be cloned. Leber hereditary optic neuropathy was the first mitochondrial disorder described. X-Linked red-green color deficiency was the first X-linked disorder described. The eye, unlike any other body organ, allows directly visualization of genetic phenomena such as skewed X-inactivation in the fundus of a female carrier of ocular albinism. Basic concepts of genetics and their application to clinical ophthalmological practice are important not only in making a precise diagnosis and appropriate referral, but also in management and genetic counseling.
Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach
Directory of Open Access Journals (Sweden)
Swati Chaturvedi
2016-01-01
Full Text Available One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches.
Peng, Yanling; Lachmuth, Susanne; Gallegos, Silvia C; Kessler, Michael; Ramsay, Paul M; Renison, Daniel; Suarez, Ricardo; Hensen, Isabell
2015-10-01
Biological responses to climatic change usually leave imprints on the genetic diversity and structure of plants. Information on the current genetic diversity and structure of dominant tree species has facilitated our general understanding of phylogeographical patterns. Using amplified fragment length polymorphism (AFLPs), we compared genetic diversity and structure of 384 adults of P. tarapacana with those of 384 seedlings across 32 forest sites spanning a latitudinal gradient of 600 km occurring between 4100 m and 5000 m a.s.l. in Polylepis tarapacana (Rosaceae), one of the world's highest treeline species endemic to the central Andes. Moderate to high levels of genetic diversity and low genetic differentiation were detected in both adults and seedlings, with levels of genetic diversity and differentiation being almost identical. Four slightly genetically divergent clusters were identified that accorded to differing geographical regions. Genetic diversity decreased from south to north and with increasing precipitation for adults and seedlings, but there was no relationship to elevation. Our study shows that, unlike the case for other Andean treeline species, recent human activities have not affected the genetic structure of P. tarapacana, possibly because its inhospitable habitat is unsuitable for agriculture. The current genetic pattern of P. tarapacana points to a historically more widespread distribution at lower altitudes, which allowed considerable gene flow possibly during the glacial periods of the Pleistocene epoch, and also suggests that the northern Argentinean Andes may have served as a refugium for historical populations. © 2015 Botanical Society of America.
Genetic secrets: Protecting privacy and confidentiality in the genetic era
Energy Technology Data Exchange (ETDEWEB)
Rothstein, M.A. [ed.
1998-07-01
Few developments are likely to affect human beings more profoundly in the long run than the discoveries resulting from advances in modern genetics. Although the developments in genetic technology promise to provide many additional benefits, their application to genetic screening poses ethical, social, and legal questions, many of which are rooted in issues of privacy and confidentiality. The ethical, practical, and legal ramifications of these and related questions are explored in depth. The broad range of topics includes: the privacy and confidentiality of genetic information; the challenges to privacy and confidentiality that may be projected to result from the emerging genetic technologies; the role of informed consent in protecting the confidentiality of genetic information in the clinical setting; the potential uses of genetic information by third parties; the implications of changes in the health care delivery system for privacy and confidentiality; relevant national and international developments in public policies, professional standards, and laws; recommendations; and the identification of research needs.
Environmental chemical mutagens and genetic risks: Lessons from radiation genetics
International Nuclear Information System (INIS)
Sankaranarayanan, K.
1996-01-01
The last three decades have witnessed substantial progress in the development and use of a variety of in vitro and in vivo assay systems for the testing of environmental chemicals which may pose a mutagenic hazard to humans. This is also true of basic studies in chemical mutagenesis on mechanisms, DNA repair, molecular dosimetry, structure-activity relationships, etc. However, the field of quantitative evaluation of genetic risks of environmental chemicals to humans is still in it infancy. This commentary addresses the question of how our experience in estimating genetic risks of exposure to ionizing radiation can be helpful in similar endeavors with environmental chemical mutagens. 24 refs., 3 tabs
Shaw, Alison; Hurst, Jane A
2008-08-01
Misconceptions about basic genetic concepts and inheritance patterns may be widespread in the general population. This paper investigates understandings of genetics, illness causality and inheritance among British Pakistanis referred to a UK genetics clinic. During participant observation of genetics clinic consultations and semi-structured interviews in Urdu or English in respondents' homes, we identified an array of environmental, behavioral and spiritual understandings of the causes of medical and intellectual problems. Misconceptions about the location of genetic information in the body and of genetic mechanisms of inheritance were common, reflected the range of everyday theories observed for White British patients and included the belief that a child receives more genetic material from the father than the mother. Despite some participants' conversational use of genetic terminology, some patients had assimilated genetic information in ways that conflict with genetic theory with potentially serious clinical consequences. Additionally, skepticism of genetic theories of illness reflected a rejection of a dominant discourse of genetic risk that stigmatizes cousin marriages. Patients referred to genetics clinics may not easily surrender their lay or personal theories about the causes of their own or their child's condition and their understandings of genetic risk. Genetic counselors may need to identify, work with and at times challenge patients' understandings of illness causality and inheritance.
The status of human and material resources used in teaching ...
African Journals Online (AJOL)
The study explored the status of human and material resources used in teaching biology in public schools in Ilorin. A descriptive survey method was adopted. All senior school students in Ilorin constituted the population, out of which 20 secondary schools were randomly selected. A checklist tagged Inventory of Resources ...
Cell and genetic predictors of human blastocyst hatching success in assisted reproduction.
Syrkasheva, Anastasiya G; Dolgushina, Nataliya V; Romanov, Andrey Yu; Burmenskaya, Olga V; Makarova, Nataliya P; Ibragimova, Espet O; Kalinina, Elena A; Sukhikh, Gennady T
2017-10-01
The aim was to identify cell and genetic predictors of human blastocyst hatching success in assisted reproduction programmes via a prospective case-control study. Blastocysts, donated by couples in assisted reproduction programmes were used. Hatching success assessment was performed after 144-146 h post-fertilization. The mRNA expression levels of cathepsin V (CTSV), GATA-binding protein 3 (GATA3) and human chorionic gonadotropin beta subunit 3, 5, 7 and 8 (CGB) genes were detected by quantitative real-time polymerase chain reaction. The odds ratio (OR) of hatching due to zona pellucida (ZP) thickness, oocyte and sperm quality, embryo quality and mRNA expression of CTSV, GATA3 and CGB genes in blastocysts was determined. From 62 blastocysts included in the study, 47 (75.8%) were unable to hatch spontaneously. The ZP thickening, and oocyte and sperm quality did not affect human blastocyst ability to hatch, except the combination of cytoplasmic and extracytoplasmic oocyte dysmorphisms (OR = 1.25; 95% confidence interval = 1.08, 1.45). Hatching-capable blastocysts had higher Gardner scale grade and mRNA expression of CTSV, GATA3 and CGB genes than hatching-incapable blastocysts. The human blastocyst hatching success depends on the blastocyst Gardner grade, but not on ZP and gamete quality. Blastocyst development was regulated by CTSV, GATA3 and CGB gene expression.
Crabbe, M James C
2003-08-29
We have developed a new simple method for transport, storage, and analysis of genetic material from the corals Agaricia agaricites, Dendrogyra cylindrica, Eusmilia ancora, Meandrina meandrites, Montastrea annularis, Porites astreoides, Porites furcata, Porites porites, and Siderastrea siderea at room temperature. All species yielded sufficient DNA from a single FTA card (19 microg-43 ng) for subsequent PCR amplification of both coral and zooxanthellar DNA. The D1 and D2 variable region of the large subunit rRNA gene (LSUrDNA) was amplified from the DNA of P. furcata and S. siderea by PCR. Electrophoresis yielded two major DNA bands: an 800-base pair (bp) DNA, which represented the coral ribosomal RNA (rRNA) gene, and a 600-bp DNA, which represented the zooxanthellar srRNA gene. Extraction of DNA from the bands yielded between 290 microg total DNA (S. siderea coral DNA) and 9 microg total DNA (P. furcata zooxanthellar DNA). The ability to transport and store genetic material from scleractinian corals without resort to laboratory facilities in the field allows for the molecular study of a far wider range and variety of coral sites than have been studied to date.
Large-Scale Culture and Genetic Modification of Human Natural Killer Cells for Cellular Therapy.
Lapteva, Natalia; Parihar, Robin; Rollins, Lisa A; Gee, Adrian P; Rooney, Cliona M
2016-01-01
Recent advances in methods for the ex vivo expansion of human natural killer (NK) cells have facilitated the use of these powerful immune cells in clinical protocols. Further, the ability to genetically modify primary human NK cells following rapid expansion allows targeting and enhancement of their immune function. We have successfully adapted an expansion method for primary NK cells from peripheral blood mononuclear cells or from apheresis products in gas permeable rapid expansion devices (G-Rexes). Here, we describe an optimized protocol for rapid and robust NK cell expansion as well as a method for highly efficient retroviral transduction of these ex vivo expanded cells. These methodologies are good manufacturing practice (GMP) compliant and could be used for clinical-grade product manufacturing.
Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia
Khaw, Yam Sim; Chan, Yoke Fun; Jafar, Faizatul Lela; Othman, Norlijah; Chee, Hui Yee
2016-01-01
Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5′ and 3′ non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63–81% among themselves and 63–96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection. PMID:27199901
Human genetics of infectious diseases: Unique insights into immunological redundancy.
Casanova, Jean-Laurent; Abel, Laurent
2018-04-01
For almost any given human-tropic virus, bacterium, fungus, or parasite, the clinical outcome of primary infection is enormously variable, ranging from asymptomatic to lethal infection. This variability has long been thought to be largely determined by the germline genetics of the human host, and this is increasingly being demonstrated to be the case. The number and diversity of known inborn errors of immunity is continually increasing, and we focus here on autosomal and X-linked recessive traits underlying complete deficiencies of the encoded protein. Schematically, four types of infectious phenotype have been observed in individuals with such deficiencies, each providing information about the redundancy of the corresponding human gene, in terms of host defense in natural conditions. The lack of a protein can confer vulnerability to a broad range of microbes in most, if not all patients, through the disruption of a key immunological component. In such cases, the gene concerned is of low redundancy. However, the lack of a protein may also confer vulnerability to a narrow range of microbes, sometimes a single pathogen, and not necessarily in all patients. In such cases, the gene concerned is highly redundant. Conversely, the deficiency may be apparently neutral, conferring no detectable predisposition to infection in any individual. In such cases, the gene concerned is completely redundant. Finally, the lack of a protein may, paradoxically, be advantageous to the host, conferring resistance to one or more infections. In such cases, the gene is considered to display beneficial redundancy. These findings reflect the current state of evolution of humans and microbes, and should not be considered predictive of redundancy, or of a lack of redundancy, in the distant future. Nevertheless, these observations are of potential interest to present-day biologists testing immunological hypotheses experimentally and physicians managing patients with immunological or infectious
Amberger, Joanna S; Bocchini, Carol A; Schiettecatte, François; Scott, Alan F; Hamosh, Ada
2015-01-01
Online Mendelian Inheritance in Man, OMIM(®), is a comprehensive, authoritative and timely research resource of curated descriptions of human genes and phenotypes and the relationships between them. The new official website for OMIM, OMIM.org (http://omim.org), was launched in January 2011. OMIM is based on the published peer-reviewed biomedical literature and is used by overlapping and diverse communities of clinicians, molecular biologists and genome scientists, as well as by students and teachers of these disciplines. Genes and phenotypes are described in separate entries and are given unique, stable six-digit identifiers (MIM numbers). OMIM entries have a structured free-text format that provides the flexibility necessary to describe the complex and nuanced relationships between genes and genetic phenotypes in an efficient manner. OMIM also has a derivative table of genes and genetic phenotypes, the Morbid Map. OMIM.org has enhanced search capabilities such as genome coordinate searching and thesaurus-enhanced search term options. Phenotypic series have been created to facilitate viewing genetic heterogeneity of phenotypes. Clinical synopsis features are enhanced with UMLS, Human Phenotype Ontology and Elements of Morphology terms and image links. All OMIM data are available for FTP download and through an API. MIMmatch is a novel outreach feature to disseminate updates and encourage collaboration. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Laws and regulations associated with ownership of human biological material in South Africa
Directory of Open Access Journals (Sweden)
Kishen Mahesh
2015-05-01
Full Text Available Ownership with regard to human biological material (HBM is addressed to some extent within South African law, specifically in chapter eight of the National Health Act (NHA and its associated regulations. However, members of the legal fraternity struggle to conceptualise ownership of such materials without objectifying a person or people and risking reducing such individuals to a state of property. This then infers a reduction in human dignity by rendering one-self or parts of that same self as a commodity. The complexity of the issue raises much debate both legally as well as ethically.Â
Selected Readings in Genetic Engineering
Mertens, Thomas R.; Robinson, Sandra K.
1973-01-01
Describes different sources of readings for understanding issues and concepts of genetic engineering. Broad categories of reading materials are: concerns about genetic engineering; its background; procedures; and social, ethical and legal issues. References are listed. (PS)