WorldWideScience

Sample records for rapid genetic disease

  1. Partial status epilepticus - rapid genetic diagnosis of Alpers' disease.

    LENUS (Irish Health Repository)

    McCoy, Bláthnaid

    2011-11-01

    We describe four children with a devastating encephalopathy characterised by refractory focal seizures and variable liver dysfunction. We describe their electroencephalographic, radiologic, genetic and pathologic findings. The correct diagnosis was established by rapid gene sequencing. POLG1 based Alpers\\' disease should be considered in any child presenting with partial status epilepticus.

  2. Sustaining global agriculture through rapid detection and deployment of genetic resistance to deadly crop diseases.

    Science.gov (United States)

    Periyannan, Sambasivam

    2017-12-04

    Contents I. II. III. IV. V. VI. VII. VIII. References SUMMARY: Genetically encoded resistance is a major component of crop disease management. Historically, gene loci conferring resistance to pathogens have been identified through classical genetic methods. In recent years, accelerated gene cloning strategies have become available through advances in sequencing, gene capture and strategies for reducing genome complexity. Here, I describe these approaches with key emphasis on the isolation of resistance genes to the cereal crop diseases that are an ongoing threat to global food security. Rapid gene isolation enables their efficient deployment through marker-assisted selection and transgenic technology. Together with innovations in genome editing and progress in pathogen virulence studies, this creates further opportunities to engineer long-lasting resistance. These approaches will speed progress towards a future of farming using fewer pesticides. © 2017 Commonwealth of Australia. New Phytologist © 2017 New Phytologist Trust.

  3. Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders

    DEFF Research Database (Denmark)

    Gregersen, N; Bross, P; Jørgensen, M M

    2000-01-01

    Many disease-causing point mutations do not seriously compromise synthesis of the affected polypeptide but rather exert their effects by impairing subsequent protein folding or stability of the folded protein. This often results in rapid degradation of the affected protein. The concepts...

  4. Defective folding and rapid degradation of mutant proteins is a common disease mechanism in genetic disorders

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter; Jørgensen, Malene Munk

    2000-01-01

    Many disease-causing point mutations do not seriously compromise synthesis of the affected polypeptides but rather exert their effects by impairing subsequent protein folding or stability of the folded protein. This often results in rapid degradation of the affected protein. The concepts...

  5. Genetic testing in cardiovascular diseases

    NARCIS (Netherlands)

    Hofman, Nynke; van Langen, Irene; Wilde, Arthur A. M.

    2010-01-01

    To review the current state and different aspects, including the yield, of genetic counseling and genetic testing in inherited heart disease. The number of counselees is growing rapidly all over the world, and the first studies about patients' perspectives and follow-up have been published. Progress

  6. Genetics of Parkinson's disease

    National Research Council Canada - National Science Library

    Klein, Christine; Westenberger, Ana

    2012-01-01

    Fifteen years of genetic research in Parkinson's disease (PD) have led to the identification of several monogenic forms of the disorder and of numerous genetic risk factors increasing the risk to develop PD...

  7. Genetics of complex diseases

    DEFF Research Database (Denmark)

    Mellerup, Erling; Møller, Gert Lykke; Koefoed, Pernille

    2012-01-01

    A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis...... for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close...

  8. Genetics of eye diseases

    Indian Academy of Sciences (India)

    vasculature, to the transparent refractive structures of lens and cornea—varied yet complementary in their roles. The field of ophthalmic genetics encompasses this diversity not only in the location and manifestation of different eye diseases but also in the spectrum of genetic causation. While the field has been predom-.

  9. Genetics, Disease Prevention and Treatment

    Science.gov (United States)

    ... can be found at USA.gov . FAQ About Genetics, Disease Prevention and Treatment Enter Search Term(s): Español ... for the genetic terms used on this page Genetics, Disease Prevention and Treatment Overview How can learning ...

  10. Genetics of gallstone disease.

    Directory of Open Access Journals (Sweden)

    Mittal B

    2002-04-01

    Full Text Available Gallstone disease is a complex disorder where both environmental and genetic factors contribute towards susceptibility to the disease. Epidemiological and family studies suggest a strong genetic component in the causation of this disease. Several genetically derived phenotypes in the population are responsible for variations in lipoprotein types, which in turn affect the amount of cholesterol available in the gall bladder. The genetic polymorphisms in various genes for apo E, apo B, apo A1, LDL receptor, cholesteryl ester transfer and LDL receptor-associated protein have been implicated in gallstone formation. However, presently available information on genetic differences is not able to account for a large number of gallstone patients. The molecular studies in the animal models have not only confirmed the present paradigm of gallstone formation but also helped in identification of novel genes in humans, which might play an important role in pathogenesis of the disease. Precise understanding of such genes and their molecular mechanisms may provide the basis of new targets for rational drug designs and dietary interventions.

  11. Genome-wide association and prediction analysis in African cassava (Manihot esculenta) reveals the genetic architecture of resistance to cassava mosaic disease and prospects for rapid genetic improvement

    Science.gov (United States)

    Cassava (Manihot esculenta) is a crucial, under-researched crop feeding millions worldwide, especially in Africa. Cassava mosaic disease (CMD) has plagued production in Africa for over a century. Bi-parental mapping studies suggest primarily a single major gene mediates resistance. To be certain and...

  12. Genetics of Proteasome Diseases

    Directory of Open Access Journals (Sweden)

    Aldrin V. Gomes

    2013-01-01

    Full Text Available The proteasome is a large, multiple subunit complex that is capable of degrading most intracellular proteins. Polymorphisms in proteasome subunits are associated with cardiovascular diseases, diabetes, neurological diseases, and cancer. One polymorphism in the proteasome gene PSMA6 (−8C/G is associated with three different diseases: type 2 diabetes, myocardial infarction, and coronary artery disease. One type of proteasome, the immunoproteasome, which contains inducible catalytic subunits, is adapted to generate peptides for antigen presentation. It has recently been shown that mutations and polymorphisms in the immunoproteasome catalytic subunit PSMB8 are associated with several inflammatory and autoinflammatory diseases including Nakajo-Nishimura syndrome, CANDLE syndrome, and intestinal M. tuberculosis infection. This comprehensive review describes the disease-related polymorphisms in proteasome genes associated with human diseases and the physiological modulation of proteasome function by these polymorphisms. Given the large number of subunits and the central importance of the proteasome in human physiology as well as the fast pace of detection of proteasome polymorphisms associated with human diseases, it is likely that other polymorphisms in proteasome genes associated with diseases will be detected in the near future. While disease-associated polymorphisms are now readily discovered, the challenge will be to use this genetic information for clinical benefit.

  13. Genetics of Alzheimer disease.

    Science.gov (United States)

    Rao, A T; Degnan, A J; Levy, L M

    2014-03-01

    Alzheimer disease prevails as a major cause of disability in the elderly population and ranks as the most common form of dementia that affects 1 of 8 individuals older than 65 years of age. Most AD cases are late in onset and are probably influenced by both genetic and environmental factors. Apart from age, the risk factors include family history; brain injury, both traumatic and vascular; and metabolic diseases, such as diabetes, hypercholesterolemia, and obesity. Based on twin studies, inheritance plays a role in approximately 80% of cases (familial and sporadic).

  14. Rapid Genetic Analysis in Congenital Hyperinsulinism

    DEFF Research Database (Denmark)

    Christesen, Henrik Thybo; Brusgaard, Klaus; Alm, Jan

    2007-01-01

    with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation....... One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. CONCLUSION: A rapid analysis...

  15. Genetics of Dyslipidemia and Ischemic Heart Disease.

    Science.gov (United States)

    Sharma, Kavita; Baliga, Ragavendra R

    2017-05-01

    Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

  16. Genetics of rapid eye movement sleep in humans

    OpenAIRE

    Adamczyk, M.; Ambrosius, U; Lietzenmaier, S; Wichniak, A; Holsboer, F.; Friess, E

    2015-01-01

    The trait-like nature of electroencephalogram (EEG) is well established. Furthermore, EEG of wake and non-rapid eye movement (non-REM) sleep has been shown to be highly heritable. However, the genetic effects on REM sleep EEG microstructure are as yet unknown. REM sleep is of special interest since animal and human data suggest a connection between REM sleep abnormalities and the pathophysiology of psychiatric and neurological diseases. Here we report the results of a study in monozygotic (MZ...

  17. A more rapid approach to systematically assessing published associations of genetic polymorphisms and disease risk: type 2 diabetes as a test case

    Directory of Open Access Journals (Sweden)

    Cho AH

    2012-01-01

    top 10 "most-studied" genes were selected for focused searches and final inclusion/exclusion determinations. To demonstrate the ability to efficiently update this two-step search for additions to the literature, an update of the second-step search was conducted 9 months later. Abstracted data were sorted based on study design, risk model, and specific SNPs. Meta-analyses were performed for individual SNPs, with separate analyses done for case-control and prospective studies, and were compared with the results of more recent genome-wide association studies.Results: The first-step search found 1116 articles covering 108 different genes. The top ten "most-studied" genes were: ABCC8 (or SUR1, ACE, CAPN10, KCNJ11 (or Kir6.2, HNF1 alpha, HNF4 alpha, IL-6, PGC-1 alpha, PPAR gamma 2, and TCF7L2. The second-step search found a total of 658 articles, yielding 124 articles for initial data abstraction and analysis. We also demonstrated the ability to update this search as newer studies appeared, using the same method almost a year later to find an additional 107 articles (77 were ultimately excluded, bringing the number of included studies to 154. From these studies, data on 90 different DNA variants within the ten genes were abstracted. Simultaneous meta-analyses found that higher-risk alleles for SNPs rs7903146 and rs12255372 in TCF7L2, rs1801282 in PPAR gamma 2, rs5219 in KCNJ11, rs3792267 in CAPN10, rs2144909 in HNF4 alpha, and rs1800795 in IL-6 appeared to be associated with increased type 2 diabetes risk. These findings were generally highly concordant with the results of traditional literature-based meta-analyses performed for individual genes.Conclusions: The methodology described in this manuscript represents a reasonable approach to more rapidly identifying and evaluating frequently studied genetic-risk markers for diseases such as type 2 diabetes. Comparison with results of traditional meta-analyses suggests that these gains in efficiency do not necessarily come at

  18. Genetic epidemiology of Scheuermann's disease

    DEFF Research Database (Denmark)

    Damborg, Frank; Engell, Vilhelm; Nielsen, Jan

    2011-01-01

    The genetic/environmental etiology of Scheuermann's disease is unclear. We estimated the heritability of the disease using an etiological model adjusted for sex and time of diagnosis, and examined whether the prevalence of Scheuermann's disease was constant over time.......The genetic/environmental etiology of Scheuermann's disease is unclear. We estimated the heritability of the disease using an etiological model adjusted for sex and time of diagnosis, and examined whether the prevalence of Scheuermann's disease was constant over time....

  19. Genetics in Ophthalmology II–Anterior Segment Diseases

    Directory of Open Access Journals (Sweden)

    Canan Aslı Utine

    2012-10-01

    Full Text Available Genetic diseases are congenital or acquired hereditary diseases that result from structural/functional disorders of the human genome. Today, the genetic factors that play a role in many diseases are being highlighted with the rapid progress in the field of genetics science. It becomes increasingly important that physicians from all disciplines have knowledge about the basic principles of genetics, patterns of inheritance, etc., so that they can follow the new developments. In genetic eye diseases, ophthalmologists should know the basic clinical and recently rapidly developing genetic characteristics of these diseases in order to properly approach the diagnosis and treatment and to provide genetic counseling. In this paper, anterior segment eye diseases of genetic origin are reviewed, and aniridia, anterior segment dysgenesis, glaucoma, corneal dystrophies, cataract, ectopia lentis, myopia, and other refractive errors are covered. (Turk J Ophthalmol 2012; 42: 378-85

  20. Genetics in chronic venous disease.

    Science.gov (United States)

    Grant, Yasmin; Onida, Sarah; Davies, Alun

    2017-02-01

    Chronic venous disease is highly prevalent in the Western world, with varicose veins being the most common form of clinical manifestation. With recent developments in sequencing technology, clinicians and geneticists alike are embarking on a journey to identify and unravel the genetic candidates of chronic venous disease. There is now currently substantial evidence to suggest the presence of genetic influences in the aetiology and pathology of venous disease. Despite this, the precise nature and profile of the genes involved in chronic venous disease remain a poorly understood entity. Moreover, it is strikingly apparent that the majority of venous genetic studies conducted over the past decade do not adhere to fundamental research principles. The emergence of high-throughput genotyping platforms permits a more systematic search for inherited components of venous disease. Pursuing a genome-wide frontier has the potential to reveal novel critical metabolic pathways and explain the genetic susceptibility of chronic venous disease. An expedited knowledge of the genetic factors in the aetiology of venous disease may translate into better prevention or treatment, which would benefit patients suffering from its clinical sequelae. Researchers should be urged to foster collaborative links and design a genome-wide case-control association study as an international consortium to provide a statistically robust paradigm in the field of chronic venous disease genetics. This will carry promise for clinically relevant progress and represent a first step towards better understanding of the genetics of chronic venous disease aetiology.

  1. Genetics of Complex Airway Disease

    OpenAIRE

    Cookson, William O. C.; Moffatt, Miriam F.

    2011-01-01

    The past 3 years have seen highly significant genetic effects identified for a wide variety of common complex diseases, including the airway disorders of asthma and chronic obstructive pulmonary disease. It appears that only a portion of the genetically mediated susceptibility to complex diseases has been identified, and there is much left to be discovered. This review briefly describes the results of the genome-wide association studies of asthma and gives an overview of the parallel and incr...

  2. Genetic testing in cardiovascular diseases.

    Science.gov (United States)

    Arndt, Anne-Karin; MacRae, Calum A

    2014-05-01

    The review is designed to outline the major developments in genetic testing in the cardiovascular arena in the past year or so. This is an exciting time in genetic testing as whole exome and whole genome approaches finally reach the clinic. These new approaches offer insight into disease causation in families in which this might previously have been inaccessible, and also bring a wide range of interpretative challenges. Among the most significant recent findings has been the extent of physiologic rare coding variation in the human genome. New disease genes have been identified through whole exome studies in neonatal arrhythmia, congenital heart disease and coronary artery disease that were simply inaccessible with other techniques. This has not only shed light on the challenges of genetic testing at this scale, but has also sharply defined the limits of prior gene-panel focused testing. As novel therapies targeting specific genetic subsets of disease become available, genetic testing will become a part of routine clinical care. The pace of change in sequencing technologies has begun to transform clinical medicine, and cardiovascular disease is no exception. The complexity of such studies emphasizes the importance of real-time communication between the genetics laboratory and genetically informed clinicians. New efforts in data and knowledge management will be central to the continued advancement of genetic testing.

  3. Genetics and Rheumatic Disease

    Science.gov (United States)

    ... are randomly passed from parents to offspring. In reality, there are approximately 22,000 genes, all varying ... between smoking and DR4 that leads to an increased rheumatoid arthritis risk. Genetics and lupus Lupus (systematic ...

  4. Genetic aspects of Alzheimer disease.

    Science.gov (United States)

    Bird, Thomas D

    2008-04-01

    Alzheimer disease is the most common cause of dementia and represents a major public health problem. The neuropathologic findings of amyloid-beta plaques and tau containing neurofibrillary tangles represent important molecular clues to the underlying pathogenesis. Genetic factors are well recognized, but complicated. Three rare forms of autosomal-dominant early-onset familial Alzheimer disease have been identified and are associated with mutations in amyloid precursor protein, presenilin 1, and presenilin 2 genes. The more common late-onset form of Alzheimer disease is assumed to be polygenic/multifactorial. However, thus far the only clearly identified genetic risk factor for Alzheimer disease is Apo lipoprotein E. The epsilon4 allele of Apo lipoprotein E influences age at onset of Alzheimer disease, but is neither necessary nor sufficient for the disease. The search continues for the discovery of additional genetic influences.

  5. Genetics Home Reference: Danon disease

    Science.gov (United States)

    ... 1 link) Genetic Testing Registry: Danon disease Other Diagnosis and Management Resources (3 links) American Heart Association: Dilated Cardiomyopathy (PDF) KidsHealth from Nemours: Getting an EKG Swedish ...

  6. Genetics Home Reference: Milroy disease

    Science.gov (United States)

    ... Other Names for This Condition congenital familial lymphedema hereditary lymphedema type I Milroy's disease Nonne-Milroy lymphedema Related Information How are genetic conditions and genes named? Additional Information & Resources MedlinePlus ( ...

  7. Genetic Aspects of Alzheimer Disease

    Science.gov (United States)

    Williamson, Jennifer; Goldman, Jill; Marder, Karen S.

    2011-01-01

    Background Alzheimer disease (AD) is a genetically complex disorder. Mutations in 3 genes, presenilin 1, amyloid precursor protein, and presenilin 2, lead to early-onset familial AD in rare families with onset of disease occurring prior to age 65. Specific polymorphisms in apolipoprotein E are associated with the more common, late-onset AD occurring after age 65. In this review, we discuss current advances in AD genetics, the implications of the known AD genes, presenilin 1, presenilin 2, amyloid precursor protein, and apolipoprotein E, and other possible genes on the clinical diagnosis, treatment, and genetic counseling of patients and families with early- and late-onset AD. Review Summary In addition to the mutations in 4 known genes associated with AD, mutations in other genes may be implicated in the pathogenesis of the disease. Most recently, 2 different research groups have reported genetic association between 2 genes, sortilin-related receptor and GAB2, and AD. These associations have not changed the diagnostic and medical management of AD. Conclusions New research in the genetics of AD have implicated novel genes as having a role in the disease, but these findings have not been replicated nor have specific disease causing mutations been identified. To date, clinical genetic testing is limited to familial early-onset disease for symptomatic individuals and asymptomatic relatives and, although not recommended, amyloid precursor protein apolipoprotein E testing as an adjunct to diagnosis of symptomatic individuals. PMID:19276785

  8. Genetics of complex airway disease.

    Science.gov (United States)

    Cookson, William O C; Moffatt, Miriam F

    2011-05-01

    The past 3 years have seen highly significant genetic effects identified for a wide variety of common complex diseases, including the airway disorders of asthma and chronic obstructive pulmonary disease. It appears that only a portion of the genetically mediated susceptibility to complex diseases has been identified, and there is much left to be discovered. This review briefly describes the results of the genome-wide association studies of asthma and gives an overview of the parallel and increasingly large-scale studies that are taking place with chronic obstructive pulmonary disease. The future impact is discussed of technological advances that allow increasingly large-scale gene expression studies, next-generation sequencing, and genome-wide testing for epigenetic effects. The use of genetic technology to examine the airway microbiota that interact with the mucosa in health and disease is described.

  9. Quantitative genetics of disease traits.

    Science.gov (United States)

    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.

  10. [Genetics of congenital heart diseases].

    Science.gov (United States)

    Bonnet, Damien

    2017-06-01

    Developmental genetics of congenital heart diseases has evolved from analysis of serial slices in embryos towards molecular genetics of cardiac morphogenesis with a dynamic view of cardiac development. Genetics of congenital heart diseases has also changed from formal genetic analysis of familial recurrences or population-based analysis to screening for mutations in candidates genes identified in animal models. Close cooperation between molecular embryologists, pathologists involved in heart development and pediatric cardiologists is crucial for further increase of knowledge in the field of cardiac morphogenesis and genetics of cardiac defects. The genetic model for congenital heart disease has to be revised to favor a polygenic origin rather than a monogenic one. The main mechanism is altered genic dosage that can account for heart diseases in chromosomal anomalies as well as in point mutations in syndromic and isolated congenital heart diseases. The use of big data grouping information from cardiac development, interactions between genes and proteins, epigenetic factors such as chromatin remodeling or DNA methylation is the current source for improving our knowledge in the field and to give clues for future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Genetic screening of heredity diseases

    OpenAIRE

    Gamudi, Donia; Blundell, Renald

    2010-01-01

    Clinical Genetics is concerned with the diagnosis and management of the medical, social and psychological aspects of hereditary disease. As in all other areas of medicine, it is essential to make the correct diagnosis and provide appropriate treatment which must include helping the affected person and family members understand and come to terms with the nature and consequences of the disease.

  12. Genetics Home Reference: rapid-onset dystonia parkinsonism

    Science.gov (United States)

    ... parkinsonism have been diagnosed with anxiety, social phobias, depression, and seizures. It is unclear whether these disorders are related to the genetic changes that cause rapid-onset dystonia parkinsonism . Related ...

  13. Habitat fragmentation causes rapid genetic differentiation and ...

    African Journals Online (AJOL)

    ... city buildings. These results were supported by multiple statistical analyses including Mantel's test, PCOORDA and AMOVA. Genetic enrichment and epigenetic variation studies can be included in habitat fragmentation analysis and its implications in inducing homogenization and susceptibility in natural plant populations.

  14. Habitat fragmentation causes rapid genetic differentiation and ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... 1Laboratory of Plant Molecular Epigenetics, Institute of Genetics and Cytology, Northeast Normal University, Changchun. 130024 ... epigenetic variation studies can be included in habitat fragmentation analysis and its implications in inducing ... together with the environment habitat selection pressure.

  15. Rapid detection of genetic modification for GMO monitoring in agriculture

    Directory of Open Access Journals (Sweden)

    Petrović Sofija

    2015-01-01

    Full Text Available Transgenic technology has expanded the ways of new genetic variability creation. Genetically modified organisms (GMOs are organisms which total genome is altered in a way that could not happen in nature. GM crops recorded a steady increase in its share in agricultural production. However, for the most part, GMO in agriculture has been limited to two cultivars - soy and corn, and the two genetic modifications, the total herbicide resistance and pest of the Lepidoptera genus. In order to monitor cultivation and trade of GMOs, tests of different precision are used, qualitatively and/or quantitatively determining the presence of genetic modification. Tests for the rapid determination of the presence of GM are suitable, since they can be implemented quickly and accurately, in terms of declared sensitivity, outside or in the laboratory. The example of the use of rapid tests demonstrates their value in use for rapid and efficient monitoring.

  16. Rapid genetic detection of ingested Amanita phalloides.

    Science.gov (United States)

    Gausterer, Christian; Penker, Martina; Krisai-Greilhuber, Irmgard; Stein, Christina; Stimpfl, Thomas

    2014-03-01

    Mushrooms are often poorly digested by humans. Thus, their remains (tissues, spores) may persist in the gastrointestinal tract and can be detected in feces several days after mushroom consumption. In this report, we present protocols for the rapid PCR-based detection of fungal traces in a variety of complex samples. Novel primers were designed to amplify portions of ribosomal DNA from deadly poisonous European members of the genus Amanita, namely the death cap (A. phalloides), the destroying angel (A. virosa) and the fool's mushroom (A. verna), respectively. Assay sensitivity was sufficient to discover diluted DNA traces in amounts below the genomic content of a single target mushroom cell. Specificity testing was performed with DNA extracts from a variety of mushroom species. Template amplification was exclusively observed with intended targets and it was not compromised by a vast excess of non-target DNA (i.e. DNA from human and human fecal origin, respectively). A series of experiments was conducted with prepared specimens in order to follow the course of mushroom food processing and digestion. Amplification by direct PCR was successful with raw, fried and digested mixed mushrooms. To improve assay performance with fecal samples, a rapid protocol for sample pre-processing (including water-ether sedimentation and bead beating) and a modified PCR reaction mix were applied. Thereby, it was possible to detect the presence of A. phalloides DNA in spiked feces as well as in clinical samples (vomit, stool) from two independent cases of suspected mushroom poisoning. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Genetics Home Reference: Gaucher disease

    Science.gov (United States)

    ... Sidransky E. Gaucher disease: insights from a rare Mendelian disorder. Discov Med. 2012 Oct;14(77):273-81. Review. Citation on PubMed or Free article on PubMed Central More from Genetics Home Reference Bulletins Crick, Watson, and Wilkins Awarded ...

  18. Genetics of Coronary Artery Disease

    DEFF Research Database (Denmark)

    McPherson, Ruth; Tybjærg-Hansen, Anne

    2016-01-01

    Genetic factors contribute importantly to the risk of coronary artery disease (CAD), and in the past decade, there has been major progress in this area. The tools applied include genome-wide association studies encompassing >200,000 individuals complemented by bioinformatic approaches, including...

  19. Genetic predisposition to Parkinson's disease

    DEFF Research Database (Denmark)

    Halling, Jónrit; Petersen, Maria Skaalum; Grandjean, Philippe

    2008-01-01

    OBJECTIVE: To investigate whether the genetic variants of CYP2D6 and HFE are more frequent in Parkinson's disease (PD) patients compared with controls in a population where the prevalence of these variants and PD are increased. METHODS: Blood samples were collected from 79 PD patients and 154...

  20. Genetic anaylsis of a disease resistance gene from loblolly pine

    Science.gov (United States)

    Yinghua Huang; Nili Jin; Alex Diner; Chuck Tauer; Yan Zhang; John Damicone

    2003-01-01

    Rapid advances in molecular genetics provide great opportunities for studies of host defense mechanisms. Examination of plant responses to disease at the cellular and molecular level permits both discovery of changes in gene expression in the tissues attacked by pathogens, and identification of genetic components involved in the interaction between host and pathogens....

  1. Genetic modifiers of Huntington's disease.

    Science.gov (United States)

    Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min

    2014-09-15

    Huntington's disease (HD) is a devastating neurodegenerative disorder that directly affects more than 1 in 10,000 persons in Western societies but, as a family disorder with a long, costly, debilitating course, it has an indirect impact on a far greater proportion of the population. Although some palliative treatments are used, no effective treatment exists for preventing clinical onset of the disorder or for delaying its inevitable progression toward premature death, approximately 15 years after diagnosis. Huntington's disease involves a movement disorder characterized by chorea, as well as a variety of psychiatric disturbances and intellectual decline, with a gradual loss of independence. A dire need exists for effective HD therapies to alleviate the suffering and costs to the individual, family, and health care system. In past decades, genetics, the study of DNA sequence variation and its consequences, provided the tools to map the HD gene to chromosome 4 and ultimately to identify its mutation as an expanded CAG trinucleotide repeat in the coding sequence of a large protein, dubbed huntingtin. Now, advances in genetic technology offer an unbiased route to the identification of genetic factors that are disease-modifying agents in human patients. Such genetic modifiers are expected to highlight processes capable of altering the course of HD and therefore to provide new, human-validated targets for traditional drug development, with the goal of developing rational treatments to delay or prevent onset of HD clinical signs. © 2014 International Parkinson and Movement Disorder Society.

  2. Genetic Testing for Inherited Heart Disease

    Science.gov (United States)

    ... of the American Heart Association Cardiology Patient Page Genetic Testing for Inherited Heart Disease Allison L. Cirino , ... for developing the family’s heart condition. What Is Genetic Testing and What Can it Tell Me? Genetic ...

  3. [Genetic diagnostics of cancer diseases].

    Science.gov (United States)

    Cobilanschi, Joana

    2013-11-27

    Cancer is caused by genetic alterations, but only 10% of the cancer diseases are inherited. The probability for an individual or a family of having inherited cancer, individual consequences of the respective results of genetic testing, as well as its costs and reimbursement by the health insurance must be addressed by expert genetic counseling which at-risk requires special expertise. Identification of a germline mutation which may predispose to a variety of different cancer types allows determination of an individual's specific life time risk in symptomatic as well as in a-symptomatic family members. Identification of the underlying defective gene in heritable cancer disorders also enables optimized preventive and novel therapeutic approaches specifically targeting the underlying molecular pathomechanisms.

  4. Nonmotor symptoms in genetic Parkinson disease

    DEFF Research Database (Denmark)

    Kasten, Meike; Kertelge, Lena; Brüggemann, Norbert

    2010-01-01

    To review current knowledge on nonmotor symptoms (NMS), particularly psychiatric features, in genetic Parkinson disease (PD) and to provide original data for genetic and idiopathic PD.......To review current knowledge on nonmotor symptoms (NMS), particularly psychiatric features, in genetic Parkinson disease (PD) and to provide original data for genetic and idiopathic PD....

  5. Rapid genetic transformation of sweetpotato ( Ipomoea batatas (L ...

    African Journals Online (AJOL)

    It indicated an auxin to cytokinin treatment could improve the regeneration of transgenic calluses. This rapid organogenesis-based transformation strategy represents an important improvement over existing methods and will facilitate producing large-scale transgenic sweetpotato plants the genetic improvement of a crop ...

  6. Large genetic animal models of Huntington's Disease.

    Science.gov (United States)

    Morton, A Jennifer; Howland, David S

    2013-01-01

    The dominant nature of the Huntington's disease gene mutation has allowed genetic models to be developed in multiple species, with the mutation causing an abnormal neurological phenotype in all animals in which it is expressed. Many different rodent models have been generated. The most widely used of these, the transgenic R6/2 mouse, carries the mutation in a fragment of the human huntingtin gene and has a rapidly progressive and fatal neurological phenotype with many relevant pathological changes. Nevertheless, their rapid decline has been frequently questioned in the context of a disease that takes years to manifest in humans, and strenuous efforts have been made to make rodent models that are genetically more 'relevant' to the human condition, including full length huntingtin gene transgenic and knock-in mice. While there is no doubt that we have learned, and continue to learn much from rodent models, their usefulness is limited by two species constraints. First, the brains of rodents differ significantly from humans in both their small size and their neuroanatomical organization. Second, rodents have much shorter lifespans than humans. Here, we review new approaches taken to these challenges in the development of models of Huntington's disease in large brained, long-lived animals. We discuss the need for such models, and how they might be used to fill specific niches in preclinical Huntington's disease research, particularly in testing gene-based therapeutics. We discuss the advantages and disadvantages of animals in which the prodromal period of disease extends over a long time span. We suggest that there is considerable 'value added' for large animal models in preclinical Huntington's disease research.

  7. The genetics of Alzheimer's disease.

    Science.gov (United States)

    Bagyinszky, Eva; Youn, Young Chul; An, Seong Soo A; Kim, SangYun

    2014-01-01

    Alzheimer's disease (AD) is a complex and heterogeneous neurodegenerative disorder, classified as either early onset (under 65 years of age), or late onset (over 65 years of age). Three main genes are involved in early onset AD: amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). The apolipoprotein E (APOE) E4 allele has been found to be a main risk factor for late-onset Alzheimer's disease. Additionally, genome-wide association studies (GWASs) have identified several genes that might be potential risk factors for AD, including clusterin (CLU), complement receptor 1 (CR1), phosphatidylinositol binding clathrin assembly protein (PICALM), and sortilin-related receptor (SORL1). Recent studies have discovered additional novel genes that might be involved in late-onset AD, such as triggering receptor expressed on myeloid cells 2 (TREM2) and cluster of differentiation 33 (CD33). Identification of new AD-related genes is important for better understanding of the pathomechanisms leading to neurodegeneration. Since the differential diagnoses of neurodegenerative disorders are difficult, especially in the early stages, genetic testing is essential for diagnostic processes. Next-generation sequencing studies have been successfully used for detecting mutations, monitoring the epigenetic changes, and analyzing transcriptomes. These studies may be a promising approach toward understanding the complete genetic mechanisms of diverse genetic disorders such as AD.

  8. Reactive biomolecular divergence in genetically altered yeast cells and isolated mitochondria as measured by biocavity laser spectroscopy : a rapid diagnostic method for studying cellular responses to stress and disease.

    Energy Technology Data Exchange (ETDEWEB)

    Yaffe, Michael P. (University of California, San Diego, CA); Gourley, Paul Lee; Copeland, Robert Guild; McDonald, Anthony Eugene; Hendricks, Judy K.; Naviaux, Robert K. (Univesity of California, San Diego, CA)

    2006-12-01

    We report an analysis of four strains of baker's yeast (Saccharomyces cerevisiae) using biocavity laser spectroscopy. The four strains are grouped in two pairs (wild type and altered), in which one strain differs genetically at a single locus, affecting mitochondrial function. In one pair, the wild-type rho+ and a rho0 strain differ by complete removal of mitochondrial DNA (mtDNA). In the second pair, the wild-type rho+ and a rho- strain differ by knock-out of the nuclear gene encoding Cox4, an essential subunit of cytochrome c oxidase. The biocavity laser is used to measure the biophysical optic parameter Deltalambda, a laser wavelength shift relating to the optical density of cell or mitochondria that uniquely reflects its size and biomolecular composition. As such, Deltalambda is a powerful parameter that rapidly interrogates the biomolecular state of single cells and mitochondria. Wild-type cells and mitochondria produce Gaussian-like distributions with a single peak. In contrast, mutant cells and mitochondria produce leptokurtotic distributions that are asymmetric and highly skewed to the right. These distribution changes could be self-consistently modeled with a single, log-normal distribution undergoing a thousand-fold increase in variance of biomolecular composition. These features reflect a new state of stressed or diseased cells that we call a reactive biomolecular divergence (RBD) that reflects the vital interdependence of mitochondria and the nucleus.

  9. The genetics of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Bagyinszky E

    2014-04-01

    Full Text Available Eva Bagyinszky,1 Young Chul Youn,2 Seong Soo A An,1,* SangYun Kim3,*1Department of BioNano Technology Gachon University, Gyeonggi-do, 2Department of Neurology, Chung-Ang University College of Medicine, Seoul, 3Department of Neurology, Seoul National University Budang Hospital, Gyeonggi-do, South Korea*These authors contributed equally to this workAbstract: Alzheimer's disease (AD is a complex and heterogeneous neurodegenerative disorder, classified as either early onset (under 65 years of age, or late onset (over 65 years of age. Three main genes are involved in early onset AD: amyloid precursor protein (APP, presenilin 1 (PSEN1, and presenilin 2 (PSEN2. The apolipoprotein E (APOE E4 allele has been found to be a main risk factor for late-onset Alzheimer's disease. Additionally, genome-wide association studies (GWASs have identified several genes that might be potential risk factors for AD, including clusterin (CLU, complement receptor 1 (CR1, phosphatidylinositol binding clathrin assembly protein (PICALM, and sortilin-related receptor (SORL1. Recent studies have discovered additional novel genes that might be involved in late-onset AD, such as triggering receptor expressed on myeloid cells 2 (TREM2 and cluster of differentiation 33 (CD33. Identification of new AD-related genes is important for better understanding of the pathomechanisms leading to neurodegeneration. Since the differential diagnoses of neurodegenerative disorders are difficult, especially in the early stages, genetic testing is essential for diagnostic processes. Next-generation sequencing studies have been successfully used for detecting mutations, monitoring the epigenetic changes, and analyzing transcriptomes. These studies may be a promising approach toward understanding the complete genetic mechanisms of diverse genetic disorders such as AD.Keywords: dementia, amyloid precursor protein, presenilin 1, presenilin 2, APOE, mutation, diagnosis, genetic testing

  10. RARE DISEASES AND GENETIC DISCRIMINATION

    Directory of Open Access Journals (Sweden)

    Mariela Yaneva – Deliverska

    2011-04-01

    Full Text Available Rare diseases are characterised by their low prevalence (less than 1/2,000 and their heterogeneity. They affect both children and adults anywhere in the world. From the medical perspective, rare diseases are characterised by the large number and broad diversity of disorders and symptoms that vary not only from disease to disease, but also within the same disease.Main characteristics of rare diseases include:· Rare diseases are often chronic, progressive, degenerative, and often life-threatening· Rare diseases are disabling: the quality of life of patients is often compromised by the lack or loss of autonomy· High level of pain and suffering for the patient and his/ her family · No existing effective cure· There are between 6000 and 8000 rare diseases· 75% of rare diseases affect children· 30% of rare disease patients die before the age of 5· 80% of rare diseases have identified genetic origins. Other rare diseases are the result of infections (bacterial or viral, allergies and environmental causes, or are degenerative and proliferative.Beyond the diversity of the diseases, rare disease patients and their families are confronted with the same wide range of difficulties arising directly from the rarity of these pathologies. The period between the emergence of the first symptoms and the appropriate diagnosis involves unacceptable and highly risky delays, as well as wrong diagnosis leading to inaccurate treatments. Living with a rare disease has implications in all areas of life, whether school, choice of future work, leisure time with friends, or affective life. It may lead to stigmatisation, isolation, exclusion from social community, discrimination for insurance subscription (health insurance, travel insurance, mortgage, and often reduced professional opportunities.Innovative treatments are often unevenly available in the EU because of delays in price determination and/or reimbursement decision, lack of experience of the treating

  11. Coeliac disease and autoimmune disease-genetic overlap and screening

    NARCIS (Netherlands)

    Lundin, Knut E. A.; Wijmenga, Cisca

    Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity

  12. Genetics Home Reference: maple syrup urine disease

    Science.gov (United States)

    ... BH. Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders. Hum Mol Genet. ... gov/books/NBK1319/ Citation on PubMed More from Genetics Home Reference Bulletins Crick, Watson, and Wilkins Awarded ...

  13. Genetic Syndromes associated with Congenital Heart Disease

    OpenAIRE

    Ko, Jung Min

    2015-01-01

    Recent research has demonstrated that genetic alterations or variations contribute considerably to the development of congenital heart disease. Many kinds of genetic tests are commercially available, and more are currently under development. Congenital heart disease is frequently accompanied by genetic syndromes showing both cardiac and extra-cardiac anomalies. Congenital heart disease is the leading cause of birth defects, and is an important cause of morbidity and mortality during infancy a...

  14. Genetics Home Reference: autoimmune Addison disease

    Science.gov (United States)

    ... features of other genetic conditions, including X-linked adrenoleukodystrophy and autoimmune polyglandular syndrome, type 1, which are ... disease Patient Support and Advocacy Resources (3 links) Adrenoleukodystrophy Foundation American Autoimmune Related Diseases Association National Adrenal ...

  15. Genetics of Behçet's Disease

    Directory of Open Access Journals (Sweden)

    Tamer İrfan Kaya

    2012-01-01

    Full Text Available Behçet's disease (BD is a systemic inflammatory disorder characterized mainly by recurrent oral and genital ulcers and eye involvement. Although the pathogenesis remains poorly understood, a variety of studies have demonstrated that genetic predisposition is a major factor in disease susceptibility. Peculiar geographical distribution of BD along the ancient Silk Road has been regarded as evidence supporting genetic influence. The observed aggregation of BD in families of patients with BD is also supportive for a genetic component in its etiology. HLA-B51 (B510101 subtype is the most strongly associated genetic marker for BD in countries on the Silk Road. In recent years, several genome-wide association studies and genetic polymorphism studies have also found new genetic associations with BD, which may have a supplementary role in disease susceptibility and/or severity. The author reviewed the HLA and non-HLA genetic association studies.

  16. [Parkinson's disease(s): recent insight into genetic factors

    NARCIS (Netherlands)

    Warrenburg, B.P.C. van de; Scheffer, H.; Heutink, P.; Bloem, B.R.

    2007-01-01

    In recent years, 5 genes have been identified that are unambiguously associated with genetic forms of Parkinson's disease. These genes probably explain less than 10% of all cases of Parkinson's disease. Clinically, these genetic forms can closely resemble idiopathic Parkinson's disease. Mutation

  17. Genetic heterogeneity of Oguchi′s disease

    Directory of Open Access Journals (Sweden)

    Singh Jai

    1990-01-01

    Full Text Available An analysis of the cases reported in Punjab, India, indicates the presence of genetic heterogeneity of Oguchi′s disease, for which autosomal recessive inheritance has been documented earlier. The autosomal dominant inheritance pattern of this disease is associated with incomplete penetrance and a distinct sex bias towards females. This recognition is important for genetic counselling.

  18. Genetic variants in periodontal health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Dumitrescu, Alexandrina L. [Tromsoe Univ. (Norway). Inst. of Clinical Dentistry; Kobayashi, Junya [Kyoto Univ. (Japan). Dept. of Genome Repair Dynamics

    2010-07-01

    Periodontitis is a complex, multifactorial disease and its susceptibility is genetically determined. The present book systematically reviews the evidence of the association between the genetic variants and periodontitis progression and/or treatment outcomes. Genetic syndromes known to be associated with periodontal disease, the candidate gene polymorphisms investigated in relation to periodontitis, the heritability of chronic and aggressive periodontitis, as well as common guidelines for association studies are described. This growing understanding of the role of genetic variation in inflammation and periodontal chronic disease presents opportunities to identify healthy persons who are at increased risk of disease and to potentially modify the trajectory of disease to prolong healthy aging. The book represents a new concept in periodontology with its pronounced focus on understanding through knowledge rather than presenting the presently valid answers. Connections between genetics and periodontology are systematically reviewed and covered in detail. (orig.)

  19. Genetics Home Reference: Alzheimer disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Alzheimer disease Alzheimer disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alzheimer disease is a degenerative disease of the brain ...

  20. Diagnosing kidney disease in the genetic era.

    Science.gov (United States)

    Prakash, Sindhuri; Gharavi, Ali G

    2015-07-01

    Recent technological improvements have increased the use of genetic testing in the clinic. This review serves to summarize the many practical benefits of genetic testing, discusses various methodologies that can be used clinically, and exemplifies ways in which genetics is propelling the field forward in nephrology. The advent of next-generation sequencing and microarray technologies has heralded an unprecedented number of discoveries in the field of nephrology, providing many opportunities for incorporating genomic diagnostics into clinical care. The use of genetic testing, particularly in pediatrics, can provide accurate diagnoses in puzzling cases, resolve misclassification of disease, and identify subsets of individuals with treatable conditions. Genetic testing may have broad benefits for patients and their families. Knowing the precise molecular etiology of disease can help clinicians determine the exact therapeutic course, and counsel patients and their families about prognosis. Genetic discoveries can also improve the classification of kidney disease and identify new targets for therapy.

  1. Genetics of liver disease: From pathophysiology to clinical practice.

    Science.gov (United States)

    Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

    2015-04-01

    Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Genetic predisposition in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Sookoian, Silvia; Pirola, Carlos J

    2017-03-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has reached global epidemic proportions. Although the disease is relatively benign in the early stages, when severe clinical forms, including nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma, occur, they result in worsening the long-term prognosis. A growing body of evidence indicates that NAFLD develops from a complex process in which many factors, including genetic susceptibility and environmental insults, are involved. In this review, we focused on the genetic component of NAFLD, with special emphasis on the role of genetics in the disease pathogenesis and natural history. Insights into the topic of the genetic susceptibility in lean individuals with NAFLD and the potential use of genetic tests in identifying individuals at risk are also discussed.

  3. Genetics Home Reference: Parkinson disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Parkinson disease Parkinson disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Parkinson disease is a progressive disorder of the nervous ...

  4. Genetics Home Reference: Kawasaki disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Kawasaki disease Kawasaki disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Kawasaki disease is a sudden and time-limited (acute) ...

  5. Genetics Home Reference: Alexander disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Alexander disease Alexander disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alexander disease is a rare disorder of the nervous system. ...

  6. Genetics Home Reference: celiac disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Celiac disease Celiac disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Celiac disease is a condition in which the immune system ...

  7. Genetics Home Reference: Cushing disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Cushing disease Cushing disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Cushing disease is caused by elevated levels of a ...

  8. Genetics Home Reference: Huntington disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Huntington disease Huntington disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Huntington disease is a progressive brain disorder that causes ...

  9. Genetics Home Reference: Sandhoff disease

    Science.gov (United States)

    ... that break down toxic substances and act as recycling centers. Within lysosomes, these enzymes break down fatty ... Neurological Disorders and Stroke: Sandhoff Disease Information Page Educational Resources (5 links) Disease InfoSearch: Sandhoff disease MalaCards: ...

  10. Genetics Home Reference: Pompe disease

    Science.gov (United States)

    ... in lysosomes , which are structures that serve as recycling centers within cells. The enzyme normally breaks down ... Neurological Disorders and Stroke: Pompe Disease Information Page Educational Resources (5 links) Disease InfoSearch: Glycogen Storage Disease ...

  11. Genetics Home Reference: Graves disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Graves disease Graves disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Graves disease is a condition that affects the function of ...

  12. Genetics Home Reference: Hirschsprung disease

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Hirschsprung disease Hirschsprung disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Hirschsprung disease is an intestinal disorder characterized by the absence ...

  13. [Recent developments in genetic kidney diseases].

    Science.gov (United States)

    Liebau, M C; Benzing, T

    2011-05-01

    The improved understanding of genetic kidney diseases has given rise to a more detailed understanding of kidney function within the last decade. Insights into the pathophysiological principles of frequent kidney diseases - partly inherited, partly acquired - have been obtained by the investigation of rare genetic disorders and can now serve as a starting point for the development of novel therapeutic strategies. In this way various clinical multicenter trials, which are based on the observations made in basic science have been established for the very common autosomal dominant polycystic kidney disease. Furthermore, the influence of genetic aspects on frequent kidney diseases, e. g. diabetic nephropathy, is becoming more obvious. This article aims to give an overview over essential recent development in the field of genetic kidney diseases. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Coeliac disease : investigation of the genetic factors underlying coeliac disease

    NARCIS (Netherlands)

    Belzen, M.J. (Martine Juliana) van

    2003-01-01

    Coeliac disease is a common food intolerance with a complex genetic aetiology. It is caused by ingestion of gluten peptides from wheat and related proteins from barley and rye in genetically susceptible individuals. The disease affects the small intestine and leads to abnormalities ranging from the

  15. Genetics Home Reference: Tangier disease

    Science.gov (United States)

    ... and CRISPR-Cas9? What is direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Leprosy Polycystic ovary syndrome Gorlin-Chaudhry-Moss syndrome All New & Updated Pages ...

  16. Modified AFLP technique for rapid genetic characterization in plants.

    Science.gov (United States)

    Ranamukhaarachchi, D G; Kane, M E; Guy, C L; Li, Q B

    2000-10-01

    The standard amplified fragment-length polymorphism (AFLP) technique was modified to develop a convenient and reliable technique for rapid genetic characterization of plants. Modifications included (i) using one restriction enzyme, one adapter molecule and primer, (ii) incorporating formamide to generate more intense and uniform bands and (iii) using agarose gel electrophoresis. Sea oats (Uniola paniculata L.), pickerel-weed (Pontederia cordata L.), Bermudagrass (Cynodon dactylon L.) and Penstemon heterophyllus Lindl. were used to determine the ability to generate adequate resolution power with both self- and cross-pollinated plant species including cultivars, ecotypes and individuals within populations. Reproducibility of bands was higher in all the AFLP experiments compared to random amplified polymorphic DNA (RAPD). Formamide with or without bovine serum albumin improved band intensities compared to dimethyl sulfoxide and the standard reaction mixture with no organic solvents. Comparison between RAPD and modified AFLP using sea-oats population samples proved that modified AFLP exhibits (i) a low number of faint bands with increased specificity of amplified bands, (ii) a significantly higher number of polymorphic loci per primer, (iii) less primer screening time, (iv) easy scoring associated with fewer faint bands and (v) greatly enhanced reproducibility. The technique described here can be applied with a high degree of accuracy for plant genetic characterization.

  17. Animal models for human genetic diseases

    African Journals Online (AJOL)

    Sharif Sons

    disturbances (including anxiety and depression). (Rosenthal and Brown, 2007). Mouse models for a rare genetic disorder of the blood platelets, May-Hegglin anomaly (MHA) showed same symptoms as occur in humans (American Institute of. Physics, 2011). Also in genetic prion disease, histopathological examination of ...

  18. Chronic obstructive pulmonary disease and genetics

    DEFF Research Database (Denmark)

    Ingebrigtsen, T.; Thomsen, S.F.; Vestbo, J.

    2008-01-01

    smokers develop COPD. This indicates a genetic contribution to the individual disease susceptibility. Although many genes have been examined, the puzzle of COPD genetics seems still largely unsolved. It is therefore important to measure phenotypes and to perform genome-wide scans of COPD patients in order...

  19. Lingual Kinematics during Rapid Syllable Repetition in Parkinson's Disease

    Science.gov (United States)

    Wong, Min Ney; Murdoch, Bruce E.; Whelan, Brooke-Mai

    2012-01-01

    Background: Rapid syllable repetition tasks are commonly used in the assessment of motor speech disorders. However, little is known about the articulatory kinematics during rapid syllable repetition in individuals with Parkinson's disease (PD). Aims: To investigate and compare lingual kinematics during rapid syllable repetition in dysarthric…

  20. The genetic basis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    A. A. Tappakhov

    2017-01-01

    Full Text Available Parkinson's disease (PD is a multifactorial disease that develops in the presence of both genetic and environmental factors. In recent years, there has been sufficient information on the role of genetic predisposition in the development of not only familial cases, but also sporadic ones. A hereditary burden in PD may not be traced in cases of recessive inheritance with a low gene penetrance, as well as in a patient's death before the onset of the disease. Active introduction of molecular genetic methods, including next generation sequencing, can annually identify new gene mutations that underlie sporadic PD cases. This paper provides an overview of the current literature on the genetic aspects of PD with emphasis on the ethnic characteristics of the disease.

  1. Genetics Home Reference: sickle cell disease

    Science.gov (United States)

    ... particular ethnic groups? Genetic Changes Mutations in the HBB gene cause sickle cell disease . Hemoglobin consists of ... globin and two subunits called beta-globin. The HBB gene provides instructions for making beta-globin. Various ...

  2. Protein misfolding and degradation in genetic diseases

    DEFF Research Database (Denmark)

    Bross, P; Corydon, T J; Andresen, B S

    1999-01-01

    Investigations of genetic diseases such as cystic fibrosis, alpha-1-antitrypsin deficiency, phenylketonuria, mitochondrial acyl-CoA dehydrogenase deficiencies, and many others have shown that enhanced proteolytic degradation of mutant proteins is a common molecular pathological mechanism. Detailed....... This appears to be the case for many missense mutations and short in-frame deletions or insertions that represent a major fraction of the mutations detected in genetic diseases. In some diseases, or under some circumstances, the degradation system is not efficient. Instead, aberrant folding leads...... in which proteins fold. Within the context of genetic diseases, we review knowledge on the molecular processes underlying protein quality control in the various subcellular compartments. The important impact of such systems for variability of the expression of genetic deficiencies is emphasised....

  3. Genetics Home Reference: juvenile Paget disease

    Science.gov (United States)

    ... J. A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype. Hum Mol Genet. ... PM, Jones JL, Podgornik MN, McAlister WH, Mumm S. Osteoprotegerin deficiency and juvenile Paget's disease. N Engl J ...

  4. Role of genetic in periodontal disease

    Directory of Open Access Journals (Sweden)

    Anand Narayanrao Wankhede

    2017-01-01

    Full Text Available Genetics is the study and understanding of the phenomena of heredity and variation. A large number of genes are associated with many systemic conditions. Periodontitis is inflammatory condition of periodontium. Periodontium consists of gingiva, periodontal ligament, cementum, and alveolar bone. It is considered being a multifactorial disease. Studies of animals and humans support the concept that a large number of genes' factor may be associated with periodontitis and clearly play a role in the predisposition and progression of periodontal diseases. It has been proven that genetic factors impair inflammatory and immune responses during periodontal diseases. Research on identifying specific genes causing periodontitis may improve and prevent the disease progression. The aim of this article is to focus on genetic risk factors and its influence for the various forms of periodontal disease.

  5. Genetics Home Reference: Schindler disease

    Science.gov (United States)

    ... childhood, with some features of autism spectrum disorders. Autism spectrum disorders are characterized by impaired communication and socialization skills. Related Information What does it mean if a disorder seems to run in my family? What is the prognosis of a genetic condition? ...

  6. Rapidly progressive post-transplant lymphoproliferative disease ...

    African Journals Online (AJOL)

    Sirolimus, a potent inhibitor of B- and T-cell activation, is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus ...

  7. Genetic Syndromes associated with Congenital Heart Disease.

    Science.gov (United States)

    Ko, Jung Min

    2015-09-01

    Recent research has demonstrated that genetic alterations or variations contribute considerably to the development of congenital heart disease. Many kinds of genetic tests are commercially available, and more are currently under development. Congenital heart disease is frequently accompanied by genetic syndromes showing both cardiac and extra-cardiac anomalies. Congenital heart disease is the leading cause of birth defects, and is an important cause of morbidity and mortality during infancy and childhood. This review introduces common genetic syndromes showing various types of congenital heart disease, including Down syndrome, Turner syndrome, 22q11 deletion syndrome, Williams syndrome, and Noonan syndrome. Although surgical techniques and perioperative care have improved substantially, patients with genetic syndromes may be at an increased risk of death or major complications associated with surgery. Therefore, risk management based on an accurate genetic diagnosis is necessary in order to effectively plan the surgical and medical management and follow-up for these patients. In addition, multidisciplinary approaches and care for the combined extra-cardiac anomalies may help to reduce mortality and morbidity accompanied with congenital heart disease.

  8. Genetic architecture of human fibrotic diseases: disease risk and disease progression

    Directory of Open Access Journals (Sweden)

    Agnès eGardet

    2013-12-01

    Full Text Available Genetic studies of human diseases have identified multiple genetic risk loci for various fibrotic diseases. This has provided insights into the myriad of biological pathways potentially involved in disease pathogenesis. These discoveries suggest that alterations in immune responses, barrier function, metabolism and telomerase activity may be implicated in the genetic risks for fibrotic diseases. In addition to genetic disease-risks, the identification of genetic disease-modifiers associated with disease complications, severity or prognosis provides crucial insights into the biological processes implicated in disease progression. Understanding the biological processes driving disease progression may be critical to delineate more effective strategies for therapeutic interventions. This review provides an overview of current knowledge and gaps regarding genetic disease-risks and genetic disease-modifiers in human fibrotic diseases.

  9. High school genetics education and Alzheimer disease.

    Science.gov (United States)

    Horsma, H G

    1999-01-01

    Improved and updated human genetics education, including Alzheimer disease (AD) awareness and education, is urgently needed. National, state, and local standards for science education agree that human genetics, biotechnology applications, and the social and ethical issues raised by modern technology need to be taught in high school science using hands-on and inquiry methods of teaching. High school science courses are the last opportunity for most individuals to learn human genetics. There are an increasing number of new and successful human genetics curriculum materials and inservice teacher education programs at the secondary school level aligned with national and state science education standards. These curricula and teacher education programs can be enhanced by collaborative partnerships of geneticists, genetics professionals, biotechnology scientists and technical personnel, and science educators, several of which are in successful operation. Because human genetics involves families and generations, genetics education tied to AD may provide a unique opportunity to educate two generations, both students and parents, to the many medical, personal, family, community, and cultural issues of human genetics and genetic conditions. Implementing human genetics and AD education provides a recipe for accurate, relevant, sustainable and exciting teaching and learning for all involved.

  10. Genetics Home Reference: moyamoya disease

    Science.gov (United States)

    ... moyamoya disease Orphanet: Moyamoya disease Stanford School of Medicine Patient Support and Advocacy Resources (3 links) American Stroke Association National Stroke Association RareConnect ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (4 ...

  11. A genetic perspective on coeliac disease

    NARCIS (Netherlands)

    Trynka, Gosia; Wijmenga, Cisca; van Heel, David A.

    2010-01-01

    Coeliac disease is an inflammatory disorder of the small intestine with an autoimmune component and strong heritability. Genetic studies have confirmed strong association to HLA and identified 39 nonHLA risk genes, mostly immune-related. Over 50% of the disease-associated single nucleotide

  12. Introduction to Protein Structure through Genetic Diseases

    Science.gov (United States)

    Schneider, Tanya L.; Linton, Brian R.

    2008-01-01

    An illuminating way to learn about protein function is to explore high-resolution protein structures. Analysis of the proteins involved in genetic diseases has been used to introduce students to protein structure and the role that individual mutations can play in the onset of disease. Known mutations can be correlated to changes in protein…

  13. De novo mutations in human genetic disease

    NARCIS (Netherlands)

    Veltman, J.A.; Brunner, H.G.

    2012-01-01

    New mutations have long been known to cause genetic disease, but their true contribution to the disease burden can only now be determined using family-based whole-genome or whole-exome sequencing approaches. In this Review we discuss recent findings suggesting that de novo mutations play a prominent

  14. Parkinson's disease: piecing together a genetic jigsaw.

    NARCIS (Netherlands)

    M.C.J. Dekker (Marieke); V. Bonifati (Vincenzo); C.M. van Duijn (Cornelia)

    2003-01-01

    textabstractThe role of genetics in the pathogenesis of Parkinson's disease has been subject to debate for decades. In recent years, the discovery of five genes and several more loci has provided important insight into its molecular aetiology. Some Parkinson's disease genes possibly cause

  15. New approach to genetic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Sasazuki, T.

    1987-01-01

    Since the 1970s, many new insights have been gained concerning the mechanisms involved in the pathogenesis of monogenic and multifactorial disorders. Molecular cloning and determination of the base sequences of genes, monoclonal antibody techniques, transformation of single cells and related events in vivo by inserting foreign genes have shed light on the pathogenesis and pathophysiology of disease. This volume contains the latest information in this dynamic area. Topics include: premature coronary artery disease, diabetes, HLA-linked disease, muscular dystrophy and cystic fibrosis.

  16. Genetic Testing and Eye Disease

    Science.gov (United States)

    Subspecialties Cataract/Anterior Segment Comprehensive Ophthalmology Cornea/External Disease Glaucoma Neuro-Ophthalmology/Orbit Pediatric Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ...

  17. Genetic risks for cardiovascular diseases

    NARCIS (Netherlands)

    Zafarmand, M.H.

    2008-01-01

    Atherosclerotic cardiovascular disease (CVD), which involves the heart, brain, and peripheral circulation, is a major health problem world-wide. The development of atherosclerosis is a complex process, and several established risk factors are involved. Nevertheless, these established risk factors

  18. Genetics Home Reference: Wilson disease

    Science.gov (United States)

    ... 482-93. Review. Citation on PubMed Ferenci P. Pathophysiology and clinical features of Wilson disease. Metab Brain ... newborn screening? New Pages MDA5 deficiency type 2 diabetes mitochondrial complex I deficiency All New & Updated Pages ...

  19. Genetics Home Reference: Refsum disease

    Science.gov (United States)

    ... dystrophy accessible to therapy. Surv Ophthalmol. 2010 Nov-Dec;55(6):531-8. doi: 10.1016/j. ... RJ, Komen JC. Peroxisomes, Refsum's disease and the alpha- and omega-oxidation of phytanic acid. Biochem Soc ...

  20. Genetics Home Reference: Fabry disease

    Science.gov (United States)

    ... in lysosomes , which are structures that serve as recycling centers within cells. Alpha-galactosidase A normally breaks ... Disorders and Stroke: Lipid Storage Diseases Fact Sheet Educational Resources (10 links) Children Living With Inherited Metabolic ...

  1. Genetics Home Reference: Charcot-Marie-Tooth disease

    Science.gov (United States)

    ... autosomal recessive Genetic Testing Registry: Charcot-Marie-Tooth disease, demyelinating, type 1b Genetic Testing Registry: Charcot-Marie-Tooth disease, demyelinating, type 1d Genetic Testing Registry: Charcot-Marie-Tooth ...

  2. Genetic influences in caries and periodontal diseases.

    Science.gov (United States)

    Hassell, T M; Harris, E L

    1995-01-01

    Deciphering the relative roles of heredity and environmental factors ("nature vs. nurture") in the pathogenesis of dental caries and diseases of the periodontium has occupied clinical and basic researchers for decades. Success in the endeavor has come more easily in the case of caries; the complex interactions that occur between host-response mechanisms and putative microbiologic pathogens in periodontal disease have made elucidation of genetic factors in disease susceptibility more difficult. In addition, during the 30-year period between 1958 and 1987, only meager resources were targeted toward the "nature" side of the nature/nurture dipole in periodontology. In this article, we present a brief history of the development of genetic epistemology, then describe the three main research mechanisms by which questions about the hereditary component of diseases in humans can be addressed. A critical discussion of the evidence for a hereditary component in caries susceptibility is next presented, also from a historical perspective. The evolution of knowledge concerning possible genetic ("endogenous", "idiotypic") factors in the pathogenesis of inflammatory periodontal disease is initiated with an analysis of some foreign-language (primarily German) literature that is likely to be unfamiliar to the reader. We identify a turning point at about 1960, when the periodontal research community turned away from genetics in favor of microbiology research. During the past five years, investigators have re-initiated the search for the hereditary component in susceptibility to common adult periodontal disease; this small but growing body of literature is reviewed. Recent applications of in vitro methods for genetic analyses in periodontal research are presented, with an eye toward a future in which persons who are at risk--genetically predisposed--to periodontal disease may be identified and targeted for interventive strategies. Critical is the realization that genes and environment

  3. Inflammatory Bowel Disease: Genetics, Epigenetics and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Italia eLoddo

    2015-11-01

    Full Text Available Inflammatory Bowel Diseases (IBDs are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Although aetiology remains largely unknown, recent research has suggested that genetic factors, environment, microbiota and immune response are involved in the pathogenesis.Epidemiological evidence for a genetic contribution is defined: 15% of patients with Crohn’s Disease (CD have an affected family member with IBD, and twin studies for CD have shown 50% concordance in monozygotic twins compared to less than 10% in dizygotics. The most recent and largest genetic association studies, which employed genome-wide association data for over 75,000 patients and controls, identified 163 susceptibility loci for IBD. More recently, a trans-ethnic analysis, including over 20,000 individuals, identified an additional 38 new IBD loci.Although most cases are correlated with polygenic contribution toward genetic susceptibility, there is a spectrum of rare genetic disorders that can contribute to early onset IBD (before 5 years or very early IBD (before 2 years. Genetic variants that cause these disorders have a wide effect on gene function. These variants are so rare in allele frequency that the genetic signals are not detected in genome-wide association studies of patients with IBD. With recent advances in sequencing techniques, approximately 50 genetic disorders have been identified and associated with IBD-like immunopathology. Monogenic defects have been found to alter intestinal immune homeostasis through many mechanisms. Candidate gene resequencing should be carried out in early-onset patients in clinical practice.The evidence that genetic factors contribute in small part to disease pathogenesis confirms the important role of microbial and environmental factors. Epigenetic factors can mediate interactions between environment and genome. Epigenetic mechanisms could affect development and progression of IBD. Epigenomics is

  4. Diametrical diseases reflect evolutionary-genetic tradeoffs

    Science.gov (United States)

    Crespi, Bernard J.; Go, Matthew C.

    2015-01-01

    Tradeoffs centrally mediate the expression of human adaptations. We propose that tradeoffs also influence the prevalence and forms of human maladaptation manifest in disease. By this logic, increased risk for one set of diseases commonly engenders decreased risk for another, diametric, set of diseases. We describe evidence for such diametric sets of diseases from epidemiological, genetic and molecular studies in four clinical domains: (i) psychiatry (autism vs psychotic-affective conditions), (ii) rheumatology (osteoarthritis vs osteoporosis), (iii) oncology and neurology (cancer vs neurodegenerative disorders) and (iv) immunology (autoimmunity vs infectious disease). Diametric disorders are important to recognize because genotypes or environmental factors that increase risk for one set of disorders protect from opposite disorders, thereby providing novel and direct insights into disease causes, prevention and therapy. Ascertaining the mechanisms that underlie disease-related tradeoffs should also indicate means of circumventing or alleviating them, and thus reducing the incidence and impacts of human disease in a more general way. PMID:26354001

  5. Equine diseases caused by known genetic mutations.

    Science.gov (United States)

    Finno, Carrie J; Spier, Sharon J; Valberg, Stephanie J

    2009-03-01

    The recent development of equine genome maps by the equine genome community and the complete sequencing of the horse genome performed at the Broad Institute have accelerated the pace of genetic discovery. This review focuses on genetic diseases in the horse for which a mutation is currently known, including hyperkalemic periodic paralysis, severe combined immunodeficiency, overo lethal white syndrome, junctional epidermolysis bullosa, glycogen branching enzyme deficiency, malignant hyperthermia, hereditary equine regional dermal asthenia, and polysaccharide storage myopathy. Emphasis is placed on the prevalence, clinical signs, etiology, diagnosis, treatment and prognosis for each disease.

  6. Chronic obstructive pulmonary disease and genetics

    DEFF Research Database (Denmark)

    Ingebrigtsen, T.; Thomsen, S.F.; Vestbo, J.

    2008-01-01

    Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and is associated with an inflammatory response of the lungs primarily caused by cigarette smoking. Cigarette smoking is by far the most important environmental risk factor for COPD, but less than half of all heavy...... smokers develop COPD. This indicates a genetic contribution to the individual disease susceptibility. Although many genes have been examined, the puzzle of COPD genetics seems still largely unsolved. It is therefore important to measure phenotypes and to perform genome-wide scans of COPD patients in order...

  7. Genetics of Parkinson’s Disease - A Clinical Perspective

    Directory of Open Access Journals (Sweden)

    Sang-Myung Cheon

    2012-10-01

    Full Text Available Discovering genes following Medelian inheritance, such as autosomal dominant-synuclein and leucine-rich repeat kinase 2 gene, or autosomal recessive Parkin, P-TEN-induced putative kinase 1 gene and Daisuke-Junko 1 gene, has provided great insights into the pathogenesis of Parkinson’s disease (PD. Genes found to be associated with PD through investigating genetic polymorphisms or via the whole genome association studies suggest that such genes could also contribute to an increased risk of PD in the general population. Some environmental factors have been found to be associated with genetic factors in at-risk patients, further implicating the role of gene-environment interactions in sporadic PD. There may be confusion for clinicians facing rapid progresses of genetic understanding in PD. After a brief review of PD genetics, we will discuss the insight of new genetic discoveries to clinicians, the implications of ethnic differences in PD genetics and the role of genetic testing for general clinicians managing PD patients.

  8. Drosophila provides rapid modeling of renal development, function, and disease

    Science.gov (United States)

    Romero, Michael F.

    2010-01-01

    The evolution of specialized excretory cells is a cornerstone of the metazoan radiation, and the basic tasks performed by Drosophila and human renal systems are similar. The development of the Drosophila renal (Malpighian) tubule is a classic example of branched tubular morphogenesis, allowing study of mesenchymal-to-epithelial transitions, stem cell-mediated regeneration, and the evolution of a glomerular kidney. Tubule function employs conserved transport proteins, such as the Na+, K+-ATPase and V-ATPase, aquaporins, inward rectifier K+ channels, and organic solute transporters, regulated by cAMP, cGMP, nitric oxide, and calcium. In addition to generation and selective reabsorption of primary urine, the tubule plays roles in metabolism and excretion of xenobiotics, and in innate immunity. The gene expression resource FlyAtlas.org shows that the tubule is an ideal tissue for the modeling of renal diseases, such as nephrolithiasis and Bartter syndrome, or for inborn errors of metabolism. Studies are assisted by uniquely powerful genetic and transgenic resources, the widespread availability of mutant stocks, and low-cost, rapid deployment of new transgenics to allow manipulation of renal function in an organotypic context. PMID:20926630

  9. Genotator: a disease-agnostic tool for genetic annotation of disease.

    Science.gov (United States)

    Wall, Dennis P; Pivovarov, Rimma; Tong, Mark; Jung, Jae-Yoon; Fusaro, Vincent A; DeLuca, Todd F; Tonellato, Peter J

    2010-10-29

    Disease-specific genetic information has been increasing at rapid rates as a consequence of recent improvements and massive cost reductions in sequencing technologies. Numerous systems designed to capture and organize this mounting sea of genetic data have emerged, but these resources differ dramatically in their disease coverage and genetic depth. With few exceptions, researchers must manually search a variety of sites to assemble a complete set of genetic evidence for a particular disease of interest, a process that is both time-consuming and error-prone. We designed a real-time aggregation tool that provides both comprehensive coverage and reliable gene-to-disease rankings for any disease. Our tool, called Genotator, automatically integrates data from 11 externally accessible clinical genetics resources and uses these data in a straightforward formula to rank genes in order of disease relevance. We tested the accuracy of coverage of Genotator in three separate diseases for which there exist specialty curated databases, Autism Spectrum Disorder, Parkinson's Disease, and Alzheimer Disease. Genotator is freely available at http://genotator.hms.harvard.edu. Genotator demonstrated that most of the 11 selected databases contain unique information about the genetic composition of disease, with 2514 genes found in only one of the 11 databases. These findings confirm that the integration of these databases provides a more complete picture than would be possible from any one database alone. Genotator successfully identified at least 75% of the top ranked genes for all three of our use cases, including a 90% concordance with the top 40 ranked candidates for Alzheimer Disease. As a meta-query engine, Genotator provides high coverage of both historical genetic research as well as recent advances in the genetic understanding of specific diseases. As such, Genotator provides a real-time aggregation of ranked data that remains current with the pace of research in the disease

  10. Genotator: A disease-agnostic tool for genetic annotation of disease

    Directory of Open Access Journals (Sweden)

    Jung Jae-Yoon

    2010-10-01

    Full Text Available Abstract Background Disease-specific genetic information has been increasing at rapid rates as a consequence of recent improvements and massive cost reductions in sequencing technologies. Numerous systems designed to capture and organize this mounting sea of genetic data have emerged, but these resources differ dramatically in their disease coverage and genetic depth. With few exceptions, researchers must manually search a variety of sites to assemble a complete set of genetic evidence for a particular disease of interest, a process that is both time-consuming and error-prone. Methods We designed a real-time aggregation tool that provides both comprehensive coverage and reliable gene-to-disease rankings for any disease. Our tool, called Genotator, automatically integrates data from 11 externally accessible clinical genetics resources and uses these data in a straightforward formula to rank genes in order of disease relevance. We tested the accuracy of coverage of Genotator in three separate diseases for which there exist specialty curated databases, Autism Spectrum Disorder, Parkinson's Disease, and Alzheimer Disease. Genotator is freely available at http://genotator.hms.harvard.edu. Results Genotator demonstrated that most of the 11 selected databases contain unique information about the genetic composition of disease, with 2514 genes found in only one of the 11 databases. These findings confirm that the integration of these databases provides a more complete picture than would be possible from any one database alone. Genotator successfully identified at least 75% of the top ranked genes for all three of our use cases, including a 90% concordance with the top 40 ranked candidates for Alzheimer Disease. Conclusions As a meta-query engine, Genotator provides high coverage of both historical genetic research as well as recent advances in the genetic understanding of specific diseases. As such, Genotator provides a real-time aggregation of ranked

  11. Genetic risk factors for autoimmune diseases

    NARCIS (Netherlands)

    Feltkamp, T.E.W.; Aarden, L.A.; Lucas, C.J.; Verweij, C.L.; Vries, R.R.P. de

    1999-01-01

    In most autoimmune diseases multigenic factors play a significant role in pathogenesis. Progress in identifying these genetic factors, many of which are located outside the major histocompatibility complex, was the subject of a recent meeting. Chemicals/CAS: Interleukin-10, 130068-27-8; Transforming

  12. The modular nature of genetic diseases.

    NARCIS (Netherlands)

    Oti, M.O.; Brunner, H.G.

    2007-01-01

    Evidence from many sources suggests that similar phenotypes are begotten by functionally related genes. This is most obvious in the case of genetically heterogeneous diseases such as Fanconi anemia, Bardet-Biedl or Usher syndrome, where the various genes work together in a single biological module.

  13. Advances in the genetics of eye diseases.

    Science.gov (United States)

    Chan, Stephanie; Freund, Paul R; MacDonald, Ian

    2013-12-01

    An update on heritable eye disease will allow informed patient counseling and improved patient care. New loci and genes have been associated with identifiable heritable ocular traits. Molecular genetic analysis is available for many of these genes either as part of research or for clinical testing. The advent of gene array technologies has enabled screening of samples for known mutations in genes linked to various disorders. Exomic sequencing has proven to be particularly successful in research protocols in identifying the genetic causation of rare genetic traits by pooling patient resources and discovering new genes. Further, genetic analysis has led improvement in patient care and counselling, as exemplified by the continued advances in our treatment of retinoblastoma. Patients and families are commonly eager to participate in either research or clinical testing to improve their understanding of the cause and heritability of an ocular condition. Many patients hope that testing will then lead to appropriate treatments or cures. The success of gene therapy in the RPE65 form of Leber congenital amaurosis has provided a brilliant example of this hope; that a similar trial may become available to other patients and families burdened by genetic disease.

  14. A genetic future for coronary heart disease?

    Science.gov (United States)

    Weiner, Kate; Martin, Paul

    2008-04-01

    This paper is concerned with changing conceptions of genetic disease. It is based on an analysis of biomedical literature and focuses on the treatment of coronary heart disease (CHD) in four published commentary papers. The aim of this analysis is to explore the ways in which CHD is constructed as genetic and the place of genetic discourses in the wider set of ideas that circulate about the disease. This analysis is then used to consider some of the claims of the geneticisation thesis (Lippman 1991, 1992). The analysis suggests that a genetic vision for understanding and managing CHD has emerged, which has many of the hallmarks of the geneticisation imagined by Lippman. However, a number of alternative and competing models of CHD are also supported within the biomedical discourse. These are related to the different disciplines with a stake in the field of CHD, and their struggles for authority. In conclusion, it is suggested that the geneticisation thesis, as a universal claim, is at odds with the diffuse and distributed nature of biomedical knowledge and practice. Rather than analysing geneticisation in a literal way, it may be more fruitful to see the thesis, itself, as a form of boundary work (Gieryn 1983).

  15. Rapid detection of genetic modification for GMO monitoring in agriculture

    National Research Council Canada - National Science Library

    Petrović Sofija; Dimitrijević Miodrag

    2015-01-01

    .... However, for the most part, GMO in agriculture has been limited to two cultivars - soy and corn, and the two genetic modifications, the total herbicide resistance and pest of the Lepidoptera genus...

  16. Genetic and environmental pathways to complex diseases

    Directory of Open Access Journals (Sweden)

    Becker Kevin G

    2009-05-01

    Full Text Available Abstract Background Pathogenesis of complex diseases involves the integration of genetic and environmental factors over time, making it particularly difficult to tease apart relationships between phenotype, genotype, and environmental factors using traditional experimental approaches. Results Using gene-centered databases, we have developed a network of complex diseases and environmental factors through the identification of key molecular pathways associated with both genetic and environmental contributions. Comparison with known chemical disease relationships and analysis of transcriptional regulation from gene expression datasets for several environmental factors and phenotypes clustered in a metabolic syndrome and neuropsychiatric subnetwork supports our network hypotheses. This analysis identifies natural and synthetic retinoids, antipsychotic medications, Omega 3 fatty acids, and pyrethroid pesticides as potential environmental modulators of metabolic syndrome phenotypes through PPAR and adipocytokine signaling and organophosphate pesticides as potential environmental modulators of neuropsychiatric phenotypes. Conclusion Identification of key regulatory pathways that integrate genetic and environmental modulators define disease associated targets that will allow for efficient screening of large numbers of environmental factors, screening that could set priorities for further research and guide public health decisions.

  17. Genetic testing in diffuse parenchymal lung disease

    Directory of Open Access Journals (Sweden)

    Spagnolo Paolo

    2012-10-01

    Full Text Available Abstract Diffuse parenchymal lung diseases (DPLD represent a diverse group of disorders affecting the distal lung parenchyma, specifically the tissue and spaces surrounding the alveoli, which may be filled with inflammatory cells, proliferating fibroblasts or established fibrosis, often leading to architectural distortion and impaired gas exchange. While the underlying pathogenetic mechanisms are known or inferred for some DPLD (such as sarcoidosis, silicosis, drug reactions and collagen vascular diseases, the pathogenesis of the majority of these entities - particularly those characterized by progressive fibrosis - is poorly understood. Several lines of evidence indicate that the development of pulmonary fibrosis is genetically determined. They include: 1. familial clustering; 2. the occurrence of pulmonary fibrosis in the context of rare inherited disorders; 3. substantial variability in the development of pulmonary fibrosis amongst individuals exposed to organic or inorganic dusts; 4. difference in susceptibility to fibrogenic stimuli amongst inbred strains of mice. This review focuses on idiopathic pulmonary fibrosis (IPF and sarcoidosis, the two most common DPLD and the two entities for which there is stronger evidence of a genetic predisposition, although how aberrant genes interact with each other and with environmental factors, such as smoking in IPF and infectious agents in sarcoidosis, in determining disease susceptibility and clinical phenotypes is largely unknown. Finally, we discuss practical issues and implications for both patients and physicians of recent advances in the genetics of sarcoidosis and IPF.

  18. Autoimmune Addison disease: pathophysiology and genetic complexity.

    Science.gov (United States)

    Mitchell, Anna L; Pearce, Simon H S

    2012-01-31

    Autoimmune Addison disease is a rare autoimmune disorder with symptoms that typically develop over months or years. Following the development of serum autoantibodies to the key steroidogenic enzyme, 21-hydroxylase, patients have a period of compensated or preclinical disease, characterized by elevations in adrenocortocotropic hormone and renin, before overt, symptomatic adrenal failure develops. We propose that local failure of steroidogenesis, causing breakdown of tolerance to adrenal antigens, might be a key factor in disease progression. The etiology of autoimmune Addison disease has a strong genetic component in man, and several dog breeds are also susceptible. Allelic variants of genes encoding molecules of both the adaptive and innate immune systems have now been implicated, with a focus on the immunological synapse and downstream participants in T lymphocyte antigen-receptor signaling. With the exception of MHC alleles, which contribute to susceptibility in both human and canine Addison disease, no major or highly penetrant disease alleles have been found to date. Future research into autoimmune Addison disease, making use of genome-wide association studies and next-generation sequencing technology, will address the gaps in our understanding of the etiology of this disease.

  19. Translating human genetics into mouse: the impact of ultra-rapid in vivo genome editing.

    Science.gov (United States)

    Aida, Tomomi; Imahashi, Risa; Tanaka, Kohichi

    2014-01-01

    Gene-targeted mutant animals, such as knockout or knockin mice, have dramatically improved our understanding of the functions of genes in vivo and the genetic diversity that characterizes health and disease. However, the generation of targeted mice relies on gene targeting in embryonic stem (ES) cells, which is a time-consuming, laborious, and expensive process. The recent groundbreaking development of several genome editing technologies has enabled the targeted alteration of almost any sequence in any cell or organism. These technologies have now been applied to mouse zygotes (in vivo genome editing), thereby providing new avenues for simple, convenient, and ultra-rapid production of knockout or knockin mice without the need for ES cells. Here, we review recent achievements in the production of gene-targeted mice by in vivo genome editing. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

  20. Transposable elements as agents of rapid adaptation may explain the genetic paradox of invasive species.

    Science.gov (United States)

    Stapley, Jessica; Santure, Anna W; Dennis, Stuart R

    2015-05-01

    Rapid adaptation of invasive species to novel habitats has puzzled evolutionary biologists for decades, especially as this often occurs in the face of limited genetic variability. Although some ecological traits common to invasive species have been identified, little is known about the possible genomic/genetic mechanisms that may underlie their success. A common scenario in many introductions is that small founder population sizes will often lead to reduced genetic diversity, but that invading populations experience large environmental perturbations, such as changes in habitat and environmental stress. Although sudden and intense stress is usually considered in a negative context, these perturbations may actually facilitate rapid adaptation by affecting genome structure, organization and function via interactions with transposable elements (TEs), especially in populations with low genetic diversity. Stress-induced changes in TE activity can alter gene action and can promote structural variation that may facilitate the rapid adaptation observed in new environments. We focus here on the adaptive potential of TEs in relation to invasive species and highlight their role as powerful mutational forces that can rapidly create genetic diversity. We hypothesize that activity of transposable elements can explain rapid adaptation despite low genetic variation (the genetic paradox of invasive species), and provide a framework under which this hypothesis can be tested using recently developed and emerging genomic technologies. © 2015 John Wiley & Sons Ltd.

  1. Highways block gene flow and cause a rapid decline in genetic diversity of desert bighorn sheep

    NARCIS (Netherlands)

    Epps, CW; Palsboll, PJ; Wehausen, JD; Roderick, GK; Ramey, RR; McCullough, DR

    2005-01-01

    The rapid expansion of road networks has reduced connectivity among populations of flora and fauna. The resulting isolation is assumed to increase population extinction rates, in part because of the loss of genetic diversity. However, there are few cases where loss of genetic diversity has been

  2. Genetically determined height and coronary artery disease.

    Science.gov (United States)

    Nelson, Christopher P; Hamby, Stephen E; Saleheen, Danish; Hopewell, Jenna C; Zeng, Lingyao; Assimes, Themistocles L; Kanoni, Stavroula; Willenborg, Christina; Burgess, Stephen; Amouyel, Phillipe; Anand, Sonia; Blankenberg, Stefan; Boehm, Bernhard O; Clarke, Robert J; Collins, Rory; Dedoussis, George; Farrall, Martin; Franks, Paul W; Groop, Leif; Hall, Alistair S; Hamsten, Anders; Hengstenberg, Christian; Hovingh, G Kees; Ingelsson, Erik; Kathiresan, Sekar; Kee, Frank; König, Inke R; Kooner, Jaspal; Lehtimäki, Terho; März, Winifred; McPherson, Ruth; Metspalu, Andres; Nieminen, Markku S; O'Donnell, Christopher J; Palmer, Colin N A; Peters, Annette; Perola, Markus; Reilly, Muredach P; Ripatti, Samuli; Roberts, Robert; Salomaa, Veikko; Shah, Svati H; Schreiber, Stefan; Siegbahn, Agneta; Thorsteinsdottir, Unnur; Veronesi, Giovani; Wareham, Nicholas; Willer, Cristen J; Zalloua, Pierre A; Erdmann, Jeanette; Deloukas, Panos; Watkins, Hugh; Schunkert, Heribert; Danesh, John; Thompson, John R; Samani, Nilesh J

    2015-04-23

    The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; Pheight. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; Pheight and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.).

  3. Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Disease.

    Science.gov (United States)

    Howell, Michael Joseph; Schenck, Carlos Hugh

    2015-06-01

    The dream enactment of rapid eye movement sleep behavior disorder (RBD) is often the first indication of an impending α-synuclein disorder, such as Parkinson disease, multiple-system atrophy, or dementia with Lewy bodies. To provide an overview of RBD from the onset of dream enactment through the emergence of a parkinsonian disorder. Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized trials, and basic science investigations, were identified in a PubMed search of articles on RBD from January 1, 1986, through July 31, 2014. Under normal conditions, vivid dream mentation combined with skeletal muscle paralysis characterizes rapid eye movement sleep. In RBD, α-synuclein abnormalities in the brainstem disinhibit rapid eye movement sleep motor activity, leading to dream enactment. The behaviors of RBD are often theatrical, with complexity, aggression, and violence; fighting and fleeing actions can be injurious to patients as well as bed partners. Rapid eye movement sleep behavior disorder is distinguished from other parasomnias by clinical features and the demonstration of rapid eye movement sleep without atonia on polysomnography. Consistent with early neurodegeneration, patients with RBD demonstrate subtle motor, cognitive, and autonomic impairments. Approximately 50% of patients with spontaneous RBD will convert to a parkinsonian disorder within a decade. Ultimately, nearly all (81%-90%) patients with RBD develop a neurodegenerative disorder. Among patients with Parkinson disease, RBD predicts a non-tremor-predominant subtype, gait freezing, and an aggressive clinical course. The most commonly cited RBD treatments include low-dose clonazepam or high-dose melatonin taken orally at bedtime. Treatment of RBD can prevent injury to patients and bed partners. Because RBD is a prodromal syndrome of Parkinson disease (or related disorder), it represents a unique opportunity for developing and testing disease

  4. Genetic Influences on Cystic Fibrosis Lung Disease Severity

    Science.gov (United States)

    Weiler, Colleen A.; Drumm, Mitchell L.

    2013-01-01

    Understanding the causes of variation in clinical manifestations of disease should allow for design of new or improved therapeutic strategies to treat the disease. If variation is caused by genetic differences between individuals, identifying the genes involved should present therapeutic targets, either in the proteins encoded by those genes or the pathways in which they function. The technology to identify and genotype the millions of variants present in the human genome has evolved rapidly over the past two decades. Originally only a small number of polymorphisms in a small number of subjects could be studied realistically, but speed and scope have increased nearly as dramatically as cost has decreased, making it feasible to determine genotypes of hundreds of thousands of polymorphisms in thousands of subjects. The use of such genetic technology has been applied to cystic fibrosis (CF) to identify genetic variation that alters the outcome of this single gene disorder. Candidate gene strategies to identify these variants, referred to as “modifier genes,” has yielded several genes that act in pathways known to be important in CF and for these the clinical implications are relatively clear. More recently, whole-genome surveys that probe hundreds of thousands of variants have been carried out and have identified genes and chromosomal regions for which a role in CF is not at all clear. Identification of these genes is exciting, as it provides the possibility for new areas of therapeutic development. PMID:23630497

  5. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Genetic Heterogeneity of Alzheimer's Disease: Embracing Research Partnerships.

    Science.gov (United States)

    Nacmias, Benedetta; Bagnoli, Silvia; Piaceri, Irene; Sorbi, Sandro

    2017-11-01

    Studies on the genetics of Alzheimer's disease (AD) have revealed the complexity and heterogeneity of the disease. All our studies have supported this evidence and contribute to the current understanding of the genetic architecture of AD. This report reviews the success of our investigations, focusing on the implications and importance of the genetics of AD, and demonstrates the relevance of research strategies embracing partnerships.

  7. Basement Membrane Defects in Genetic Kidney Diseases

    Directory of Open Access Journals (Sweden)

    Christine Chew

    2018-01-01

    Full Text Available The glomerular basement membrane (GBM is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1 and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease.

  8. Shared genetic origins of allergy and autoimmune diseases

    DEFF Research Database (Denmark)

    Waage, J. E.; Kreiner-Møller, E.; Standl, M.

    2015-01-01

    Parallel increases in allergy and autoimmune disease prevalence in recent time suggest shared, but yet unknown, etiologies. Here, we investigated shared genetic loci and molecular pathways to identify possible shared disease mechanisms between allergy and autoimmune diseases....

  9. Genetic influences on cognitive decline in Parkinson's disease.

    Science.gov (United States)

    Morley, James F; Xie, Sharon X; Hurtig, Howard I; Stern, Matthew B; Colcher, Amy; Horn, Stacy; Dahodwala, Nabila; Duda, John E; Weintraub, Daniel; Chen-Plotkin, Alice S; Van Deerlin, Vivianna; Falcone, Dana; Siderowf, Andrew

    2012-04-01

    The role of genetic factors in cognitive decline associated with Parkinson's disease (PD) is unclear. We examined whether variations in apolipoprotein E (APOE), microtubule-associated protein tau (MAPT), or catechol-O-methytransferase (COMT) genotypes are associated with cognitive decline in PD. We performed a prospective cohort study of 212 patients with a clinical diagnosis of PD. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. The ε4 allele of APOE was associated with more rapid decline (loss of 2.9; 95% confidence interval [CI]: 1.7-4.1) of more points per year; P disease stages. Carrying at least one APOE ε4 allele is associated with more rapid cognitive decline in PD, supporting the idea of a component of shared etiology between PD dementia and Alzheimer's disease. Clinically, these results suggest that genotyping can provide information about the risk of future cognitive decline for PD patients. Copyright © 2012 Movement Disorder Society.

  10. Genetic basis for rapidly evolved tolerance in the wild ...

    Science.gov (United States)

    Atlantic killifish (Fundulus heteroclitus) residing in some urban and industrialized estuaries of the US eastern seaboard demonstrate recently evolved and extreme tolerance to toxic aryl hydrocarbon pollutants, characterized as dioxin-like compounds (DLCs). Here we provide an unusually comprehensive accounting (69%) through Quantitative Trait Locus (QTL) analysis of the genetic basis for DLC tolerance in killifish inhabiting an urban estuary contaminated with PCB congeners, the most toxic of which are DLCs. Consistent with mechanistic knowledge of DLC toxicity in fish and other vertebrates, the Aryl Hydrocarbon Receptor (ahr2) region accounts for 17% of trait variation; however, QTLs on independent linkage groups and their interactions have even greater explanatory power (44%). QTLs interpreted within the context of recently available Fundulus genomic resources and shared synteny among fish species suggest adaptation via inter-acting components of a complex stress response network. Some QTLs were also enriched in other killifish populations characterized as DLC tolerant and residing in distant urban estuaries contaminated with unique mixtures of pollutants. Together, our results suggest that DLC tolerance in killifish represents an emerging example of parallel contemporary evolution that has been driven by intense human-mediated selection on natural populations. This manuscript describes experimental studies that contribute to our understanding of the ecological

  11. Genetics and genomics of disease resistance in salmonid species

    Directory of Open Access Journals (Sweden)

    José Manuel Yáñez

    2014-11-01

    Full Text Available Infectious and parasitic diseases generate large economic losses in salmon farming. A feasible and sustainable alternative to prevent disease outbreaks may be represented by genetic improvement for disease resistance. To include disease resistance into the breeding goal, prior knowledge of the levels of genetic variation for these traits is required. Furthermore, the information from the genetic architecture and molecular factors involved in resistance against diseases may be used to accelerate the genetic progress for these traits. In this regard, marker assisted selection and genomic selection are approaches which incorporate molecular information to increase the accuracy when predicting the genetic merit of selection candidates. In this article we review and discuss key aspects related to disease resistance in salmonid species, from both a genetic and genomic perspective, with emphasis in the applicability of disease resistance traits into breeding programs in salmonids.

  12. The statistics of genetic diversity in rapidly adapting populations.

    Science.gov (United States)

    Desai, Michael

    2013-03-01

    Evolutionary adaptation is driven by the accumulation of beneficial mutations, but the sequence-level dynamics of this process are poorly understood. The traditional view is that adaptation is dominated by rare beneficial ``driver'' mutations that occur sporadically and then rapidly increase in frequency until they fix (a ``selective sweep''). Yet in microbial populations, multiple beneficial mutations are often present simultaneously. Selection cannot act on each mutation independently, but only on linked combinations. This means that the fate of any mutation depends on a complex interplay between its own fitness effect, the genomic background in which it arises, and the rest of the sequence variation in the population. The balance between these factors determines which mutations fix, the patterns of sequence diversity within populations, and the degree to which evolution in replicate populations will follow parallel (or divergent) trajectories at the sequence level. Earlier work has uncovered signatures of these effects, but the dynamics of genomic sequence evolution in adapting microbial populations have not yet been directly observed. In this talk, I will describe how full-genome whole-population sequencing can be used to provide a detailed view of these dynamics at high temporal resolution over 1000 generations in 40 adapting Saccharomyces cerevisiaepopulations. This data shows how patterns of sequence evolution are driven by a balance between chance interference and hitchhiking effects, which increase stochastic variation in evolutionary outcomes, and the deterministic action of selection on individual mutations, which favors parallel solutions in replicate populations.

  13. Genetic Diseases and Genetic Determinism Models in French Secondary School Biology Textbooks

    Science.gov (United States)

    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…

  14. An atlas of genetic correlations across human diseases and traits

    DEFF Research Database (Denmark)

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri

    2015-01-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods...... overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity, and educational attainment and several diseases. These results highlight the power of genome-wide analyses...

  15. Rapid non-invasive tests for diagnostics of infectious diseases

    Science.gov (United States)

    Malamud, Daniel

    2014-06-01

    A rapid test for an infectious disease that can be used at point-of-care at a physician's office, a pharmacy, or in the field is critical for the prompt and appropriate therapeutic intervention. Ultimately by treating infections early on will decrease transmission of the pathogen. In contrast to metabolic diseases or cancer where multiple biomarkers are required, infectious disease targets (e.g. antigen, antibody, nucleic acid) are simple and specific for the pathogen causing the disease. Our laboratory has focused on three major infectious disease; HIV, Tuberculosis, and Malaria. These diseases are pandemic in much of the world thus putting natives, tourists and military personnel at risk for becoming infected, and upon returning to the U.S., transmitting these diseases to their contacts. Our devices are designed to detect antigens, antibodies or nucleic acids in blood or saliva samples in less than 30 minutes. An overview describing the current status of each of the three diagnostic platforms is presented. These microfluidic point-of-care devices will be relatively inexpensive, disposable, and user friendly.

  16. Eye and rare genetic diseases: Case series and literature review ...

    African Journals Online (AJOL)

    Genetic diseases are generally characterised by a multi visceral pathogenesis. Although orphan, these diseases interest many disciplines due to their clinical expression. Eye is sometimes part of the clinical polymorphism of some rare genetic diseases. Ocular signs are in some cases leading to the diagnosis of these ...

  17. Population Genetics and Natural Selection in Rheumatic Disease.

    Science.gov (United States)

    Ramos, Paula S

    2017-08-01

    Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Natural selection is an important influence on human genetic variation. Because immune and inflammatory function genes are enriched for signals of positive selection, the prevalence of rheumatic disease-risk alleles seen in different populations is partially the result of differing selective pressures (eg, due to pathogens). This review summarizes the genetic regions associated with susceptibility to different rheumatic diseases and concomitant evidence for natural selection, including known agents of selection exerting selective pressure in these regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Disease-Concordant Twins Empower Genetic Association Studies

    DEFF Research Database (Denmark)

    Tan, Qihua; Li, Weilong; Vandin, Fabio

    2017-01-01

    concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases...... of an ordinary case-control design, with variations depending on genetic mode. Importantly, the enriched power for dizygotic twins also applies to disease-concordant sibling pairs, which largely extends the application of the concordant twin design. Overall, our simulation revealed a high value of disease......-concordant twins in genetic association studies and encourages the use of genetically related individuals for highly efficiently identifying both common and rare genetic variants underlying human complex diseases without increasing laboratory cost....

  19. A history into genetic and epigenetic evolution of food tolerance: how humanity rapidly evolved by drinking milk and eating wheat.

    Science.gov (United States)

    Blanchard, Carine

    2017-12-01

    Human exposure to wheat and milk is almost global worldwide. Yet the introduction of milk and wheat is very recent (5000-10 000 years) when compared to the human evolution. The last 4 decades have seen a rise in food allergy and food intolerance to milk and wheat. Often described as plurifactorial, the cause of allergic diseases is the result from an interplay between genetic predisposition and epigenetic in the context of environmental changes. Genetic and epigenetic understanding and their contribution to allergy or other antigen-driven diseases have considerably advanced in the last few years. Yet, environmental factors are also quite difficult to identify and associate with disease risk. Can we rethink our old findings and learn from human history and recent genetic studies? More than one million years separate Homo habilis to today's mankind, more than 1 million years to develop abilities to obtain food by foraging in diverse environments. One million year to adjust and fine-tune our genetic code and adapt; and only 1% of this time, 10 000 years, to face the three biggest revolutions of the human kind: the agricultural revolution, the industrial revolution and the postindustrial revolution. With big and rapid environmental changes come adaptation but with no time for fine-tuning. Today tolerance and adverse reactions to food may be a testimony of adaptation successes and mistakes.

  20. Genetics and genomics of psychiatric disease.

    Science.gov (United States)

    Geschwind, Daniel H; Flint, Jonathan

    2015-09-25

    Large-scale genomic investigations have just begun to illuminate the molecular genetic contributions to major psychiatric illnesses, ranging from small-effect-size common variants to larger-effect-size rare mutations. The findings provide causal anchors from which to understand their neurobiological basis. Although these studies represent enormous success, they highlight major challenges reflected in the heterogeneity and polygenicity of all of these conditions and the difficulty of connecting multiple levels of molecular, cellular, and circuit functions to complex human behavior. Nevertheless, these advances place us on the threshold of a new frontier in the pathophysiological understanding, diagnosis, and treatment of psychiatric disease. Copyright © 2015, American Association for the Advancement of Science.

  1. Genetic Testing for Complex Diseases: a Simulation Study Perspective

    OpenAIRE

    Vinh, Nguyen Xuan

    2011-01-01

    It is widely recognized nowadays that complex diseases are caused by, amongst the others, multiple genetic factors. The recent advent of genome-wide association study (GWA) has triggered a wave of research aimed at discovering genetic factors underlying common complex diseases. While the number of reported susceptible genetic variants is increasing steadily, the application of such findings into diseases prognosis for the general population is still unclear, and there are doubts about whether...

  2. Genetic drift and rapid evolution of viviparity in insular fire salamanders (Salamandra salamandra).

    Science.gov (United States)

    Velo-Antón, G; Zamudio, K R; Cordero-Rivera, A

    2012-04-01

    Continental islands offer an excellent opportunity to investigate adaptive processes and to time microevolutionary changes that precede macroevolutionary events. We performed a population genetic study of the fire salamander (Salamandra salamandra), a species that displays unique intraspecific diversity of reproductive strategies, to address the microevolutionary processes leading to phenotypic and genetic differentiation of island, coastal and interior populations. We used eight microsatellite markers to estimate genetic diversity, population structure and demographic parameters in viviparous insular populations and ovoviviparous coastal and interior populations. Our results show considerable genetic differentiation (F(ST) range: 0.06-0.27), and no clear signs of gene flow among populations, except between the large and admixed interior populations. We find no support for island colonization by rafting or intentional/accidental anthropogenic introductions, indicating that rising sea levels were responsible for isolation of the island populations approximately 9000 years ago. Our study provides evidence of rapid genetic differentiation between island and coastal populations, and rapid evolution of viviparity driven by climatic selective pressures on island populations, geographic isolation with genetic drift, or a combination of these factors. Studies of these viviparous island populations in early stages of divergence help us better understand the microevolutionary processes involved in rapid phenotypic shifts.

  3. Genetics of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Dongiovanni, Paola; Valenti, Luca

    2016-08-01

    Epidemiological, familial, and twin studies indicate that non-alcoholic fatty liver disease, now the leading cause of liver damage in developed countries, has a strong heritability. The common I148M variant of PNPLA3 impairing hepatocellular lipid droplets remodeling is the major genetic determinant of hepatic fat content. The I148M variant has a strong impact on the full spectrum of liver damage related to fatty liver, encompassing non-alcoholic steatohepatitis, advanced fibrosis, and hepatocellular carcinoma, and influences the response to therapeutic approaches. Common variants in GCKR enhance de novo hepatic lipogenesis in response to glucose and liver inflammation. Furthermore, the low-frequency E167K variant of TM6SF2 and rare mutations in APOB, which impair very low-density lipoproteins secretion, predispose to progressive fatty liver. These and other recent findings reviewed here indicate that impaired lipid handling by hepatocytes has a major role in the pathogenesis of non-alcoholic fatty liver disease by triggering inflammation, fibrogenesis, and carcinogenesis. These discoveries have provided potential novel biomarkers for clinical use and have revealed intriguing therapeutic targets. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Genetic architecture: the shape of the genetic contribution to human traits and disease.

    Science.gov (United States)

    Timpson, Nicholas J; Greenwood, Celia M T; Soranzo, Nicole; Lawson, Daniel J; Richards, J Brent

    2018-02-01

    Genetic architecture describes the characteristics of genetic variation that are responsible for heritable phenotypic variability. It depends on the number of genetic variants affecting a trait, their frequencies in the population, the magnitude of their effects and their interactions with each other and the environment. Defining the genetic architecture of a complex trait or disease is central to the scientific and clinical goals of human genetics, which are to understand disease aetiology and aid in disease screening, diagnosis, prognosis and therapy. Recent technological advances have enabled genome-wide association studies and emerging next-generation sequencing studies to begin to decipher the nature of the heritable contribution to traits and disease. Here, we describe the types of genetic architecture that have been observed, how architecture can be measured and why an improved understanding of genetic architecture is central to future advances in the field.

  5. Genetic and Functional Profiling of Crohn's Disease: Autophagy Mechanism and Susceptibility to Infectious Diseases

    Science.gov (United States)

    Bianco, Anna Monica; Girardelli, Martina; Tommasini, Alberto; Martelossi, Stefano

    2013-01-01

    Crohn's disease is a complex disease in which genome, microbiome, and environment interact to produce the immunological background of the disease. Disease in childhood is more extensive and characterized by a rapid progression, leading to severe repercussions in the course of the disorder. Several genetic variations have been associated with an increased risk of developing the disease and most of these are also implicated in other autoimmune disorders. The gut has many tiers of defense against incursion by luminal microbes, including the epithelial barrier and the innate and adaptive immune responses. Moreover, recent evidence shows that bacterial and viral infections, as well as inflammasome genes and genes involved in the autophagy process, are implicated in Crohn's disease pathogenesis. The aim of this review is to establish how much the diagnostic system can improve, thus increasing the success of Crohn's disease diagnosis. The major expectation for the near future is to be able to anticipate the possible consequences of the disease already in childhood, thus preventing associated complications, and to choose the best treatment for each patient. PMID:23738324

  6. [Parkinson Disease With Rapid Eye Movement Sleep Behavior Disorder].

    Science.gov (United States)

    Hu, Yang; Zhang, Wei

    2015-06-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by lack of muscle atonia during REM sleep and enactment of dream content. RBD is associated with Parkinson disease (PD) and has high incidence in PD patients. PD patient with RBD mainly presents rigid type, has longer disease duration, more severe motor and non-motor symptoms and poorer activity of daily living and life quality. The pathophysiological mechanisms of RBD may be related to dysfunctions of pontine tegmentum, locus coeruleus/sub-locus coeruleus complex and related projections. The diagnosis of RBD depends on clinical histories and video-polysomnography (v-PSG). Besides treatment for PD, protective measures have to be taken for patients and their sleep partners. If abnormal behaviors during sleep cause distress and danger,patients should be given drug therapy.

  7. Genetics Home Reference: critical congenital heart disease

    Science.gov (United States)

    ... hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the ... Information What information about a genetic condition can statistics provide? Why are some genetic conditions more common ...

  8. Genetic Alterations in Intervertebral Disc Disease

    Directory of Open Access Journals (Sweden)

    Nikolay L. Martirosyan

    2016-11-01

    Full Text Available Background: Intervertebral disc degeneration (IVDD is considered a multifactorial disease. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single nucleotide polymorphisms (SNPs that are associated with IVDD.Aim: This review explores and presents updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD.Results: SNPs in the genes coding for structural proteins linked with IVDD or disc bulging include the Sp1 polymorphism of COL1A1, Trp3 polymorphism of COL9A3, several polymorphisms of COL11A1 and COL11A2, and a variable number tandem repeat polymorphism of ACAN. The rs4148941 SNP of CHST3 coding for an aggrecan sulfation enzyme is also associated with IVDD. The FokI, TaqI, and ApaI SNPs of the vitamin D receptor gene that is involved in chondrocyte functioning are also associated with IVDD. SNPs relevant to cytokine imbalance in IVDD include 889C/T of IL1a and 15T/A, as well as other SNPs (rs1800795, rs1800796, and rs1800797, of IL6, with effects limited to certain genders and populations. SNPs in collagenase genes include -1605G/D (guanine insertion/deletion of MMP1, -1306C/T of MMP2, -1562C/T and a 5-adenosine (5A variant (in the promotor region of MMP3, -1562C/T of MMP9, and -378T/C of MMP-14. SNPs in aggrecanase genes include 1877T/U of ADAMTS-4 and rs162509 of ADAMTS-5. Among the apoptosis-mediating genes, 1595T/C of the caspase 9 gene, 1525A/G and 1595T/C of the TRAIL gene, and 626C/G of the death receptor 4 gene (DR4 are SNPs associated with IVDD. Among the growth factors involved in disc homeostasis, the rs4871857 SNP of GDF5 was associated with IVDD. VEGF SNPs -2578C/A and -634G/C could foster neovascularization observed in IVDD.Conclusion: Improved understanding of the numerous genetic variants behind various

  9. Minding the Genes: a Multidisciplinary Approach towards Genetic Assessment of Cardiovascular Disease.

    Science.gov (United States)

    Rhodes, Ashley; Rosman, Lindsey; Cahill, John; Ingles, Jodie; Murray, Brittney; Tichnell, Crystal; James, Cynthia A; Sears, Samuel F

    2017-04-01

    Genetic assessment for inherited cardiovascular disease (CVD) is increasingly available, due in part to rapid innovations in genetic sequencing technologies. While genetic testing is aimed at reducing uncertainty, it also produces awareness of potential medical conditions and can leave patients feeling uncertain about their risk, especially if there are ambiguous results. This uncertainty can produce psychological distress for patients and their families undergoing the assessment process. Additionally, patients may experience psychological distress related to living with inherited CVD. In order to more effectively manage the psychosocial challenges related to genetic assessment for CVD, a multidisciplinary model expanded to include psychologists and other allied health professionals is outlined. A case study is provided to illustrate how psychological distress can manifest in a patient living with inherited CVD, as well as proposed psychological management of this patient. Finally, a guide for genetic counselors is provided to aid in identifying and managing common psychological reactions to genetic assessment for CVD.

  10. Perceived genetic knowledge, attitudes toward genetic testing, and the relationship between these among patients with a chronic disease.

    NARCIS (Netherlands)

    Morren, M.; Rijken, M.; Baanders, A.N.; Bensing, J.

    2007-01-01

    OBJECTIVE: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition,

  11. Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease

    NARCIS (Netherlands)

    Morren, M.; Rijken, M.; Baanders, A.N.; Bensing, J.

    2007-01-01

    Objective: Genetics increasingly permeate everyday medicine. When patients want to make informed decisions about genetic testing, they require genetic knowledge. This study examined the genetic knowledge and attitudes of patients with chronic diseases, and the relationship between both. In addition,

  12. A cumulative genetic risk score predicts progression in Parkinson's disease.

    Science.gov (United States)

    Pihlstrøm, Lasse; Morset, Kristina Rebekka; Grimstad, Espen; Vitelli, Valeria; Toft, Mathias

    2016-04-01

    The contribution of genetic variability to clinical heterogeneity in Parkinson's disease is insufficiently understood. We aimed to investigate the effect of cumulative genetic risk on clinical outcomes. In a single-center study of 336 patients we genotyped 19 independent susceptibility variants identified in genome-wide association studies of Parkinson's disease. We tested for association between a cumulative genetic risk score and 3 outcome measures: survival, time until progression to Hoehn and Yahr stage 3, and Unified Parkinson's Disease Rating Scale motor score severity. Genetic risk score was significantly associated with time from diagnosis to Hoehn and Yahr stage 3 in a Cox regression model (P = 0.010). We observed no clear association for the other outcomes. We present results linking cumulative genetic risk to a motor outcome in Parkinson's disease. Our findings provide a valuable starting point for future large-scale efforts to map the genetic determinants of phenotypic variability. © 2016 International Parkinson and Movement Disorder Society.

  13. Risk factors for Alzheimer's disease : a genetic-epidemiologic study

    NARCIS (Netherlands)

    C.M. van Duijn (Cornelia)

    1992-01-01

    textabstractThe work presented in this thesis has been motivated by the Jack of knowledge of risk factors for Alzheimer's disease. It has been long recognised that genetic factors are implicated, in particular in early-onset Alzheimer's disease.4 But to what extent are genetic factors involved?

  14. Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

    NARCIS (Netherlands)

    A. McNeill (Alisdair); R-M. Wu (Ruey-Meei); K.-Y. Tzen (Kai-Yuan); P.C. Aguiar (Patricia); J.M. Arbelo (Jose); P. Barone (Paolo); K.P. Bhatia (Kailash); O.G. Barsottini (Orlando); V. Bonifati (Vincenzo); S. Bostantjopoulou (Sevasti); R.A. Bressan (Rodrigo); G. Cossu (Giovanni); P. Cortelli (Pietro); A.C. Felicio (Andre); H.B. Ferraz (Henrique); J. Herrera (Joanna); H. Houlden (Henry); M. Hoexter (Marcelo); C. Isla (Concepcion); A.J. Lees (Andrew); O. Lorenzo-Betancor (Oswaldo); N.E. Mencacci (Niccolo); P. Pastor (Pau); S. Pappata (Sabina); M.T. Pellecchia (Maria Teresa); L. Silveria-Moriyama (Laura); A. Varrone (Andrea); T. Foltynie (Thomas); A.H.V. Schapira (Anthony)

    2013-01-01

    textabstractObjectives:To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.Methods:A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated

  15. Genetic testing and counselling in inherited eye disease

    DEFF Research Database (Denmark)

    Brøndum-Nielsen, Karen; Jensen, Hanne; Timshel, Susanne

    2013-01-01

    Advances in genetics have made genetic testing in patients with inherited eye disease increasingly accessible, and the initiation of clinical intervention trials makes it increasingly clinically relevant. Based on a multidisciplinary collaboration between ophthalmologists and clinical geneticists......, the extensive register of families with monogenic inherited eye diseases at the National Eye Clinic of the Kennedy Center in Denmark provides a valuable asset waiting to be exploited in the global effort to reduce blindness caused by genetic defects....

  16. Genetics

    Science.gov (United States)

    ... Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... mother and medications). These include: Asthma Cancer Coronary heart disease Diabetes Hypertension Stroke MITOCHONDRIAL DNA-LINKED DISORDERS Mitochondria ...

  17. Rapid identification of genetic modifications in Bacillus anthracis using whole genome draft sequences generated by 454 pyrosequencing.

    Directory of Open Access Journals (Sweden)

    Peter E Chen

    Full Text Available BACKGROUND: The anthrax letter attacks of 2001 highlighted the need for rapid identification of biothreat agents not only for epidemiological surveillance of the intentional outbreak but also for implementing appropriate countermeasures, such as antibiotic treatment, in a timely manner to prevent further casualties. It is clear from the 2001 cases that survival may be markedly improved by administration of antimicrobial therapy during the early symptomatic phase of the illness; i.e., within 3 days of appearance of symptoms. Microbiological detection methods are feasible only for organisms that can be cultured in vitro and cannot detect all genetic modifications with the exception of antibiotic resistance. Currently available immuno or nucleic acid-based rapid detection assays utilize known, organism-specific proteins or genomic DNA signatures respectively. Hence, these assays lack the ability to detect novel natural variations or intentional genetic modifications that circumvent the targets of the detection assays or in the case of a biological attack using an antibiotic resistant or virulence enhanced Bacillus anthracis, to advise on therapeutic treatments. METHODOLOGY/PRINCIPAL FINDINGS: We show here that the Roche 454-based pyrosequencing can generate whole genome draft sequences of deep and broad enough coverage of a bacterial genome in less than 24 hours. Furthermore, using the unfinished draft sequences, we demonstrate that unbiased identification of known as well as heretofore-unreported genetic modifications that include indels and single nucleotide polymorphisms conferring antibiotic and phage resistances is feasible within the next 12 hours. CONCLUSIONS/SIGNIFICANCE: Second generation sequencing technologies have paved the way for sequence-based rapid identification of both known and previously undocumented genetic modifications in cultured, conventional and newly emerging biothreat agents. Our findings have significant implications in

  18. Genetic Evidence for PLASMINOGEN as a Shared Genetic Risk Factor of Coronary Artery Disease and Periodontitis

    NARCIS (Netherlands)

    Schaefer, Arne S.; Bochenek, Gregor; Jochens, Arne; Ellinghaus, David; Dommisch, Henrik; Guezeldemir-Akcakanat, Esra; Graetz, Christian; Harks, Inga; Jockel-Schneider, Yvonne; Weinspach, Knut; Meyle, Joerg; Eickholz, Peter; Linden, Gerry J.; Cine, Naci; Nohutcu, Rahime; Weiss, Ervin; Houri-Haddad, Yael; Iraqi, Fuad; Folwaczny, Mathias; Noack, Barbara; Strauch, Konstantin; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Wijmenga, Cisca; Yilmaz, Engin; Lieb, Wolfgang; Rosenstiel, Philip; Doerfer, Christof; Bruckmann, Corinna; Erdmann, Jeannette; Koenig, Inke; Jepsen, Soren; Loos, Bruno G.; Schreiber, Stefan

    Background-Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms. Methods and

  19. Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis

    NARCIS (Netherlands)

    Schaefer, A.S.; Bochenek, G.; Jochens, A.; Ellinghaus, D.; Dommisch, H.; Güzeldemir-Akçakanat, E.; Graetz, C.; Harks, I.; Jockel-Schneider, Y.; Weinspach, K.; Meyle, J.; Eickholz, P.; Linden, G.J.; Cine, N.; Nohutcu, R.; Weiss, E.; Houri-Haddad, Y.; Iraqi, F.; Folwaczny, M.; Noack, B.; Strauch, K.; Gieger, C.; Waldenberger, M.; Peters, A.; Wijmenga, C.; Yilmaz, E.; Lieb, W.; Rosenstiel, P.; Doerfer, C.; Bruckmann, C.; Erdmann, J.; König, I.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2015-01-01

    Background—Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms. Methods and

  20. Genetic association studies: discovery of the genetic basis of renal disease

    NARCIS (Netherlands)

    Verduijn, Marion; Jager, Kitty J.; Zoccali, Carmine; Dekker, Friedo W.

    2011-01-01

    Genetic association studies are a means to investigate the causal role of genes in diseases in order to unravel pathways involved in the etiology of disease. There are two types of genetic association studies: hypothesis-driven studies, i.e. candidate gene studies, targeting genes with a known or

  1. Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing.

    LENUS (Irish Health Repository)

    Murphy, Sinead M

    2012-07-01

    Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.

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

    Science.gov (United States)

    Wendell, Douglas L.; Pickard, Dawn

    2007-01-01

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

  3. Genetic heterogeneity and Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Schellenberg, G.D.; Wijsman, E.M. [Univ. of Washington, Seattle (United States); Bird, T.D. [Veteran`s Affairs Medical Center, Seattle, WA (United States)

    1994-09-01

    In some early-onset Alzheimer`s disease (AD) families, inheritance is autosomal dominant. (Early-onset AD is arbitarily defined as onset at {le} 60 years.) Two loci have been identified which are causative for early-onset familial AD (FAD). One is the amyloid precursor protein gene in which specific mutation have been identified. The second is a locus at 14q24.3 (AD3) which has been localized by linkage analysis; the gene and specific mutations have not been identified. Linkage studies place this locus between D14S61 and D14S63. These 2 loci, however, do not account for all early-onset FAD. The Volga German (VG) kindreds are descendants of families which emigrated from Germany to the Volga river region of Russia and subsequently to the US; AD in these families is hypothesized to be the result of a common genetic founder. The average age-at-onset in these families is 57 years. Linkage analysis for this group has been negative for the APP gene and for chromosome 14 markers. Thus, there is at least 1 other early-onset FAD locus. Recently, the {epsilon}4 allele of apolipoprotein E (ApoE) was identified as a risk-factor for late-onset AD. In a series of 53 late-onset kindreds, a strong genetic association was observed between the ApoE {epsilon}4 allele and AD. However, when linkage analysis was performed using a highly polymorphic locus at the ApoCII gene, which is within 30 kb of ApoE, significant evidence for co-segregation was not observed. This and other data suggests that while ApoE is an age-at-onset modifying locus, another gene(s), located elsewhere, contribute(s) to late-onset AD. Thus, there is probably at least 1 other late-onset locus. Once the VG locus is identified, it will be possible to determine whether an allelic variant of this locus is responsible for late-onset FAD.

  4. Rapid genetic diversification within dog breeds as evidenced by a case study on Schnauzers.

    Science.gov (United States)

    Streitberger, K; Schweizer, M; Kropatsch, R; Dekomien, G; Distl, O; Fischer, M S; Epplen, J T; Hertwig, S T

    2012-10-01

    As a result of strong artificial selection, the domesticated dog has arguably become one of the most morphologically diverse vertebrate species, which is mirrored in the classification of around 400 different breeds. To test the influence of breeding history on the genetic structure and variability of today's dog breeds, we investigated 12 dog breeds using a set of 19 microsatellite markers from a total of 597 individuals with about 50 individuals analysed per breed. High genetic diversity was noted over all breeds, with the ancient Asian breeds (Akita, Chow Chow, Shar Pei) exhibiting the highest variability, as was indicated chiefly by an extraordinarily high number of rare and private alleles. Using a Bayesian clustering method, we detected significant genetic stratification within the closely related Schnauzer breeds. The individuals of these three recently differentiated breeds (Miniature, Standard and Giant Schnauzer) could not be assigned to a single cluster each. This hidden genetic structure was probably caused by assortative mating owing to breeders' preferences regarding coat colour types and the underlying practice of breeding in separate lineages. Such processes of strong artificial disruptive selection for different morphological traits in isolated and relatively small lineages can result in the rapid creation of new dog types and potentially new breeds and represent a unique opportunity to study the evolution of genetic and morphological differences in recently diverged populations. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.

  5. Rapid changes in genetic architecture of behavioural syndromes following colonization of a novel environment.

    Science.gov (United States)

    Karlsson Green, K; Eroukhmanoff, F; Harris, S; Pettersson, L B; Svensson, E I

    2016-01-01

    Behavioural syndromes, that is correlated behaviours, may be a result from adaptive correlational selection, but in a new environmental setting, the trait correlation might act as an evolutionary constraint. However, knowledge about the quantitative genetic basis of behavioural syndromes, and the stability and evolvability of genetic correlations under different ecological conditions, is limited. We investigated the quantitative genetic basis of correlated behaviours in the freshwater isopod Asellus aquaticus. In some Swedish lakes, A. aquaticus has recently colonized a novel habitat and diverged into two ecotypes, presumably due to habitat-specific selection from predation. Using a common garden approach and animal model analyses, we estimated quantitative genetic parameters for behavioural traits and compared the genetic architecture between the ecotypes. We report that the genetic covariance structure of the behavioural traits has been altered in the novel ecotype, demonstrating divergence in behavioural correlations. Thus, our study confirms that genetic correlations behind behaviours can change rapidly in response to novel selective environments. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  6. Applying genetics in inflammatory disease drug discovery

    DEFF Research Database (Denmark)

    Folkersen, Lasse; Biswas, Shameek; Frederiksen, Klaus Stensgaard

    2015-01-01

    , with several notable exceptions, the journey from a small-effect genetic variant to a functional drug has proven arduous, and few examples of actual contributions to drug discovery exist. Here, we discuss novel approaches of overcoming this hurdle by using instead public genetics resources as a pragmatic guide...... alongside existing drug discovery methods. Our aim is to evaluate human genetic confidence as a rationale for drug target selection....

  7. Stratification by Genetic and Demographic Characteristics Improves Diagnostic Accuracy of Cerebrospinal Fluid Biomarkers in Rapidly Progressive Dementia.

    Science.gov (United States)

    Karch, André; Llorens, Franc; Schmitz, Matthias; Arora, Amandeep Singh; Zafar, Saima; Lange, Peter; Schmidt, Christian; Zerr, Inga

    2016-10-18

    Cerebrospinal fluid (CSF) biomarkers are routinely used for the differential diagnosis of rapidly progressive dementia, but are also affected by patients' characteristics. To assess if stratification by age, sex, and genetic risk factors improves the accuracy of cerebrospinal fluid (CSF) biomarkers in patients with rapidly progressive dementia. 1,538 individuals with sporadic Creutzfeldt-Jakob disease (CJD), 173 with classic Alzheimer's disease (cAD), 37 with rapidly progressive Alzheimer's disease (rpAD), and 589 without signs of dementia were included in this retrospective diagnostic study. The effect of age, sex, PRNP codon 129, and APOE genotype on CSF levels of tau, p-tau, Aβ1-42, and Aβ1-40 values measured at time of diagnostic work-up was assessed. Tau was a better marker for the differentiation of CJD and rpAD in older (AUC:0.97; 95% CI:0.96-1.00) than in younger (AUC:0.91; 95% CI:0.87-0.94) patients as tau levels increased with age in CJD patients, but not in rpAD patients. PRNP codon 129 and APOE genotype had complex effects on biomarkers in all diseases, making stratification by genotype a powerful tool. In females (AUC:0.78; 95% CI:0.65-0.91) and patients older than 70 (AUC:0.78; 95% CI:0.62-0.93), tau was able to differentiate with moderate accuracy between cAD and rpAD patients. Implementation of stratum-specific reference ranges improves the diagnostic accuracy of CSF biomarkers for the differential diagnosis of rapidly progressive dementia. Diagnostic criteria developed for this setting have to take this into account.

  8. Genetics of animal health and disease in cattle

    Directory of Open Access Journals (Sweden)

    Berry Donagh P

    2011-03-01

    Full Text Available Abstract There have been considerable recent advancements in animal breeding and genetics relevant to disease control in cattle, which can now be utilised as part of an overall programme for improved cattle health. This review summarises the contribution of genetic makeup to differences in resistance to many diseases affecting cattle. Significant genetic variation in susceptibility to disease does exist among cattle suggesting that genetic selection for improved resistance to disease will be fruitful. Deficiencies in accurately recorded data on individual animal susceptibility to disease are, however, currently hindering the inclusion of health and disease resistance traits in national breeding goals. Developments in 'omics' technologies, such as genomic selection, may help overcome some of the limitations of traditional breeding programmes and will be especially beneficial in breeding for lowly heritable disease traits that only manifest themselves following exposure to pathogens or environmental stressors in adulthood. However, access to large databases of phenotypes on health and disease will still be necessary. This review clearly shows that genetics make a significant contribution to the overall health and resistance to disease in cattle. Therefore, breeding programmes for improved animal health and disease resistance should be seen as an integral part of any overall national disease control strategy.

  9. Genetics Home Reference: polycystic kidney disease

    Science.gov (United States)

    ... Twitter Home Health Conditions Polycystic kidney disease Polycystic kidney disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Polycystic kidney disease is a disorder that affects the kidneys and ...

  10. Genetics Home Reference: fish-eye disease

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Fish-eye disease Fish-eye disease Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Fish-eye disease , also called partial LCAT deficiency, is ...

  11. A convenient and rapid method for genetic transformation of E. coli with plasmids.

    Science.gov (United States)

    Chen, X; Guo, P; Xie, Z; Shen, P

    2001-12-01

    A convenient and rapid method for the genetic transformation of Escherichia coli with plasmids is proposed. By mixing the recipient cells and plasmid DNA and spreading them directly on selective medium plates containing Ca2+, the so-called 'plate transformation' could achieve almost the same transformation efficiency as the classical transformation method with calcium. The whole protocol takes only about 2 min, its simplicity compared favorably, not only to the usual protocol, but also to all other documented modifications.

  12. New multiplex PCR methods for rapid screening of genetically modified organisms in foods

    OpenAIRE

    Nelly eDatukishvili; Tamara eKutateladze; Inga eGabriadze; Kakha eBitskinashvili; Boris eVishnepolsky

    2015-01-01

    We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of C...

  13. Shared Genetic Relationships Underlying Generalized Vitiligo and Autoimmune Thyroid Disease

    Science.gov (United States)

    2010-01-01

    Background Generalized vitiligo is an autoimmune disease of skin pigmentation that is associated with increased prevalence of other autoimmune diseases, particularly autoimmune thyroid disease (AITD; principally Hashimoto's disease and Graves' disease), both in vitiligo patients and their close relatives, suggesting a heritable predisposition involving, in part, shared susceptibility genes. Summary This review summarizes current knowledge of vitiligo epidemiology and genetics, highlighting recent findings from genome-wide approaches to disease gene identification, emphasizing susceptibility loci shared with other autoimmune diseases, particularly AITD, as well as some important differences. Conclusions Inherited susceptibility to generalized vitiligo involves a number of specific genes, many of which are shared with other autoimmune diseases that are epidemiologically associated with vitiligo, including AITD, confirming a longstanding hypothesis about the genetic basis of these disorders. These genes provide potential therapeutic targets for novel approaches to treatment as well as for approaches to presymptomatic diagnosis and disease prevention in individuals with inherited susceptibility to this group of autoimmune diseases. PMID:20578892

  14. A review of ocular genetics and inherited eye diseases

    Directory of Open Access Journals (Sweden)

    S. D. Mathebula

    2012-12-01

    Full Text Available During the past twenty years, there has been an exponential increase in the knowledge and under-standing of ocular genetic diseases and syndromes. The number of human eye diseases that have a known genetic or hereditary component continues to increase. In addition, genetic diseases are the most common cause of blindness in infants and children in developed countries. Optometrists are likely to encounter patients with inherited eye disorders. They may be the first clinician the patient consults. Inherited eye diseases may be isolated (only affecting the eye or part of a complicated syndrome. Both isolated eye diseases and genetic syndromes can have identifiable gene mutation known to cause the disease.Knowledge of the clinical and molecular features of ocular genetics and inherited eye diseases is important for appropriate diagnosis and patient management. This article reviews the current information on ocular genetics and inherited eye diseases.The ocular conditions described in the review have significant visual impairment and blindness consequences. Therefore, optometrists (as the mostly likely first line of consultation should be able todiagnose the condition appropriately first before they could make any management, care or referralplan. Visual aids are, of course, one of the management options for such patients with visual impairment. (S Afr Optom 2012 71(4 178-189

  15. Rapid and liquid-based selection of genetic switches using nucleoside kinase fused with aminoglycoside phosphotransferase.

    Directory of Open Access Journals (Sweden)

    Masahiro Tominaga

    Full Text Available The evolutionary design of genetic switches and circuits requires iterative rounds of positive (ON- and negative (OFF- selection. We previously reported a rapid OFF selection system based on the kinase activity of herpes simplex virus thymidine kinase (hsvTK on the artificial mutator nucleoside dP. By fusing hsvTK with the kanamycin resistance marker aminoglycoside-(3'-phosphotransferase (APH, we established a novel selector system for genetic switches. Due to the bactericidal nature of kanamycin and nucleoside-based lethal mutagenesis, both positive and negative selection could be completed within several hours. Using this new selector system, we isolated a series of homoserine lactone-inducible genetic switches with different expression efficiencies from libraries of the Vibrio fischeri lux promoter in two days, using only liquid handling.

  16. Immortalizing the Complexity of Cancer Metastasis Genetic Features of Lethal Metastatic Pancreatic Cancer Obtained from Rapid Autopsy

    Science.gov (United States)

    Embuscado, Erlinda E.; Laheru, Daniel; Ricci, Francesca; Yun, Ki Jung; de Boom Witzel, Sten; Seigel, Allison; Flickinger, Katie; Hidalgo, Manuel; Bova, G. Steven; Iacobuzio-Donahue, Christine A.

    2009-01-01

    The virtual lack of well-characterized metastatic pancreatic cancer tissues for study has limited systematic studies of the metastatic process of this deadly disease. To address this important issue, we have instituted a rapid autopsy protocol for the collection of high quality tissues from patients with metastatic pancreatic cancer, called the Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP). At the time of preparation of this manuscript, 20 patients with metastatic pancreatic cancer and one patient with metastatic colon cancer have undergone a rapid autopsy in association with the GICRMDP. The average time interval achieved for these 21 patients was 8.0 hours, with more than 500 individual samples of matched high quality primary and metastatic pancreatic cancer tissues, peritoneal/pleural fluid and blood obtained so far. For the first four patients in which the autopsy was performed in <6 hours, we have successfully xenografted the primary tumor and/or two to four independent matched metastases from a variety of target organ sites, with a take rate of almost 60% for the first 26 xenografted tumors attempted. In an initial survey of KRAS2, TP53 and DPC4 genetic status in lethal metastatic pancreatic cancers, activating KRAS2 mutations were detected in 82% of cases and inactivating TP53 mutations in 55% of cases, consistent with rates of genetic alteration of these genes in early stage pancreatic cancers. However, DPC4 inactivation was found in 75% of patients analyzed, suggesting that genetic inactivation of the DPC4 tumor suppressor gene continues to be selected for with growth at the primary site and metastatic spread to other organs. The invaluable tissue resources generated by the success of the GICRMDP will provide an unparalleled resource for study of metastatic pancreatic cancer and of the metastatic process in general. PMID:15846069

  17. Immortalizing the complexity of cancer metastasis: genetic features of lethal metastatic pancreatic cancer obtained from rapid autopsy.

    Science.gov (United States)

    Embuscado, Erlinda E; Laheru, Daniel; Ricci, Francesca; Yun, Ki Jung; de Boom Witzel, Sten; Seigel, Allison; Flickinger, Katie; Hidalgo, Manuel; Bova, G Steven; Iacobuzio-Donahue, Christine A

    2005-05-01

    The virtual lack of well-characterized metastatic pancreatic cancer tissues for study has limited systematic studies of the metastatic process of this deadly disease. To address this important issue, we have instituted a rapid autopsy protocol for the collection of high quality tissues from patients with metastatic pancreatic cancer, called the Gastrointestinal Cancer Rapid Medical Donation Program (GICRMDP). At the time of preparation of this manuscript, 20 patients with metastatic pancreatic cancer and one patient with metastatic colon cancer have undergone a rapid autopsy in association with the GICRMDP. The average time interval achieved for these 21 patients was 8.0 hours, with more than 500 individual samples of matched high quality primary and metastatic pancreatic cancer tissues, peritoneal/pleural fluid and blood obtained so far. For the first four patients in which the autopsy was performed in <6 hours, we have successfully xenografted the primary tumor and/or two to four independent matched metastases from a variety of target organ sites, with a take rate of almost 60% for the first 26 xenografted tumors attempted. In an initial survey of KRAS2, TP53 and DPC4 genetic status in lethal metastatic pancreatic cancers, activating KRAS2 mutations were detected in 82% of cases and inactivating TP53 mutations in 55% of cases, consistent with rates of genetic alteration of these genes in early stage pancreatic cancers. However, DPC4 inactivation was found in 75% of patients analyzed, suggesting that genetic inactivation of the DPC4 tumor suppressor gene continues to be selected for with growth at the primary site and metastatic spread to other organs. The invaluable tissue resources generated by the success of the GICRMDP will provide an unparalleled resource for study of metastatic pancreatic cancer and of the metastatic process in general.

  18. Triplet repeat DNA structures and human genetic disease: dynamic ...

    Indian Academy of Sciences (India)

    Unknown

    of triplet repeats (Pearson and Sinden 1998a; Sinden. 1999). Expansions or deletions can occur by simple. Table 1. Trinucleotide repeats in human genetic disease. Repeat length. Disease. Gene. Locus. Repeata. Normal. Pre- mutation. Disease. Protein/possible biological effect of expansion. Fragile X syndrome. FMR1.

  19. Complex host genetics influence the microbiome in inflammatory bowel disease

    NARCIS (Netherlands)

    Knights, Dan; Silverberg, Mark S.; Weersma, Rinse K.; Gevers, Dirk; Dijkstra, Gerard; Huang, Hailiang; Tyler, Andrea D.; van Sommeren, Suzanne; Imhann, Floris; Stempak, Joanne M.; Huang, Hu; Vangay, Pajau; Al-Ghalith, Gabriel A.; Russell, Caitlin; Sauk, Jenny; Knight, Jo; Daly, Mark J.; Huttenhower, Curtis; Xavier, Ramnik J.

    2014-01-01

    Background: Human genetics and host-associated microbial communities have been associated independently with a wide range of chronic diseases. One of the strongest associations in each case is inflammatory bowel disease (IBD), but disease risk cannot be explained fully by either factor individually.

  20. Genetics Home Reference: central core disease

    Science.gov (United States)

    ... F. Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders. Neuromuscul Disord. 2005 Oct;15( ... 2007 May 4. Citation on PubMed More from Genetics Home Reference Bulletins Crick, Watson, and Wilkins Awarded ...

  1. Genetics Home Reference: Unverricht-Lundborg disease

    Science.gov (United States)

    ... and CRISPR-Cas9? What is direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Leprosy Polycystic ovary syndrome Gorlin-Chaudhry-Moss syndrome All New & Updated Pages ...

  2. Genetics Home Reference: Tay-Sachs disease

    Science.gov (United States)

    ... and CRISPR-Cas9? What is direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Leprosy Polycystic ovary syndrome Gorlin-Chaudhry-Moss syndrome All New & Updated Pages ...

  3. Genetics Home Reference: CLN10 disease

    Science.gov (United States)

    ... and CRISPR-Cas9? What is direct-to-consumer genetic testing? What is precision medicine? What is newborn screening? New Pages Leprosy Polycystic ovary syndrome Gorlin-Chaudhry-Moss syndrome All New & Updated Pages ...

  4. Genetics Home Reference: Niemann-Pick disease

    Science.gov (United States)

    ... of molecules. Acid sphingomyelinase is responsible for the conversion of a fat (lipid) called sphingomyelin into another ... Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related ...

  5. Etiology of Human Genetic Disease on the Fly.

    Science.gov (United States)

    Chow, Clement Y; Reiter, Lawrence T

    2017-06-01

    The model organism Drosophila melanogaster has been at the forefront of genetic studies since before the discovery of DNA. Although human disease modeling in flies may still be rather novel, recent advances in genetic tool design and genome sequencing now confer huge advantages in the fly system when modeling human disease. In this review, we focus on new genomic tools for human gene variant analysis; new uses for the Drosophila Genetic Reference Panel (DGRP) in detection of background alleles that influence a phenotype; and several examples of how multigenic conditions, both complex disorders and duplication and/or deletion syndromes, can be effectively studied in the fly model system. Fruit flies are a far cry from the quaint genetic model of the past, but rather, continue to evolve as a powerful system for the study of human genetic disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Role of Genetic Testing in Inherited Cardiovascular Disease: A Review.

    Science.gov (United States)

    Cirino, Allison L; Harris, Stephanie; Lakdawala, Neal K; Michels, Michelle; Olivotto, Iacopo; Day, Sharlene M; Abrams, Dominic J; Charron, Philippe; Caleshu, Colleen; Semsarian, Christopher; Ingles, Jodie; Rakowski, Harry; Judge, Daniel P; Ho, Carolyn Y

    2017-10-01

    Genetic testing is a valuable tool for managing inherited cardiovascular disease in patients and families, including hypertrophic, dilated, and arrhythmogenic cardiomyopathies and inherited arrhythmias. By identifying the molecular etiology of disease, genetic testing can improve diagnostic accuracy and refine family management. However, unique features associated with genetic testing affect the interpretation and application of results and differentiate it from traditional laboratory-based diagnostics. Clinicians and patients must have accurate and realistic expectations about the yield of genetic testing and its role in management. Familiarity with the rationale, implications, benefits, and limitations of genetic testing is essential to achieve the best possible outcomes. Successfully incorporating genetic testing into clinical practice requires (1) recognizing when inherited cardiovascular disease may be present, (2) identifying appropriate individuals in the family for testing, (3) selecting the appropriate genetic test, (4) understanding the complexities of result interpretation, and (5) effectively communicating the results and implications to the patient and family. Obtaining a detailed family history is critical to identify families who will benefit from genetic testing, determine the best strategy, and interpret results. Instead of focusing on an individual patient, genetic testing requires consideration of the family as a unit. Consolidation of care in centers with a high level of expertise is recommended. Clinicians without expertise in genetic testing will benefit from establishing referral or consultative networks with experienced clinicans in specialized multidisciplinary clinics. Genetic testing provides a foundation for transitioning to more precise and individualized management. By distinguishing phenotypic subgroups, identifying disease mechanisms, and focusing family care, gene-based diagnosis can improve management. Successful integration of

  7. Sleep disorders and Parkinson disease; lessons from genetics.

    Science.gov (United States)

    Gan-Or, Ziv; Alcalay, Roy N; Rouleau, Guy A; Postuma, Ronald B

    2018-01-31

    Parkinson disease is a common, age-related neurodegenerative disorder, projected to afflict millions of individuals in the near future. Understanding its etiology and identifying clinical, genetic or biological markers for Parkinson disease onset and progression is therefore of major importance. Various sleep-related disorders are the most common group of non-motor symptoms in advanced Parkinson disease, but they can also occur during its prodromal phase. However, with the exception of REM sleep behavior disorder, it is unclear whether they are part of the early pathological process of Parkinson disease, or if they develop as Parkinson disease advances because of treatments and neurodegeneration progression. The advancements in genetic studies in the past two decades have generated a wealth of information, and recent genetic studies offer new insight on the association of sleep-related disorders with Parkinson disease. More specifically, comparing genetic data between Parkinson disease and sleep-related disorders can clarify their association, which may assist in determining whether they can serve as clinical markers for Parkinson disease risk or progression. In this review, we discuss the current knowledge on the genetics of sleep-related disorders in Parkinson disease context, and the potential implications on research, diagnosis, counseling and treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Pervasive Sharing of Genetic Effects in Autoimmune Disease

    DEFF Research Database (Denmark)

    Cotsapas, Chris; Voight, Benjamin F.; Rossin, Elizabeth

    2011-01-01

    and clinical evidence, this suggests that some genetic risk factors may be shared across diseases-as is the case with alleles in the Major Histocompatibility Locus. In this work we evaluate the extent of this sharing for 107 immune disease-risk SNPs in seven diseases: celiac disease, Crohn's disease, multiple......Genome-wide association (GWA) studies have identified numerous, replicable, genetic associations between common single nucleotide polymorphisms (SNPs) and risk of common autoimmune and inflammatory (immune-mediated) diseases, some of which are shared between two diseases. Along with epidemiological......-mediated disease risk SNPs are associated to multiple-but not all-immune-mediated diseases (SNP-wise P-CPMA...

  9. Exploration of genetic susceptibility factors for Parkinson's disease ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 89; Issue 2. Exploration of genetic susceptibility factors for Parkinson's disease in a South American sample. Bruno A. Benitez Diego A. Forero Gonzalo H. Arboleda Luis A. Granados Juan J. Yunis William Fernandez Humberto Arboleda. Research Note Volume 89 Issue 2 ...

  10. 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 ...

  11. Genetic Variations and their Association with Diseases among ...

    African Journals Online (AJOL)

    The aim of this study was therefore investigate the possible role genetics plays in disease, death and infections. The mode of study involved a combination of a retrospective study and the analysis of genetic variation among Kenyan ethnic populations using ABO blood group system. The results showed that there was ...

  12. Genetics and behavioral medicine: Risk factors for cardiovascular disease

    NARCIS (Netherlands)

    Vogler, G.P.; McClearn, G.E.; Snieder, H.; Boomsma, D.I.; Palmer, R.; Knijff, P. de; Slagboom, P.E.

    1997-01-01

    This is the second in a series of three articles addressing the intersection of interests in behavioral genetics and behavioral medicine. In this article, we use risk factors for cardiovascular disease as a prototypical trait for which behavioral genetic approaches provide powerful tools for

  13. Dopaminergic neuronal imaging in genetic Parkinson's disease: insights into pathogenesis.

    Directory of Open Access Journals (Sweden)

    Alisdair McNeill

    Full Text Available OBJECTIVES: To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease. METHODS: A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated. RESULTS: Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin. The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations. CONCLUSIONS: The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss.

  14. Currently Clinical Views on Genetics of Wilson's Disease

    OpenAIRE

    Chen Chen; Bo Shen; Jia-Jia Xiao; Rong Wu; Sarah Jane Duff Canning; Xiao-Ping Wang

    2015-01-01

    Objective: The objective of this study was to review the research on clinical genetics of Wilson′s disease (WD). Data Sources: We searched documents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic, ATP7B gene, gene mutation, genotype, phenotype. Study Selection: Publications about the ATP7B gene and protein function associated with clinical features were selected. Results: Wilson′s disease, also named hepat...

  15. Genetic influences on chronic obstructive pulmonary disease - a twin study

    DEFF Research Database (Denmark)

    Sylvan Ingebrigtsen, Truls; Thomsen, Simon Francis; Vestbo, Jørgen

    2010-01-01

    Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted.......Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted....

  16. Genetic influences on Chronic Obstructive Pulmonary Disease - a twin study

    DEFF Research Database (Denmark)

    Ingebrigtsen, Truls; Thomsen, Simon F; Vestbo, Jørgen

    2010-01-01

    Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted.......Genes that contribute to the risk of developing Chronic Obstructive Pulmonary Disease (COPD) have been identified, but an attempt to accurately quantify the total genetic contribution to COPD has to our knowledge never been conducted....

  17. Molecular investigation of genetic assimilation during the rapid adaptive radiations of East African cichlid fishes.

    Science.gov (United States)

    Gunter, Helen M; Schneider, Ralf F; Karner, Immanuel; Sturmbauer, Christian; Meyer, Axel

    2017-12-01

    Adaptive radiations are characterized by adaptive diversification intertwined with rapid speciation within a lineage resulting in many ecologically specialized, phenotypically diverse species. It has been proposed that adaptive radiations can originate from ancestral lineages with pronounced phenotypic plasticity in adaptive traits, facilitating ecologically driven phenotypic diversification that is ultimately fixed through genetic assimilation of gene regulatory regions. This study aimed to investigate how phenotypic plasticity is reflected in gene expression patterns in the trophic apparatus of several lineages of East African cichlid fishes, and whether the observed patterns support genetic assimilation. This investigation used a split brood experimental design to compare adaptive plasticity in species from within and outside of adaptive radiations. The plastic response was induced in the crushing pharyngeal jaws through feeding individuals either a hard or soft diet. We find that nonradiating, basal lineages show higher levels of adaptive morphological plasticity than the derived, radiated lineages, suggesting that these differences have become partially genetically fixed during the formation of the adaptive radiations. Two candidate genes that may have undergone genetic assimilation, gif and alas1, were identified, in addition to alterations in the wiring of LPJ patterning networks. Taken together, our results suggest that genetic assimilation may have dampened the inducibility of plasticity related genes during the adaptive radiations of East African cichlids, flattening the reaction norms and canalizing their feeding phenotypes, driving adaptation to progressively more narrow ecological niches. © 2017 John Wiley & Sons Ltd.

  18. Genetic variation associated with cardiovascular risk in autoimmune diseases.

    Science.gov (United States)

    Perrotti, Pedro P; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L; Lasanta, María L; Marsal, Sara; Julià, Antonio

    2017-01-01

    Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.

  19. Genetics Home Reference: CLN1 disease

    Science.gov (United States)

    ... AAIDD) Batten Disease Family Association Batten Disease Support & Research ... Sources for This Page Getty AL, Pearce DA. Interactions of the proteins of neuronal ceroid lipofuscinosis: clues to function. Cell ...

  20. Genetics Home Reference: chronic granulomatous disease

    Science.gov (United States)

    ... All About the Immune System Orphanet: Chronic granulomatous disease US Immunodeficiency Network Patient Support and Advocacy Resources (5 links) CGD Society Immune Deficiency Foundation: Chronic Granulomatous Disease and Other Phagocytic Cell Disorders International Patient Organisation ...

  1. Genetics Home Reference: chylomicron retention disease

    Science.gov (United States)

    ... Resources (1 link) CLIMB: Children Living with Inherited Metabolic Diseases ... R, Biselli R, Bosman C. Chylomicron retention disease--the role of ultrastructural examination in differential diagnosis. Pathol Res Pract. 2001;197(11):753-7. ...

  2. Genetics Home Reference: CLN8 disease

    Science.gov (United States)

    ... The seizures in this form involve uncontrollable muscle jerks (myoclonic epilepsy). Individuals with the more-severe form ... Page Educational Resources (5 links) Centers for Disease Control and Prevention: Epilepsy Disease InfoSearch: Ceroid Lipofuscinosis Neuronal ...

  3. Population genetics of fungal diseases of plants

    Directory of Open Access Journals (Sweden)

    Giraud T.

    2008-09-01

    Full Text Available Although parasitism is one of the most common lifestyles among eukaryotes, population genetics on parasites lag far behind those on free-living organisms. Yet, the advent of molecular markers offers great tools for studying important processes, such as dispersal, mating systems, adaptation to host and speciation. Here we highlight some studies that used molecular markers to address questions about the population genetics of fungal (including oomycetes plant pathogens. We conclude that population genetics approaches have provided tremendous insights into the biology of a few fungal parasites and warrant more wide use in phytopathology. However, theoretical advances are badly needed to best apply the existing methods. Fungi are of prime interest not only because they are major parasites of plants and animals, but they also constitute tractable and highly useful models for understanding evolutionary processes. We hope that the emerging field of fungal evolution will attract more evolutionary biologists in the near future.

  4. Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases.

    Science.gov (United States)

    Lee, Wen-Chung

    2016-06-09

    The Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use.

  5. Genetic Influences on the Development of Fibrosis in Crohn's Disease.

    Science.gov (United States)

    Verstockt, Bram; Cleynen, Isabelle

    2016-01-01

    Fibrostenotic strictures are an important complication in patients with Crohn's disease (CD), very often necessitating surgery. This fibrotic process develops in a genetically susceptible individual and is influenced by an interplay with environmental, immunological, and disease-related factors. A deeper understanding of the genetic factors driving this fibrostenotic process might help to unravel the pathogenesis, and ultimately lead to development of new, anti-fibrotic therapy. Here, we review the genetic factors that have been associated with the development of fibrosis in patients with CD, as well as their potential pathophysiological mechanism(s). We also hypothesize on clinical implications, if any, and future research directions.

  6. Genetics of Congenital Heart Disease: Past and Present.

    Science.gov (United States)

    Muntean, Iolanda; Togănel, Rodica; Benedek, Theodora

    2017-04-01

    Congenital heart disease is the most common congenital anomaly, representing an important cause of infant morbidity and mortality. Congenital heart disease represents a group of heart anomalies that include septal defects, valve defects, and outflow tract anomalies. The exact genetic, epigenetic, or environmental basis of congenital heart disease remains poorly understood, although the exact mechanism is likely multifactorial. However, the development of new technologies including copy number variants, single-nucleotide polymorphism, next-generation sequencing are accelerating the detection of genetic causes of heart anomalies. Recent studies suggest a role of small non-coding RNAs, micro RNA, in congenital heart disease. The recently described epigenetic factors have also been found to contribute to cardiac morphogenesis. In this review, we present past and recent genetic discoveries in congenital heart disease.

  7. Familial Creutzfeldt-Jakob Disease: Case report and role of genetic counseling in post mortem testing.

    Science.gov (United States)

    Clift, Kristin; Guthrie, Kimberly; Klee, Eric W; Boczek, Nicole; Cousin, Margot; Blackburn, Patrick; Atwal, Paldeep

    2016-11-01

    Here we present a case of an asymptomatic 53-year-old woman who sought genetic testing for Familial Creutzfeldt-Jakob Disease (fCJD) after learning that her mother had fCJD. The patient's mother had a sudden onset of memory problems and rapidly deteriorating mental faculties in her late 70s, which led to difficulties ambulating, progressive non-fluent aphasia, dysphagia and death within ∼1 y of symptom onset. The cause of death was reported as "rapid onset dementia." The patient's family, unhappy with the vague diagnosis, researched prion disorders online and aggressively pursued causation and submitted frozen brain tissue from the mother to the National Prion Disease Surveillance Center, where testing revealed a previously described 5-octapeptide repeat insertion (5-OPRI) in the prion protein gene (PRNP) that is known to cause fCJD. The family had additional questions about the implications of this result and thus independently sought out genetic counseling.  While rare, fCJD is likely underdiagnosed due to clinical heterogeneity, rapid onset, early non-specific symptomatology, and overlap in the differential diagnosis of Alzheimer disease and Lewy body dementias. When fCJD is identified, a multidisciplinary approach to return of results that includes the affected patient's provider, genetics professionals, and mental health professionals is key to the care of the family. We present an example case which discusses the psychosocial issues encountered and the role of genetic counseling in presymptomatic testing for incurable neurodegenerative conditions. Ordering physicians should be aware of the basic issues surrounding presymptomatic genetic testing and identify local genetic counseling resources for their patients.

  8. Sex reversal triggers the rapid transition from genetic to temperature-dependent sex.

    Science.gov (United States)

    Holleley, Clare E; O'Meally, Denis; Sarre, Stephen D; Marshall Graves, Jennifer A; Ezaz, Tariq; Matsubara, Kazumi; Azad, Bhumika; Zhang, Xiuwen; Georges, Arthur

    2015-07-02

    Sex determination in animals is amazingly plastic. Vertebrates display contrasting strategies ranging from complete genetic control of sex (genotypic sex determination) to environmentally determined sex (for example, temperature-dependent sex determination). Phylogenetic analyses suggest frequent evolutionary transitions between genotypic and temperature-dependent sex determination in environmentally sensitive lineages, including reptiles. These transitions are thought to involve a genotypic system becoming sensitive to temperature, with sex determined by gene-environment interactions. Most mechanistic models of transitions invoke a role for sex reversal. Sex reversal has not yet been demonstrated in nature for any amniote, although it occurs in fish and rarely in amphibians. Here we make the first report of reptile sex reversal in the wild, in the Australian bearded dragon (Pogona vitticeps), and use sex-reversed animals to experimentally induce a rapid transition from genotypic to temperature-dependent sex determination. Controlled mating of normal males to sex-reversed females produces viable and fertile offspring whose phenotypic sex is determined solely by temperature (temperature-dependent sex determination). The W sex chromosome is eliminated from this lineage in the first generation. The instantaneous creation of a lineage of ZZ temperature-sensitive animals reveals a novel, climate-induced pathway for the rapid transition between genetic and temperature-dependent sex determination, and adds to concern about adaptation to rapid global climate change.

  9. Genetic architectures of seropositive and seronegative rheumatic diseases.

    Science.gov (United States)

    Kirino, Yohei; Remmers, Elaine F

    2015-07-01

    Rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and some other rheumatic diseases are genetically complex, with evidence of familial clustering, but not of Mendelian inheritance. These diseases are thought to result from contributions and interactions of multiple genetic and nongenetic risk factors, which have small effects individually. Genome-wide association studies (GWAS) of large collections of data from cases and controls have revealed many genetic factors that contribute to non-Mendelian rheumatic diseases, thus providing insights into associated molecular mechanisms. This Review summarizes methods for the identification of gene variants that influence genetically complex diseases and focuses on what we have learned about the rheumatic diseases for which GWAS have been reported. Our review of the disease-associated loci identified to date reveals greater sharing of risk loci among the groups of seropositive (diseases in which specific autoantibodies are often present) or seronegative diseases than between these two groups. The nature of the shared and discordant loci suggests important similarities and differences among these diseases.

  10. Investigation of the Genetics of Hematologic Diseases

    Science.gov (United States)

    2017-10-17

    Bone Marrow Failure Syndromes; Erythrocyte Disorder; Leukocyte Disorder; Hemostasis; Blood Coagulation Disorder; Sickle Cell Disease; Dyskeratosis Congenita; Diamond-Blackfan Anemia; Congenital Thrombocytopenia; Severe Congenital Neutropenia; Fanconi Anemia

  11. Establishment of an Australian National Genetic Heart Disease Registry.

    Science.gov (United States)

    Ingles, Jodie; McGaughran, Julie; Vohra, Jitendra; Weintraub, Robert G; Davis, Andrew; Atherton, John; Semsarian, Christopher

    2008-12-01

    A National Genetic Heart Disease Registry has recently been established, with the aim to enroll every family in Australia with a genetically determined cardiomyopathy or primary arrhythmic disorder. The Registry seeks to further our understanding of the impact and burden of disease in this population; increase awareness and provide education to health professionals and families; and establish a large cardiac genetic cohort as a resource for approved research studies. The Registry is currently recruiting families with inherited cardiomyopathies (e.g. hypertrophic cardiomyopathy) and primary arrhythmogenic disorders (e.g. long QT syndrome), with scope to expand this in the future. Affected individuals, as well as their first-degree (at-risk) family members are eligible to enroll. Participants are currently being recruited from cardiac genetics clinics in approved recruitment sites and hope to expand to other Australian centres including general cardiology practice in the future. A significant focus of the Registry is to improve understanding and create awareness of inherited heart diseases, which includes ensuring families are aware of genetic testing options and current clinical screening recommendations for at-risk family members. A Registry Advisory Committee has been established under the NHMRC Guidelines, and includes a representative from each major recruitment centre. This committee approves all decisions relating to the Registry including approval of research studies. A National Genetic Heart Disease Registry will provide a valuable resource to further our knowledge of the clinical and genetic aspects of these diseases. Since most of the current data about the prevalence, natural history and outcomes of genetic heart diseases has emanated from the United States and Europe, characterising these Australian populations will be of significant benefit, allowing for more informed and specific health care planning and resource provision.

  12. Genetics Home Reference: CLN3 disease

    Science.gov (United States)

    ... age, and people with CLN3 disease are often blind by late childhood or adolescence. Also around age 4 to 8, children with CLN3 disease start to fall behind in school. They have difficulty learning new information and lose previously acquired skills (developmental regression), usually ...

  13. ORIGINAL ARTICLES Huntington's disease: Genetic heterogeneity ...

    African Journals Online (AJOL)

    2008-03-01

    Mar 1, 2008 ... George Huntington's description of Huntington's disease. (HD) in 1872 (at the age of 22 years) remains the basic pillar of diagnosis: 'A hereditary chorea, tendency to insanity and suicide and its manifesting itself as a grave disease in adulthood'.1 HD is a progressive autosomal dominant disorder ...

  14. Genetics Home Reference: rippling muscle disease

    Science.gov (United States)

    ... may also occur as a feature of other muscle disorders such as limb-girdle muscular dystrophy . Related Information What does it mean if a ... Patient Support and Advocacy Resources (1 link) Muscular Dystrophy Association GeneReviews (1 link) ... RIPPLING MUSCLE DISEASE 1 RIPPLING MUSCLE DISEASE 2 Sources for ...

  15. Multi-locus models of genetic risk of disease

    Science.gov (United States)

    2010-01-01

    Background Evidence for genetic contribution to complex diseases is described by recurrence risks to relatives of diseased individuals. Genome-wide association studies allow a description of the genetics of the same diseases in terms of risk loci, their effects and allele frequencies. To reconcile the two descriptions requires a model of how risks from individual loci combine to determine an individual's overall risk. Methods We derive predictions of risk to relatives from risks at individual loci under a number of models and compare them with published data on disease risk. Results The model in which risks are multiplicative on the risk scale implies equality between the recurrence risk to monozygotic twins and the square of the recurrence risk to sibs, a relationship often not observed, especially for low prevalence diseases. We show that this theoretical equality is achieved by allowing impossible probabilities of disease. Other models, in which probabilities of disease are constrained to a maximum of one, generate results more consistent with empirical estimates for a range of diseases. Conclusions The unconstrained multiplicative model, often used in theoretical studies because of its mathematical tractability, is not a realistic model. We find three models, the constrained multiplicative, Odds (or Logit) and Probit (or liability threshold) models, all fit the data on risk to relatives. Currently, in practice it would be difficult to differentiate between these models, but this may become possible if genetic variants that explain the majority of the genetic variance are identified. PMID:20181060

  16. Studying the genetics of Hirschsprung's disease : unraveling an oligogenic disorder

    NARCIS (Netherlands)

    Brooks, AS; Oostra, BA; Hofstra, RMW

    Hirschsprung's disease is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the gastrointestinal tract. Genetic dissection was successful as nine genes and four loci for Hirschsprung's disease susceptibility were identified. Different approaches were used to

  17. Genetic risk prediction for common diseases : methodology and applications

    NARCIS (Netherlands)

    R. Mihaescu (Raluca)

    2013-01-01

    textabstractThis thesis describes methodological and empirical studies of genetic risk prediction of common diseases. The methodological studies involved the evaluation of traditional and new methods of model performance, the evaluation of rare variants for risk prediction of common diseases, the

  18. Huntington\\'s disease: Genetic heterogeneity in black African patients

    African Journals Online (AJOL)

    Objective. Huntington's disease (HD) has been reported to occur rarely in black patients. A new genetic variant– Huntington's disease-like 2 (HDL2) – occurring more frequently in blacks, has recently been described. The absence of an expanded trinucleotide repeat at the chromosome 4 HD locus was previously regarded ...

  19. Epidemiology and etiology of Alzheimer's disease: from genetic to non-genetic factors.

    Science.gov (United States)

    Jiang, Teng; Yu, Jin-Tai; Tian, Yan; Tan, Lan

    2013-10-01

    At present, the etiology of Alzheimer's disease (AD) is still unclear, but both genetic and non-genetic factors are thought to take part in the etiopathogenesis of AD. Epidemiologic researches revealed that genetic factors played a decisive role in the development of both early-onset AD (EOAD) and late-onset AD (LOAD). The mutations in APP, PSEN1 and PSEN2 are inherited in a Mendelian fashion and directly lead to the EOAD, while recent genome-wide association studies have identified numbers of risky genes, which influences the susceptibility to LOAD. Although genetic factors are inherited and fixed, non-genetic factors, such as occupational exposures (exposure to pesticides, electromagnetic fields, organic solvents and volatile anesthetics), pre-existing medical conditions (cerebrovascular disease, hypertension, diabetes, dyslipidemia, traumatic brain injury, depression and cancer) and lifestyle factors (smoking, consumptions of alcohol and coffee, body mass index, physical activity and cognitive activity), are partly environmentally-determined. Timely interventions targeted at these non-genetic risk factors may offer opportunities for prevention and treatment of AD. In the future, more high-quality and large-sample epidemiologic studies are needed to identify risk factors for AD, and the interaction models between genetic and non-genetic risk factors required further investigation. In addition, public health campaigns targeted at modification of non-genetic risk factors should be developed among population at high risk of AD.

  20. Genetic Testing for Respiratory Disease: Are We There Yet?

    Directory of Open Access Journals (Sweden)

    Peter D Paré

    2012-01-01

    Full Text Available The human genome project promised a revolution in health care – the development of ‘personalized medicine’, where knowledge of an individual’s genetic code enables the prediction of risk for specific diseases and the potential to alter that risk based on preventive measures and lifestyle modification. The present brief review provides a report card on the progress toward that goal with respect to respiratory disease. Should generalized population screening for genetic risk factors for respiratory disease be instituted? Or not?

  1. Prospect of Induced Pluripotent Stem Cell Genetic Repair to Cure Genetic Diseases

    Directory of Open Access Journals (Sweden)

    Jeanne Adiwinata Pawitan

    2012-01-01

    Full Text Available In genetic diseases, where the cells are already damaged, the damaged cells can be replaced by new normal cells, which can be differentiated from iPSC. To avoid immune rejection, iPSC from the patient’s own cell can be developed. However, iPSC from the patients’s cell harbors the same genetic aberration. Therefore, before differentiating the iPSCs into required cells, genetic repair should be done. This review discusses the various technologies to repair the genetic aberration in patient-derived iPSC, or to prevent the genetic aberration to cause further damage in the iPSC-derived cells, such as Zn finger and TALE nuclease genetic editing, RNA interference technology, exon skipping, and gene transfer method. In addition, the challenges in using the iPSC and the strategies to manage the hurdles are addressed.

  2. Currently Clinical Views on Genetics of Wilson's Disease.

    Science.gov (United States)

    Chen, Chen; Shen, Bo; Xiao, Jia-Jia; Wu, Rong; Duff Canning, Sarah Jane; Wang, Xiao-Ping

    2015-07-05

    The objective of this study was to review the research on clinical genetics of Wilson's disease (WD). We searched documents from PubMed and Wanfang databases both in English and Chinese up to 2014 using the keywords WD in combination with genetic, ATP7B gene, gene mutation, genotype, phenotype. Publications about the ATP7B gene and protein function associated with clinical features were selected. Wilson's disease, also named hepatolenticular degeneration, is an autosomal recessive genetic disorder characterized by abnormal copper metabolism caused by mutations to the copper-transporting gene ATP7B. Decreased biliary copper excretion and reduced incorporation of copper into apoceruloplasmin caused by defunctionalization of ATP7B protein lead to accumulation of copper in many tissues and organs, including liver, brain, and cornea, finally resulting in liver disease and extrapyramidal symptoms. It is the most common genetic neurological disorder in the onset of adolescents, second to muscular dystrophy in China. Early diagnosis and medical therapy are of great significance for improving the prognosis of WD patients. However, diagnosis of this disease is usually difficult because of its complicated phenotypes. In the last 10 years, an increasing number of clinical studies have used molecular genetics techniques. Improved diagnosis and prediction of the progression of this disease at the molecular level will aid in the development of more individualized and effective interventions, which is a key to transition from molecular genetic research to the clinical study. Clinical genetics studies are necessary to understand the mechanism underlying WD at the molecular level from the genotype to the phenotype. Clinical genetics research benefits newly emerging medical treatments including stem cell transplantation and gene therapy for WD patients.

  3. Genetics Home Reference: Pelizaeus-Merzbacher disease

    Science.gov (United States)

    ... in my area? Other Names for This Condition Cockayne-Pelizaeus-Merzbacher disease HLD1 hypomyelinating leukodystrophy, 1 PMD ... is newborn screening? New Pages Leprosy Polycystic ovary syndrome Gorlin-Chaudhry-Moss syndrome All New & Updated Pages ...

  4. Genetics Home Reference: von Willebrand disease

    Science.gov (United States)

    ... Jun;5(6):1165-9. Citation on PubMed Kessler CM. Diagnosis and treatment of von Willebrand disease: ... consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Customer ...

  5. Genetics Home Reference: CLN4 disease

    Science.gov (United States)

    ... CLN4 disease often develop seizures and uncontrollable muscle jerks (myoclonic epilepsy), a decline in intellectual function (dementia), ... 1 link) CEROID LIPOFUSCINOSIS, NEURONAL, 4B, AUTOSOMAL DOMINANT Sources for This Page Cadieux-Dion M, Andermann E, ...

  6. Managing marine disease emergencies in an era of rapid change.

    Science.gov (United States)

    Groner, Maya L; Maynard, Jeffrey; Breyta, Rachel; Carnegie, Ryan B; Dobson, Andy; Friedman, Carolyn S; Froelich, Brett; Garren, Melissa; Gulland, Frances M D; Heron, Scott F; Noble, Rachel T; Revie, Crawford W; Shields, Jeffrey D; Vanderstichel, Raphaël; Weil, Ernesto; Wyllie-Echeverria, Sandy; Harvell, C Drew

    2016-03-05

    Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease-promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information-sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require. © 2016 The Author(s).

  7. CLINICAL AND GENETIC PARALLELS ALONG CELIAC DISEASE AMONG TOMSK CHILDREN

    OpenAIRE

    E.I. Kondrat’eva; Puzyrev, V.P.; L.P. Nazarenko; A. A. Rudko; G.N. Yankina; E.V. Loshkova

    2007-01-01

    The article is devoted to the analysis of the genetic predisposition to celiac disease. The authors studied the associations of the HLA genes and modifier genes of the immune response (interleukine 1, inter leukine 1 receptor antagonist, inter leukine 4, α-subunits of interleukine 4 receptor, receptor to D vitamin) along with predisposition to the disease, as well as the variants of its run and accompanied autoimmune diseases (autoimmune thyroiditis, insular diabetes type 1).Key words: celiac...

  8. Clinical and genetic features of Huntington disease in Sri Lanka.

    Science.gov (United States)

    Sumathipala, Dulika S; Jayasekara, Rohan W; Dissanayake, Vajira H W

    2013-12-05

    Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka. Data of 35 consecutive patients tested from 2007 to 2012 at the Human Genetics Unit, Faculty of Medicine, University of Colombo was analyzed retrospectively. Clinical data and genetic diagnostic results were reviewed. Statistical analysis was performed using descriptive statistics. Thirty patients had fully penetrant (FP) CAG repeat mutations and 5 had reduced penetrant (RP) CAG repeat mutations. In the FP group mean ages of onset and diagnosis were 37.5 and 40.4 years, while in the RP group it was 63.0 and 64.8 years respectively. The age of diagnosis ranged from 15 to 72 years, with 2 patients with Juvenile onset (60 years) Huntington disease. The symptoms at diagnosis were predominantly motor (32/35 -91%). Three patients had psychiatric and behavioral disorders. The age difference between onset and genetic diagnosis showed significant delay in females compared to males (p Huntington disease in the Sri Lankan study population were similar to that previously reported in literature.

  9. Homogenous Population Genetic Structure of the Non-Native Raccoon Dog (Nyctereutes procyonoides) in Europe as a Result of Rapid Population Expansion.

    Science.gov (United States)

    Drygala, Frank; Korablev, Nikolay; Ansorge, Hermann; Fickel, Joerns; Isomursu, Marja; Elmeros, Morten; Kowalczyk, Rafał; Baltrunaite, Laima; Balciauskas, Linas; Saarma, Urmas; Schulze, Christoph; Borkenhagen, Peter; Frantz, Alain C

    2016-01-01

    The extent of gene flow during the range expansion of non-native species influences the amount of genetic diversity retained in expanding populations. Here, we analyse the population genetic structure of the raccoon dog (Nyctereutes procyonoides) in north-eastern and central Europe. This invasive species is of management concern because it is highly susceptible to fox rabies and an important secondary host of the virus. We hypothesized that the large number of introduced animals and the species' dispersal capabilities led to high population connectivity and maintenance of genetic diversity throughout the invaded range. We genotyped 332 tissue samples from seven European countries using 16 microsatellite loci. Different algorithms identified three genetic clusters corresponding to Finland, Denmark and a large 'central' population that reached from introduction areas in western Russia to northern Germany. Cluster assignments provided evidence of long-distance dispersal. The results of an Approximate Bayesian Computation analysis supported a scenario of equal effective population sizes among different pre-defined populations in the large central cluster. Our results are in line with strong gene flow and secondary admixture between neighbouring demes leading to reduced genetic structuring, probably a result of its fairly rapid population expansion after introduction. The results presented here are remarkable in the sense that we identified a homogenous genetic cluster inhabiting an area stretching over more than 1500km. They are also relevant for disease management, as in the event of a significant rabies outbreak, there is a great risk of a rapid virus spread among raccoon dog populations.

  10. Genetic architecture of quantitative traits and complex diseases.

    Science.gov (United States)

    Fu, Wenqing; O'Connor, Timothy D; Akey, Joshua M

    2013-12-01

    More than 150 years after Mendel discovered the laws of heredity, the genetic architecture of phenotypic variation remains elusive. Here, we discuss recent progress in deciphering how genotypes map onto phenotypes, sources of genetic complexity, and how model organisms are illuminating general principles about the relationship between genetic and phenotypic variation. Moreover, we highlight insights gleaned from large-scale sequencing studies in humans, and how this knowledge informs outstanding questions about the genetic architecture of quantitative traits and complex diseases. Finally, we articulate how the confluence of technologies enabling whole-genome sequencing, comprehensive phenotyping, and high-throughput functional assays of polymorphisms will facilitate a more principled and mechanistic understanding of the genetic architecture of phenotypic variation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Curing genetic disease with gene therapy.

    Science.gov (United States)

    Williams, David A

    2014-01-01

    Development of viral vectors that allow high efficiency gene transfer into mammalian cells in the early 1980s foresaw the treatment of severe monogenic diseases in humans. The application of gene transfer using viral vectors has been successful in diseases of the blood and immune systems, albeit with several curative studies also showing serious adverse events (SAEs). In children with X-linked severe combined immunodeficiency (SCID-X1), chronic granulomatous disease, and Wiskott-Aldrich syndrome, these SAEs were caused by inappropriate activation of oncogenes. Subsequent studies have defined the vector sequences responsible for these transforming events. Members of the Transatlantic Gene Therapy Consortium [TAGTC] have collaboratively developed new vectors that have proven safer in preclinical studies and used these vectors in new clinical trials in SCID-X1. These trials have shown evidence of early efficacy and preliminary integration analysis data from the SCID-X1 trial suggest an improved safety profile.

  12. Genetic management of infectious diseases: a heterogeneous epidemio-genetic model illustrated with S. aureus mastitis

    Directory of Open Access Journals (Sweden)

    Detilleux Johann C

    2005-07-01

    Full Text Available Abstract Given that individuals are genetically heterogeneous in their degree of resistance to infection, a model is proposed to formulate appropriate choices that will limit the spread of an infectious disease. The model is illustrated with data on S. aureus mastitis and is based on parameters characterizing the spread of the disease (contact rate, probability of infection after contact, and rate of recovery after infection, the demography (replacement and culling rates and the genetic composition (degree of relationship and heritability of the disease trait of the animal population. To decrease infection pressure, it is possible to apply non-genetic procedures that increase the culling (e.g., culling of chronically infected cows and recovery (e.g., antibiotic therapy rates of infected cows. But the contribution of the paper is to show that genetic management of infectious disease is also theoretically possible as a control measure complementary to non-genetic actions. Indeed, the probability for an uninfected individual to become infected after contact with an infected one is partially related to their degree of kinship: the more closely they are related, the more likely they are to share identical genes like those associated to the non-resistance to infection. Different prospective genetic management procedures are proposed to decrease the contact rate between infected and uninfected relatives and keep the number of secondary cases generated by one infected animal below 1.

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

    Science.gov (United States)

    Pogue, A I; Lukiw, W J

    2016-06-01

    The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex and intricate process as genetic operations such as transcription involve the very rapid translocation and polymerization of ribonucleotides using RNA polymerases, accessory transcription protein complexes and other interrelated chromatin proteins and genetic factors. As both free ribonucleotides and polymerized single-stranded RNA chains, ribonucleotides are highly charged with phosphate, and this genetic system is extremely vulnerable to disruption by a large number of electrostatic forces, and primarily by cationic metals such as aluminum. Aluminum has been shown by independent researchers to be particularly genotoxic to the genetic apparatus, and it has become reasonably clear that aluminum disturbs genetic signaling programs in the CNS that bear a surprising resemblance to those observed in Alzheimer's disease (AD) brain. This paper will focus on a discussion of two molecular-genetic aspects of aluminum genotoxicity: (1) the observation that micro-RNA (miRNA)-mediated global gene expression patterns in aluminum-treated transgenic animal models of AD (Tg-AD) strongly resemble those found in AD; and (2) the concept of "human biochemical individuality" and the hypothesis that individuals with certain gene expression patterns may be especially sensitive and perhaps predisposed to aluminum genotoxicity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Human genetic insights into lipoproteins and risk of cardiometabolic disease.

    Science.gov (United States)

    Stitziel, Nathan O

    2017-04-01

    Human genetic studies have been successfully used to identify genes and pathways relevant to human biology. Using genetic instruments composed of loci associated with human lipid traits, recent studies have begun to clarify the causal role of major lipid fractions in risk of cardiometabolic disease. The causal relationship between LDL cholesterol and coronary disease has been firmly established. Of the remaining two major fractions, recent studies have found that HDL cholesterol is not likely to be a causal particle in atherogenesis, and have instead shifted the causal focus to triglyceride-rich lipoproteins. Subsequent results are refining this view to suggest that triglycerides themselves might not be causal, but instead may be a surrogate for the causal cholesterol content within this fraction. Other studies have used a similar approach to address the association between lipid fractions and risk of type 2 diabetes. Beyond genetic variation in the target of statin medications, reduced LDL cholesterol associated with multiple genes encoding current or prospective drug targets associated with increased diabetic risk. In addition, genetically lower HDL cholesterol and genetically lower triglycerides both appear to increase risk of type 2 diabetes. Results of these and future human genetic studies are positioned to provide substantive insights into the causal relationship between lipids and human disease, and should highlight mechanisms with important implications for our understanding of human biology and future lipid-altering therapeutic development.

  15. Genetic and environmental influences in Dupuytren's disease

    DEFF Research Database (Denmark)

    Larsen, Søren; Krogsgaard, D G; Larsen, Lisbeth Aagaard

    2015-01-01

    We aimed to assess the relative contribution of genes and environment in the aetiology of Dupuytren's disease by studying Danish twins born between 1870 and 2000. Twins with a diagnosis (n = 365) and the subgroup who also had an operation (n = 259) after 1977 were identified through linkage with ...

  16. Genetics of hyperhomocysteinemia in vascular disease

    NARCIS (Netherlands)

    Lievers, Caroline Joan Antoinette

    2002-01-01

    Homocysteine is an amino acid that plays a pivotal role in methionine metabolism. Moderately elevated plasma homocysteine concentrations are considered to be a risk factor for cardiovascular diseases (CVD). Plasma homocysteine concentrations are influenced by environmental factors, such as diet and

  17. Genetic manipulation for inherited neurodegenerative diseases: myth or reality?

    Science.gov (United States)

    Yu-Wai-Man, Patrick

    2016-10-01

    Rare genetic diseases affect about 7% of the general population and over 7000 distinct clinical syndromes have been described with the majority being due to single gene defects. This review will provide a critical overview of genetic strategies that are being pioneered to halt or reverse disease progression in inherited neurodegenerative diseases. This field of research covers a vast area and only the most promising treatment paradigms will be discussed with a particular focus on inherited eye diseases, which have paved the way for innovative gene therapy paradigms, and mitochondrial diseases, which are currently generating a lot of debate centred on the bioethics of germline manipulation. 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/

  18. Rapid evolution of the intersexual genetic correlation for fitness in Drosophila melanogaster

    Science.gov (United States)

    Collet, Julie M.; Fuentes, Sara; Hesketh, Jack; Hill, Mark S.; Innocenti, Paolo; Morrow, Edward H.; Fowler, Kevin; Reuter, Max

    2016-01-01

    Sexual antagonism (SA) arises when male and female phenotypes are under opposing selection, yet genetically correlated. Until resolved, antagonism limits evolution toward optimal sex‐specific phenotypes. Despite its importance for sex‐specific adaptation and existing theory, the dynamics of SA resolution are not well understood empirically. Here, we present data from Drosophila melanogaster, compatible with a resolution of SA. We compared two independent replicates of the “LHM” population in which SA had previously been described. Both had been maintained under identical, controlled conditions, and separated for around 200 generations. Although heritabilities of male and female fitness were similar, the intersexual genetic correlation differed significantly, being negative in one replicate (indicating SA) but close to zero in the other. Using population sequencing, we show that phenotypic differences were associated with population divergence in allele frequencies at nonrandom loci across the genome. Large frequency changes were more prevalent in the population without SA and were enriched at loci mapping to genes previously shown to have sexually antagonistic relationships between expression and fitness. Our data suggest that rapid evolution toward SA resolution has occurred in one of the populations and open avenues toward studying the genetics of SA and its resolution. PMID:27077679

  19. Recent Developments in Genetic Study of Allergic Disease in the Japanese Population

    Directory of Open Access Journals (Sweden)

    Masao Suzuki

    2005-01-01

    Full Text Available Allergy is a common immune disorder characterized by raised IgE levels, which leads to clinical disorders such as asthma, rhinitis and eczema. Our understanding of the pathogenesis of allergic disease is largely dependent on our current understanding of the related pathophysiology and the available technology. Recent advances in molecular biology techniques have allowed a rapid and accurate identification of polymorphisms in various genes that may be important for determining the susceptibility to allergic disorders. In this review, we present some developments in genetic studies of allergic disease with particular focus on asthma and atopy in the Japanese population.

  20. The right to ignore genetic status of late onset genetic disease in the genomic era; Prenatal testing for Huntington disease as a paradigm.

    Science.gov (United States)

    Erez, A; Plunkett, K; Sutton, V R; McGuire, A L

    2010-07-01

    During the last decade, the field of human genome research has gone through a phase of rapid discovery that has provided scientists and physicians with a wide variety of research tools that are applicable to important medical issues. We describe a true case of familial Huntington disease (HD) in which we modified personal details to protect patient's privacy, where the proband at risk preferred not to know his disease status but wanted to know the status in his unborn child. Once we found the father to be negative, the case raised an important ethical question regarding the management of this as well as future pregnancies. This article discusses the arguments for and against the right not to know of one's carrier status, as well as professional obligations in the context of withholding unwanted information that may have direct implications not only for the patient himself but also for other family members. HD has served as a model for many other adult onset genetic diseases in terms of carrier testing guidelines. Hence, we feel it is time to revisit the issue of prenatal testing for HD and consider updating the current recommendations regarding the patient's right to "genetic ignorance", or the right not to know genetic information. (c) 2010 Wiley-Liss, Inc.

  1. The genetic landscape of Alzheimer disease: clinical implications and perspectives.

    Science.gov (United States)

    Van Cauwenberghe, Caroline; Van Broeckhoven, Christine; Sleegers, Kristel

    2016-05-01

    The search for the genetic factors contributing to Alzheimer disease (AD) has evolved tremendously throughout the years. It started from the discovery of fully penetrant mutations in Amyloid precursor protein, Presenilin 1, and Presenilin 2 as a cause of autosomal dominant AD, the identification of the ɛ4 allele of Apolipoprotein E as a strong genetic risk factor for both early-onset and late-onset AD, and evolved to the more recent detection of at least 21 additional genetic risk loci for the genetically complex form of AD emerging from genome-wide association studies and massive parallel resequencing efforts. These advances in AD genetics are positioned in light of the current endeavor directing toward translational research and personalized treatment of AD. We discuss the current state of the art of AD genetics and address the implications and relevance of AD genetics in clinical diagnosis and risk prediction, distinguishing between monogenic and multifactorial AD. Furthermore, the potential and current limitations of molecular reclassification of AD to streamline clinical trials in drug development and biomarker studies are addressed.Genet Med 18 5, 421-430.

  2. Genetic testing in congenital heart disease: A clinical approach

    Science.gov (United States)

    Chaix, Marie A; Andelfinger, Gregor; Khairy, Paul

    2016-01-01

    Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel. PMID:26981213

  3. Genetics of hereditary large vessel diseases.

    Science.gov (United States)

    Morisaki, Takayuki; Morisaki, Hiroko

    2016-01-01

    Recent progress in the study of hereditary large vessel diseases such as Marfan syndrome (MFS) have not only identified responsible genes but also provided better understanding of the pathophysiology and revealed possible new therapeutic targets. Genes identified for these diseases include FBN1, TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, SKI, EFEMP2, COL3A1, FLNA, ACTA2, MYH11, MYLK and SLC2A10, as well as others. Their dysfunction disrupts the function of transforming growth factor-β (TGF-β) signaling pathways, as well as that of the extracellular matrix and smooth muscle contractile apparatus, resulting in progression of structural damage to large vessels, including aortic aneurysms and dissections. Notably, it has been shown that the TGF-β signaling pathway has a key role in the pathogenesis of MFS and related disorders, which may be important for development of strategies for medical and surgical treatment of thoracic aortic aneurysms and dissections.

  4. Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy

    DEFF Research Database (Denmark)

    Hornstrup, Louise S; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

    2013-01-01

    Transthyretin can cause amyloidosis attributable to destabilization of transthyretin tetramers in plasma. We tested the hypothesis that genetic stabilization of transthyretin associates with reduced risk of vascular disease and increased life expectancy. APPROACH AND RESULTS: We included 68 602...... participants from 2 prospective studies of the general population. We genotyped for 2 stabilizing genetic variants in the transthyretin gene (TTR), R104H and T119M, and determined the association of genotypes with plasma levels of transthyretin, measures of thyroid function, risk of vascular disease, and life...

  5. Genetics and Epigenetics of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Fabio Coppedè

    2012-01-01

    Full Text Available In 1997 a mutation in the a-synuclein (SNCA gene was associated with familial autosomal dominant Parkinson’s disease (PD. Since then, several loci (PARK1-15 and genes have been linked to familial forms of the disease. There is now sufficient evidence that six of the so far identified genes at PARK loci (a-synuclein, leucine-rich repeat kinase 2, parkin, PTEN-induced putative kinase 1, DJ-1, and ATP13A2 cause inherited forms of typical PD or parkinsonian syndromes. Other genes at non-PARK loci (MAPT, SCA1, SCA2, spatacsin, POLG1 cause syndromes with parkinsonism as one of the symptoms. The majority of PD cases are however sporadic “idiopathic” forms, and the recent application of genome-wide screening revealed almost 20 genes that might contribute to disease risk. In addition, increasing evidence suggests that epigenetic mechanisms, such as DNA methylation, histone modifications, and small RNA-mediated mechanisms, could regulate the expression of PD-related genes.

  6. The Counselor and Genetic Disease: Huntington's Disease as a Model.

    Science.gov (United States)

    Wexler, Nancy S.

    This speech offers a brief description of Huntington's Disease (HD): its causes, symptoms, and incidence. It then concentrates on the psychological problems of persons one of whose parents had the disease, and the role of the counselor in helping these humans cope with their fears about contacting it themselves. A relatively detailed case study is…

  7. The genetic predisposition and the interplay of host genetics and gut microbiome in Crohn disease.

    Science.gov (United States)

    Jianzhong, Hu

    2014-12-01

    Extensive genetic studies have identified more than 140 loci predisposing to Crohn disease (CD). Several major CD susceptibility genes have been shown to impair biological function with regard to immune response to recognizing and clearance of bacterial infection. Recent human microbiome studies suggest that the gut microbiome composition is differentiated in carriers of many risk variants of major CD susceptibility genes. This interplay between host genetics and its associated gut microbiome may play an essential role in the pathogenesis of CD. The ongoing microbiome research is aimed to investigate the detailed host genetics-microbiome interacting mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. A Parallel Genetic Algorithm to Discover Patterns in Genetic Markers that Indicate Predisposition to Multifactorial Disease

    Science.gov (United States)

    Rausch, Tobias; Thomas, Alun; Camp, Nicola J.; Cannon-Albright, Lisa A.; Facelli, Julio C.

    2008-01-01

    This paper describes a novel algorithm to analyze genetic linkage data using pattern recognition techniques and genetic algorithms (GA). The method allows a search for regions of the chromosome that may contain genetic variations that jointly predispose individuals for a particular disease. The method uses correlation analysis, filtering theory and genetic algorithms (GA) to achieve this goal. Because current genome scans use from hundreds to hundreds of thousands of markers, two versions of the method have been implemented. The first is an exhaustive analysis version that can be used to visualize, explore, and analyze small genetic data sets for two marker correlations; the second is a GA version, which uses a parallel implementation allowing searches of higher-order correlations in large data sets. Results on simulated data sets indicate that the method can be informative in the identification of major disease loci and gene-gene interactions in genome-wide linkage data and that further exploration of these techniques is justified. The results presented for both variants of the method show that it can help genetic epidemiologists to identify promising combinations of genetic factors that might predispose to complex disorders. In particular, the correlation analysis of IBD expression patterns might hint to possible gene-gene interactions and the filtering might be a fruitful approach to distinguish true correlation signals from noise. PMID:18547558

  9. Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases

    Science.gov (United States)

    Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

    2012-10-01

    The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

  10. Niemann-Pick disease type C: Genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Vanier, M.T.; Duthel, S.; Rodriguez-Lafrasse, C. [Lyon-Sud Medical School, Oullins (France)] [and others

    1994-09-01

    Although the primary defect is yet unknown, Niemann-Pick disease type C is at present best defined by unique abnormalities of intracellular translocation of exogenous cholesterol. A considerable variation in severity of clinical and biochemical expression has been described: nevertheless, our first genetic complementation study including eleven unrelated patients of varying phenotypes indicated that they all belonged to a single complementation group. We recently mapped the gene responsible for this major group to chromosome 18. In a recent meeting, Fensom and associates reported complementation between the cell line from one patient and those from seven other families. In conjunction with linkage studies, we have now expanded our investigation to the study of 28 unrelated patients. We have found that cell lines from 3 of those patients were able to complement the defect (intralysosomal storage of cholesterol evaluated by filipin staining) in cell lines from the main complementation group (25/28), and did not complement among themselves. Two of the patients had presented with a severe rapidly fatal clinical form while the two affected members in the third family had a slow progressive juvenile phenotype. They all belonged to the classical (severe) biochemical phenotype and had different ethnic origin. Since we learned that one of those cases was the same as that studied by Fensom (personal communication), all Niemann-Pick type C patients studied so far can be divided into two complementation groups. Using microsatellite markers in our multiplex family, we could further show that the gene responsible for the second minor complementation group does not map to the location of the major gene.

  11. Additional mechanisms conferring genetic susceptibility to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Miguel eCalero

    2015-04-01

    Full Text Available Familial Alzheimer's disease (AD, mostly associated with early onset, is caused by mutations in three genes (APP, PSEN1 and PSEN2 involved in the production of the amyloid  peptide. In contrast, the molecular mechanisms that trigger the most common late onset sporadic AD remain largely unknown. With the implementation of an increasing number of case-control studies and the upcoming of large-scale genome-wide association studies (GWAS there is a mounting list of genetic risk factors associated to common genetic variants that have been associated to sporadic AD. Besides APOE, that presents a strong association with the disease (OR~4, the rest of these genes have moderate or low degrees of association, with OR ranging from 0.88 to 1.23. Taking together, these genes may account only for a fraction of the attributable AD risk and therefore, rare variants and epistastic gene interactions should be taken into account in order to get the full picture of the genetic risks associated to AD. Here, we review recent whole-exome studies looking for rare variants, somatic brain mutations with a strong association to the disease, and several studies dealing with epistasis as additional mechanisms conferring genetic susceptibility to AD. Altogether, recent evidence underlines the importance of defining molecular and genetic pathways and networks rather than the contribution of specific genes.

  12. Genetic Polymorphisms of Infectious Diseases in Case-Control Studies

    Directory of Open Access Journals (Sweden)

    Antonio G. Pacheco

    2009-01-01

    Full Text Available In the past decade, genetic epidemiological analyses in infectious diseases have increased drastically since the publication of human genome and all the subsequent projects analyzing human diversity at molecular level. The great majority of studies use classical epidemiological designs applied to genetic data, and more than 80% of published studies use population-based case-control designs with widely spread genetic markers in human genome, like short tandem repeats (STR or single nucleotide polymorphisms (SNP, in genes chosen by their physiological association with the disease (candidate genes. Even though genetic data is less prone to several bias issues inherent to case-control studies, some care has to be taken when designing, performing, analyzing and interpreting results from such studies. Here we discuss some basic concepts of genetics and epidemiology as a departure to evaluate and review every step that should be followed to design, conduct, analyze, interpret and present data from those studies, using particularities of infectious diseases, especially leprosy and tuberculosis as models.

  13. Amyloid heart disease: genetics translated into disease-modifying therapy.

    Science.gov (United States)

    Sperry, Brett W; Tang, W H Wilson

    2017-06-01

    Given increased awareness and improved non-invasive diagnostic tools, cardiac amyloidosis has become an increasingly recognised aetiology of increased ventricular wall thickness and heart failure with preserved ejection fraction. Once considered a rare disease with no treatment options, translational research has harnessed novel pathways and led the way to promising treatment options. Gene variants that contribute to amyloid heart disease provide unique opportunities to explore potential disease-modifying therapeutic strategies. Amyloidosis has become the model disease through which gene therapy using small interfering RNAs and antisense oligonucleotides has evolved. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Caroli's disease: prenatal diagnosis, postnatal outcome and genetic analysis.

    Science.gov (United States)

    Sgro, M; Rossetti, S; Barozzino, T; Toi, A; Langer, J; Harris, P C; Harvey, E; Chitayat, D

    2004-01-01

    Caroli's disease is a rare autosomal recessive condition characterized by cystic dilatation of the intrahepatic bile ducts and infantile polycystic kidney disease. We report a case with Caroli's disease detected prenatally at 33 weeks' gestation with fetal ultrasound findings of a cystic liver mass and echogenic kidneys. Postnatal investigation confirmed enlarged and echogenic kidneys with dilatation of the intrahepatic bile ducts consistent with the diagnosis of Caroli's disease. Genetic analysis of the gene, PKHD1, associated with autosomal recessive polycystic kidney disease (ARPKD) showed that the patient had compound heterozygous mutations, confirming that this early onset Caroli's disease was part of the spectrum of ARPKD. To our knowledge this is the third case of Caroli's disease detected prenatally and the first in which the infant survived. Copyright 2003 ISUOG. Published by John Wiley & Sons, Ltd.

  15. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    OpenAIRE

    Shrestha Palikhe, Nami; Kim, Seung-Hyun; Jin, Hyun Jung; Hwang, Eui-Kyung; Nam, Young Hee; Park, Hae-Sim

    2012-01-01

    Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the resp...

  16. Modern vitiligo genetics sheds new light on an ancient disease

    Science.gov (United States)

    SPRITZ, Richard A.

    2013-01-01

    Vitiligo is a complex disorder in which autoimmune destruction of melanocytes results in white patches of skin and overlying hair. Over the past several years, extensive genetic studies have outlined a biological framework of vitiligo pathobiology that underscores its relationship to other autoimmune diseases. This biological framework offers insight into both vitiligo pathogenesis and perhaps avenues towards more effective approaches to treatment and even disease prevention. PMID:23668538

  17. Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes.

    OpenAIRE

    Esterina ePascale; Maria Elena eDi Battista; Alfonso eRubino; Carlo ePurcaro; Marcella eValente; Francesco eFattapposta; Giampiero eFerraguti; Giuseppe eMeco

    2016-01-01

    The microtubule-associated protein tau (MAPT) region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease. Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk...

  18. Rapid global expansion of the fungal disease chytridiomycosis into declining and healthy amphibian populations.

    Directory of Open Access Journals (Sweden)

    Timothy Y James

    2009-05-01

    Full Text Available The fungal disease chytridiomycosis, caused by Batrachochytrium dendrobatidis, is enigmatic because it occurs globally in both declining and apparently healthy (non-declining amphibian populations. This distribution has fueled debate concerning whether, in sites where it has recently been found, the pathogen was introduced or is endemic. In this study, we addressed the molecular population genetics of a global collection of fungal strains from both declining and healthy amphibian populations using DNA sequence variation from 17 nuclear loci and a large fragment from the mitochondrial genome. We found a low rate of DNA polymorphism, with only two sequence alleles detected at each locus, but a high diversity of diploid genotypes. Half of the loci displayed an excess of heterozygous genotypes, consistent with a primarily clonal mode of reproduction. Despite the absence of obvious sex, genotypic diversity was high (44 unique genotypes out of 59 strains. We provide evidence that the observed genotypic variation can be generated by loss of heterozygosity through mitotic recombination. One strain isolated from a bullfrog possessed as much allelic diversity as the entire global sample, suggesting the current epidemic can be traced back to the outbreak of a single clonal lineage. These data are consistent with the current chytridiomycosis epidemic resulting from a novel pathogen undergoing a rapid and recent range expansion. The widespread occurrence of the same lineage in both healthy and declining populations suggests that the outcome of the disease is contingent on environmental factors and host resistance.

  19. The genetics of very early onset Alzheimer disease.

    Science.gov (United States)

    Filley, Christopher M; Rollins, Yvonne D; Anderson, C Alan; Arciniegas, David B; Howard, Katherine L; Murrell, Jill R; Boyer, Philip J; Kleinschmidt-DeMasters, Belte K; Ghetti, Bernardino

    2007-09-01

    This study was undertaken to clarify the genetics of very early onset Alzheimer disease (VEOAD), defined as AD beginning before age 35. Early onset AD (EOAD) is defined by onset of symptoms before age 65, and affected individuals may harbor a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein. VEOAD is exceedingly rare, and PSEN1 mutations have been implicated. We encountered a man with phenotypic frontotemporal dementia beginning at age 32 and a strong family history of an autosomal dominant dementia who was found at autopsy to have AD. Histologic and genetic analyses of the patient's brain were undertaken, and a review of all published VEOAD cases was performed. Histologic findings were diagnostic of advanced stage AD. Genetic evaluation of brain tissue identified an intronic PSEN1 polymorphism; no known pathogenic mutation was found. Literature review (1934 to 2007) disclosed 101 cases of VEOAD; the youngest age of dementia onset was 24 years. In all cases in which definitive genetic analysis was available, either a PSEN1 mutation or linkage to chromosome 14 was found. VEOAD can present with atypical clinical features, including findings suggestive of frontotemporal dementia. All reported cases of VEOAD with conclusive genetic analysis seem to be associated with PSEN1 mutations. Genetic testing in adults younger than 35 with dementia can identify the genetic defect and assist in diagnosis and family counseling.

  20. 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.

  1. Context-specific effects of genetic variants associated with autoimmune disease

    NARCIS (Netherlands)

    Jonkers, Iris H.; Wijmenga, Cisca

    2017-01-01

    Autoimmune diseases such as rheumatoid arthritis and coeliac disease are typical examples of complex genetic diseases caused by a combination of genetic and non-genetic risk factors. Insight into the genetic risk factors (single nucleotide polymorphisms (SNPs)) has increased since genome-wide

  2. Environmental and genetic factors in pediatric inflammatory demyelinating diseases.

    Science.gov (United States)

    Waubant, Emmanuelle; Ponsonby, Anne-Louise; Pugliatti, Maura; Hanwell, Heather; Mowry, Ellen M; Hintzen, Rogier Q

    2016-08-30

    The onset of multiple sclerosis (MS) occurs in childhood in about 5% of all patients with MS. The disease in adults has a complex genetic and environmental inheritability. One of the main risk factors, also confirmed in pediatric MS, is HLA DRB1*1501 In addition to genetic factors, a large part of disease susceptibility in adults is conferred by environmental risk factors such as low vitamin D status, exposure to cigarette smoking, and remote Epstein-Barr virus (EBV) infection. In children, both exposure to cigarette smoking and prior EBV infection have been reported consistently as risk factors for MS. The role of vitamin D remains to be confirmed in this age category. Finally, although very likely critical in disease processes, few gene-environment interactions and epigenetic changes have been reported for adult and pediatric MS susceptibility. Of interest, some of the risk factors for MS have also been associated with disease course modification, such as low 25(OH) vitamin D serum levels in pediatric and adult MS. Age is also a clear disease modifier of clinical, CSF, and MRI phenotype in children with the disease. Finally, although much has yet to be unraveled regarding molecular processes at play in MS, there is a larger gap in our knowledge of genetic and environmental risk factors for pediatric neuromyelitis optica spectrum disorders and acute disseminated encephalomyelitis and only collaborative studies will answer those questions. © 2016 American Academy of Neurology.

  3. Teaching Mitochondrial Genetics & Disease: A GENA Project Curriculum Intervention

    Science.gov (United States)

    Reardon, Ryan A.; Sharer, J. Daniel

    2012-01-01

    This report describes a novel, inquiry-based learning plan developed as part of the GENA educational outreach project. Focusing on mitochondrial genetics and disease, this interactive approach utilizes pedigree analysis and laboratory techniques to address non-Mendelian inheritance. The plan can be modified to fit a variety of educational goals…

  4. Genetic variation in Toll-like receptors and disease susceptibility

    NARCIS (Netherlands)

    Netea, Mihai G.; Wijmenga, Cisca; O'Neill, Luke A. J.

    Toll-like receptors (TLRs) are key initiators of the innate immune response and promote adaptive immunity. Much has been learned about the role of TLRs in human immunity from studies linking TLR genetic variation with disease. First, monogenic disorders associated with complete deficiency in certain

  5. Unraveling the genetics of chronic kidney disease using animal models

    NARCIS (Netherlands)

    Korstanje, Ron; DiPetrillo, K.

    2004-01-01

    Identifying genes underlying common forms of kidney disease in humans has proven difficult, expensive, and time consuming. Quantitative trait loci (QTL) for several complex traits are concordant among mice, rats, and humans, suggesting that genetic findings from these animal models are relevant to

  6. Genetic contribution of the leukotriene pathway to coronary artery disease

    Science.gov (United States)

    We evaluated the genetic contribution of the leukotriene (LT) pathway to risk of coronary artery disease (CAD) in 4,512 Caucasian and African American subjects ascertained through elective cardiac evaluation. Of the three previously associated variants, the shorter "3" and "4" alleles of a promoter ...

  7. Exploration of genetic susceptibility factors for Parkinson's disease ...

    Indian Academy of Sciences (India)

    6Present address: Biomedical Science Research Group, School of Medicine, Universidad Antonio Nari˜no, Bogotá, Colombia. Introduction. The genetic susceptibility factors for Parkinson's disease. (PD) in non-European populations, including those from. Latin American countries, are unknown (Thomas and Beal. 2007).

  8. Genetic epidemiology of coronary artery disease: an Asian Indian ...

    Indian Academy of Sciences (India)

    Coronary artery disease (CAD) has emerged as a major cause of morbidity and mortality worldwide. Recent findings on the role of genetic factors in the aetiopathology of CAD have implicated novel genes and variants in addition to those involved in lipid and lipoprotein metabolism. However, our present knowledge is ...

  9. Exploring Genetic Factors Involved in Huntington Disease Age of Onset

    DEFF Research Database (Denmark)

    Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel

    2015-01-01

    Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim...

  10. Clinical and genetic data of Huntington disease in Moroccan patients

    African Journals Online (AJOL)

    Background: Huntington's disease (HD) occurs worldwide with prevalence varying from 0.1 to 10 /100,000 depending of the ethnic origin. Since no data is available in the Maghreb population, the aim of this study is to describe clinical and genetic characteristics of Huntington patients of Moroccan origin. Methods: Clinical ...

  11. Clipboard: The Indian genetic landscape and disease-related genes

    Indian Academy of Sciences (India)

    2008-11-19

    Nov 19, 2008 ... Home; Journals; Journal of Biosciences; Volume 33; Issue 5. Clipboard: The Indian genetic landscape and disease-related genes. Evelyne Heyer. Volume 33 Issue 5 December 2008 pp 631-633. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/jbsc/033/05/0631- ...

  12. Triplet repeat DNA structures and human genetic disease: dynamic ...

    Indian Academy of Sciences (India)

    Triplet repeat DNA structures and human genetic disease: dynamic mutations from dynamic DNA. Richard R Sinden Vladimir N ... Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, ...

  13. Hirschsprung disease, associated syndromes and genetics : a review

    NARCIS (Netherlands)

    Amiel, J.; Sproat-Emison, E.; Garcia-Barcelo, M.; Lantieri, F.; Burzynski, G.; Borrego, S.; Pelet, A.; Arnold, S.; Miao, X.; Griseri, P.; Brooks, A. S.; Antinolo, G.; de Pontual, L.; Clement-Ziza, M.; Munnich, A.; Kashuk, C.; West, K.; Wong, K. K-Y; Lyonnet, S.; Chakravarti, A.; Tam, P. K-H; Ceccherini, I.; Hofstra, R. M. W.; Fernandez, R.

    Hirschsprung disease ( HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of

  14. Late onset Pompe disease- new genetic variant: Case report ...

    African Journals Online (AJOL)

    The patient was not given enzyme replacement therapy due to cost but received high protein therapy and Oxygen supplementation using Oxygen extractor machine. She is worsening due to respiratory failure. Conclusion: This is a new genetic variant isolated of late-onset Pompe disease which presents with almost pure ...

  15. Genetic and epigenetic studies of adiposity and cardiometabolic disease.

    Science.gov (United States)

    Holmes, Michael V; Pulit, Sara L; Lindgren, Cecilia M

    2017-09-18

    Over 300 million adults are obese, but little is known about the impact of obesity on cardiovascular health. We discuss recent genetic and epigenetic studies of adiposity that indicate a causal role for general and central adiposity in cardiometabolic disease, and highlight potential mechanisms including insulin resistance and gene expression.

  16. Drug Repositioning in Inflammatory Bowel Disease Based on Genetic Information

    NARCIS (Netherlands)

    Collij, Valerie; Festen, Eleonora A. M.; Alberts, Rudi; Weersma, Rinse K.

    2016-01-01

    Background:Currently, 200 genetic risk loci have been identified for inflammatory bowel disease (IBD). Although these findings have significantly advanced our insight into IBD biology, there has been little progress in translating this knowledge toward clinical practice, like more cost-efficient

  17. Insights into metabolic disease from studying genetics in isolated populations

    DEFF Research Database (Denmark)

    Zeggini, Ele; Gloyn, A L; Hansen, Torben

    2016-01-01

    variation on disease risk. Current efforts are now focused on extending this to genetic variants in the rare and low-frequency spectrum by capitalising on next-generation sequencing technologies. This review discusses the important contributions that studies in isolated populations are making to this effort...

  18. Genetic analysis of resistance to early blight disease in tomato

    African Journals Online (AJOL)

    use

    2011-12-12

    Dec 12, 2011 ... Genetic analysis of resistance to early blight disease in tomato. Özer Çalış* and Şerife Topkaya. Gaziosmanpasa University, Faculty of Agriculture, Plant Protection Department, 60250 Tasliciftlik, Tokat, Turkey. Accepted 12 October, 2011. Early blight is a fungal pathogen that causes destructive necrotic and ...

  19. Is there a Common Genetic Basis for Autoimmune Diseases?

    Directory of Open Access Journals (Sweden)

    Juan-Manuel Anaya

    2006-01-01

    Full Text Available Autoimmune diseases (ADs represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS syndrome or type 1 diabetes mellitus (T1D. A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22 influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies.

  20. Rapid recent human evolution and the accumulation of balanced genetic polymorphisms.

    Science.gov (United States)

    Wills, Christopher

    2011-01-01

    All evolutionary change can be traced to alterations in allele frequencies in populations over time. DNA sequencing on a massive scale now permits us to follow the genetic consequences as our species has diverged from our close relatives and as we have colonized different parts of the world and adapted to them. But it has been difficult to disentangle natural selection from many other factors that alter frequencies. These factors include mutation and intragenic reciprocal recombination, gene conversion, segregation distortion, random drift, and gene flow between populations (these last two are greatly influenced by splits and coalescences of populations over time). The first part of this review examines recent studies that have had some success in dissecting out the role of natural selection, especially in humans and Drosophila. Among many examples, these studies include those that have followed the rapid evolution of traits that may permit adaptation to high altitude in Tibetan and Andean populations. In some cases, directional selection has been so strong that it may have swept alleles close to fixation in the span of a few thousand years, a rapidity of change that is also sometimes encountered in other organisms. The second part of the review summarizes data showing that remarkably few alleles have been carried completely to fixation during our recent evolution. Some of the alleles that have not reached fixation may be approaching new internal equilibria, which would indicate polymorphisms that are maintained by balancing selection. Finally, the review briefly examines why genetic polymorphisms, particularly those that are maintained by negative frequency dependence, are likely to have played an important role in the evolution of our species. A method is suggested for measuring the contribution of these polymorphisms to our gene pool. Such polymorphisms may add to the ability of our species to adapt to our increasingly complex and challenging environment.

  1. Advances in the Genetics of Congenital Heart Disease: A Clinician's Guide.

    Science.gov (United States)

    Blue, Gillian M; Kirk, Edwin P; Giannoulatou, Eleni; Sholler, Gary F; Dunwoodie, Sally L; Harvey, Richard P; Winlaw, David S

    2017-02-21

    Our understanding of the genetics of congenital heart disease (CHD) is rapidly expanding; however, many questions, particularly those relating to sporadic forms of disease, remain unanswered. Massively parallel sequencing technology has made significant contributions to the field, both from a diagnostic perspective for patients and, importantly, also from the perspective of disease mechanism. The importance of de novo variation in sporadic disease is a recent highlight, and the genetic link between heart and brain development has been established. Furthermore, evidence of an underlying burden of genetic variation contributing to sporadic and familial forms of CHD has been identified. Although we are still unable to identify the cause of CHD for most patients, recent findings have provided us with a much clearer understanding of the types of variants and their individual contributions and collectively mark an important milestone in our understanding of both familial and sporadic forms of disease. Copyright © 2017 American College of Cardiology Foundation. All rights reserved.

  2. Genetic and environmental modifiers of Wilson disease.

    Science.gov (United States)

    Medici, Valentina; Weiss, Karl-Heinz

    2017-01-01

    Wilson disease (WD) is characterized by remarkable variety in its phenotypic presentation. Patients with WD can present with hepatic, neurologic, and psychiatric symptoms combined in different and unpredictable ways. Importantly, no convincing phenotype-genotype correlation has ever been identified, opening the possibility that other genes, aside from ATPase copper-transporting beta (ATP7B), are involved in the pathogenesis of this condition. In addition, modifier genes, or genes that can affect the expression of other genes, may be involved. Clinical and basic science data indicate that environmental and dietary factors can potentially modify gene expression in WD and, consequently, its clinical presentation and course. In particular, previously studied genes include copper metabolism domain-containing 1 (COMMD1), antioxidant 1 copper chaperone (ATOX1), X-linked inhibitor of apoptosis (XIAP), apolipoprotein E (APOE), hemochromatosis (HFE), and 5,10-methylenetetrahydrofolate reductase (MTHFR). Dietary factors include iron and methyl group donors which could affect methionine metabolism and epigenetic mechanisms of gene expression regulation. Most of the work conducted in this field is in its initial stages but it has the potential to change the diagnosis and treatment of WD. © 2017 Elsevier B.V. All rights reserved.

  3. Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration

    National Research Council Canada - National Science Library

    Tobinick, Edward L; Gross, Hyman

    2008-01-01

    ...) is centrally involved in the pathogenesis of Alzheimer's disease. In addition to its pro-inflammatory functions, TNF-alpha has recently been recognized to be a gliotransmitter that regulates synaptic function in neural networks...

  4. The genetics of breast cancer: risk factors for disease

    Directory of Open Access Journals (Sweden)

    Andrew Collins

    2011-01-01

    Full Text Available Andrew Collins, Ioannis PolitopoulosGenetic Epidemiology and Bioinformatics Research Group, Human Genetics Research Division, Southampton General Hospital, School of Medicine, University of Southampton, Southampton, UKAbstract: The genetic factors known to be involved in breast cancer risk comprise about 30 genes. These include the high-penetrance early-onset breast cancer genes, BRCA1 and BRCA2, a number of rare cancer syndrome genes, and rare genes with more moderate penetrance. A larger group of common variants has more recently been identified through genome-wide association studies. Quite a number of these common variants are mapped to genomic regions without being firmly associated with specific genes. It is thought that most of these variants have gene regulatory functions, but their precise roles in disease susceptibility are not well understood. Common variants account for only a small percentage of the risk of disease because they have low penetrance. Collectively, the breast cancer genes identified to date contribute only ~30% of the familial risk. Therefore, there is much interest in accounting for the missing heritability, and possible sources include loss of information through ignoring phenotype heterogeneity (disease subtypes have genetic differences, gene–gene and gene–environment interaction, and rarer forms of variation. Identification of these rarer variations in coding regions is now feasible and cost effective through exome sequencing, which has already identified high-penetrance variants for some rare diseases. Targeting more ‘extreme’ breast cancer phenotypes, particularly cases with early-onset disease, a strong family history (not accounted for by BRCA mutations, and with specific tumor subtypes, provides a route to progress using next-generation sequencing methods.Keywords: breast cancer, common and rare genetic variation, missing heritability, bioinformatics, exome sequencing

  5. Genetic convergence of Parkinson's disease and lysosomal storage disorders.

    Science.gov (United States)

    Deng, Hao; Xiu, Xiaofei; Jankovic, Joseph

    2015-01-01

    Parkinson's disease is a common progressive neurodegenerative disorder characterized by predominant degeneration of the dopaminergic neurons in the substantia nigra pars compacta and the presence of intracellular inclusions enriched in α-synuclein, resulting in a variety motor and nonmotor symptoms. Lysosomal storage disorders are a group of disorders including Gaucher disease, Niemann-Pick disease, and neuronal ceroid lipofuscinoses caused by the defective activity of lysosomal and nonlysosomal proteins. In addition to an overlap in some clinical features between lysosomal storage disorders and Parkinson's disease, the two disorders may be also linked pathogenically. There is growing support for the notion that mutations in genes causing lysosomal storage disorders including the glucocerebrosidase gene, the sphingomyelin phosphodiesterase 1 gene, and the NPC1 gene may increase risk for developing Parkinson's disease. In this review, we discuss the recent advances in the genetic convergence of Parkinson's disease and lysosomal storage disorders, shedding new light on the understanding of shared pathogenic pathways.

  6. Identification of genetic variants associated with Huntington's disease progression

    DEFF Research Database (Denmark)

    Hensman Moss, Davina J; Pardiñas, Antonio F; Langbehn, Douglas

    2017-01-01

    BACKGROUND: Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate...... indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008-11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers...... at this SNP was associated with a 0·4 units per year (95% CI 0·16-0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06-0·18) in the rate of change of UHDRS Total Functional Capacity score...

  7. Invasive Group A Streptococcal Disease. National Epidemiology and Genetic Analysis

    NARCIS (Netherlands)

    Vlaminckx, B.J.M.

    2006-01-01

    Infections with group A streptococci (GAS), or S. pyogenes, range from mild and superficial to very severe and lethal invasive disease. In severe invasive GAS infections, hypotension and multiorgan failure may develop rapidly resulting in the development of toxic shock-like syndrome (TSS). In the

  8. Genetic isolation and morphological divergence mediated by high-energy rapids in two cichlid genera from the lower Congo rapids

    Directory of Open Access Journals (Sweden)

    Stiassny Melanie LJ

    2010-05-01

    Full Text Available Abstract Background It is hypothesized that one of the mechanisms promoting diversification in cichlid fishes in the African Great Lakes has been the well-documented pattern of philopatry along shoreline habitats leading to high levels of genetic isolation among populations. However lake habitats are not the only centers of cichlid biodiversity - certain African rivers also contain large numbers of narrowly endemic species. Patterns of isolation and divergence in these systems have tended to be overlooked and are not well understood. Results We examined genetic and morphological divergence among populations of two narrowly endemic cichlid species, Teleogramma depressum and Lamprologus tigripictilis, from a 100 km stretch of the lower Congo River using both nDNA microsatellites and mtDNA markers along with coordinate-based morphological techniques. In L. tigripictilis, the strongest genetic break was concordant with measurable phenotypic divergence but no morphological disjunction was detected for T. depressum despite significant differentiation at mtDNA and nDNA microsatellite markers. Conclusions The genetic markers revealed patterns of philopatry and estimates of genetic isolation that are among the highest reported for any African cichlid species over a comparable geographic scale. We hypothesize that the high levels of philopatry observed are generated and maintained by the extreme hydrology of the lower Congo River.

  9. Genetic Determinants of Epigenetic Patterns: Providing Insight into Disease.

    Science.gov (United States)

    Cazaly, Emma; Charlesworth, Jac; Dickinson, Joanne L; Holloway, Adele F

    2015-03-26

    The field of epigenetics and our understanding of the mechanisms that regulate the establishment, maintenance and heritability of epigenetic patterns continue to grow at a remarkable rate. This information is providing increased understanding of the role of epigenetic changes in disease, insight into the underlying causes of these epigenetic changes and revealing new avenues for therapeutic intervention. Epigenetic modifiers are increasingly being pursued as therapeutic targets in a range of diseases, with a number of agents targeting epigenetic modifications already proving effective in diseases such as cancer. Although it is well established that DNA mutations and aberrant expression of epigenetic modifiers play a key role in disease, attention is now turning to the interplay between genetic and epigenetic factors in complex disease etiology. The role of genetic variability in determining epigenetic profiles, which can then be modified by environmental and stochastic factors, is becoming more apparent. Understanding the interplay between genetic and epigenetic factors is likely to aid in identifying individuals most likely to benefit from epigenetic therapies. This goal is coming closer to realization because of continual advances in laboratory and statistical tools enabling improvements in the integration of genomic, epigenomic and phenotypic data.

  10. Genetic Markers of Cardiovascular Disease in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Luis Rodríguez-Rodríguez

    2012-01-01

    Full Text Available Cardiovascular (CV disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA. It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1*04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G>A, rs1800629 of the TNFA locus, the rs1801131 polymorphism (A>C; position + 1298 of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA.

  11. Types of marriages, population structure and genetic disease.

    Science.gov (United States)

    Machado, T M B; Bomfim, T F; Souza, L V; Soares, N; Santos, F L; Acosta, A X; Abe-Sandes, K

    2013-07-01

    A high occurrence rate of consanguineous marriages may favour the onset and increased frequency of autosomal recessive diseases in a population. The population of Monte Santo, Bahia, Brazil, has a high frequency of rare genetic diseases such as mucopolysaccharidosis type VI, whose observed frequency in this population is 1:5000, while the incidence of this disease recorded in other regions of the world varies from 1:43,261 in Turkey to 1:1,505,160 in Switzerland. To verify the influence of consanguineous marriage on the increased frequency of observed genetic diseases in this population, the population structure and frequency of different types of marriage during different time periods were evaluated. A total of 9765 marriages were found in an analysis of parish marriage records from the city. Over three periods, 1860-1895, 1950-1961 and 1975-2010, the inbreeding rates were 37.1%, 13.2% and 4.2% respectively. Although there was a high rate of inbreeding, endogamic marriages were the dominant marriage type in all three periods. In the most recent period, there was an increase in the number of exogamous marriages and those among immigrants, but most of these occurred among individuals from cities that neighbour Monte Santo. The low rate of migration and high frequency of endogamic and consanguineous marriages show that growth of this population is predominantly internal and could explain the occurrence, and increase in frequency, of recessive genetic diseases in the city.

  12. The genetic epidemiology of diverticulosis and diverticular disease: Emerging evidence

    Science.gov (United States)

    Reichert, Matthias C

    2015-01-01

    Diverticular disease (DD) is one of the most prevalent gastrointestinal disorders. The pathogenesis of diverticulosis and DD is controversially discussed. Current studies call the traditional concept of a fibre-deficient diet causing the development of diverticula into question. Data from two recent twin studies have provided conclusive evidence for a strong genetic component to diverticulosis. Although genomewide association studies have provided new insights into the polygenic architecture of human diseases, genomic research in diverticulosis and DD has just been started. This is an astonishing fact given the high morbidity and mortality of the disease, as well as the substantial economic burden on health care systems. For this review, we provide an update of the molecular pathobiology and summarise recent evidence supporting the hypothesis that distinct, yet unidentified genetic variants contribute to the development of diverticulosis and DD. PMID:26535118

  13. THERAPEUTIC IMPLICATIONS OF GENETIC RISK VARIANTS FOR CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    Rajiv Kumar Srivastava

    2017-02-01

    Full Text Available BACKGROUND This review covers therapeutic implication of genetic risk variant responsible for coronary artery disease by utilising the highdensity single-nucleotide microarrays to screen the entire human genome. The sequence of the human genome provides the blueprint for life. Approximately, 99.5% of the human genome Deoxyribonucleic Acid (DNA sequence is identical among humans with 0.5% of the genome sequence (15 million bps accounting for all individual differences. MATERIALS AND METHODS The new technology of the computerised chip array of millions of Single-Nucleotide Polymorphisms (SNPs as Deoxyribonucleic Acid (DNA markers makes it possible to study and detect genetic predisposition to common polygenic disorders such as Coronary Artery Disease (CAD. The sample sizes required for these studies are massive and large; worldwide consortiums such as Coronary Artery Disease Genome-wide Replication and Meta-Analysis (CARDIoGRAM study have been formed to accommodate this requirement. After the identification of 9p21 progress to detect genetic predisposition has been remarkable. RESULTS There are currently a total of 50 genetic risk variants predisposing to CAD of genome-wide significance with confirmation in independent populations. Rare variants (Minor Allele Frequency, MAF <5% will require direct sequencing to detect genetic predisposition. CONCLUSION We can develop new biomarkers for detecting early CAD as well as unique targets for novel therapy. The challenge for the future will be to identify the molecular mechanisms mediating the risk of those genetic risk variants that act through nonconventional risk factors. The ultimate objective for the future is the sequencing and functional analysis of the causative polymorphisms for its therapeutic implications.

  14. Rapid eye movement sleep disturbances in Huntington disease

    DEFF Research Database (Denmark)

    Arnulf, I.; Nielsen, J.; Lohmann, E.

    2008-01-01

    Background: Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). Objective: To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages and the l......Background: Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD). Objective: To evaluate the HD sleep-wake phenotype (including abnormal motor activity during sleep) in patients with various HD stages...

  15. Systematic analysis, comparison, and integration of disease based human genetic association data and mouse genetic phenotypic information

    Directory of Open Access Journals (Sweden)

    Wang S Alex

    2010-01-01

    Full Text Available Abstract Background The genetic contributions to human common disorders and mouse genetic models of disease are complex and often overlapping. In common human diseases, unlike classical Mendelian disorders, genetic factors generally have small effect sizes, are multifactorial, and are highly pleiotropic. Likewise, mouse genetic models of disease often have pleiotropic and overlapping phenotypes. Moreover, phenotypic descriptions in the literature in both human and mouse are often poorly characterized and difficult to compare directly. Methods In this report, human genetic association results from the literature are summarized with regard to replication, disease phenotype, and gene specific results; and organized in the context of a systematic disease ontology. Similarly summarized mouse genetic disease models are organized within the Mammalian Phenotype ontology. Human and mouse disease and phenotype based gene sets are identified. These disease gene sets are then compared individually and in large groups through dendrogram analysis and hierarchical clustering analysis. Results Human disease and mouse phenotype gene sets are shown to group into disease and phenotypically relevant groups at both a coarse and fine level based on gene sharing. Conclusion This analysis provides a systematic and global perspective on the genetics of common human disease as compared to itself and in the context of mouse genetic models of disease.

  16. Autoimmune thyroid disease: mechanism, genetics and current knowledge.

    Science.gov (United States)

    Dong, Y H; Fu, D G

    2014-01-01

    Recent epidemiological studies recognized a steady increase in the incidence of different autoimmune endocrine disorders, including autoimmune thyroid disease (AITD). The etiology of AITD is multifactorial and involves genetic and environmental factors and apparently with a strong preponderance in females. There are mainly two types of AITD, Graves' disease and Hashimoto's disease and both of these show strong association in age groups above 45-50 years. Among environmental factors smoking and alcohol have significant effects, both protective as well as for aggravating the disease, even though the precise nature of these effects are not clearly known. There are elevated levels of circulating antibodies against the thyroid proteins, mainly thyroid oxidase, thyroglobulin and thyroid stimulating hormone receptor, in patients with Graves' disease or Hashimoto's disease. Linkage and association studies in AITD identified several major genes that are relevant for the onset of AITD, including the thyroid-specific genes, thyroglobulin and thyroid-stimulating hormone receptor and also many immune-regulatory genes. In this review we addressed many aspects of AITD including disease mechanisms, involved thyroid antigens, environmental factors and genetic factors.

  17. Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance.

    Science.gov (United States)

    Hernandez, Dena G; Reed, Xylena; Singleton, Andrew B

    2016-10-01

    Parkinson's disease is a common, progressive neurodegenerative disorder, affecting 3% of those older than 75 years of age. Clinically, Parkinson's disease (PD) is associated with resting tremor, postural instability, rigidity, bradykinesia, and a good response to levodopa therapy. Over the last 15 years, numerous studies have confirmed that genetic factors contribute to the complex pathogenesis of PD. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for PD in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for PD. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease; however, no treatment methodologies have developed. Furthermore, for identified common risk alleles, the functional basis underlying risk principally remains unknown. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants in tandem with additional high-content, integrated datasets. This review discusses monogenic risk factors and mechanisms of Mendelian inheritance of Parkinson disease. Highly penetrant mutations in SNCA, Parkin, DJ-1, PINK 1, LRRK2 and VPS35 produce rare, monogenic forms of the disease, while unique variants within LRRK2 and GBA show incomplete penetrance and are strong risk factors for PD. Additionally, over 20 common variants with small effect sizes modulate disease risk. The challenge over the next decade is to strengthen genetic findings by assessing direct, biological consequences of risk variants in tandem with high-content, integrated datasets. This article is part of a special

  18. Is There Any Evidence for Rapid, Genetically-Based, Climatic Niche Expansion in the Invasive Common Ragweed?

    OpenAIRE

    Gallien, Laure; Thuiller, Wilfried; Fort, No?mie; Boleda, Marti; Alberto, Florian J.; Rioux, Delphine; Lain?, Juliette; Lavergne, S?bastien

    2016-01-01

    Climatic niche shifts have been documented in a number of invasive species by comparing the native and adventive climatic ranges in which they occur. However, these shifts likely represent changes in the realized climatic niches of invasive species, and may not necessarily be driven by genetic changes in climatic affinities. Until now the role of rapid niche evolution in the spread of invasive species remains a challenging issue with conflicting results. Here, we document a likely genetically...

  19. Controlling futures? Online Genetic Testing and Neurodegenerative Disease : Comment on "Personal Genomic Testing, Genetic Inheritance, and Uncertainty".

    Science.gov (United States)

    Warren, Narelle; Gardner, John

    2017-12-01

    Online personalized genetic testing services offer accessible and convenient options for satisfying personal curiosity about health and obtaining answers about one's genetic provenance. They are especially attractive to healthy people who wish to learn about their future risk of disease, as Paul Mason's (2017) case study of "Jordan" illustrates. In this response, we consider how online genetic testing services are used by people diagnosed with a common neurodegenerative disease, Parkinson's disease, to gain a sense of certainty regarding the future.

  20. Genetic risk of APOL1 and kidney disease in children and young adults of African ancestry.

    Science.gov (United States)

    Reidy, Kimberly J; Hjorten, Rebecca; Parekh, Rulan S

    2018-02-05

    Understanding the genetic risk of APOL1 in children and young adults is important given the lifetime risk of hypertension and kidney disease among children of African descent. We review recent epidemiologic and biologic findings on the effects of APOL1 and kidney disease. APOL1 in children and young adults is associated with hypertension, albuminuria and more rapid decline in kidney function and progression to end-stage kidney disease, especially among those with glomerular causes of kidney disease, and those affected by sickle cell disease or HIV. There are conflicting data on the APOL1 association with cardiovascular disease in children and young adults. APOL1 functions as part of the innate immune system. Podocyte expression of APOL1 likely contributes to the development of kidney disease. In cell culture and model organisms, APOL1 expression disrupts autophagic and ion flux, leads to defects in mitochondrial respiration and induces cell death. APOL1 explains almost 70% of the excess risk of kidney disease in those of African descent, and is common in children with glomerular disease. Evolving understanding of the pathogenesis of APOL1-mediated kidney damage may aid in personalized medicine approaches to APOL1 attributable kidney disease.

  1. Genetic kidney diseases: Caenorhabditis elegans as model system.

    Science.gov (United States)

    Ganner, Athina; Neumann-Haefelin, Elke

    2017-07-01

    Despite its apparent simplicity, the nematode Caenorhabditis elegans has a high rating as a model in molecular and developmental biology and biomedical research. C. elegans has no excretory system comparable with the mammalian kidney but many of the genes and molecular pathways involved in human kidney diseases are conserved in C. elegans. The plethora of genetic, molecular and imaging tools available in C. elegans has enabled major discoveries in renal research and advanced our understanding of the pathogenesis of genetic kidney diseases. In particular, studies in C. elegans have pioneered the fundamental role of cilia for cystic kidney diseases. In addition, proteins of the glomerular filtration barrier and podocytes are critical for cell recognition, assembly of functional neuronal circuits, mechanosensation and signal transduction in C. elegans. C. elegans has also proved tremendously valuable for aging research and the Von Hippel-Lindau tumor suppressor gene has been shown to modulate lifespan in the nematode. Further, studies of the excretory canal, membrane transport and ion channel function in C. elegans have provided insights into mechanisms of tubulogenesis and cellular homeostasis. This review recounts the way that C. elegans can be used to investigate various aspects of genetic and molecular nephrology. This model system opens up an exciting and new area of study of renal development and diseases.

  2. When does an illness begin: genetic discrimination and disease manifestation.

    Science.gov (United States)

    Prince, Anya E R; Berkman, Benjamin E

    2012-01-01

    The Genetic Information Nondiscrimination Act of 2008 (GINA) was passed to encourage patients to seek genetic testing that could improve health outcomes and provide opportunities for preventive measures. GINA protects individuals from discrimination based upon genetic information, but not upon manifested diseases and conditions. Because the manifestation of a disease establishes a threshold of protection for individuals under GINA, the definition of manifestation is crucial to understanding the scope of the bill. This paper examines the range of possible legal definitions of disease manifestation and explores the historical struggle that courts have faced when trying to apply these different definitions. Specifically, the paper examines three frameworks that courts have used in the past to interpret the manifestation of a disease; "manifestation as apparent symptoms,"manifestation as patient action," and "manifestation as physician action." We argue that the "manifestation as physician action" is the best framework to utilize in this law generally, but that the definition of manifestation should be read in the light most favorable to a plaintiff in order to achieve the underlying goals of GINA. © 2012 American Society of Law, Medicine & Ethics, Inc.

  3. Rapid Detection and Characterization of Emerging Foreign Animal Disease Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Jaing, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-11-18

    To best safeguard human and animal health requires early detection and characterization of disease events. This must include effective surveillance for emerging infectious diseases. Both deliberate and natural outbreaks have enormous economic and public health impacts, and can present serious threats to national security. In this project, we developed novel next generation detection technologies to protect the agricultural economy and biosecurity. The first technology is a multiplexed assay to simultaneously detection 10 swine viral and bacterial pathogens. The second one is the Lawrence Livermore Microbial Detection Array (LLMDA) which can detect more than 10,000 microbial species including 4219 viruses, 5367 bacteria, 265 fungi, 117 protozoa and 293 archaea. We analyzed a series of swine clinical samples from past disease events to demonstrate the utility of the assays for faster and cheaper detection of emerging and foreign animal disease pathogens, and their utility as s routine diagnosis and surveillance tool. A second goal of the study is to better understand mechanisms of African swine fever virus (ASFV) infection in pigs to aid the development of countermeasures and diagnostics. There is no vaccine available for ASF. ASF outbreak is on the rise on several European countries. Though ASF is not currently in the U.S., a potential outbreak in the U.S. would be detrimental to the swine industry and the US agricultural economy. We pursued a genome-wide approach to characterize the pig immune responses after ASFV infection. We used RNA sequencing and bioinformatics methods to identify genes and pathways that are affected during ASF infection. We have identified a list of most differentially expressed genes that are in the immune response pathways.

  4. Systems genetics of complex diseases using RNA-sequencing methods

    DEFF Research Database (Denmark)

    Mazzoni, Gianluca; Kogelman, Lisette; Suravajhala, Prashanth

    2015-01-01

    Next generation sequencing technologies have enabled the generation of huge quantities of biological data, and nowadays extensive datasets at different ‘omics levels have been generated. Systems genetics is a powerful approach that allows to integrate different ‘omics level and understand...... non-coding RNAs (ncRNAs). The integration of transcriptomics data with genomic data in a systems genetics context represents a valuable possibility to go deep into the causal and regulatory mechanisms that generate complex traits and diseases. However RNA-Seq data have to be treated carefully...... and the choice of the right methodology could have a great impact on the final results. Furthermore the integration of different level is not trivial. Here we give a comprehensive systems genetics overview of the methods and tools for analysis and the integration of RNA-Seq data including ncRNAs. We focused...

  5. Multifocal Best's disease: The importance of genetic tests.

    Science.gov (United States)

    Alba Linero, C; Rodríguez Calvo de Mora, M; España Contreras, M; Hernando Ayala, C

    2017-11-14

    Our objective is to describe a multifocal vitelliform presentation of Best's disease. The lesions in this disease may vary in size and shape, some may be a disc diameter in size, and often have some irregularity in their contour. The case is described of a 21-year-old male patient referred to our ophthalmology department due to a progressive loss of vision. His poor visual acuity was confirmed, and a complete examination was performed, in which macular flecks were observed, with yellow pigment arranged in oval distribution near their periphery. Due to the suspicion of Best's multifocal disease, genetic tests were performed. Multifocal vitelliform disease with the same features as those in Best's disease occurs most frequently in patients with a normal electro-oculogram (EOG), and a normal family history. Best's multifocal disease must be suspected in case of multiple vitelliruptive lesions close to the posterior pole. Genetic testing is essential for its diagnosis. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Bardet–Biedl syndrome: Genetics, molecular pathophysiology, and disease management

    Directory of Open Access Journals (Sweden)

    Sathya Priya

    2016-01-01

    Full Text Available Primary cilia play a key role in sensory perception and various signaling pathways. Any defect in them leads to group of disorders called ciliopathies, and Bardet–Biedl syndrome (BBS, OMIM 209900 is one among them. The disorder is clinically and genetically heterogeneous, with various primary and secondary clinical manifestations, and shows autosomal recessive inheritance and highly prevalent in inbred/consanguineous populations. The disease mapped to at least twenty different genes (BBS1-BBS20, follow oligogenic inheritance pattern. BBS proteins localizes to the centerosome and regulates the biogenesis and functions of the cilia. In BBS, the functioning of various systemic organs (with ciliated cells gets deranged and results in systemic manifestations. Certain components of the disease (such as obesity, diabetes, and renal problems when noticed earlier offer a disease management benefit to the patients. However, the awareness of the disease is comparatively low and most often noticed only after severe vision loss in patients, which is usually in the first decade of the patient's age. In the current review, we have provided the recent updates retrieved from various types of scientific literature through journals, on the genetics, its molecular relevance, and the clinical outcome in BBS. The review in nutshell would provide the basic awareness of the disease that will have an impact in disease management and counseling benefits to the patients and their families.

  7. Prevalence and mode of inheritance of major genetic eye diseases in China.

    OpenAIRE

    Hu, D N

    1987-01-01

    The prevalence and mode of inheritance of major genetic eye diseases have been investigated in China since the establishment of the Section of Ophthalmic Genetics of the Chinese Society of Genetics. Mass screening of genetic eye diseases has been undertaken in many districts in China, covering more than 700,000 people, and more than 5000 pedigrees of genetic eye diseases have been collected and analysed all over China. Based on these data, the prevalence and mode of inheritance of dyschromato...

  8. Identifying Multimodal Intermediate Phenotypes Between Genetic Risk Factors and Disease Status in Alzheimer's Disease.

    Science.gov (United States)

    Hao, Xiaoke; Yao, Xiaohui; Yan, Jingwen; Risacher, Shannon L; Saykin, Andrew J; Zhang, Daoqiang; Shen, Li

    2016-10-01

    Neuroimaging genetics has attracted growing attention and interest, which is thought to be a powerful strategy to examine the influence of genetic variants (i.e., single nucleotide polymorphisms (SNPs)) on structures or functions of human brain. In recent studies, univariate or multivariate regression analysis methods are typically used to capture the effective associations between genetic variants and quantitative traits (QTs) such as brain imaging phenotypes. The identified imaging QTs, although associated with certain genetic markers, may not be all disease specific. A useful, but underexplored, scenario could be to discover only those QTs associated with both genetic markers and disease status for revealing the chain from genotype to phenotype to symptom. In addition, multimodal brain imaging phenotypes are extracted from different perspectives and imaging markers consistently showing up in multimodalities may provide more insights for mechanistic understanding of diseases (i.e., Alzheimer's disease (AD)). In this work, we propose a general framework to exploit multi-modal brain imaging phenotypes as intermediate traits that bridge genetic risk factors and multi-class disease status. We applied our proposed method to explore the relation between the well-known AD risk SNP APOE rs429358 and three baseline brain imaging modalities (i.e., structural magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and F-18 florbetapir PET scans amyloid imaging (AV45)) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The empirical results demonstrate that our proposed method not only helps improve the performances of imaging genetic associations, but also discovers robust and consistent regions of interests (ROIs) across multi-modalities to guide the disease-induced interpretation.

  9. Genetic characterization and disease mechanism of retinitis pigmentosa; current scenario.

    Science.gov (United States)

    Ali, Muhammad Umar; Rahman, Muhammad Saif Ur; Cao, Jiang; Yuan, Ping Xi

    2017-08-01

    Retinitis pigmentosa is a group of genetically transmitted disorders affecting 1 in 3000-8000 individual people worldwide ultimately affecting the quality of life. Retinitis pigmentosa is characterized as a heterogeneous genetic disorder which leads by progressive devolution of the retina leading to a progressive visual loss. It can occur in syndromic (with Usher syndrome and Bardet-Biedl syndrome) as well as non-syndromic nature. The mode of inheritance can be X-linked, autosomal dominant or autosomal recessive manner. To date 58 genes have been reported to associate with retinitis pigmentosa most of them are either expressed in photoreceptors or the retinal pigment epithelium. This review focuses on the disease mechanisms and genetics of retinitis pigmentosa. As retinitis pigmentosa is tremendously heterogeneous disorder expressing a multiplicity of mutations; different variations in the same gene might induce different disorders. In recent years, latest technologies including whole-exome sequencing contributing effectively to uncover the hidden genesis of retinitis pigmentosa by reporting new genetic mutations. In future, these advancements will help in better understanding the genotype-phenotype correlations of disease and likely to develop new therapies.

  10. Splicing modulation therapy in the treatment of genetic diseases

    Directory of Open Access Journals (Sweden)

    Arechavala-Gomeza V

    2014-12-01

    Full Text Available Virginia Arechavala-Gomeza,1 Bernard Khoo,2 Annemieke Aartsma-Rus3 1Neuromuscular Disorders Group, BioCruces Health Research Institute, Barakaldo, Bizkaia, Spain; 2Endocrinology, Division of Medicine, University College London, London, UK; 3Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands All authors contributed equally to this manuscript Abstract: Antisense-mediated splicing modulation is a tool that can be exploited in several ways to provide a potential therapy for rare genetic diseases. This approach is currently being tested in clinical trials for Duchenne muscular dystrophy and spinal muscular atrophy. The present review outlines the versatility of the approach to correct cryptic splicing, modulate alternative splicing, restore the open reading frame, and induce protein knockdown, providing examples of each. Finally, we outline a possible path forward toward the clinical application of this approach for a wide variety of inherited rare diseases. Keywords: splicing, therapy, antisense oligonucleotides, cryptic splicing, alternative splicing

  11. Rapid genetic algorithm optimization of a mouse computational model: benefits for anthropomorphization of neonatal mouse cardiomyocytes.

    Science.gov (United States)

    Bot, Corina T; Kherlopian, Armen R; Ortega, Francis A; Christini, David J; Krogh-Madsen, Trine

    2012-01-01

    While the mouse presents an invaluable experimental model organism in biology, its usefulness in cardiac arrhythmia research is limited in some aspects due to major electrophysiological differences between murine and human action potentials (APs). As previously described, these species-specific traits can be partly overcome by application of a cell-type transforming clamp (CTC) to anthropomorphize the murine cardiac AP. CTC is a hybrid experimental-computational dynamic clamp technique, in which a computationally calculated time-dependent current is inserted into a cell in real-time, to compensate for the differences between sarcolemmal currents of that cell (e.g., murine) and the desired species (e.g., human). For effective CTC performance, mismatch between the measured cell and a mathematical model used to mimic the measured AP must be minimal. We have developed a genetic algorithm (GA) approach that rapidly tunes a mathematical model to reproduce the AP of the murine cardiac myocyte under study. Compared to a prior implementation that used a template-based model selection approach, we show that GA optimization to a cell-specific model results in a much better recapitulation of the desired AP morphology with CTC. This improvement was more pronounced when anthropomorphizing neonatal mouse cardiomyocytes to human-like APs than to guinea pig APs. CTC may be useful for a wide range of applications, from screening effects of pharmaceutical compounds on ion channel activity, to exploring variations in the mouse or human genome. Rapid GA optimization of a cell-specific mathematical model improves CTC performance and may therefore expand the applicability and usage of the CTC technique.

  12. Genetic impact on the treatment & management of Hirschsprung disease.

    Science.gov (United States)

    Moore, Sam W

    2017-02-01

    The identification of Hirschsprung's disease (HD) as a genetic condition has been a major step forward in understanding the development of the enteric nervous system and conditions arising from ganglion cell maldevelopment. A study of the role of genetics in HD was carried out based on previously published findings from more than 400 cases of HD. There are at least 7 pertinent clinical questions related to HD which were further investigated. These included: diagnosis, familial recurrence, long segment and total colonic aganglionosis, syndromic associations, the question of HD-associated enterocolitis, potential causes of postoperative obstructive symptoms after successful surgery, and the apparent low prevalence in premature infants. This review aimed at evaluating the most important concepts of where we have got to in our understanding of where genetic solutions/directions to these clinical problems might lie. Possible genetic reasons for the low prevalence in premature infants was also considered and the possible plasticity of the ENS at that stage as a potential "door of hope" in the future management of HD. The study of genetics has made a massive contribution to the understanding and management of HD. It opens a "door of hope" to the future management of the condition. Level V. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. [Genetic screening for risk factors in the development of respiratory diseases caused by fiberglass dust].

    Science.gov (United States)

    Artamonova, V G; Kuznetsov, N F; Gadzhiev, A S

    1995-01-01

    The article represents results of genetic screening among workers engaged into fiber glass production. Propensity and resistance to occupational pulmonary diseases were believed to depend on genotype. Applied methods of genetic screening enabled to improve primary prophylaxis of respiratory diseases.

  14. Ethical considerations of genetic presymptomatic testing for Huntington's disease.

    Science.gov (United States)

    Coustasse, Alberto; Pekar, Alicia; Sikula, Andrew; Lurie, Sue

    2009-01-01

    The aim of this literature review was to determine if there is adequate ethical justification for presymptomatic genetic testing on potential Huntington's disease patients. Huntington's disease is a neurological genetic disorder characterized by midlife onset which consists of cognitive, physical, and emotional deterioration. Although genetic testing has traditionally been guided by the principle of autonomy, severe psychological consequences such as depression, anxiety, survival guilt, and suicide have complicated the ethical issue of providing a presymptomatic yet definitive diagnosis for an incurable disease. An analysis of available articles yielded inconclusive findings, namely due to insufficient evidence, self-selection bias of test participants, or lack of a longitudinal design. Additional results indicated psychological distress is not solely associated with test result, but rather with individual characteristics including, but not limited to, psychological history, test motivation, level of preparation, social support, and age. In the interest of upholding the principles of autonomy, beneficence, nonmaleficence, and justice, it is recommended that medical professionals follow strict protocol, provide extensive counseling, and employ vigilance when assessing at-risk individuals for HD presymptomatic test eligibility to ensure psychological well-being.

  15. Clinical and genetic study in Chinese patients with Alexander disease.

    Science.gov (United States)

    Ye Wu; Qiang Gu; Jingmin Wang; Yanling Yang; Xiru Wu; Yuwu Jiang

    2008-02-01

    Alexander disease is a rare progressive leukoencephalopathy inherited in an autosomal dominant manner. The infantile form is the most common, with onset before 2 years of age. The typical clinical signs include psychomotor retardation and regression, seizures, and megalencephaly. Juvenile and adult forms are also recognized. The neuropathology of Alexander disease is characterized by abundant presence of Rosenthal fibers in astrocytes in the brain. GFAP has been identified to be the only gene associated with Alexander disease since 2001. Only 1 patient with Alexander disease confirmed by genetic testing has been reported in mainland China. To get further information of the clinical and genetic characteristics of Chinese patients, we analyzed an additional 3 cases with the infantile or juvenile form. A novel mutation, Y83H, and a previously reported mutation, R88C, were identified in these patients. Both mutations were heterozygous and de novo. The results of this research expand the number of patients with Alexander disease found to have GFAP coding mutations in mainland China. A novel missense mutation, Y83H, is identified.

  16. Understanding Celiac Disease From Genetics to the Future Diagnostic Strategies

    Directory of Open Access Journals (Sweden)

    Carolina Salazar

    2017-07-01

    Full Text Available Celiac disease (CD is an autoimmune disorder characterized by the permanent inflammation of the small bowel, triggered by the ingestion of gluten. It is associated with a number of symptoms, the most common being gastrointestinal. The prevalence of this illness worldwide is 1%. One of the main problems of CD is its difficulty to be diagnosed due to the various presentations of the disease. Besides, in many cases, CD is asymptomatic. Celiac disease is a multifactorial disease, HLA-DQ2 and HLA-DQ8 haplotypes are predisposition factors. Nowadays, molecular markers are being studied as diagnostic tools. In this review, we explore CD from its basic concept, manifestations, types, current and future methods of diagnosis, and associated disorders. Before addressing the therapeutic approaches, we also provide a brief overview of CD genetics and treatment.

  17. [Clinical and genetic analysis of a pedigree of Kennedy disease].

    Science.gov (United States)

    Ou-Yang, Zhi-yuan; Song, Shui-jiang; Liu, Jian-ren; Zhang, Bao-rong; Wu, Ding-wen

    2011-09-01

    To review the clinical and genetic features of a pedigree of Kennedy disease in China. The clinical data of patients from a Kennedy disease family were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis. In the pedigree, 4 patients were identified as Kennedy disease. Clinical manifested with adult-onset, progressive proximal limb muscle weakness and atrophy, gynecomastia, oligospermia were also presented. The number of trinucleotide CAG repeats in exon 1 of the androgen receptor gene was 51 in the proband. The electrophysiological study showed sensory and motor involvement and their serum triglycerides values were elevated significantly. Androgen receptors gene testing is the most reliable diagnosing method, the patients suspected as Kennedy disease should have a gene testing of androgen receptors.

  18. Crohn disease: a current perspective on genetics, autophagy and immunity.

    Science.gov (United States)

    Stappenbeck, Thaddeus S; Rioux, John D; Mizoguchi, Atsushi; Saitoh, Tatsuya; Huett, Alan; Darfeuille-Michaud, Arlette; Wileman, Tom; Mizushima, Noboru; Carding, Simon; Akira, Shizuo; Parkes, Miles; Xavier, Ramnik J

    2011-04-01

    Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract. Prevalence in Western populations is 100-150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk.

  19. Genetic counseling in the adult with congenital heart disease: what is the role?

    Science.gov (United States)

    Burchill, Luke; Greenway, Steven; Silversides, Candice K; Mital, Seema

    2011-08-01

    New discoveries using high-resolution methods for detecting genetic aberrations indicate that the genetic contribution to congenital heart disease has been significantly underestimated in the past. DNA diagnostics have become more accessible and genetic test results are increasingly being used to guide clinical management. Adult congenital heart disease specialists seeking to counsel adults with congenital heart disease about the genetic aspects of their condition face the challenge of keeping abreast of new genetic techniques and discoveries. The emphasis of this review is on the genetic basis of structural cardiovascular defects. A framework for identifying adult congenital heart disease patients most likely to benefit from genetic testing is suggested, along with a summary of current techniques for genetic testing. The clinical and ethical challenges associated with genetic counseling are highlighted. Finally, emerging technologies and future directions in genetics and adult congenital heart disease are discussed.

  20. Rapid cloning of disease-resistance genes in plants using mutagenesis and sequence capture

    Science.gov (United States)

    Genetic solutions to protect crops against pests and pathogens are preferable to agrichemicals 1. Wild crop relatives carry immense diversity of disease resistance (R) genes that could enable more sustainable disease control. However, recruiting R genes for crop improvement typically involves long b...

  1. Homogenous Population Genetic Structure of the Non-Native Raccoon Dog (Nyctereutes procyonoides in Europe as a Result of Rapid Population Expansion.

    Directory of Open Access Journals (Sweden)

    Frank Drygala

    Full Text Available The extent of gene flow during the range expansion of non-native species influences the amount of genetic diversity retained in expanding populations. Here, we analyse the population genetic structure of the raccoon dog (Nyctereutes procyonoides in north-eastern and central Europe. This invasive species is of management concern because it is highly susceptible to fox rabies and an important secondary host of the virus. We hypothesized that the large number of introduced animals and the species' dispersal capabilities led to high population connectivity and maintenance of genetic diversity throughout the invaded range. We genotyped 332 tissue samples from seven European countries using 16 microsatellite loci. Different algorithms identified three genetic clusters corresponding to Finland, Denmark and a large 'central' population that reached from introduction areas in western Russia to northern Germany. Cluster assignments provided evidence of long-distance dispersal. The results of an Approximate Bayesian Computation analysis supported a scenario of equal effective population sizes among different pre-defined populations in the large central cluster. Our results are in line with strong gene flow and secondary admixture between neighbouring demes leading to reduced genetic structuring, probably a result of its fairly rapid population expansion after introduction. The results presented here are remarkable in the sense that we identified a homogenous genetic cluster inhabiting an area stretching over more than 1500km. They are also relevant for disease management, as in the event of a significant rabies outbreak, there is a great risk of a rapid virus spread among raccoon dog populations.

  2. Ethical aspects of research into Alzheimer disease. A European Delphi Study focused on genetic and non-genetic research.

    NARCIS (Netherlands)

    Vorm, A. van der; Vernooij-Dassen, M.J.F.J.; Kehoe, P.G.; Olde Rikkert, M.G.M.; Leeuwen, E. van; Dekkers, W.J.M.

    2009-01-01

    BACKGROUND: Although genetic research into Alzheimer disease (AD) is increasing, the ethical aspects of this kind of research and the differences between ethical issues related to genetic and non-genetic research into AD have not yet received much attention. OBJECTIVES: (1) To identify and compare

  3. Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease

    NARCIS (Netherlands)

    van der Harst, Pim; Verweij, Niek

    2018-01-01

    Rationale: Coronary artery disease (CAD) is a complex phenotype driven by genetic and environmental factors. Ninety-seven genetic risk loci have been identified to date, but the identification of additional susceptibility loci might be important to enhance our understanding of the genetic

  4. New multiplex PCR methods for rapid screening of genetically modified organisms in foods.

    Science.gov (United States)

    Datukishvili, Nelly; Kutateladze, Tamara; Gabriadze, Inga; Bitskinashvili, Kakha; Vishnepolsky, Boris

    2015-01-01

    We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs). New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV) 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS) terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps) gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab) gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS) and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.

  5. A Toolbox of Genetically Encoded FRET-Based Biosensors for Rapid l-Lysine Analysis

    Science.gov (United States)

    Steffen, Victoria; Otten, Julia; Engelmann, Susann; Radek, Andreas; Limberg, Michael; Koenig, Bernd W.; Noack, Stephan; Wiechert, Wolfgang; Pohl, Martina

    2016-01-01

    Background: The fast development of microbial production strains for basic and fine chemicals is increasingly carried out in small scale cultivation systems to allow for higher throughput. Such parallelized systems create a need for new rapid online detection systems to quantify the respective target compound. In this regard, biosensors, especially genetically encoded Förster resonance energy transfer (FRET)-based biosensors, offer tremendous opportunities. As a proof-of-concept, we have created a toolbox of FRET-based biosensors for the ratiometric determination of l-lysine in fermentation broth. Methods: The sensor toolbox was constructed based on a sensor that consists of an optimized central lysine-/arginine-/ornithine-binding protein (LAO-BP) flanked by two fluorescent proteins (enhanced cyan fluorescent protein (ECFP), Citrine). Further sensor variants with altered affinity and sensitivity were obtained by circular permutation of the binding protein as well as the introduction of flexible and rigid linkers between the fluorescent proteins and the LAO-BP, respectively. Results: The sensor prototype was applied to monitor the extracellular l-lysine concentration of the l-lysine producing Corynebacterium glutamicum (C. glutamicum) strain DM1933 in a BioLector® microscale cultivation device. The results matched well with data obtained by HPLC analysis and the Ninhydrin assay, demonstrating the high potential of FRET-based biosensors for high-throughput microbial bioprocess optimization. PMID:27690044

  6. A Toolbox of Genetically Encoded FRET-Based Biosensors for Rapid l-Lysine Analysis

    Directory of Open Access Journals (Sweden)

    Victoria Steffen

    2016-09-01

    Full Text Available Background: The fast development of microbial production strains for basic and fine chemicals is increasingly carried out in small scale cultivation systems to allow for higher throughput. Such parallelized systems create a need for new rapid online detection systems to quantify the respective target compound. In this regard, biosensors, especially genetically encoded Förster resonance energy transfer (FRET-based biosensors, offer tremendous opportunities. As a proof-of-concept, we have created a toolbox of FRET-based biosensors for the ratiometric determination of l-lysine in fermentation broth. Methods: The sensor toolbox was constructed based on a sensor that consists of an optimized central lysine-/arginine-/ornithine-binding protein (LAO-BP flanked by two fluorescent proteins (enhanced cyan fluorescent protein (ECFP, Citrine. Further sensor variants with altered affinity and sensitivity were obtained by circular permutation of the binding protein as well as the introduction of flexible and rigid linkers between the fluorescent proteins and the LAO-BP, respectively. Results: The sensor prototype was applied to monitor the extracellular l-lysine concentration of the l-lysine producing Corynebacterium glutamicum (C. glutamicum strain DM1933 in a BioLector® microscale cultivation device. The results matched well with data obtained by HPLC analysis and the Ninhydrin assay, demonstrating the high potential of FRET-based biosensors for high-throughput microbial bioprocess optimization.

  7. A Toolbox of Genetically Encoded FRET-Based Biosensors for Rapid l-Lysine Analysis.

    Science.gov (United States)

    Steffen, Victoria; Otten, Julia; Engelmann, Susann; Radek, Andreas; Limberg, Michael; Koenig, Bernd W; Noack, Stephan; Wiechert, Wolfgang; Pohl, Martina

    2016-09-28

    Background: The fast development of microbial production strains for basic and fine chemicals is increasingly carried out in small scale cultivation systems to allow for higher throughput. Such parallelized systems create a need for new rapid online detection systems to quantify the respective target compound. In this regard, biosensors, especially genetically encoded Förster resonance energy transfer (FRET)-based biosensors, offer tremendous opportunities. As a proof-of-concept, we have created a toolbox of FRET-based biosensors for the ratiometric determination of l-lysine in fermentation broth. Methods: The sensor toolbox was constructed based on a sensor that consists of an optimized central lysine-/arginine-/ornithine-binding protein (LAO-BP) flanked by two fluorescent proteins (enhanced cyan fluorescent protein (ECFP), Citrine). Further sensor variants with altered affinity and sensitivity were obtained by circular permutation of the binding protein as well as the introduction of flexible and rigid linkers between the fluorescent proteins and the LAO-BP, respectively. Results: The sensor prototype was applied to monitor the extracellular l-lysine concentration of the l-lysine producing Corynebacterium glutamicum (C. glutamicum) strain DM1933 in a BioLector(®) microscale cultivation device. The results matched well with data obtained by HPLC analysis and the Ninhydrin assay, demonstrating the high potential of FRET-based biosensors for high-throughput microbial bioprocess optimization.

  8. New multiplex PCR methods for rapid screening of genetically modified organisms in foods

    Directory of Open Access Journals (Sweden)

    Nelly eDatukishvili

    2015-07-01

    Full Text Available We present novel multiplex PCR methods for rapid and reliable screening of genetically modified organisms (GMOs. New designed PCR primers targeting four frequently used GMO specific sequences permitted identification of new DNA markers, in particular 141 bp fragment of cauliflower mosaic virus (CaMV 35S promoter, 224 bp fragment of Agrobacterium tumefaciens nopaline synthase (NOS terminator, 256 bp fragment of 5-enolppyruvylshikimate-phosphate synthase (epsps gene and 258 bp fragment of Cry1Ab delta-endotoxin (cry1Ab gene for GMO screening. The certified reference materials containing Roundup Ready soybean (RRS and maize MON 810 were applied for the development and optimization of uniplex and multiplex PCR systems. Evaluation of amplification products by agarose gel electrophoresis using negative and positive controls confirmed high specificity and sensitivity at 0.1% GMO for both RRS and MON 810. The fourplex PCR was developed and optimized that allows simultaneous detection of three common transgenic elements, such as: CaMV 35S promoter, NOS terminator, epsps gene together with soybean-specific lectin gene. The triplex PCR developed enables simultaneous identification of transgenic elements, such as: 35S promoter and cry1Ab gene together with maize zein gene. The analysis of different processed foods demonstrated that multiplex PCR methods developed in this study are useful for accurate and fast screening of GM food products.

  9. HCCI Intelligent Rapid Modeling by Artificial Neural Network and Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    AbdoulAhad Validi

    2012-01-01

    Full Text Available A Dynamic model of Homogeneous Charge Compression Ignition (HCCI, based on chemical kinetics principles and artificial intelligence, is developed. The model can rapidly predict the combustion probability, thermochemistry properties, and exact timing of the Start of Combustion (SOC. A realization function is developed on the basis of the Sandia National Laboratory chemical kinetics model, and GRI3.0 methane chemical mechanism. The inlet conditions are optimized by Genetic Algorithm (GA, so that combustion initiates and SOC timing posits in the desired crank angle. The best SOC timing to achieve higher performance and efficiency in HCCI engines is between 5 and 15 degrees crank angle (CAD after top dead center (TDC. To achieve this SOC timing, in the first case, the inlet temperature and equivalence ratio are optimized simultaneously and in the second case, compression ratio is optimized by GA. The model’s results are validated with previous works. The SOC timing can be predicted in less than 0.01 second and the CPU time savings are encouraging. This model can successfully be used for real engine control applications.

  10. Genetic modifiers of Mendelian disease: Huntington's disease and the trinucleotide repeat disorders.

    Science.gov (United States)

    Holmans, Peter A; Massey, Thomas H; Jones, Lesley

    2017-10-01

    In the decades since the genes and mutations associated with the commoner Mendelian disorders were first discovered, technological advances in genetic analysis have made finding genomic variation a much less onerous task. Recently, the global efforts to collect subjects with Mendelian disorders, to better define the disorders and to empower appropriate clinical trials, along with improved genetic technologies, have allowed the identification of genetic variation that does not cause disease, but substantially modifies disease presentation. The advantage of this is it identifies biological pathways and molecules, that, if modified in people, might alter disease presentation. In Huntington's disease (HD), caused by an expanded CAG repeat tract in HTT, genetic variation has been uncovered that is associated with change in the onset or progression of disease. Some of this variation lies in genes that are part of the DNA damage response, previously suggested to be important in modulating expansion of the repeat tract in germline and somatic cells. The genetic evidence implicates a DNA damage response-related pathway in modulating the pathogenicity of the repeat tracts in HD, and possibly, in other trinucleotide repeat disorders. These findings offer new targets for drug development in these currently intractable disorders. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Heterogeneity among patients with Parkinson's disease: cluster analysis and genetic association.

    Science.gov (United States)

    Ma, Ling-Yan; Chan, Piu; Gu, Zhu-Qin; Li, Fang-Fei; Feng, Tao

    2015-04-15

    The clinical heterogeneity of Parkinson's disease (PD) reveals the presence of several PD subtypes. The objectives of this study were to identify PD subtypes using cluster analysis (CA) and to determine the association between the subtypes and the polymorphisms in LRRK2 (G2385R and R1628P) and GBA (L444P) genes. A k-means CA of demographics, disease progression, motor and non-motor symptoms was performed from 1,510 Chinese PD patients from the Chinese National Consortium on Neurodegenerative Diseases. Pearson correlation analysis was performed to eliminate uninformative characteristics. Blood samples from 852 patients were obtained for genetic analysis of LRRK2 and GBA. Genotypic associations between various subtypes and genetic variants were examined using chi-square test. We identified four different subtypes: subtype 1 was non-tremor dominant (NTD, n=469; 31.1%); subtype 2 had a rapid disease progression with late onset (RDP-LO, n=67; 4.4%); subtype 3 had benign pure motor characteristics (BPM, n=778; 51.5%) without non-motor disturbances; and subtype 4 was tremor dominant with slow disease progression (TD-SP, n=196; 13.0%). Subtypes 1, 2, and 4 had similar mean age of onset. No associations were identified between polymorphisms in LRRK2 (R1628P) and GBA (L444P) genes and the four subtypes (P>0.05). Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Glycogen pathways in disease: new developments in a classical field of medical genetics.

    Science.gov (United States)

    Kilimann, Manfred W; Oldfors, Anders

    2015-05-01

    Glycogen is the storage form of glucose in animal cells. Its degradation can rapidly provide fuel for energy production (particularly important in muscle), or replenish blood glucose during fasting by the liver. Genetic defects of glycogen metabolism give rise to glycogen storage diseases (GSDs), manifesting histologically in abnormal quantity or quality of glycogen in the cells. GSDs can be caused by defects of proteins participating in the synthesis or degradation of glycogen itself, in the glycolytic degradation of glucose phosphates in muscle and erythrocytes, in the release of glucose from liver and kidney into the bloodstream, in the clearance of glycogen from lysosomes (all, "primary GSDs"), or in the control of these pathways ("secondary GSDs"). Most genes responsible for classical, primary GSDs have probably been identified, and future progress in understanding the biochemical and genetic defects underlying unsolved disorders presenting with glycogen storage abnormalities will perhaps be predominantly in the field of secondary GSDs.

  13. Rapid cortical bone loss in patients with chronic kidney disease.

    Science.gov (United States)

    Nickolas, Thomas L; Stein, Emily M; Dworakowski, Elzbieta; Nishiyama, Kyle K; Komandah-Kosseh, Mafo; Zhang, Chiyuan A; McMahon, Donald J; Liu, Xiaowei S; Boutroy, Stephanie; Cremers, Serge; Shane, Elizabeth

    2013-08-01

    Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2 to 5D, we used dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (range 0.9 to 4.3 years); bone changes were annualized and compared with baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% confidence interval [CI] -2.1 to -0.6) and -2.4% (95% CI -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density, and thickness and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4), respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates. Copyright © 2013 American Society for Bone and Mineral Research.

  14. Genome supranucleosomal organization and genetic susceptibility to diseases

    Science.gov (United States)

    Jablonski, K. P.; Fretter, C.; Carron, L.; Forné, T.; Hütt, M.-T.; Lesne, A.

    2017-09-01

    The notion of disease-associated single-nucleotide polymorphisms (da-SNP), as determined in genome-wide association studies (GWAS), is relevant for many complex pathologies, including cancers. It appeared that da-SNPs are not only markers of causal genetic variation but may contribute to the disease development through an influence on gene expression levels. We argue that understanding this possible functional role of da-SNPs requires to consider their embedding in the tridimensional (3D) multi-scale organization of the human genome. We then focus on the potential impact of da-SNPs on chromatin loops and recently observed topologically associating domains (TADs). We show that for some diseases and cancer types, da-SNPs are over-represented in the borders of these topological domains, in a way that cannot be explained by an increased exon density. This analysis of the distribution of da-SNPs within the 3D genome organization suggests candidate loci for further experimental investigation of the mechanisms underlying genetic susceptibility to diseases, in particular cancer.

  15. Rapid eye movement sleep behavior disorder in Parkinson's disease: magnetic resonance imaging study.

    Science.gov (United States)

    Ford, Andrew H; Duncan, Gordon W; Firbank, Michael J; Yarnall, Alison J; Khoo, Tien K; Burn, David J; O'Brien, John T

    2013-06-01

    Rapid eye movement sleep behavior disorder has poor prognostic implications for Parkinson's disease. The authors recruited 124 patients with early Parkinson's disease to compare clinical and neuroimaging findings based on the presence of this sleep disorder. The presence of rapid eye movement sleep behavior disorder was assessed with the Mayo Sleep Questionnaire. Magnetic resonance imaging sequences were obtained for voxel-based morphometry and diffusion tensor imaging. Patients with sleep disorder had more advanced disease, but groups had similar clinical characteristics and cognitive performance. Those with sleep disorder had areas of reduced cortical grey matter volume and white matter changes compared with those who did not have sleep disorder. However, differences were slight and were not significant when the analyses were adjusted for multiple comparisons. Rapid eye movement sleep behavior disorder was associated with subtle changes in white matter integrity and grey matter volume in patients with early Parkinson's disease. Copyright © 2013 Movement Disorder Society.

  16. Mechanisms of arterial remodeling: lessons from genetic diseases

    Directory of Open Access Journals (Sweden)

    Bernard eVan Varik

    2012-12-01

    Full Text Available Vascular disease is still the leading cause of morbidity and mortality in the Western world, and the primary cause of myocardial infarction, stroke, and ischemia. The biology of vascular disease is complex and still poorly understood in terms of causes and consequences. Vascular function is determined by structural and functional properties of the arterial vascular wall. Arterial stiffness, that is a pathological alteration of the vascular wall, ultimately results in target-organ damage and increased mortality. Arterial remodeling is accelerated under conditions that adversely affect the balance between arterial function and structure such as hypertension, atherosclerosis, diabetes mellitus, chronic kidney disease, inflammatory disease, lifestyle aspects (smoking, drugs (vitamin K antagonists and genetic abnormalities (e.g. pseudoxanthoma elasticum, Marfan’s disease. The aim of this review is to provide an overview of the complex mechanisms and different factors that underlie arterial remodeling, learning from single gene defect diseases like PXE, and PXE-like, Marfan’s disease and Keutel syndrome in vascular remodeling.

  17. Clinical and genetic data of Huntington disease in Moroccan patients.

    Science.gov (United States)

    Bouhouche, Ahmed; Regragui, Wafaa; Lamghari, Hind; Khaldi, Khadija; Birouk, Nazha; Lytim, Safaa; Bellamine, Soufiane; Kriouile, Yamna; Bouslam, Naima; Haddou, El Hachmia Ait Ben; Faris, Mustapha Alaoui; Benomar, Ali; Yahyaoui, Mohamed

    2015-12-01

    Huntington's disease (HD) occurs worldwide with prevalence varying from 0.1 to 10/100,000 depending of the ethnic origin. Since no data is available in the Maghreb population, the aim of this study is to describe clinical and genetic characteristics of Huntington patients of Moroccan origin. Clinical and genetics data of 21 consecutive patients recruited from 2009 to 2014 from the outpatient clinic of six medical centers were analyzed. Statistical analysis was performed using descriptive statistics. Twenty one patients from 17 families were diagnosed positive for the IT15 gene CAG expansion. Clinical symptoms were predominantly motor (19/21). Twelve patients had psychiatric and behavioral disorders, and 11 patients had cognitive disorders essentially of memory impairment. Analysis of genetic results showed that 5 patients had reduced penetrant (RP) alleles and 16 had fully penetrant (FP) alleles. The mean CAG repeat length in patients with RP alleles was 38.4 ± 0.54, and 45.37 ± 8.30 in FP alleles. The age of onset and the size of the CAG repeat length showed significant inverse correlation (p <0.001, r = -0.754). Clinical and genetic data of Moroccan patients are similar to those of Caucasian populations previously reported in the literature.

  18. Ethical aspects of genetic predisposition to environmentally-related disease.

    Science.gov (United States)

    Grandjean, P; Sorsa, M

    1996-05-17

    Some individuals are highly susceptible to disease caused by chemical exposures and this hypersusceptibility can be genetically determined. Because biomarker technology for the determination of genetic predisposition is at the disposal of researchers, the capability therefore exists to include genetic screening in epidemiologic studies. The application of this technological advance in population-based research is, however, fraught with ethical tensions heretofore unknown. Moral duties alone are of limited use in resolving these problems. Scientific documentation is almost always insufficient to clarify the exact nature of the ethical implications, and ways to deal with uncertainties arising as a result of information generated from genetic screening studies must be considered. The most important tensions relate to autonomy and the right to privacy, fairness and equality, while balancing potential public interest in paternalistic measures. Because no moral framework has been accepted for dealing with this technological advance, an ethical discourse in an open forum is required with all affected parties. Scientists alone, or any other group in isolation, should not expect to resolve these questions, but they should participate in and facilitate the process.

  19. Genetic variants associated with celiac disease and the risk for coronary artery disease.

    Science.gov (United States)

    Jansen, Henning; Willenborg, Christina; Schlesinger, Sabrina; Ferrario, Paola G; König, Inke R; Erdmann, Jeanette; Samani, Nilesh J; Lieb, Wolfgang; Schunkert, Heribert

    2015-10-01

    Epidemiological evidence suggests that patients with celiac disease are at increased risk for coronary artery disease (CAD). Genetic-epidemiological analyses identified many single nucleotide polymorphisms (SNPs) associated with celiac disease. If there is a causal relation between celiac disease and CAD, one might expect that risk alleles primarily associated with celiac disease also increase the risk of CAD. In this study we identified from literature 41 SNPs that have been previously described to be genome-wide associated with celiac disease (p DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) dataset, a meta-analysis comprising genome-wide SNP association data from 22,233 CAD cases and 64,762 controls. 24 out of 41 (58.5 %) risk alleles for celiac disease displayed a positive association with CAD (CAD-OR range 1.001-1.081). The remaining risk alleles for celiac disease (n = 16) revealed CAD-ORs of ≤1.0 (range 0.951-1.0). The proportion of CAD associated alleles was greater but did not differ significantly from the proportion of 50 % expected by chance (p = 0.069). One SNP (rs653178 at the SH2B3/ATXN2 locus) displayed study-wise statistically significant association with CAD with directionality consistent effects on celiac disease and CAD. However, the effect of this locus is most likely driven by pleiotropic effects on multiple other diseases. In conclusion, this genetically based approach provided no convincing evidence that SNPs associated with celiac disease contribute to the risk of CAD. Hence, common non-genetic factors may play a more important role explaining the coincidence of these two complex disease conditions.

  20. Shared genetic contribution to ischemic stroke and Alzheimer's disease

    Science.gov (United States)

    Adib‐Samii, Poneh; Harold, Denise; Dichgans, Martin; Williams, Julie; Lewis, Cathryn M.; Markus, Hugh S.; Fornage, Myriam; Holliday, Elizabeth G; Sharma, Pankaj; Bis, Joshua C; Psaty, Bruce M; Seshadri, Sudha; Nalls, Mike A; Devan, William J; Boncoraglio, Giorgio; Malik, Rainer; Mitchell, Braxton D; Kittner, Steven J; Ikram, M Arfan; Clarke, Robert; Rosand, Jonathan; Meschia, James F; Sudlow, Cathie; Rothwell, Peter M; Levi, Christopher; Bevan, Steve; Kilarski, Laura L; Walters, Matthew; Thijs, Vincent; Slowik, Agnieszka; Lindgren, Arne; de Bakker, Paul I W; Lambert, Jean‐Charles; Ibrahim‐Verbaas, Carla A; Harold, Denise; Naj, Adam C; Sims, Rebecca; Bellenguez, Céline; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier‐Boley, Benjamin; Russo, Giancarlo; Thornton‐Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao‐Feng; Gerrish, Amy; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie‐Thçrèse; Choi, Seung‐Hoan; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Ramirez, Alfredo; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Morón, Francisco J; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiçvet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger‐Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Green, Robert; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; St George‐Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petroula; Collinge, John; Sorbi, Sandro; Sanchez‐Garcia, Florentino; Fox, Nick C; Hardy, John; Deniz Naranjo, Maria Candida; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Matthews, Fiona; Moebus, Susanne; Mecocci, Patrizia; Del Zompo, Maria; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton‐Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Wang, Li‐San; Dartigues, Jean‐François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Jones, Lesley; Haines, Jonathan L; Holmans, Peter A; Lathrop, Mark; Pericak‐Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broeckhoven, Christine; Moskvina, Valentina; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D; Amouyel, Philippe

    2016-01-01

    Objective Increasing evidence suggests epidemiological and pathological links between Alzheimer's disease (AD) and ischemic stroke (IS). We investigated the evidence that shared genetic factors underpin the two diseases. Methods Using genome‐wide association study (GWAS) data from METASTROKE + (15,916 IS cases and 68,826 controls) and the International Genomics of Alzheimer's Project (IGAP; 17,008 AD cases and 37,154 controls), we evaluated known associations with AD and IS. On the subset of data for which we could obtain compatible genotype‐level data (4,610 IS cases, 1,281 AD cases, and 14,320 controls), we estimated the genome‐wide genetic correlation (rG) between AD and IS, and the three subtypes (cardioembolic, small vessel, and large vessel), using genome‐wide single‐nucleotide polymorphism (SNP) data. We then performed a meta‐analysis and pathway analysis in the combined AD and small vessel stroke data sets to identify the SNPs and molecular pathways through which disease risk may be conferred. Results We found evidence of a shared genetic contribution between AD and small vessel stroke (rG [standard error] = 0.37 [0.17]; p = 0.011). Conversely, there was no evidence to support shared genetic factors in AD and IS overall or with the other stroke subtypes. Of the known GWAS associations with IS or AD, none reached significance for association with the other trait (or stroke subtypes). A meta‐analysis of AD IGAP and METASTROKE + small vessel stroke GWAS data highlighted a region (ATP5H/KCTD2/ICT1) associated with both diseases (p = 1.8 × 10−8). A pathway analysis identified four associated pathways involving cholesterol transport and immune response. Interpretation Our findings indicate shared genetic susceptibility to AD and small vessel stroke and highlight potential causal pathways and loci. Ann Neurol 2016;79:739–747 PMID:26913989

  1. Epigenetics in Cystic Fibrosis: Epigenetic Targeting of a Genetic Disease.

    Science.gov (United States)

    Sirinupong, Nualpun; Yang, Zhe

    2015-01-01

    Cystic fibrosis (CF) is a deadly genetic disease that affects the lungs and digestive system. A mutation in the CF transmembrane conductance regulator (CFTR) gene is the cause of the disease. How epigenetics contributes to CFTR expression is still poorly understood. Epigenetics is a mechanism that alters gene expression without changing the underlying DNA sequence. Epigenetic mechanisms include DNA methylation and histone modification. Both mechanisms have been implicated in CFTR gene regulation. Here we review epigenetic regulation of CFTR transcription while discussing potential epigenetic targeting strategies including DNA methyltransferase, histone deacetylase, and histone methyltransferase and demethylase inhibition. Because of the reversibility of epigenetics, targeting epigenetic mechanisms has been an attractive therapeutic approach. However, epigenetic targeting of CF disease is still at its infant stage.

  2. Leveraging rapid community-based hiv testing campaigns for non-communicable diseases in rural uganda

    OpenAIRE

    Gabriel Chamie; Dalsone Kwarisiima; Clark, Tamara D; Jane Kabami; Vivek Jain; Elvin Geng; Petersen, Maya L; Harsha Thirumurthy; Moses R Kamya; Havlir, Diane V.; Charlebois, Edwin D.

    2012-01-01

    Background The high burden of undiagnosed HIV in sub-Saharan Africa limits treatment and prevention efforts. Community-based HIV testing campaigns can address this challenge and provide an untapped opportunity to identify non-communicable diseases (NCDs). We tested the feasibility and diagnostic yield of integrating NCD and communicable diseases into a rapid HIV testing and referral campaign for all residents of a rural Ugandan parish. Methods A five-day, multi-disease campaign, offering diag...

  3. Genetic Manipulations of PPARs: Effects on Obesity and Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Yaacov Barak

    2007-01-01

    Full Text Available The interest in genetic manipulations of PPARs is as old as their discovery as receptors of ligands with beneficial clinical activities. Considering the effects of PPAR ligands on critical aspects of systemic physiology, including obesity, lipid metabolism, insulin resistance, and diabetes, gene knockout (KO in mice is the ideal platform for both hypothesis testing and discovery of new PPAR functions in vivo. With the fervent pursuit of the magic bullet to eradicate the obesity epidemic, special emphasis has been placed on the impacts of PPARs on obesity and its associated diseases. As detailed in this review, understanding how PPARs regulate gene expression and basic metabolic pathways is a necessary intermediate en route to deciphering their effects on obesity. Over a decade and dozens of genetic modifications of PPARs into this effort, valuable lessons have been learned, but we are left with more questions to be answered. These lessons and future prospects are the subject of this review.

  4. Development of Rapid Detection and Genetic Characterization of Salmonella in Poultry Breeder Feeds

    Directory of Open Access Journals (Sweden)

    Steven C. Ricke

    2009-07-01

    Full Text Available Salmonella is a leading cause of foodborne illness in the United States, with poultry and poultry products being a primary source of infection to humans. Poultry may carry some Salmonella serovars without any signs or symptoms of disease and without causing any adverse effects to the health of the bird. Salmonella may be introduced to a flock by multiple environmental sources, but poultry feed is suspected to be a leading source. Detecting Salmonella in feed can be challenging because low levels of the bacteria may not be recovered using traditional culturing techniques. Numerous detection methodologies have been examined over the years for quantifying Salmonella in feeds and many have proven to be effective for Salmonella isolation and detection in a variety of feeds. However, given the potential need for increased detection sensitivity, molecular detection technologies may the best candidate for developing rapid sensitive methods for identifying small numbers of Salmonella in the background of large volumes of feed. Several studies have been done using polymerase chain reaction (PCR assays and commercial kits to detect Salmonella spp. in a wide variety of feed sources. In addition, DNA array technology has recently been utilized to track the dissemination of a specific Salmonella serotype in feed mills. This review will discuss the processing of feeds and potential points in the process that may introduce Salmonella contamination to the feed. Detection methods currently used and the need for advances in these methods also will be discussed. Finally, implementation of rapid detection for optimizing control methods to prevent and remove any Salmonella contamination of feeds will be considered.

  5. Development of Rapid Detection and Genetic Characterization of Salmonella in Poultry Breeder Feeds

    Science.gov (United States)

    Jarquin, Robin; Hanning, Irene; Ahn, Soohyoun; Ricke, Steven C.

    2009-01-01

    Salmonella is a leading cause of foodborne illness in the United States, with poultry and poultry products being a primary source of infection to humans. Poultry may carry some Salmonella serovars without any signs or symptoms of disease and without causing any adverse effects to the health of the bird. Salmonella may be introduced to a flock by multiple environmental sources, but poultry feed is suspected to be a leading source. Detecting Salmonella in feed can be challenging because low levels of the bacteria may not be recovered using traditional culturing techniques. Numerous detection methodologies have been examined over the years for quantifying Salmonella in feeds and many have proven to be effective for Salmonella isolation and detection in a variety of feeds. However, given the potential need for increased detection sensitivity, molecular detection technologies may the best candidate for developing rapid sensitive methods for identifying small numbers of Salmonella in the background of large volumes of feed. Several studies have been done using polymerase chain reaction (PCR) assays and commercial kits to detect Salmonella spp. in a wide variety of feed sources. In addition, DNA array technology has recently been utilized to track the dissemination of a specific Salmonella serotype in feed mills. This review will discuss the processing of feeds and potential points in the process that may introduce Salmonella contamination to the feed. Detection methods currently used and the need for advances in these methods also will be discussed. Finally, implementation of rapid detection for optimizing control methods to prevent and remove any Salmonella contamination of feeds will be considered. PMID:22346699

  6. Analysis of genetics and risk factors of Alzheimer's Disease.

    Science.gov (United States)

    Panpalli Ates, M; Karaman, Y; Guntekin, S; Ergun, M A

    2016-06-14

    Alzheimer's Disease is the leading neurodegenerative cause of dementia. The pathogenesis is not clearly understood yet, is believed to be the complex interaction between genetic and environmental factors. Consequently vascular risk factors and Apolipoprotein E genotyping are increasingly gaining importance. This study aimed at assessing the relationships between Alzheimer's Disease and Apolipoprotein E phenotype and vascular risk factors. Patients diagnosed with "possible Alzheimer's Disease" in the Gazi University, Department of Neurology, were included in the study and age-matched volunteer patients who attended the polyclinic were included as a control group. In this study, the risk factors including low education level, smoking, hyperlipidemia, higher serum total cholesterol levels, and hyperhomocysteinemia were found to be statistically significantly more common in the Alzheimer's Disease group in comparison to the Control Group, while all Apolipoprotein E ε4/ε4 genotypes were found in the Alzheimer's Disease group. The presence of the Apolipoprotein E ε4 allele is believed to increase vascular risk factors as well as to affect Alzheimer's Disease directly. The biological indicators which are used in identifying the patients' genes will be probably used in the treatment plan of the patients in the future. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Use of Genomic Estimated Breeding Values Results in Rapid Genetic Gains for Drought Tolerance in Maize

    Directory of Open Access Journals (Sweden)

    B.S. Vivek

    2017-03-01

    Full Text Available More than 80% of the 19 million ha of maize ( L. in tropical Asia is rainfed and prone to drought. The breeding methods for improving drought tolerance (DT, including genomic selection (GS, are geared to increase the frequency of favorable alleles. Two biparental populations (CIMMYT-Asia Population 1 [CAP1] and CAP2 were generated by crossing elite Asian-adapted yellow inbreds (CML470 and VL1012767 with an African white drought-tolerant line, CML444. Marker effects of polymorphic single-nucleotide polymorphisms (SNPs were determined from testcross (TC performance of F families under drought and optimal conditions. Cycle 1 (C1 was formed by recombining the top 10% of the F families based on TC data. Subsequently, (i C2[PerSe_PS] was derived by recombining those C1 plants that exhibited superior per se phenotypes (phenotype-only selection, and (ii C2[TC-GS] was derived by recombining a second set of C1 plants with high genomic estimated breeding values (GEBVs derived from TC phenotypes of F families (marker-only selection. All the generations and their top crosses to testers were evaluated under drought and optimal conditions. Per se grain yields (GYs of C2[PerSe_PS] and that of C2[TC-GS] were 23 to 39 and 31 to 53% better, respectively, than that of the corresponding F population. The C2[TC-GS] populations showed superiority of 10 to 20% over C2[PerSe-PS] of respective populations. Top crosses of C2[TC-GS] showed 4 to 43% superiority of GY over that of C2[PerSe_PS] of respective populations. Thus, GEBV-enabled selection of superior phenotypes (without the target stress resulted in rapid genetic gains for DT.

  8. A rapid, strong, and convergent genetic response to urban habitat fragmentation in four divergent and widespread vertebrates.

    Science.gov (United States)

    Delaney, Kathleen Semple; Riley, Seth P D; Fisher, Robert N

    2010-09-16

    Urbanization is a major cause of habitat fragmentation worldwide. Ecological and conservation theory predicts many potential impacts of habitat fragmentation on natural populations, including genetic impacts. Habitat fragmentation by urbanization causes populations of animals and plants to be isolated in patches of suitable habitat that are surrounded by non-native vegetation or severely altered vegetation, asphalt, concrete, and human structures. This can lead to genetic divergence between patches and in turn to decreased genetic diversity within patches through genetic drift and inbreeding. We examined population genetic patterns using microsatellites in four common vertebrate species, three lizards and one bird, in highly fragmented urban southern California. Despite significant phylogenetic, ecological, and mobility differences between these species, all four showed similar and significant reductions in gene flow over relatively short geographic and temporal scales. For all four species, the greatest genetic divergence was found where development was oldest and most intensive. All four animals also showed significant reduction in gene flow associated with intervening roads and freeways, the degree of patch isolation, and the time since isolation. Despite wide acceptance of the idea in principle, evidence of significant population genetic changes associated with fragmentation at small spatial and temporal scales has been rare, even in smaller terrestrial vertebrates, and especially for birds. Given the striking pattern of similar and rapid effects across four common and widespread species, including a volant bird, intense urbanization may represent the most severe form of fragmentation, with minimal effective movement through the urban matrix.

  9. The effect of genetic bottlenecks and inbreeding on the incidence of two major autoimmune diseases in standard poodles, sebaceous adenitis and Addison’s disease

    OpenAIRE

    Pedersen, Niels C.; Brucker, Lynn; Tessier, Natalie Green; Liu, Hongwei; Penedo, Maria Cecilia T; Hughes, Shayne; Oberbauer, Anita; Sacks, Ben

    2015-01-01

    Background Sebaceous adenitis (SA) and Addison’s disease (AD) increased rapidly in incidence among Standard Poodles after the mid-twentieth century. Previous attempts to identify specific genetic causes using genome wide association studies and interrogation of the dog leukocyte antigen (DLA) region have been non-productive. However, such studies led us to hypothesize that positive selection for desired phenotypic traits that arose in the mid-twentieth century led to intense inbreeding and th...

  10. Gender differences in genetic risk profiles for cardiovascular disease.

    Science.gov (United States)

    Silander, Kaisa; Alanne, Mervi; Kristiansson, Kati; Saarela, Olli; Ripatti, Samuli; Auro, Kirsi; Karvanen, Juha; Kulathinal, Sangita; Niemelä, Matti; Ellonen, Pekka; Vartiainen, Erkki; Jousilahti, Pekka; Saarela, Janna; Kuulasmaa, Kari; Evans, Alun; Perola, Markus; Salomaa, Veikko; Peltonen, Leena

    2008-01-01

    Cardiovascular disease (CVD) incidence, complications and burden differ markedly between women and men. Although there is variation in the distribution of lifestyle factors between the genders, they do not fully explain the differences in CVD incidence and suggest the existence of gender-specific genetic risk factors. We aimed to estimate whether the genetic risk profiles of coronary heart disease (CHD), ischemic stroke and the composite end-point of CVD differ between the genders. We studied in two Finnish population cohorts, using the case-cohort design the association between common variation in 46 candidate genes and CHD, ischemic stroke, CVD, and CVD-related quantitative risk factors. We analyzed men and women jointly and also conducted genotype-gender interaction analysis. Several allelic variants conferred disease risk for men and women jointly, including rs1801020 in coagulation factor XII (HR = 1.31 (1.08-1.60) for CVD, uncorrected p = 0.006 multiplicative model). Variant rs11673407 in the fucosyltransferase 3 gene was strongly associated with waist/hip ratio (uncorrected p = 0.00005) in joint analysis. In interaction analysis we found statistical evidence of variant-gender interaction conferring risk of CHD and CVD: rs3742264 in the carboxypeptidase B2 gene, p(interaction) = 0.009 for CHD, and rs2774279 in the upstream stimulatory factor 1 gene, p(interaction) = 0.007 for CHD and CVD, showed strong association in women but not in men, while rs2069840 in interleukin 6 gene, p(interaction) = 0.004 for CVD, showed strong association in men but not in women (uncorrected p-values). Also, two variants in the selenoprotein S gene conferred risk for ischemic stroke in women, p(interaction) = 0.003 and 0.007. Importantly, we identified a larger number of gender-specific effects for women than for men. A false discovery rate analysis suggests that we may expect half of the reported findings for combined gender analysis to be true positives, while at least third of

  11. Genetics of sputum gene expression in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Weiliang Qiu

    Full Text Available Previous expression quantitative trait loci (eQTL studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs. The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5, the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus.

  12. Genetics of sputum gene expression in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Qiu, Weiliang; Cho, Michael H; Riley, John H; Anderson, Wayne H; Singh, Dave; Bakke, Per; Gulsvik, Amund; Litonjua, Augusto A; Lomas, David A; Crapo, James D; Beaty, Terri H; Celli, Bartolome R; Rennard, Stephen; Tal-Singer, Ruth; Fox, Steven M; Silverman, Edwin K; Hersh, Craig P

    2011-01-01

    Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus.

  13. Genetics of Sputum Gene Expression in Chronic Obstructive Pulmonary Disease

    Science.gov (United States)

    Qiu, Weiliang; Cho, Michael H.; Riley, John H.; Anderson, Wayne H.; Singh, Dave; Bakke, Per; Gulsvik, Amund; Litonjua, Augusto A.; Lomas, David A.; Crapo, James D.; Beaty, Terri H.; Celli, Bartolome R.; Rennard, Stephen; Tal-Singer, Ruth; Fox, Steven M.; Silverman, Edwin K.; Hersh, Craig P.

    2011-01-01

    Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus. PMID:21949713

  14. Ethical aspects of research into Alzheimer disease. A European Delphi Study focused on genetic and non-genetic research.

    Science.gov (United States)

    van der Vorm, A; Vernooij-Dassen, M J F J; Kehoe, P G; Olde Rikkert, M G M; van Leeuwen, E; Dekkers, W J M

    2009-02-01

    Although genetic research into Alzheimer disease (AD) is increasing, the ethical aspects of this kind of research and the differences between ethical issues related to genetic and non-genetic research into AD have not yet received much attention. (1) To identify and compare the five ethical issues considered most important by surveyed expert panellists in non-genetic and genetic AD research and (2) to compare our empirical findings with ethical issues in genetic research in general as described in the literature. A modified Delphi study in two rounds Genetic and non-genetic research into AD generated an approximately equal number of topics with a considerable overlap. Different priorities in the ethics of both types of research were found. Genetic research raised new topics such as "confidentiality of genetic information" and "implications of research for relatives" which changes the impact and application of existing ethical topics such as "informed consent" and is judged to have more impact on both individuals and society. A difference with the results of more theoretical approaches on ethical aspects related to AD research was also found. Different priorities are given to ethical issues in genetic and non-genetic research. These arise partly because genetic research causes unique and new questions, mostly related to the position of family members and the status of and access to genetic information. Differences found between the results of our empirical study and the more theoretical literature, suggest an additional value for empirical research in medical ethics.

  15. Genetic contribution of the leukotriene pathway to coronary artery disease

    OpenAIRE

    Hartiala, Jaana; Li, Dalin; Conti, David V; VIKMAN, Susanna; Patel, Yesha; Wilson Tang, W. H.; Brennan, Marie-Louise; Newman, John W.; Stephensen, Charles B.; Armstrong, Patrice; Hazen, Stanley L.; Allayee, Hooman

    2011-01-01

    We evaluated the genetic contribution of the leukotriene (LT) pathway to risk of coronary artery disease (CAD) in 4,512 Caucasian and African American subjects ascertained through elective cardiac evaluation. Of the three previously associated variants, the shorter “3” and “4” alleles of a promoter repeat polymorphism in ALOX5 increased risk of CAD in African Americans (OR = 1.4, 95% CI 1.0–1.9; p = 0.04), whereas a haplotype of LTA4H (HapK) was associated with CAD in Caucasians (OR = 1.2, 95...

  16. A rapid genetic assay for the identification of the most common Pocillopora damicornis genetic lineages on the Great Barrier Reef.

    Directory of Open Access Journals (Sweden)

    Gergely Torda

    Full Text Available Pocillopora damicornis (Linnaeus, 1758; Scleractinia, Pocilloporidae has recently been found to comprise at least five distinct genetic lineages in Eastern Australia, some of which likely represent cryptic species. Due to similar and plastic gross morphology of these lineages, field identification is often difficult. Here we present a quick, cost effective genetic assay as well as three novel microsatellite markers that distinguish the two most common lineages found on the Great Barrier Reef. The assay is based on PCR amplification of two regions within the mitochondrial putative control region, which show consistent and easily identifiable fragment size differences for the two genetic lineages after Alu1 restriction enzyme digestion of the amplicons.

  17. Ethnicity, genetics, and breast cancer: media portrayal of disease identities.

    Science.gov (United States)

    Donelle, L; Hoffman-Goetz, L; Clarke, J N

    2005-08-01

    To describe, compare, and analyze how the risk of breast cancer is framed in newspapers directed towards an ethnic minority population (Jewish) with higher risk of inherited breast cancer compared with newspaper coverage for the general population (Anglo-Canadian) without this risk. This investigation utilized a mixed methods (quantitative and qualitative) approach. The design emphasized a content analysis conducted on ethnically specific and non-ethnic newspaper articles. It is noteworthy that the 'Jewish' newspapers devote a substantially larger proportion of articles on breast cancer to genetic risk as the key risk factor for this disease. Articles in the Jewish newspapers tend to link being a Jewish woman with being at risk for a diagnosis of breast cancer. This ethnic 'identity' is reinforced through the repeated association of Jewish heritage and genetic breast cancer risk at the exclusion of other known risk factors. This isolated genetic link to breast cancer is not a message that is replicated within the provincial newsprint articles. These findings assist in the facilitation of prevention and treatment of those with or at risk of breast cancer. The health policy implications of this portrayal as well as suggestions for change are considered.

  18. The Congenital Heart Disease Genetic Network Study: Cohort description.

    Science.gov (United States)

    Hoang, Thanh T; Goldmuntz, Elizabeth; Roberts, Amy E; Chung, Wendy K; Kline, Jennie K; Deanfield, John E; Giardini, Alessandro; Aleman, Adolfo; Gelb, Bruce D; Mac Neal, Meghan; Porter, George A; Kim, Richard; Brueckner, Martina; Lifton, Richard P; Edman, Sharon; Woyciechowski, Stacy; Mitchell, Laura E; Agopian, A J

    2018-01-01

    The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart Disease Genetic Network Study to provide phenotype and genotype data for a large congenital heart defects (CHDs) cohort. This article describes the PCGC cohort, overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow tract obstructions (e.g., hypoplastic left heart syndrome). Cases with CHDs were recruited through ten sites, 2010-2014. Information on cases (N = 9,727) and their parents was collected through interviews and medical record abstraction. Four case characteristics, eleven parental characteristics, and thirteen parent-reported neurodevelopment outcomes were summarized using counts and frequencies and compared across CHD types and subtypes. Eleven percent of cases had a genetic diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal heart defects (40%) or left ventricular outflow tract obstruction (21%). Across CHD types, there were significant differences (ptypes and subtypes, provides a reference work for investigators who are interested in collaborating with or using publically available resources from the PCGC.

  19. Toxin-Induced and Genetic Animal Models of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara

    2011-01-01

    Full Text Available Parkinson's disease (PD is a common progressive neurodegenerative disorder. The major pathological hallmarks of PD are the selective loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal aggregates termed Lewy bodies (LBs, but the pathophysiological mechanisms are not fully understood. Epidemiologically, environmental neurotoxins such as pesticides are promising candidates for causative factors of PD. Oxidative stress and mitochondrial dysfunction induced by these toxins could contribute to the progression of PD. While most cases of PD are sporadic, specific mutations in genes that cause familial forms of PD have led to provide new insights into its pathogenesis. This paper focuses on animal models of both toxin-induced and genetically determined PD that have provided significant insight for understanding this disease. We also discuss the validity, benefits, and limitations of representative models.

  20. GENETICS AND NEUROPATHOLOGY OF HUNTINGTON’S DISEASE

    Science.gov (United States)

    Reiner, Anton; Dragatsis, Ioannis; Dietrich, Paula

    2015-01-01

    Huntington’s disease (HD) is an autosomal dominant progressive neurodegenerative disorder that prominently affects the basal ganglia, leading to affective, cognitive, behavioral and motor decline. The basis of HD is a CAG repeat expansion to >35 CAG in a gene that codes for a ubiquitous protein known as huntingtin, resulting in an expanded N-terminal polyglutamine tract. The size of the expansion is correlated with disease severity, with increasing CAG accelerating the age of onset. A variety of possibilities have been proposed as to the mechanism by which the mutation causes preferential injury to the basal ganglia. The present chapter provides a basic overview of the genetics and pathology of HD. PMID:21907094

  1. [Pulmonary surfactant homeostasis associated genetic abnormalities and lung diseases].

    Science.gov (United States)

    Jiang, Xiaojing; Sun, Xiuzhu; Du, Weihua; Hao, Haisheng; Zhao, Xueming; Wang, Dong; Zhu, Huabin; Liu, Yan

    2016-08-01

    Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.

  2. Neurofibromatosis type 1 and multiple sclerosis: Genetically related diseases

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    Solaf M. Elsayed

    2017-07-01

    Full Text Available Neurofibromatosis type I (NF1 is an autosomal dominant disorder with involvement of both the cutaneous and nervous systems. Patients are susceptible to neurological complication in the form of tumors of the brain and spinal cord. Multiple sclerosis (MS is a chronic autoimmune disease that affects the myelinated axons in the central nervous system. Unlike MS, none of the neurological complications of NF1 is demyelinating. The association of these two diseases in the same patient is rare and could be genetically related. Early detection of the presence of MS in patients with NF1 is of utmost importance as treatment will certainly decrease further neurological disability. Here we report the first Egyptian lady with this association.

  3. Genetic Alterations of δ-Catenin/NPRAP/Neurojungin (CTNND2): Functional Implications in Complex Human Diseases

    Science.gov (United States)

    Lu, Qun; Aguilar, Byron J.; Li, Mingchuan; Jiang, Yongguang; Chen, Yan-Hua

    2016-01-01

    Some genes involved in complex human diseases are particularly vulnerable to genetic variations such as single nucleotide polymorphism, copy number variations, and mutations. For example, Ras mutations account for over 30% of all human cancers. Additionally, there are some genes that can display different variations with functional impact in different diseases that are unrelated. One such gene stands out: δ-catenin/NPRAP/Neurojungin with gene designation as CTNND2 on chromosome 5p15.2. Recent advances in genome wide association as well as molecular biology approaches have uncovered striking involvement of δ-catenin gene variations linked to complex human disorders. These disorders include cancer, bipolar disorder, schizophrenia, autism, Cri-du-chat syndrome, myopia, cortical cataract-linked Alzheimer’s disease, and infectious diseases. This list has rapidly grown longer in recent years, underscoring the pivotal roles of δ-catenin in critical human diseases. δ-Catenin is an adhesive junction-associated protein in the delta subfamily of the β-catenin superfamily. δ-Catenin functions in Wnt signaling to regulate gene expression and modulate Rho GTPases of the Ras superfamily in cytoskeletal reorganization. δ-Catenin likely lies where Wnt signaling meets Rho GTPases and is a unique and vulnerable common target for mutagenesis in different human diseases. PMID:27380241

  4. Rapid identification of a Mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum

    Directory of Open Access Journals (Sweden)

    Camus Nimmo

    2017-09-01

    Discussion: Compared to rapid molecular tests (which can only examine a limited number of mutations and WGS of culture isolates (which requires a culture step, WGS directly from sputum can quickly generate a complete genetic drug resistance profile. In this case, WGS altered the clinical management of drug-resistant tuberculosis and demonstrated potential for guiding individualized drug treatment where second-line drug resistance is common.

  5. Genetic counseling and presymptomatic testing programs for Machado-Joseph Disease : lessons from Brazil and Portugal

    OpenAIRE

    Lavínia Schuler-Faccini; Claudio Maria Osorio; Flavia Romariz; Milena Paneque; Jorge Sequeiros; Laura Bannach Jardim

    2014-01-01

    Machado-Joseph disease (MJD) is an autosomal dominant, late-onset neurological disorder and the most common form of spinocerebellar ataxia (SCA) worldwide. Diagnostic genetic testing is available to detect the disease-causing mutation by direct sizing of the CAG repeat tract in the ataxin 3 gene. Presymptomatic testing (PST) can be used to identify persons at risk of developing the disease. Genetic counseling provides patients with information about the disease, genetic risks, PST, and the de...

  6. Noninvasive prenatal testing in China: Future detection of rare genetic diseases?

    OpenAIRE

    Mei, Lin; Tang, Qi; Sun, Baiyu; Xu, Lingzhong

    2014-01-01

    Noninvasive prenatal testing (NIPT) provides an innovative method to detect genetic conditions in fetuses using a maternal blood sample, thus avoiding the risk of miscarriage associated with traditional invasive procedures. Since 80% of rare diseases are genetic diseases, NIPT has the potential to detect rare genetic diseases early on and it has been used in many countries and regions. Since China has the world's largest population of patients with rare diseases, NIPT has been implemented in ...

  7. Rapid genetic and epigenetic alterations under intergeneric genomic shock in newly synthesized Chrysanthemum morifolium x Leucanthemum paludosum hybrids (Asteraceae).

    Science.gov (United States)

    Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

    2014-01-01

    The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5-50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses.

  8. Rapid Genetic and Epigenetic Alterations under Intergeneric Genomic Shock in Newly Synthesized Chrysanthemum morifolium × Leucanthemum paludosum Hybrids (Asteraceae)

    Science.gov (United States)

    Wang, Haibin; Jiang, Jiafu; Chen, Sumei; Qi, Xiangyu; Fang, Weimin; Guan, Zhiyong; Teng, Nianjun; Liao, Yuan; Chen, Fadi

    2014-01-01

    The Asteraceae family is at the forefront of the evolution due to frequent hybridization. Hybridization is associated with the induction of widespread genetic and epigenetic changes and has played an important role in the evolution of many plant taxa. We attempted the intergeneric cross Chrysanthemum morifolium × Leucanthemum paludosum. To obtain the success in cross, we have to turn to ovule rescue. DNA profiling of the amphihaploid and amphidiploid was investigated using amplified fragment length polymorphism, sequence-related amplified polymorphism, start codon targeted polymorphism, and methylation-sensitive amplification polymorphism (MSAP). Hybridization induced rapid changes at the genetic and the epigenetic levels. The genetic changes mainly involved loss of parental fragments and gaining of novel fragments, and some eliminated sequences possibly from the noncoding region of L. paludosum. The MSAP analysis indicated that the level of DNA methylation was lower in the amphiploid (∼45%) than in the parental lines (51.5–50.6%), whereas it increased after amphidiploid formation. Events associated with intergeneric genomic shock were a feature of C. morifolium × L. paludosum hybrid, given that the genetic relationship between the parental species is relatively distant. Our results provide genetic and epigenetic evidence for understanding genomic shock in wide crosses between species in Asteraceae and suggest a need to expand our current evolutionary framework to encompass a genetic/epigenetic dimension when seeking to understand wide crosses. PMID:24407856

  9. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes : a genetic association study

    NARCIS (Netherlands)

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L. Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M.; Annese, Vito; Brand, Stephan; Brant, Steven R.; Cho, Judy H.; Daly, Mark J.; Dubinsky, Marla; Duerr, Richard H.; Ferguson, Lynnette R.; Franke, Andre; Gearry, Richard B.; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R.; Huang, Hailang; Kennedy, Nicholas A.; Kupcinskas, Limas; Lawrance, Ian C.; Lee, James C.; Satsangi, Jack; Schreiber, Stephan; Theatre, Emilie; van der Meulen-de Jong, Andrea E.; Weersma, Rinse K.; Wilson, David C.; Parkes, Miles; Vermeire, Severine; Rioux, John D.; Mansfield, John; Silverberg, Mark S.; Radford-Smith, Graham; McGovern, Dermot P. B.; Barrett, Jeffrey C.; Lees, Charlie W.

    2015-01-01

    Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between

  10. Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

    Directory of Open Access Journals (Sweden)

    Agostino Di Ciaula

    2013-01-01

    Full Text Available Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.

  11. Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

    Directory of Open Access Journals (Sweden)

    Nami Shrestha Palikhe

    2012-01-01

    Full Text Available Aspirin-exacerbated respiratory disease (AERD refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis.

  12. Genetically engineered bananas resistant to Xanthomonas wilt disease and nematodes.

    Science.gov (United States)

    Tripathi, Leena; Atkinson, Howard; Roderick, Hugh; Kubiriba, Jerome; Tripathi, Jaindra N

    2017-05-01

    Banana is an important staple food crop feeding more than 100 million Africans, but is subject to severe productivity constraints due to a range of pests and diseases. Banana Xanthomonas wilt caused by Xanthomonas campestris pv. musacearum is capable of entirely destroying a plantation while nematodes can cause losses up to 50% and increase susceptibility to other pests and diseases. Development of improved varieties of banana is fundamental in order to tackle these challenges. However, the sterile nature of the crop and the lack of resistance in Musa germplasm make improvement by traditional breeding techniques either impossible or extremely slow. Recent developments using genetic engineering have begun to address these problems. Transgenic banana expressing sweet pepper Hrap and Pflp genes have demonstrated complete resistance against X. campestris pv. musacearum in the field. Transgenic plantains expressing a cysteine proteinase inhibitors and/or synthetic peptide showed enhanced resistance to a mixed species population of nematodes in the field. Here, we review the genetic engineering technologies which have potential to improve agriculture and food security in Africa.

  13. Drifting to oblivion? Rapid genetic differentiation in an endangered lizard following habitat fragmentation and drought

    Science.gov (United States)

    Vandergast, Amy; Wood, Dustin A.; Thompson, Andrew R.; Fisher, Mark; Barrows, Cameron W.; Grant, Tyler J.

    2016-01-01

    Aim The frequency and severity of habitat alterations and disturbance are predicted to increase in upcoming decades, and understanding how disturbance affects population integrity is paramount for adaptive management. Although rarely is population genetic sampling conducted at multiple time points, pre- and post-disturbance comparisons may provide one of the clearest methods to measure these impacts. We examined how genetic properties of the federally threatened Coachella Valley fringe-toed lizard (Uma inornata) responded to severe drought and habitat fragmentation across its range. Location Coachella Valley, California, USA. Methods We used 11 microsatellites to examine population genetic structure and diversity in 1996 and 2008, before and after a historic drought. We used Bayesian assignment methods and F-statistics to estimate genetic structure. We compared allelic richness across years to measure loss of genetic diversity and employed approximate Bayesian computing methods and heterozygote excess tests to explore the recent demographic history of populations. Finally, we compared effective population size across years and to abundance estimates to determine whether diversity remained low despite post-drought recovery. Results Genetic structure increased between sampling periods, likely as a result of population declines during the historic drought of the late 1990s–early 2000s, and habitat loss and fragmentation that precluded post-drought genetic rescue. Simulations supported recent demographic declines in 3 of 4 main preserves, and in one preserve, we detected significant loss of allelic richness. Effective population sizes were generally low across the range, with estimates ≤100 in most sites. Main conclusions Fragmentation and drought appear to have acted synergistically to induce genetic change over a short time frame. Progressive deterioration of connectivity, low Ne and measurable loss of genetic diversity suggest that conservation efforts have

  14. Alcoholism and liver disease in Mexico: Genetic and environmental factors

    Science.gov (United States)

    Roman, Sonia; Zepeda-Carrillo, Eloy Alfonso; Moreno-Luna, Laura Eugenia; Panduro, Arturo

    2013-01-01

    Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide. PMID:24307790

  15. Alcoholism and liver disease in Mexico: genetic and environmental factors.

    Science.gov (United States)

    Roman, Sonia; Zepeda-Carrillo, Eloy Alfonso; Moreno-Luna, Laura Eugenia; Panduro, Arturo

    2013-11-28

    Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide.

  16. Genetics of the neuronal ceroid lipofuscinoses (Batten disease).

    Science.gov (United States)

    Mole, Sara E; Cotman, Susan L

    2015-10-01

    The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders that affect children and adults and are grouped together by similar clinical features and the accumulation of autofluorescent storage material. More than a dozen genes containing over 430 mutations underlying human NCLs have been identified. These genes encode lysosomal enzymes (CLN1, CLN2, CLN10, CLN13), a soluble lysosomal protein (CLN5), a protein in the secretory pathway (CLN11), two cytoplasmic proteins that also peripherally associate with membranes (CLN4, CLN14), and many transmembrane proteins with different subcellular locations (CLN3, CLN6, CLN7, CLN8, CLN12). For most NCLs, the function of the causative gene has not been fully defined. Most of the mutations in these genes are associated with a typical disease phenotype, but some result in variable disease onset, severity, and progression, including distinct clinical phenotypes. There remain disease subgroups with unknown molecular genetic backgrounds. This article is part of a Special Issue entitled: "Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)." Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Respiratory Syncytial Virus: Virology, Reverse Genetics, and Pathogenesis of Disease

    Science.gov (United States)

    Fearns, Rachel; Graham, Barney S.

    2016-01-01

    Human respiratory syncytial virus (RSV) is an enveloped, nonsegmented negative-strand RNA virus of family Paramyxoviridae. RSV is the most complex member of the family in terms of the number of genes and proteins. It is also relatively divergent and distinct from the prototype members of the family. In the past 30 years, we have seen a tremendous increase in our understanding of the molecular biology of RSV based on a succession of advances involving molecular cloning, reverse genetics, and detailed studies of protein function and structure. Much remains to be learned. RSV disease is complex and variable, and the host and viral factors that determine tropism and disease are poorly understood. RSV is notable for a historic vaccine failure in the 1960s involving a formalin-inactivated vaccine that primed for enhanced disease in RSV naïve recipients. Live vaccine candidates have been shown to be free of this complication. However, development of subunit or other protein-based vaccines for pediatric use is hampered by the possibility of enhanced disease and the difficulty of reliably demonstrating its absence in preclinical studies. PMID:24362682

  18. Rapid Molecular detection of citrus brown spot disease using ACT gene in Alternaria alternata

    Directory of Open Access Journals (Sweden)

    Hamid Moghimi

    2017-06-01

    Full Text Available Introduction:Using rapid detection methods is important for detection of plant pathogens and also prevention through spreading pests in agriculture. Citrus brown spot disease caused by pathogenic isolates of Alternaria alternata is a common disease in Iran. Materials and methods: In this study, for the first time a PCR based molecular method was used for rapid diagnosis of brown spot disease. Nine isolates of A. Alternata were isolated in PDA medium from different citrus gardens. The plant pathogenic activity was examined in tangerine leaves for isolates. Results showed that these isolates are the agents of brown spot disease. PCR amplification of specific ACT-toxin gene was performed for DNA extracted from A. alternata isolates, with 11 different fungal isolates as negative controls and 5 DNA samples extracted from soil. Results: Results showed that A. alternata, the causal agent of brown spot disease, can be carefully distinguished from other pathogenic agents by performing PCR amplification with specific primers for ACT toxin gene. Also, the results from Nested-PCR method confirmed the primary reaction and the specificity of A. alternata for brown spot disease. PCR results to control samples of the other standard fungal isolates, showed no amplification band. In addition, PCR with the DNA extracted from contaminated soils confirmed the presence of ACT toxin gene. Discussion and conclusion: Molecular procedure presented here can be used in rapid identification and prevention of brown spot infection in citrus gardens all over the country.

  19. The National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) is a national genetics data repository facilitating access to genotypic...

  20. Genetics Home Reference: inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

    Science.gov (United States)

    ... with Paget Disease of Bone and/or Frontotemporal Dementia General Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How are genetic ...

  1. Rapid test for fecal calprotectin levels in children with crohn disease

    DEFF Research Database (Denmark)

    Kolho, K L; Turner, D; Veereman-Wauters, G

    2012-01-01

    Assessment of fecal calprotectin, a surrogate marker of mucosal inflammation, is a promising means to monitor therapeutic response in pediatric inflammatory bowel disease, especially if the result is readily available. We tested the performance of a novel calprotectin rapid test, Quantum Blue...

  2. Rapid Newcastle Disease Virus Detection Based on Loop-Mediated Isothermal Amplification and Optomagnetic Readout

    DEFF Research Database (Denmark)

    Tian, Bo; Ma, Jing; Zardán Gómez de la Torre, Teresa

    2016-01-01

    efficiency of loop-mediated isothermal amplification (LAMP) with an optomagnetic nanoparticle-based readout system, we demonstrate ultrasensitive and rapid detection of Newcastle disease virus RNA. Biotinylated amplicons of LAMP and reverse transcription LAMP (RT-LAMP) bind to streptavidin-coated magnetic...

  3. Genetic Factors Affecting Late-Onset Alzheimer's Disease Susceptibility.

    Science.gov (United States)

    Rezazadeh, Maryam; Khorrami, Aziz; Yeghaneh, Tarlan; Talebi, Mahnaz; Kiani, Seyed Jalal; Heshmati, Yaser; Gharesouran, Jalal

    2016-03-01

    Alzheimer's disease is considered a progressive brain disease in the older population. Late-onset Alzheimer's disease (LOAD) as a multifactorial dementia has a polygenic inheritance. Age, environment, and lifestyle along with a growing number of genetic factors have been reported as risk factors for LOAD. Our aim was to present results of LOAD association studies that have been done in northwestern Iran, and we also explored possible interactions with apolipoprotein E (APOE) status. We re-evaluated the association of these markers in dominant, recessive, and additive models. In all, 160 LOAD and 163 healthy control subjects of Azeri Turkish ethnicity were studied. The Chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. A Bonferroni-corrected p value, based on the number of statistical tests, was considered significant. Our results confirmed that chemokine receptor type 2 (CCR2), estrogen receptor 1 (ESR1), toll-like receptor 2 (TLR2), tumor necrosis factor alpha (TNF α), APOE, bridging integrator 1 (BIN1), and phosphatidylinositol-binding clathrin assembly protein (PICALM) are LOAD susceptibility loci in Azeri Turk ancestry populations. Among them, variants of CCR2, ESR1, TNF α, and APOE revealed associations in three different genetic models. After adjusting for APOE, the association (both allelic and genotypic) with CCR2, BIN1, and ESRα (PvuII) was evident only among subjects without the APOE ε4, whereas the association with CCR5, without Bonferroni correction, was significant only among subjects carrying the APOE ε4 allele. This result is an evidence of a synergistic and antagonistic effect of APOE on variant associations with LOAD.

  4. Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes.

    Directory of Open Access Journals (Sweden)

    Esterina ePascale

    2016-04-01

    Full Text Available The microtubule-associated protein tau (MAPT region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease. Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; 2 =9.9; OR,1.7; 95% CI, 1.2-2.4; p=0.002. The effect was more evident in non tremor dominant PD subjects (NTD-PD (82 vs 69.5%; 2 =13.6; OR, 2.03; 95% CI, 1.4-3; p=0.0003, while no difference emerged between PD subgroup of tremor dominant patients (TD-PD and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p=0.007, OR 2.9; 95%CI 1.3-6.3. Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype.

  5. Genetics Home Reference: hepatic veno-occlusive disease with immunodeficiency

    Science.gov (United States)

    ... liver (hepatomegaly), a buildup of scar tissue (hepatic fibrosis), and liver failure. Children with VODI are prone to recurrent ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (1 link) Genetic Testing Registry: ...

  6. Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis.

    Science.gov (United States)

    Schaefer, Arne S; Bochenek, Gregor; Jochens, Arne; Ellinghaus, David; Dommisch, Henrik; Güzeldemir-Akçakanat, Esra; Graetz, Christian; Harks, Inga; Jockel-Schneider, Yvonne; Weinspach, Knut; Meyle, Joerg; Eickholz, Peter; Linden, Gerry J; Cine, Naci; Nohutcu, Rahime; Weiss, Ervin; Houri-Haddad, Yael; Iraqi, Fuad; Folwaczny, Mathias; Noack, Barbara; Strauch, Konstantin; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Wijmenga, Cisca; Yilmaz, Engin; Lieb, Wolfgang; Rosenstiel, Philip; Doerfer, Christof; Bruckmann, Corinna; Erdmann, Jeannette; König, Inke; Jepsen, Søren; Loos, Bruno G; Schreiber, Stefan

    2015-02-01

    Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms. In-depth genotyping of 46 published CAD risk loci of genome-wide significance in the worldwide largest case-control sample of the severe early-onset phenotype aggressive periodontitis (AgP) with the Illumina Immunochip (600 German AgP cases, 1448 controls) and the Affymetrix 500K array set (283 German AgP cases and 972 controls) highlighted ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.9×10(-5); odds ratio, 1.27; 95% confidence interval, 1.3-1.4 [adjusted for smoking and sex]; 818 cases; 5309 controls). Subsequent combined analyses of several genome-wide data sets of CAD and AgP suggested TGFBRAP1 to be associated with AgP (rs2679895: P=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1-1.5]; 703 cases; 2.143 controls) and CAD (P=0.0003; odds ratio, 0.84 [95% confidence interval, 0.8-0.9]; n=4117 cases; 5824 controls). The study further provides evidence that in addition to PLG, the currently known shared susceptibility loci of CAD and periodontitis, ANRIL and CAMTA1/VAMP3, are subjected to transforming growth factor-β regulation. PLG is the third replicated shared genetic risk factor of atherosclerosis and periodontitis. All known shared risk genes of CAD and periodontitis are members of transforming growth factor-β signaling. © 2014 American Heart Association, Inc.

  7. Risk variants of the α-synuclein locus and REM sleep behavior disorder in Parkinson's disease: a genetic association study.

    Science.gov (United States)

    Bjørnarå, Kari Anne; Pihlstrøm, Lasse; Dietrichs, Espen; Toft, Mathias

    2018-02-21

    Parkinson's disease is a heterogeneous disorder where genetic factors may underlie clinical variability. Rapid eye movement sleep behavior disorder (RBD) is a parasomnia strongly linked to synucleinopathies, including Parkinson's disease. We hypothesized that SNCA variants conferring risk of Parkinson's disease would also predispose to an RBD phenotype. We assessed possible RBD (pRBD) status using the RBD screening questionnaire and investigated known susceptibility variants for Parkinson's disease located in the α-synuclein (SNCA) and tau (MAPT) gene loci in 325 Parkinson's disease patients. Associations between genetic risk variants and RBD were investigated by logistic regression, and an independent dataset of 382 patients from the Parkinson's Progression Marker Initiative (PPMI) study was used for replication. pRBD was associated with rs3756063 located in the 5' region of SNCA (two-sided p = 0.018, odds ratio 1.44). We replicated this finding in the PPMI dataset (one-sided p = 0.036, odds ratio 1.35) and meta-analyzed the results (two-sided p = 0.0032, odds ratio 1.40). The Parkinson's disease risk variant in the 3' region of SNCA and the MAPT variant showed no association with pRBD. Our findings provide proof of principle that a largely stable, dichotomous clinical feature of Parkinson's disease can be linked to a specific genetic susceptibility profile. Indirectly, it also supports the hypothesis of RBD as relevant marker for a distinct subtype of the disorder.

  8. The sense and nonsense of direct-to-consumer genetic testing for cardiovascular disease

    OpenAIRE

    Janssens, A. C. J. W.; Wilde, A. A. M.; van Langen, I. M.

    2011-01-01

    textabstractExpectations are high that increasing knowledge of the genetic basis of cardiovascular disease will eventually lead to personalised medicine-to preventive and therapeutic interventions that are targeted to at-risk individuals on the basis of their genetic profiles. Most cardiovascular diseases are caused by a complex interplay of many genetic variants interacting with many non-genetic risk factors such as diet, exercise, smoking and alcohol consumption. Since several years, geneti...

  9. Fractal and Transgenerational Genetic Effects on Phenotypic Variation and Disease Risk

    Science.gov (United States)

    Nadeau, Joe

    To understand human biology and to manage heritable diseases, a complete picture of the genetic basis for phenotypic variation and disease risk is needed. Unexpectedly however, most of these genetic variants, even for highly heritable traits, continue to elude discovery for poorly understood reasons. The genetics community is actively exploring the usual explanations for missing heritability. But given the extraordinary work that has already been done and the exceptional magnitude of the problem, it seems likely that unconventional genetic properties are involved.

  10. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  11. Genetic Testing Protocol Reduces Costs and Increases Rate of Genetic Diagnosis in Infants with Congenital Heart Disease.

    Science.gov (United States)

    Geddes, Gabrielle C; Basel, Donald; Frommelt, Peter; Kinney, Aaron; Earing, Michael

    2017-10-01

    Genetic testing is routinely performed on infants with critical congenital heart disease (CHD). This project reviewed the effect of implementing a genetic testing protocol in this population. Charts of infants with critical CHD were reviewed for genetic testing and results across two time periods: the time before implementation of a genetic testing protocol (pre-protocol) and the time after implementation (post-protocol). The use of karyotype, 22q11.2 Deletion testing, and chromosomal microarray were compared across these two time periods. Records of 891 infants were reviewed. 562 (63%) had at least one of the target genetic tests completed. During the pre-protocol time period, 66% of patients who had genetic testing underwent multiple tests versus 24% during the post-protocol time period (p testing increased from 60% in the pre-protocol time period to 77% in the post-protocol time period (p tests and more likely to have a diagnosis of genetic disease. In addition there was a significant reduction in cost per diagnosis during the post-protocol time period. Genetic testing protocols for infants with critical CHD promoted more efficient use of genetic testing and increased the rate of diagnosis of genetic conditions in this population.

  12. Gene Editing and Genetic Lung Disease. Basic Research Meets Therapeutic Application.

    Science.gov (United States)

    Alapati, Deepthi; Morrisey, Edward E

    2017-03-01

    Although our understanding of the genetics and pathology of congenital lung diseases such as surfactant protein deficiency, cystic fibrosis, and alpha-1 antitrypsin deficiency is extensive, treatment options are lacking. Because the lung is a barrier organ in direct communication with the external environment, targeted delivery of gene corrective technologies to the respiratory system via intratracheal or intranasal routes is an attractive option for therapy. CRISPR/Cas9 gene-editing technology is a promising approach to repairing or inactivating disease-causing mutations. Recent reports have provided proof of concept by using CRISPR/Cas9 to successfully repair or inactivate mutations in animal models of monogenic human diseases. Potential pulmonary applications of CRISPR/Cas9 gene editing include gene correction of monogenic diseases in pre- or postnatal lungs and ex vivo gene editing of patient-specific airway stem cells followed by autologous cell transplant. Strategies to enhance gene-editing efficiency and eliminate off-target effects by targeting pulmonary stem/progenitor cells and the assessment of short-term and long-term effects of gene editing are important considerations as the field advances. If methods continue to advance rapidly, CRISPR/Cas9-mediated gene editing may provide a novel opportunity to correct monogenic diseases of the respiratory system.

  13. Genetic association study of synphilin-1 in idiopathic Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Farrer Matthew J

    2008-03-01

    Full Text Available Abstract Background Post-mortem Lewy body and Lewy neuritic inclusions are a defining feature of Parkinson's disease (PD and dementia with Lewy bodies (DLB. With the discovery of missense and multiplication mutations in the alpha-synuclein gene (SNCA in familial parkinsonism, Lewy inclusions were found to stain intensely with antibodies raised against the protein. Yeast-two-hybrid studies identified synphilin-1 as an interacting partner of alpha-synuclein, and both proteins show co-immunolocalization in a subset of Lewy body inclusions. In the present study, we have investigated whether common variability in synphilin-1, including coding substitutions are genetically associated with disease pathogenesis. Methods We screened the synphilin-1 gene for 11 single nucleotide polymorphisms (SNPs in 300 affected subjects with idiopathic Parkinson's disease and 412 healthy controls. Six of these were rare variants including five previously identified amino acid substitutions that were chosen in a direct approach for association of rare disease causing mutations. An additional five highly heterozygous SNPs were chosen for an indirect association approach including haplotype analysis, based on the assumption that any disease causing mutations might be in linkage disequilibrium with the SNPs selected. We also genotyped a microsatellite marker (D5S2950 within intron 6 of the gene and five additional microsatellites clustered downstream of the 5p23.1-23.3 synphilin-1 locus. Genome-wide linkage analysis, in a number of independent studies, has previously highlighted suggestive linkage to PD in this region of chromosome 5. Results Screening of previously known amino acid substitutions in the synphilin-1 gene, identified the C1861>T (R621C substitution in four patients (chromosomes n = 600 and 10 control subjects (chromosomes n = 824, whereas the G2125>C (E706Q substitution was detected in one patient and four control subject, suggesting both these substitutions

  14. Estimating the contribution of genetic variants to difference in incidence of disease between population groups.

    Science.gov (United States)

    Moonesinghe, Ramal; Ioannidis, John P A; Flanders, W Dana; Yang, Quanhe; Truman, Benedict I; Khoury, Muin J

    2012-08-01

    Genome-wide association studies have identified multiple genetic susceptibility variants to several complex human diseases. However, risk-genotype frequency at loci showing robust associations might differ substantially among different populations. In this paper, we present methods to assess the contribution of genetic variants to the difference in the incidence of disease between different population groups for different scenarios. We derive expressions for the contribution of a single genetic variant, multiple genetic variants, and the contribution of the joint effect of a genetic variant and an environmental factor to the difference in the incidence of disease. The contribution of genetic variants to the difference in incidence increases with increasing difference in risk-genotype frequency, but declines with increasing difference in incidence between the two populations. The contribution of genetic variants also increases with increasing relative risk and the contribution of joint effect of genetic and environmental factors increases with increasing relative risk of the gene-environmental interaction. The contribution of genetic variants to the difference in incidence between two populations can be expressed as a function of the population attributable risks of the genetic variants in the two populations. The contribution of a group of genetic variants to the disparity in incidence of disease could change considerably by adding one more genetic variant to the group. Any estimate of genetic contribution to the disparity in incidence of disease between two populations at this stage seems to be an elusive goal.

  15. Identification of susceptibility genes and genetic modifiers of human diseases

    Science.gov (United States)

    Abel, Kenneth; Kammerer, Stefan; Hoyal, Carolyn; Reneland, Rikard; Marnellos, George; Nelson, Matthew R.; Braun, Andreas

    2005-03-01

    The completion of the human genome sequence enables the discovery of genes involved in common human disorders. The successful identification of these genes is dependent on the availability of informative sample sets, validated marker panels, a high-throughput scoring technology, and a strategy for combining these resources. We have developed a universal platform technology based on mass spectrometry (MassARRAY) for analyzing nucleic acids with high precision and accuracy. To fuel this technology, we generated more than 100,000 validated assays for single nucleotide polymorphisms (SNPs) covering virtually all known and predicted human genes. We also established a large DNA sample bank comprised of more than 50,000 consented healthy and diseased individuals. This combination of reagents and technology allows the execution of large-scale genome-wide association studies. Taking advantage of MassARRAY"s capability for quantitative analysis of nucleic acids, allele frequencies are estimated in sample pools containing large numbers of individual DNAs. To compare pools as a first-pass "filtering" step is a tremendous advantage in throughput and cost over individual genotyping. We employed this approach in numerous genome-wide, hypothesis-free searches to identify genes associated with common complex diseases, such as breast cancer, osteoporosis, and osteoarthritis, and genes involved in quantitative traits like high density lipoproteins cholesterol (HDL-c) levels and central fat. Access to additional well-characterized patient samples through collaborations allows us to conduct replication studies that validate true disease genes. These discoveries will expand our understanding of genetic disease predisposition, and our ability for early diagnosis and determination of specific disease subtype or progression stage.

  16. The importance of genetics in the diagnosis of animal diseases - A ...

    African Journals Online (AJOL)

    Genetic diseases have always been present in the animal population but their significance has increased in recent decades. The wealth of knowledge on genomic information, systems biology and mechanisms of diseases provide great opportunities to elucidate the genetic bases of diseases. The use of recombinant DNA ...

  17. Reproduction in farm animals in an era of rapid genetic change: will genetic change outpace our knowledge of physiology?

    Science.gov (United States)

    Foxcroft, G R

    2012-08-01

    Compared with other domestic species, genetic nucleus selection has gradually increased both prolificacy and productivity of the breeding sow and the post-natal growth performance of commercial progeny. However, increasing variation in litter birth weight and foetal development may be indirect consequences of interactions among multiple genes controlling prolificacy and prenatal development. Phenotypic plasticity in the litter phenotype also results from effects of sow metabolic state on the developing embryo. New genomic tools may provide the opportunity to better balance the selection of genes controlling the component traits affecting the size and quality of litters born, particularly in multiparous sows. © 2012 Blackwell Verlag GmbH.

  18. Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hai-yang JIANG

    2017-10-01

    Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

  19. Surface plasmon resonance based biosensor: A new platform for rapid diagnosis of livestock diseases

    Directory of Open Access Journals (Sweden)

    Pravas Ranjan Sahoo

    2016-12-01

    Full Text Available Surface plasmon resonance (SPR based biosensors are the most advanced and developed optical label-free biosensor technique used for powerful detection with vast applications in environmental protection, biotechnology, medical diagnostics, drug screening, food safety, and security as well in livestock sector. The livestock sector which contributes the largest economy of India, harbors many bacterial, viral, and fungal diseases impacting a great loss to the production and productive potential which is a major concern in both small and large ruminants. Hence, an accurate, sensitive, and rapid diagnosis is required for prevention of these above-mentioned diseases. SPR based biosensor assay may fulfill the above characteristics which lead to a greater platform for rapid diagnosis of different livestock diseases. Hence, this review may give a detail idea about the principle, recent development of SPR based biosensor techniques and its application in livestock sector.

  20. Molecular and Chemical Genetic Approaches to Developmental Origins of Aging and Disease in Zebrafish

    Science.gov (United States)

    Sasaki, Tomoyuki; Kishi, Shuji

    2013-01-01

    The incidence of diseases increases rapidly with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but mostly inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states in response to different environmental or genetic perturbations. On the one hand, we hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds of adaptive plasticity by chemical genetic approaches, we have been investigating whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during embryogenesis (“embryonic senescence”), subsequently showing shortened lifespan in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes and small molecular compounds that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins

  1. Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire.

    Science.gov (United States)

    Bolitho, Samuel J; Naismith, Sharon L; Terpening, Zoe; Grunstein, Ron R; Melehan, Kerri; Yee, Brendon J; Coeytaux, Alessandra; Gilat, Moran; Lewis, Simon J G

    2014-05-01

    Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinson's disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty-six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self-report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future. © 2014 International Parkinson and Movement Disorder Society.

  2. Rapid genotyping by low-coverage resequencing to construct genetic linkage maps of fungi: a case study in Lentinula edodes.

    Science.gov (United States)

    Au, Chun Hang; Cheung, Man Kit; Wong, Man Chun; Chu, Astley Kin Kan; Law, Patrick Tik Wan; Kwan, Hoi Shan

    2013-08-02

    Genetic linkage maps are important tools in breeding programmes and quantitative trait analyses. Traditional molecular markers used for genotyping are limited in throughput and efficiency. The advent of next-generation sequencing technologies has facilitated progeny genotyping and genetic linkage map construction in the major grains. However, the applicability of the approach remains untested in the fungal system. Shiitake mushroom, Lentinula edodes, is a basidiomycetous fungus that represents one of the most popular cultivated edible mushrooms. Here, we developed a rapid genotyping method based on low-coverage (~0.5 to 1.5-fold) whole-genome resequencing. We used the approach to genotype 20 single-spore isolates derived from L. edodes strain L54 and constructed the first high-density sequence-based genetic linkage map of L. edodes. The accuracy of the proposed genotyping method was verified experimentally with results from mating compatibility tests and PCR-single-strand conformation polymorphism on a few known genes. The linkage map spanned a total genetic distance of 637.1 cM and contained 13 linkage groups. Two hundred sequence-based markers were placed on the map, with an average marker spacing of 3.4 cM. The accuracy of the map was confirmed by comparing with previous maps the locations of known genes such as matA and matB. We used the shiitake mushroom as an example to provide a proof-of-principle that low-coverage resequencing could allow rapid genotyping of basidiospore-derived progenies, which could in turn facilitate the construction of high-density genetic linkage maps of basidiomycetous fungi for quantitative trait analyses and improvement of genome assembly.

  3. Genetically-Predicted Adult Height and Alzheimer's Disease.

    Science.gov (United States)

    Larsson, Susanna C; Traylor, Matthew; Burgess, Stephen; Markus, Hugh S

    2017-01-01

    Observational studies have linked increased adult height with better cognitive performance and reduced risk of Alzheimer's disease (AD). It is unclear whether the associations are due to shared biological processes that influence height and AD or due to confounding by early life exposures or environmental factors. To use a genetic approach to investigate the association between adult height and AD. We selected 682 single nucleotide polymorphisms (SNPs) associated with height at genome-wide significance (p height and AD was calculated using the inverse-variance weighted method. The odds ratio of AD was 0.91 (95% confidence interval, 0.86-0.95; p = 9.8×10-5) per one standard deviation increase (about 6.5 cm) in genetically predicted height based on 682 SNPs, which were clustered in 419 loci. In an analysis restricted to one SNP from each height-associated locus (n = 419 SNPs), the corresponding OR was 0.92 (95% confidence interval, 0.86-0.97; p = 4.8×10-3). This finding suggests that biological processes that influence adult height may have a role in the etiology of AD.

  4. [Genetic factors associated with dementia in Parkinson's disease (PD)].

    Science.gov (United States)

    Romo-Gutiérrez, Diego; Yescas, Petra; López-López, Marisol; Boll, Marie-Catherine

    2015-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms. Dementia is a frequent complication of idiopathic Parkinsonism or PD, usually occurring later in the protracted course of the illness. Some risk factors to develop dementia in PD are aging, severe Parkinson´s symptoms, rigid-akinetic form, hallucinations, and mild cognitive impairment documented at the first examinations. It is not yet clear if some genetic factors are either risk or protector for progression to dementia. In a review of the literature, we found that mutations in the alpha-synuclein gene are the most responsible for developing dementia, either from PARK1 or 4 mutations. GBA (glucocerebrosidase) is another accountable factor. However, the vast majority of patients suffer from non-Mendelian or complex forms of PD, which are likely caused by the combined effects of genetic and environmental factors. There is not until now a clear relation between some polymorphisms in candidate genes and cognitive deterioration, as many studies have not clearly identified this phenotype.

  5. Non-genetic therapeutic approaches to Canavan disease.

    Science.gov (United States)

    Roscoe, Rebecca B; Elliott, Christina; Zarros, Apostolos; Baillie, George S

    2016-07-15

    Canavan disease (CD) is a rare leukodystrophy characterized by diffuse spongiform white matter degeneration, dysmyelination and intramyelinic oedema with consequent impairment of psychomotor development and early death. The molecular cause of CD has been identified as being mutations of the gene encoding the enzyme aspartoacylase (ASPA) leading to its functional deficiency. The physiological role of ASPA is to hydrolyse N-acetyl-l-aspartic acid (NAA), producing l-aspartic acid and acetate; as a result, its deficiency leads to abnormally high central nervous system NAA levels. The aim of this article is to review what is currently known regarding the aetiopathogenesis and treatment of CD, with emphasis on the non-genetic therapeutic strategies, both at an experimental and a clinical level, by highlighting: (a) major related hypotheses, (b) the results of the available experimental simulatory approaches, as well as (c) the relevance of the so far examined markers of CD neuropathology. The potential and the limitations of the current non-genetic neuroprotective approaches to the treatment of CD are particularly discussed in the current article, in a context that could be used to direct future experimental and (eventually) clinical work in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. [Blau syndrome--a chronic granulomatous, genetic disease].

    Science.gov (United States)

    Milman, Nils; Byg, Keld-Erik

    2006-10-16

    Blau syndrome is a rare hereditary granulomatous disease presenting in patients of young age with exanthema, granulomatous arthritis and uveitis. Genetic analysis has shown an autosomal dominant inheritance and a number of specific mutations on chromosome 16q in codon 334, of which the most predominant are R334W and R334Q. Blau syndrome exists in Caucasian, Asian and Afro-American families, and de novo mutations have been reported. The estimated minimum incidence in Denmark is 0.05 per 100,000 person-years. Blau syndrome has pathological, clinical and therapeutic features in common with sarcoidosis but rarely involves the lungs or other parenchymatous organs. Discrimination between Blau syndrome and early-onset sarcoidosis should rely on chromosome analysis.

  7. Genetic testing for early-onset Alzheimer disease.

    Science.gov (United States)

    Tsao, Jack W

    2013-04-01

    The availability of testing for identified risk genes for Alzheimer disease (AD) in patients with clinically probable AD or their at-risk family members raises important questions for the neurologist. Because the potential benefits and risks of testing vary for each patient, physicians need to evaluate whether it is appropriate on a case-by-case basis. This article outlines the testing decision process and serves as a guide to assist clinicians with associated counseling and result disclosure. Because genetic testing is relatively new and preventive and therapeutic options for AD remain limited, it is important to remain sensitive to and understand the specific challenges associated with obtaining these tests in the routine clinical setting.

  8. Hereditary fructose intolerance and celiac disease: a novel genetic association.

    Science.gov (United States)

    Ciacci, Carolina; Gennarelli, Daniela; Esposito, Gabriella; Tortora, Raffaella; Salvatore, Francesco; Sacchetti, Lucia

    2006-05-01

    Celiac disease (CD) has been associated with several genetic disorders, but has not been associated with hereditary fructose intolerance (HFI). We identified CD in 4 female patients affected by HFI from among 38 Italian HFI patients. Three of these patients were children in whom the CD-associated signs were hypertransaminasemia, failure to thrive, low weight, and short stature, whereas the adult patient had protracted diarrhea notwithstanding a fructose-free diet. The incidence of CD in our group of HFI patients was higher (>10%) than in the general population (1%-3%) (P<.02). The possibility of an association between these 2 gastrointestinal disorders is important, particularly in the management of HFI patients with persisting symptoms.

  9. A rapid chemical-genetic screen utilizing impaired movement phenotypes in C. elegans: Input into genetics of neurodevelopmental disorders.

    Science.gov (United States)

    Schmeisser, Kathrin; Fardghassemi, Yasmin; Parker, J Alex

    2017-07-01

    Autism spectrum disorder (ASD) is the most common neurodevelopmental disorder with a constantly increasing prevalence. Model organisms may be tools to identify underlying cellular and molecular mechanisms, as well as aid the discovery and development of novel therapeutic approaches. A simple animal such as the nematode Caenorhabditis elegans may provide insights into the extreme complexity of ASD genetics. Despite its potential, using C. elegans in ASD research is a controversial approach and has not yet been used extensively in this context. In this study, we present a screening approach of potential C. elegans mutants as potential ASD models. We screened these mutants for motor-deficiency phenotypes, which can be exploited to study underlying mechanisms of the disorder. Selected motor-deficient mutants were then used in a comprehensive drug screen of over 3900 compounds, including many FDA-approved and natural molecules, that were analyzed for their ability to suppress motility defects caused by ASD-associated gene orthologues. This genetic-chemical approach, i.e. establishing C. elegans models for ASD and screening of a well-characterized compound library, might be a promising first step to understand the mechanisms of how gene variations cause neuronal dysfunction, leading to ASD and other neurological disorders. Positively acting compounds could also be promising candidates for preclinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Genetic susceptibility for Alzheimer disease neuritic plaque pathology.

    Science.gov (United States)

    Shulman, Joshua M; Chen, Kewei; Keenan, Brendan T; Chibnik, Lori B; Fleisher, Adam; Thiyyagura, Pradeep; Roontiva, Auttawut; McCabe, Cristin; Patsopoulos, Nikolaos A; Corneveaux, Jason J; Yu, Lei; Huentelman, Matthew J; Evans, Denis A; Schneider, Julie A; Reiman, Eric M; De Jager, Philip L; Bennett, David A

    2013-09-01

    While numerous genetic susceptibility loci have been identified for clinical Alzheimer disease (AD), it is important to establish whether these variants are risk factors for the underlying disease pathology, including neuritic plaques. To investigate whether AD susceptibility loci from genome-wide association studies affect neuritic plaque pathology and to additionally identify novel risk loci for this trait. Candidate analysis of single-nucleotide polymorphisms and genome-wide association study in a joint clinicopathologic cohort, including 725 deceased subjects from the Religious Orders Study and the Rush Memory and Aging Project (2 prospective, community-based studies), followed by targeted validation in an independent neuroimaging cohort, including 114 subjects from multiple clinical and research centers. A quantitative measure of neuritic plaque pathologic burden, based on assessments of silver-stained tissue averaged from multiple brain regions. Validation based on β-amyloid load by immunocytochemistry, and replication with fibrillar β-amyloid positron emission tomographic imaging with Pittsburgh Compound B or florbetapir. Besides the previously reported APOE and CR1 loci, we found that the ABCA7 (rs3764650; P = .02) and CD2AP (rs9349407; P = .03) AD susceptibility loci are associated with neuritic plaque burden. In addition, among the top results of our genome-wide association study, we discovered a novel variant near the amyloid precursor protein gene (APP, rs2829887) that is associated with neuritic plaques (P = 3.3 × 10-6). This polymorphism was associated with postmortem β-amyloid load as well as fibrillar β-amyloid in 2 independent cohorts of adults with normal cognition. These findings enhance understanding of AD risk factors by relating validated susceptibility alleles to increased neuritic plaque pathology and implicate common genetic variation at the APP locus in the earliest, presymptomatic stages of AD.

  11. Genetic characterization of Aleutian mink disease viruses isolated in China.

    Science.gov (United States)

    Li, Yanwu; Huang, Juan; Jia, Yun; Du, Yijun; Jiang, Ping; Zhang, Rui

    2012-08-01

    Aleutian mink disease virus (AMDV) is a parvovirus that causes an immune complex mediated disease in minks. To understand the genetic characterization of AMDV in China, the genomic sequences of three isolates, ADV-LN1, ADV-LN2, and ADV-LN3, from different farms in the Northern China were analyzed. The results showed that the lengths of genomic sequences of three isolates were 4,543, 4,566, and 4,566 bp, respectively. They shared only 95.5-96.3 % nucleotide identity with each other. The nucleotide and amino acid homology of genome sequence between the Chinese isolates and European or American strains (ADV-G, ADV-Utah1, and ADV-SL3) were 92.4-95.0 % and 92.1-93.8 %, respectively. The amino acid substitutions randomly distributed in the genome, especially NS gene. ADV-LN1 strain had a 9-amino-acid deletion at amino acid positions 70 and 72-79 in the VP1 gene, comparing with ADV-G strain; ADV-LN2 and ADV-LN3 strains had 1-amino-acid deletion at amino acid positions 70 in the VP1. Some potential glycosylation site mutations in VP and NS genes were also observed. Phylogenetic analysis results showed that the three strains belonged to two different branches based on the complete coding sequence of VP2 gene. However, they all were in the same group together with the strains from United States based on the NS1 sequence. It indicated that Chinese AMDV isolates had genetic diversity. The origin of the ancestors of the Chinese AMDV strains might be associated with the American strains.

  12. Genetic overlap between Alzheimer’s disease and Parkinson’s disease at the MAPT locus

    Science.gov (United States)

    Desikan, Rahul S.; Schork, Andrew J.; Wang, Yunpeng; Witoelar, Aree; Sharma, Manu; McEvoy, Linda K.; Holland, Dominic; Brewer, James B.; Chen, Chi-Hua; Thompson, Wesley K.; Harold, Denise; Williams, Julie; Owen, Michael J.; O’Donovan, Michael C.; Pericak-Vance, Margaret A.; Mayeux, Richard; Haines, Jonathan L.; Farrer, Lindsay A.; Schellenberg, Gerard D.; Heutink, Peter; Singleton, Andrew B.; Brice, Alexis; Wood, Nicolas W.; Hardy, John; Martinez, Maria; Choi, Seung Hoi; DeStefano, Anita; Ikram, M. Arfan; Bis, Joshua C.; Smith, Albert; Fitzpatrick, Annette L.; Launer, Lenore; van Duijn, Cornelia; Seshadri, Sudha; Ulstein, Ingun Dina; Aarsland, Dag; Fladby, Tormod; Djurovic, Srdjan; Hyman, Bradley T.; Snaedal, Jon; Stefansson, Hreinn; Stefansson, Kari; Gasser, Thomas; Andreassen, Ole A.; Dale, Anders M.

    2015-01-01

    We investigated genetic overlap between Alzheimer’s disease (AD) and Parkinson’s disease (PD). Using summary statistics (p-values) from large recent genomewide association studies (GWAS) (total n = 89,904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis p-value across 5 independent AD cohorts = 1.65 × 10−7). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD and extending prior work, we show that the MAPT region increases risk of Alzheimer’s neurodegeneration. PMID:25687773

  13. B-Cell Depletion Salvage Therapy in Rapidly Progressive Dermatomyositis Related Interstitial Lung Disease.

    Science.gov (United States)

    Eissa, Khaled; Palomino, Jaime

    2016-01-01

    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with idiopathic inflammatory myopathies (IIM). Glucocorticoids are the initial standard treatment. However, many patients fail to respond and continue to progress despite treatment with high dose glucocorticoids. The efficacy of rituximab has been suggested in case reports and case series of refractory antisynthetase (AS) syndrome, but data on patients without auto-antibodies or with rapidly progressive ILD are scarce. We report a case of rapidly progressive dermatomyositis (DM) associated ILD treated successfully with B-cell depletion therapy.

  14. Reconstructing transmission trees for communicable diseases using densely sampled genetic data

    Science.gov (United States)

    Worby, Colin J.; O'Neill, Philip D.; Kypraios, Theodore; Robotham, Julie V.; De Angelis, Daniela; Cartwright, Edward J. P.; Peacock, Sharon J.; Cooper, Ben S.

    2016-01-01

    Whole genome sequencing of pathogens from multiple hosts in an epidemic offers the potential to investigate who infected whom with unparalleled resolution, potentially yielding important insights into disease dynamics and the impact of control measures. We considered disease outbreaks in a setting with dense genomic sampling, and formulated stochastic epidemic models to investigate person-to-person transmission, based on observed genomic and epidemiological data. We constructed models in which the genetic distance between sampled genotypes depends on the epidemiological relationship between the hosts. A data augmented Markov chain Monte Carlo algorithm was used to sample over the transmission trees, providing a posterior probability for any given transmission route. We investigated the predictive performance of our methodology using simulated data, demonstrating high sensitivity and specificity, particularly for rapidly mutating pathogens with low transmissibility. We then analyzed data collected during an outbreak of methicillin-resistant Staphylococcus aureus in a hospital, identifying probable transmission routes and estimating epidemiological parameters. Our approach overcomes limitations of previous methods, providing a framework with the flexibility to allow for unobserved infection times, multiple independent introductions of the pathogen, and within-host genetic diversity, as well as allowing forward simulation. PMID:27042253

  15. Apomorphine: a rapid rescue agent for the management of motor fluctuations in advanced Parkinson disease.

    Science.gov (United States)

    Kolls, Brad J; Stacy, Mark

    2006-01-01

    Parkinson disease is one of the most common neurodegenerative diseases in the United States, and the number of late stage patients is rising. In advance-stage disease, fluctuations in motor function, variability in response to dopaminergic therapy, and dyskinesias related to increasing doses of dopamine agonists and levodopa, present a variety of challenges to a managing physician. Traditional methods of treatment have concentrated on therapies to anticipate or prevent states of poor motor function. With the approval of apomorphine as a rapid-acting, subcutaneous injectable anti-Parkinson disease therapy, these off periods may now be treated with apomorphine as a "rescue" medication when they occur. This article reviews the pharmacology of apomorphine, the clinical data that support its use and suggest dosing and methods for initiating therapy in this challenging population of patients with Parkinson disease.

  16. Genetic heterogeneity of polycystic kidney disease in Bulgaria

    Energy Technology Data Exchange (ETDEWEB)

    Bogdanova, N. [Faculty of Medicine, Sofia (Bulgaria)]|[Westfaelische Wihelms-Universitaet, Muenster (Germany); Dragova, D.; Kalaydiieva, L. [Faculty of Medicine, Sofia (Bulgaria)] [and others

    1994-09-01

    Autosomal dominant polycystic kidney disease (PKD) is a common genetic disorder whose frequency in Bulgaria has been estimated at 1 in 950. One gene (PKD1) causing this disease has been mapped to the short arm of chromosome 16 in 1985. Linkage analysis showed that in a considerable proportion of PKD families (approximately 14% in Europe) the disease is not linked to this locus, suggesting the existance of mutations in additional genes. In 1993 a PKD2-gene has been mapped to the long arm of chromosome 4. Here we report data of the first extensive investigation of PKD in Bulgaria. Initially 35 families with 341 individuals (178 affected, 89 unaffected family members, 74 spouses) were included in the study. Clinical diagnosis, mainly based on ultrasonographic examination of the kidneys, has been performed for all individuals. Linkage analysis was performed on 22 large pedigrees with microsatellites 16SC2.5 (D16S291) and SM7 (D16S283), which are closely linked to the PKD1 locus, as well as microsatellites D4S392, D4S400, D4S231 (proximal to the PDK2 locus) and D4S423, D4S414, D4S411 (distal to PKD2 locus). The study showed that the disease is caused in 14 families by mutations within the PKD1 gene and was clearly linked to the PDK2 locus in 5 families. In 3 families no clear conclusions about the linkage could be reached and analysis of additional markers from this region is in progress. The investigation has revealed the highest proportion of PKD2 families reported so far in Europe (23%). In addition, comparison of the severity of the clinical course of PKD1 and PKD2 families failed to confirm statistically significant differences which have been reported.

  17. Genetic analysis of emerging risk factors in coronary artery disease.

    Science.gov (United States)

    van Iperen, Erik P A; Sivapalaratnam, Suthesh; Holmes, Michael V; Hovingh, G Kees; Zwinderman, Aeilko H; Asselbergs, Folkert W

    2016-11-01

    Type 2 diabetes (T2D), low-density lipoprotein-cholesterol (LDL-c), body mass index (BMI), blood pressure and smoking are established risk factors that play a causal role in coronary artery disease (CAD). Numerous common genetic variants associating with these and other risk factors have been identified, but their association with CAD has not been comprehensively examined in a single study. Our goal was to comprehensively evaluate the associations of established and emerging risk factors with CAD using genetic variants identified from Genome-wide Association Studies (GWAS). We tested the effect of 60 traditional and putative risk factors with CAD, using summary statistics obtained in GWAS. We approximated the regression of a response variable onto an additive multi-SNP genetic risk score in the Coronary Artery DIsease Genomewide Replication And Meta-analysis (CARDIoGRAM) consortium dataset weighted by the effect of the SNP on the risk factors. The strongest association with risk of CAD was for LDL-c SNPs (p = 3.96E-34). For non-established CAD risk factors, we found significant CAD associations for coronary artery calcification (CAC), Lp(a), LP-PLA2 activity, plaque, vWF and FVIII. In an attempt to identify independent associations between risk factors and CAD, only SNPs with an effect on the target trait were included. This identified CAD associations for Lp(a)(p = 1.77E-21), LDL-c (p = 4.16E-06), triglycerides (TG) (p = 1.94E-05), height (p = 2.06E-05), CAC (p = 3.13E-23) and carotid plaque (p = 2.08E-05). We identified SNPs associated with the emerging risk factors Lp(a), TG, plaque, height and CAC to be independently associated with risk of CAD. This provides further support for-ongoing clinical trials of Lp(a) and TG, and suggests that CAC and plaque could be used as surrogate markers for CAD in clinical trials. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Etiology and pathophysiology of frontotemporal dementia, Parkinson disease and Alzheimer disease: lessons from genetic studies.

    Science.gov (United States)

    Wider, Christian; Wszolek, Zbigniew K

    2008-01-01

    Genetic studies have led to major discoveries in the pathogenesis of various neurodegenerative diseases. Ubiquitin-positive familial frontotemporal dementia was recently found to be caused by mutations in the progranulin gene (PGRN), and the major constituent of the inclusions, TDP-43, was subsequently identified. The tau gene (MAPT) causes frontotemporal dementia with parkinsonism linked to chromosome 17. In Parkinson disease, LRRK2 mutations have emerged as a major cause of both familial and sporadic forms, adding to the previously known genes SNCA,PRKN,DJ1 and PINK1. Several genes have been implicated in Alzheimer disease, including the APP gene and the PSEN genes. Recently, variants in the sortilin-related receptor 1 gene, SORL1, were associated with Alzheimer disease. 2008 S. Karger AG, Basel

  19. Etiology and Pathophysiology of Frontotemporal Dementia, Parkinson Disease and Alzheimer Disease: Lessons from Genetic Studies

    Science.gov (United States)

    Wider, Christian; Wszolek, Zbigniew K.

    2008-01-01

    Genetic studies have led to major discoveries in the pathogenesis of various neurodegenerative diseases. Ubiquitin-positive familial frontotemporal dementia was recently found to be caused by mutations in the progranulin gene (PGRN), and the major constituent of the inclusions, TDP-43, was subsequently identified. The tau gene (MAPT) causes frontotemporal dementia with parkinsonism linked to chromosome 17. In Parkinson disease, LRRK2 mutations have emerged as a major cause of both familial and sporadic forms, adding to the previously known genes SNCA, PRKN, DJ1 and PINK1. Several genes have been implicated in Alzheimer disease, including the APP gene and the PSEN genes. Recently, variants in the sortilin-related receptor 1 gene, SORL1, were associated with Alzheimer disease. PMID:18322368

  20. Convergent genetic and expression data implicate immunity in Alzheimer's disease

    Science.gov (United States)

    Jones, Lesley; Lambert, Jean-Charles; Wang, Li-San; Choi, Seung-Hoan; Harold, Denise; Vedernikov, Alexey; Escott-Price, Valentina; Stone, Timothy; Richards, Alexander; Bellenguez, Céline; Ibrahim-Verbaas, Carla A; Naj, Adam C; Sims, Rebecca; Gerrish, Amy; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letteneur, Luc; Kornhuber, Johanes; Tárraga, Lluís; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Emilsson, Valur; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Kehoe, Pat; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleὀ, Alberti; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick; Hardy, John; Naranjo, Maria Candida Deniz; Razquin, Cristina; Bosco, Paola; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Moebus, Susanne; Mecocci, Patrizia; del Zompo, Maria; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Jessen, Frank; Dichgans, Martin; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alavarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O'Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee FAG; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John SK; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Pastor, Pau; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Haines, Jonathan L; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broekhoven, Christine; Ramirez, Alfredo; Schellenberg, Gerard D; Seshadri, Sudha; Amouyel, Philippe; Holmans, Peter A

    2015-01-01

    Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics. PMID:25533204

  1. Behcet's disease: demographic and genetic aspects (a literature review

    Directory of Open Access Journals (Sweden)

    Fatima Ismailovna Izmailova

    2014-03-01

    Full Text Available A review of literature focused on Behcet's disease (BD is presented. BD is systemic vasculitis of unknown etiology affecting multiple organs. BD is endemic in the countries along the Eastern Mediterranean coast and the areas of Central and East Asia. We report the data on BD prevalence in different regions and the effect of population migration on BD incidence rate. Patients were found to be younger at the onset of the disease in Arab countries, Turkey, and Israel (19.9; 25.6; and 26 years, respectively than those in East Asia countries (31.7 years. We summarized the data attesting to the genetic susceptibility in BD patients: HLA B51-positive individuals, family aggregation observed when studying twins, etc. The clinical polymorphism in BD patients was shown to depend on their region of residence and ethnicity. The data of a series of large cohort studies are reported; the frequencies of the international criteria of BD in the US and Japanese patients are compared in these studies. The question regarding the need for cross-sectional population-based and case-control studies using the standard criteria and clear definition of ethnicity is brought up in some publications.

  2. Behcet's disease: demographic and genetic aspects (a literature review

    Directory of Open Access Journals (Sweden)

    Fatima Ismailovna Izmailova

    2014-01-01

    Full Text Available A review of literature focused on Behcet's disease (BD is presented. BD is systemic vasculitis of unknown etiology affecting multiple organs. BD is endemic in the countries along the Eastern Mediterranean coast and the areas of Central and East Asia. We report the data on BD prevalence in different regions and the effect of population migration on BD incidence rate. Patients were found to be younger at the onset of the disease in Arab countries, Turkey, and Israel (19.9; 25.6; and 26 years, respectively than those in East Asia countries (31.7 years. We summarized the data attesting to the genetic susceptibility in BD patients: HLA B51-positive individuals, family aggregation observed when studying twins, etc. The clinical polymorphism in BD patients was shown to depend on their region of residence and ethnicity. The data of a series of large cohort studies are reported; the frequencies of the international criteria of BD in the US and Japanese patients are compared in these studies. The question regarding the need for cross-sectional population-based and case-control studies using the standard criteria and clear definition of ethnicity is brought up in some publications.

  3. Periodontal disease in individuals with Down Syndrome: genetic focus

    Directory of Open Access Journals (Sweden)

    Lícia Bezerra Cavalcante

    2009-12-01

    Full Text Available Fundamental concepts of etiology, inheritance and clinical characteristics of Down syndrome are used in this review as a basis for submission of studies that focus on periodontal disease in individuals with Down syndrome, since almost 100% of them develop the disease in adult life. It is believed that in association with environmental and cultural factors related to hygiene and disabilities of coordination, the immunological characteristics that are found altered in individuals with Down syndrome, such as deficient neutrophil chemotaxis and reduced number of mature T lymphocytes, may contribute to the greater prevalence and severity of periodontal involvement in patients with Down syndrome. Moreover, the pattern of periodontal destruction observed in individuals with Down syndrome is consistent with aggressive periodontitis, with a predominance of periodontopathogens such as Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythensis during childhood and adolescence of Down’s syndrome patients. It is possible to note a relationship between the development of molecular techniques and the evolution of knowledge about Down syndrome, for example: identification of the trisomy syndrome by observing only part of chromosome 21 (distal long arm; identification of genes in this trisomic region and the pattern of superexpression (or not of these genes. Moreover, in this review future perspectives are presented with regard to better understanding Down syndrome in the genetic context, which will reflect in more individualized and effective clinical treatments that will provide these patients with a better quality of life.

  4. Genetic Modification of Oncolytic Newcastle Disease Virus for Cancer Therapy.

    Science.gov (United States)

    Cheng, Xing; Wang, Weijia; Xu, Qi; Harper, James; Carroll, Danielle; Galinski, Mark S; Suzich, JoAnn; Jin, Hong

    2016-06-01

    Clinical development of a mesogenic strain of Newcastle disease virus (NDV) as an oncolytic agent for cancer therapy has been hampered by its select agent status due to its pathogenicity in avian species. Using reverse genetics, we have generated a lead candidate oncolytic NDV based on the mesogenic NDV-73T strain that is no longer classified as a select agent for clinical development. This recombinant NDV has a modification at the fusion protein (F) cleavage site to reduce the efficiency of F protein cleavage and an insertion of a 198-nucleotide sequence into the HN-L intergenic region, resulting in reduced viral gene expression and replication in avian cells but not in mammalian cells. In mammalian cells, except for viral polymerase (L) gene expression, viral gene expression is not negatively impacted or increased by the HN-L intergenic insertion. Furthermore, the virus can be engineered to express a foreign gene while still retaining the ability to grow to high titers in cell culture. The recombinant NDV selectively replicates in and kills tumor cells and is able to drive potent tumor growth inhibition following intratumoral or intravenous administration in a mouse tumor model. The candidate is well positioned for clinical development as an oncolytic virus. Avian paramyxovirus type 1, NDV, has been an attractive oncolytic agent for cancer virotherapy. However, this virus can cause epidemic disease in poultry, and concerns about the potential environmental and economic impact of an NDV outbreak have precluded its clinical development. Here we describe generation and characterization of a highly potent oncolytic NDV variant that is unlikely to cause Newcastle disease in its avian host, representing an essential step toward moving NDV forward as an oncolytic agent. Several attenuation mechanisms have been genetically engineered into the recombinant NDV that reduce chicken pathogenicity to a level that is acceptable worldwide without impacting viral production in

  5. Moyamoya disease and syndromes: from genetics to clinical management

    Directory of Open Access Journals (Sweden)

    Guey S

    2015-02-01

    . Revascularization surgery can be indicated, with several techniques. Characteristics of genetic moyamoya syndromes are presented, with a focus on recently reported mutations in BRCC3/MTCP1 and GUCY1A3 genes. Identification of the genes involved in moyamoya disease and several monogenic moyamoya syndromes unraveled different pathways involved in the development of this angiopathy. Studying genes and pathways involved in monogenic moyamoya syndromes may help to give insights into pathophysiological models and discover potential candidates for medical treatment strategies. Keywords: moyamoya disease, moyamoya syndrome, stroke, surgical revascularization, genetics

  6. Rapid growth and genetic diversity retention in an isolated reintroduced black bear population in the central appalachians

    Science.gov (United States)

    Murphy, Sean M.; Cox, John J.; Clark, Joseph D.; Augustine, Benjamin J.; Hast, John T.; Gibbs, Dan; Strunk, Michael; Dobey, Steven

    2015-01-01

    Animal reintroductions are important tools of wildlife management to restore species to their historical range, and they can also create unique opportunities to study population dynamics and genetics from founder events. We used non-invasive hair sampling in a systematic, closed-population capture-mark-recapture (CMR) study design at the Big South Fork (BSF) area in Kentucky during 2010 and Tennessee during 2012 to estimate the demographic and genetic characteristics of the black bear (Ursus americanus) population that resulted from a reintroduced founding population of 18 bears in 1998. We estimated 38 (95% CI: 31–66) and 190 (95% CI: 170–219) bears on the Kentucky and Tennessee study areas, respectively. Based on the Tennessee abundance estimate alone, the mean annual growth rate was 18.3% (95% CI: 17.4–19.5%) from 1998 to 2012. We also compared the genetic characteristics of bears sampled during 2010–2012 to bears in the population during 2000–2002, 2–4 years following reintroduction, and to the source population. We found that the level of genetic diversity since reintroduction as indicated by expected heterozygosity (HE) remained relatively constant (HE(source, 2004) = 0.763, HE(BSF, 2000–2002) = 0.729, HE(BSF, 2010–2012) = 0.712) and the effective number of breeders (NB) remained low but had increased since reintroduction in the absence of sufficient immigration (NB(BSF, 2000–2002) = 12, NB(BSF, 2010–2012)  = 35). This bear population appears to be genetically isolated, but contrary to our expectations, we did not find evidence of genetic diversity loss or other deleterious genetic effects typically observed from small founder groups. We attribute that to high initial genetic diversity in the founder group combined with overlapping generations and rapid population growth. Although the population remains relatively small, the reintroduction using a small founder group appears to be demographically and genetically

  7. Multiple reciprocal adaptations and rapid genetic change upon experimental coevolution of an animal host and its microbial parasite.

    Science.gov (United States)

    Schulte, Rebecca D; Makus, Carsten; Hasert, Barbara; Michiels, Nico K; Schulenburg, Hinrich

    2010-04-20

    The coevolution between hosts and parasites is predicted to have complex evolutionary consequences for both antagonists, often within short time periods. To date, conclusive experimental support for the predictions is available mainly for microbial host systems, but for only a few multicellular host taxa. We here introduce a model system of experimental coevolution that consists of the multicellular nematode host Caenorhabditis elegans and the microbial parasite Bacillus thuringiensis. We demonstrate that 48 host generations of experimental coevolution under controlled laboratory conditions led to multiple changes in both parasite and host. These changes included increases in the traits of direct relevance to the interaction such as parasite virulence (i.e., host killing rate) and host resistance (i.e., the ability to survive pathogens). Importantly, our results provide evidence of reciprocal effects for several other central predictions of the coevolutionary dynamics, including (i) possible adaptation costs (i.e., reductions in traits related to the reproductive rate, measured in the absence of the antagonist), (ii) rapid genetic changes, and (iii) an overall increase in genetic diversity across time. Possible underlying mechanisms for the genetic effects were found to include increased rates of genetic exchange in the parasite and elevated mutation rates in the host. Taken together, our data provide comprehensive experimental evidence of the consequences of host-parasite coevolution, and thus emphasize the pace and complexity of reciprocal adaptations associated with these antagonistic interactions.

  8. Cell biology and genetics of minimal change disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Moin A. Saleem

    2016-03-01

    Full Text Available Minimal change disease (MCD is an important cause of nephrotic syndrome and is characterized by massive proteinuria and hypoalbuminemia, resulting in edema and hypercholesterolemia. The podocyte plays a key role in filtration and its disruption results in a dramatic loss of function leading to proteinuria. Immunologic disturbance has been suggested in the pathogenesis of MCD. Because of its clinical features, such as recurrent relapse/remission course, steroid response in most patients, and rare familial cases, a genetic defect has been thought to be less likely in MCD. Recent progress in whole-exome sequencing reveals pathogenic mutations in familial cases in steroid-sensitive nephrotic syndrome (SSNS and sheds light on possible mechanisms and key molecules in podocytes in MCD. On the other hand, in the majority of cases, the existence of circulating permeability factors has been implicated along with T lymphocyte dysfunction. Observations of benefit with rituximab added B cell involvement to the disease. Animal models are unsatisfactory, and the humanized mouse may be a good model that well reflects MCD pathophysiology to investigate suggested “T cell dysfunction” directly related to podocytes in vivo. Several candidate circulating factors and their effects on podocytes have been proposed but are still not sufficient to explain whole mechanisms and clinical features in MCD. Another circulating factor disease is focal segmental glomerulosclerosis (FSGS, and it is not clear if this is a distinct entity, or on the same spectrum, implicating the same circulating factor(s. These patients are mostly steroid resistant and often have a rapid relapse after transplantation. In clinical practice, predicting relapse or disease activity and response to steroids is important and is an area where novel biomarkers can be developed based on our growing knowledge of podocyte signaling pathways. In this review, we discuss recent findings in genetics and

  9. The genetic architecture of coronary artery disease: current knowledge and future opportunities

    Science.gov (United States)

    Recent Findings Large-scale studies in human populations, coupled with rapid advances in genetic technologies over the last decade, have clearly established the association of common genetic variation with risk of CAD. However, the effect sizes of the susceptibility alleles are for the most part mod...

  10. Is There Any Evidence for Rapid, Genetically-Based, Climatic Niche Expansion in the Invasive Common Ragweed?

    Directory of Open Access Journals (Sweden)

    Laure Gallien

    Full Text Available Climatic niche shifts have been documented in a number of invasive species by comparing the native and adventive climatic ranges in which they occur. However, these shifts likely represent changes in the realized climatic niches of invasive species, and may not necessarily be driven by genetic changes in climatic affinities. Until now the role of rapid niche evolution in the spread of invasive species remains a challenging issue with conflicting results. Here, we document a likely genetically-based climatic niche expansion of an annual plant invader, the common ragweed (Ambrosia artemisiifolia L., a highly allergenic invasive species causing substantial public health issues. To do so, we looked for recent evolutionary change at the upward migration front of its adventive range in the French Alps. Based on species climatic niche models estimated at both global and regional scales we stratified our sampling design to adequately capture the species niche, and localized populations suspected of niche expansion. Using a combination of species niche modeling, landscape genetics models and common garden measurements, we then related the species genetic structure and its phenotypic architecture across the climatic niche. Our results strongly suggest that the common ragweed is rapidly adapting to local climatic conditions at its invasion front and that it currently expands its niche toward colder and formerly unsuitable climates in the French Alps (i.e. in sites where niche models would not predict its occurrence. Such results, showing that species climatic niches can evolve on very short time scales, have important implications for predictive models of biological invasions that do not account for evolutionary processes.

  11. Is There Any Evidence for Rapid, Genetically-Based, Climatic Niche Expansion in the Invasive Common Ragweed?

    Science.gov (United States)

    Gallien, Laure; Thuiller, Wilfried; Fort, Noémie; Boleda, Marti; Alberto, Florian J; Rioux, Delphine; Lainé, Juliette; Lavergne, Sébastien

    2016-01-01

    Climatic niche shifts have been documented in a number of invasive species by comparing the native and adventive climatic ranges in which they occur. However, these shifts likely represent changes in the realized climatic niches of invasive species, and may not necessarily be driven by genetic changes in climatic affinities. Until now the role of rapid niche evolution in the spread of invasive species remains a challenging issue with conflicting results. Here, we document a likely genetically-based climatic niche expansion of an annual plant invader, the common ragweed (Ambrosia artemisiifolia L.), a highly allergenic invasive species causing substantial public health issues. To do so, we looked for recent evolutionary change at the upward migration front of its adventive range in the French Alps. Based on species climatic niche models estimated at both global and regional scales we stratified our sampling design to adequately capture the species niche, and localized populations suspected of niche expansion. Using a combination of species niche modeling, landscape genetics models and common garden measurements, we then related the species genetic structure and its phenotypic architecture across the climatic niche. Our results strongly suggest that the common ragweed is rapidly adapting to local climatic conditions at its invasion front and that it currently expands its niche toward colder and formerly unsuitable climates in the French Alps (i.e. in sites where niche models would not predict its occurrence). Such results, showing that species climatic niches can evolve on very short time scales, have important implications for predictive models of biological invasions that do not account for evolutionary processes.

  12. Portable microfluidic raman system for rapid, label-free early disease signature detection

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Meiye [Sandia National Laboratories (SNL-CA), Livermore, CA (United States); Davis, Ryan Wesley [Sandia National Laboratories (SNL-CA), Livermore, CA (United States); Hatch, Anson [Sandia National Laboratories (SNL-CA), Livermore, CA (United States)

    2015-09-01

    In the early stages of infection, patients develop non-specific or no symptoms at all. While waiting for identification of the infectious agent, precious window of opportunity for early intervention is lost. The standard diagnostics require affinity reagents and sufficient pathogen titers to reach the limit of detection. In the event of a disease outbreak, triaging the at-risk population rapidly and reliably for quarantine and countermeasure is more important than the identification of the pathogen by name. To expand Sandia's portfolio of Biological threat management capabilities, we will utilize Raman spectrometry to analyze immune subsets in whole blood to rapidly distinguish infected from non-infected, and bacterial from viral infection, for the purpose of triage during an emergency outbreak. The goal of this one year LDRD is to determine whether Raman spectroscopy can provide label-free detection of early disease signatures, and define a miniaturized Raman detection system meeting requirements for low- resource settings.

  13. Infertility etiologies are genetically and clinically linked with other diseases in single meta-diseases.

    Science.gov (United States)

    Tarín, Juan J; García-Pérez, Miguel A; Hamatani, Toshio; Cano, Antonio

    2015-04-15

    The present review aims to ascertain whether different infertility etiologies share particular genes and/or molecular pathways with other pathologies and are associated with distinct and particular risks of later-life morbidity and mortality. In order to reach this aim, we use two different sources of information: (1) a public web server named DiseaseConnect ( http://disease-connect.org ) focused on the analysis of common genes and molecular mechanisms shared by diseases by integrating comprehensive omics and literature data; and (2) a literature search directed to find clinical comorbid relationships of infertility etiologies with only those diseases appearing after infertility is manifested. This literature search is performed because DiseaseConnect web server does not discriminate between pathologies emerging before, concomitantly or after infertility is manifested. Data show that different infertility etiologies not only share particular genes and/or molecular pathways with other pathologies but they have distinct clinical relationships with other diseases appearing after infertility is manifested. In particular, (1) testicular and high-grade prostate cancer in male infertility; (2) non-fatal stroke and endometrial cancer, and likely non-fatal coronary heart disease and ovarian cancer in polycystic ovary syndrome; (3) osteoporosis, psychosexual dysfunction, mood disorders and dementia in premature ovarian failure; (4) breast and ovarian cancer in carriers of BRCA1/2 mutations in diminished ovarian reserve; (5) clear cell and endometrioid histologic subtypes of invasive ovarian cancer, and likely low-grade serous invasive ovarian cancer, melanoma and non-Hodgkin lymphoma in endometriosis; and (6) endometrial and ovarian cancer in idiopathic infertility. The present data endorse the principle that the occurrence of a disease (in our case infertility) is non-random in the population and suggest that different infertility etiologies are genetically and clinically

  14. Rapid Py-GC/MS assessment of the structural alterations of lignins in genetically modified plants

    NARCIS (Netherlands)

    Rencoret, Jorge; Del Río, José Carlos; Nierop, Klaas G J; Gutiérrez, Ana; Ralph, John

    Genetic modifications for perturbing the lignin pathway in three different species of angiosperm plants, including non-woody (Arabidopsis and alfalfa) and woody (poplar) plants, were readily evaluated by analytical pyrolysis coupled to gas chromatography-mass spectrometry (Py-GC/MS). Pyrolysis

  15. Shared genetic variants suggest common pathways in allergy and autoimmune diseases

    NARCIS (Netherlands)

    Kreiner, Eskil; Waage, Johannes; Standl, Marie; Brix, Susanne; Pers, Tune H; Couto Alves, Alexessander; Warrington, Nicole M; Tiesler, Carla Mt; Fuertes, Elaine; Franke, Lude; Hirschhorn, Joel N; James, Alan; Simpson, Angela; Tung, Joyce Y; Koppelman, Gerard H; Postma, Dirkje S; Pennell, Craig E; Jarvelin, Marjo-Riitta; Custovic, Adnan; Timpson, Nicholas; Ferreira, Manuel A; Strachan, David P; Henderson, John; Hinds, David; Bisgaard, Hans; Bønnelykke, Klaus

    Background: The relationship between allergy and autoimmune disorders is complex and poorly understood. Objective: We sought to investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. Methods: We meta-analyzed 2

  16. Use of Genetically Altered Stem Cells for the Treatment of Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Andrew T. Crane

    2014-03-01

    Full Text Available Transplantation of stem cells for the treatment of Huntington’s disease (HD garnered much attention prior to the turn of the century. Several studies using mesenchymal stem cells (MSCs have indicated that these cells have enormous therapeutic potential in HD and other disorders. Advantages of using MSCs for cell therapies include their ease of isolation, rapid propagation in culture, and favorable immunomodulatory profiles. However, the lack of consistent neuronal differentiation of transplanted MSCs has limited their therapeutic efficacy to slowing the progression of HD-like symptoms in animal models of HD. The use of MSCs which have been genetically altered to overexpress brain derived neurotrophic factor to enhance support of surviving cells in a rodent model of HD provides proof-of-principle that these cells may provide such prophylactic benefits. New techniques that may prove useful for cell replacement therapies in HD include the use of genetically altering fate-restricted cells to produce induced pluripotent stem cells (iPSCs. These iPSCs appear to have certain advantages over the use of embryonic stem cells, including being readily available, easy to obtain, less evidence of tumor formation, and a reduced immune response following their transplantation. Recently, transplants of iPSCs have shown to differentiate into region-specific neurons in an animal model of HD. The overall successes of using genetically altered stem cells for reducing neuropathological and behavioral deficits in rodent models of HD suggest that these approaches have considerable potential for clinical use. However, the choice of what type of genetically altered stem cell to use for transplantation is dependent on the stage of HD and whether the end-goal is preserving endogenous neurons in early-stage HD, or replacing the lost neurons in late-stage HD. This review will discuss the current state of stem cell technology for treating the different stages of HD and

  17. Investigation of Genetic Variants Associated with Alzheimer Disease in Parkinson Disease Cognition.

    Science.gov (United States)

    Barrett, Matthew J; Koeppel, Alexander F; Flanigan, Joseph L; Turner, Stephen D; Worrall, Bradford B

    2016-01-01

    Meta-analysis of genome-wide association studies have implicated multiple single nucleotide polymorphisms (SNPs) and associated genes with Alzheimer disease. The role of these SNPs in cognitive impairment in Parkinson disease (PD) remains incompletely evaluated. The objective of this study was to test alleles associated with risk of Alzheimer disease for association with cognitive impairment in Parkinson disease (PD). Two datasets with PD subjects accessed through the NIH database of Genotypes and Phenotypes contained both single nucleotide polymorphism (SNP) arrays and mini-mental state exam (MMSE) scores. Genetic data underwent rigorous quality control and we selected SNPs for genes associated with AD other than APOE. We constructed logistic regression and ordinal regression models, adjusted for sex, age at MMSE, and duration of PD, to assess the association between selected SNPs and MMSE score. In one dataset, PICALM rs3851179 was associated with cognitive impairment (MMSE  70 years old (OR = 2.3; adjusted p-value = 0.017; n = 250) but not in PD subjects ≤ 70 years old. Our finding suggests that PICALM rs3851179 could contribute to cognitive impairment in older patients with PD. It is important that future studies consider the interaction of age and genetic risk factors in the development of cognitive impairment in PD.

  18. Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome.

    Science.gov (United States)

    Zemojtel, Tomasz; Köhler, Sebastian; Mackenroth, Luisa; Jäger, Marten; Hecht, Jochen; Krawitz, Peter; Graul-Neumann, Luitgard; Doelken, Sandra; Ehmke, Nadja; Spielmann, Malte; Oien, Nancy Christine; Schweiger, Michal R; Krüger, Ulrike; Frommer, Götz; Fischer, Björn; Kornak, Uwe; Flöttmann, Ricarda; Ardeshirdavani, Amin; Moreau, Yves; Lewis, Suzanna E; Haendel, Melissa; Smedley, Damian; Horn, Denise; Mundlos, Stefan; Robinson, Peter N

    2014-09-03

    Less than half of patients with suspected genetic disease receive a molecular diagnosis. We have therefore integrated next-generation sequencing (NGS), bioinformatics, and clinical data into an effective diagnostic workflow. We used variants in the 2741 established Mendelian disease genes [the disease-associated genome (DAG)] to develop a targeted enrichment DAG panel (7.1 Mb), which achieves a coverage of 20-fold or better for 98% of bases. Furthermore, we established a computational method [Phenotypic Interpretation of eXomes (PhenIX)] that evaluated and ranked variants based on pathogenicity and semantic similarity of patients' phenotype described by Human Phenotype Ontology (HPO) terms to those of 3991 Mendelian diseases. In computer simulations, ranking genes based on the variant score put the true gene in first place less than 5% of the time; PhenIX placed the correct gene in first place more than 86% of the time. In a retrospective test of PhenIX on 52 patients with previously identified mutations and known diagnoses, the correct gene achieved a mean rank of 2.1. In a prospective study on 40 individuals without a diagnosis, PhenIX analysis enabled a diagnosis in 11 cases (28%, at a mean rank of 2.4). Thus, the NGS of the DAG followed by phenotype-driven bioinformatic analysis allows quick and effective differential diagnostics in medical genetics. Copyright © 2014, American Association for the Advancement of Science.

  19. Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer's disease

    OpenAIRE

    Gross Hyman; Tobinick Edward L

    2008-01-01

    Abstract Background Recent clinical studies point to rapid and sustained clinical, cognitive, and behavioral improvement in both Alzheimer's disease and primary progressive aphasia following weekly perispinal administration of etanercept, a TNF-alpha inhibitor that acts by blocking the binding of this cytokine to its receptors. This outcome is concordant with recent basic science studies suggesting that TNF-alpha functions in vivo as a gliotransmitter that regulates synaptic function in the b...

  20. PNA FISH: an intelligent stain for rapid diagnosis of infectious diseases.

    Science.gov (United States)

    Stender, Henrik

    2003-09-01

    Fluorescence in situ hybridization using peptide nucleic acid probes (PNA FISH) is a novel diagnostic technique combining the simplicity of traditional staining procedures with the unique performance of PNA probes to provide rapid and accurate diagnosis of infectious diseases; a feature that makes PNA FISH well suited for routine application and enables clinical microbiology laboratories to report important information for patient therapy within a time frame not possible using classic biochemical methods. Having transitioned from an academic curiosity into an advanced diagnostic tool, PNA probes are now debuting on the infectious disease stage, representing the new generation of therapy-directing diagnostics.

  1. Rapid infusion with rituximab: short term safety in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Larsen, Janni Lisander; Jacobsen, Soren

    2013-01-01

    To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre...... (1.8%) had grade 2 events on both infusions and two patients (3.6%) had a grade 3 event on both infusions. RA patients more often had an infusion-related reaction (IRR) (9.2%) than the rest. The types of IRR were mostly of allergic or angio-oedematic nature. In practise, the rapid infusion...

  2. Genetically decreased vitamin D and risk of Alzheimer disease.

    Science.gov (United States)

    Mokry, Lauren E; Ross, Stephanie; Morris, John A; Manousaki, Despoina; Forgetta, Vincenzo; Richards, J Brent

    2016-12-13

    To test whether genetically decreased vitamin D levels are associated with Alzheimer disease (AD) using mendelian randomization (MR), a method that minimizes bias due to confounding or reverse causation. We selected single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels (p Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) Consortium (N = 33,996) to act as instrumental variables for the MR study. We measured the effect of each of these SNPs on 25OHD levels in the Canadian Multicentre Osteoporosis Study (CaMos; N = 2,347) and obtained the corresponding effect estimates for each SNP on AD risk from the International Genomics of Alzheimer's Project (N = 17,008 AD cases and 37,154 controls). To produce MR estimates, we weighted the effect of each SNP on AD by its effect on 25OHD and meta-analyzed these estimates using a fixed-effects model to provide a summary effect estimate. The SUNLIGHT Consortium identified 4 SNPs to be genome-wide significant for 25OHD, which described 2.44% of the variance in 25OHD in CaMos. All 4 SNPs map to genes within the vitamin D metabolic pathway. MR analyses demonstrated that a 1-SD decrease in natural log-transformed 25OHD increased AD risk by 25% (odds ratio 1.25, 95% confidence interval 1.03-1.51, p = 0.021). After sensitivity analysis in which we removed SNPs possibly influenced by pleiotropy and population stratification, the results were largely unchanged. Our results provide evidence supporting 25OHD as a causal risk factor for AD. These findings provide further rationale to understand the effect of vitamin D supplementation on cognition and AD risk in randomized controlled trials. © 2016 American Academy of Neurology.

  3. Genetic determinants and stroke in children with sickle cell disease,

    Directory of Open Access Journals (Sweden)

    Daniela O.W. Rodrigues

    Full Text Available Abstract Objective: To verify genetic determinants associated with stroke in children with sickle cell disease (SCD. Methods: Prospective cohort with 110 children submitted to neonatal screening by the Neonatal Screening Program, between 1998 and 2007, with SCD diagnosis, followed at a regional reference public service for hemoglobinopathies. The analyzed variables were type of hemoglobinopathy, gender, coexistence with alpha thalassemia (α-thal, haplotypes of the beta globin chain cluster, and stroke. The final analysis was conducted with 66 children with sickle cell anemia (SCA, using the chi-squared test in the program SPSS® version 14.0. Results: Among children with SCD, 60% had SCA. The prevalence of coexistence with α-thal was 30.3% and the Bantu haplotype (CAR was identified in 89.2%. The incidence of stroke was significantly higher in those with SCA (27.3% vs. 2.3%; p = 0.001 and males (24.1% vs. 9.6%; p = 0.044. The presence of α-thal (p = 0.196, the CAR haplotype (p = 0.543, and socioeconomic factors were not statistically significant in association with the occurrence of stroke. Conclusion: There is a high incidence of stroke in male children and in children with SCA. Coexistence with α-thal and haplotypes of the beta globin chain cluster did not show any significant association with stroke. The heterogeneity between previously evaluated populations, the non-reproducibility between studies, and the need to identify factors associated with stroke in patients with SCA indicate the necessity of conducting further research to demonstrate the relevance of genetic factors in stroke related to SCD.

  4. Rapid eye movement sleep behavioral events: a new marker for neurodegeneration in early Parkinson disease?

    Science.gov (United States)

    Sixel-Döring, Friederike; Trautmann, Ellen; Mollenhauer, Brit; Trenkwalder, Claudia

    2014-03-01

    To analyze potential markers in sleep for early recognition of neurodegenerative disease in newly diagnosed, unmedicated patients with Parkinson disease (PD) compared to controls. Videopolysomnography (vPSG) was available in 158 newly diagnosed, unmedicated patients with PD and 110 age-, sex-, and education-matched healthy controls (HC). Rapid eye movement (REM) sleep was analyzed for REM without atonia (RWA) and studied by review of time-synchronized video. Motor behaviors and/or vocalizations in REM sleep with a purposeful component other than comfort moves were identified as REM sleep behavioral events (RBE). Two or more events had to be present to be classified as "RBE positive." RBE subjects included rapid eye movement sleep behavior disorder (RBD) and non-RBD subjects based on the presence or absence of RWA > 18.2%. RBE were detected in 81 of 158 patients with de novo PD (51%) and 17 of 110 HC (15%) (P sleep (P = 0.002) and a higher periodic leg movements in sleep index (P = 0.022) compared to subjects without RBE. This first description of REM sleep behavioral events (RBE) shows it occurs more frequently in patients with de novo Parkinson disease (PD) than in healthy controls and may be an early sign of neurodegeneration and precede rapid eye movement sleep behavior disorder (RBD). There is no specific phenotype of PD associated with newly defined RBE or RBD at this early stage.

  5. The sense and nonsense of direct-to-consumer genetic testing for cardiovascular disease.

    Science.gov (United States)

    Janssens, A C J W; Wilde, A A M; van Langen, I M

    2011-02-01

    Expectations are high that increasing knowledge of the genetic basis of cardiovascular disease will eventually lead to personalised medicine-to preventive and therapeutic interventions that are targeted to at-risk individuals on the basis of their genetic profiles. Most cardiovascular diseases are caused by a complex interplay of many genetic variants interacting with many non-genetic risk factors such as diet, exercise, smoking and alcohol consumption. Since several years, genetic susceptibility testing for cardiovascular diseases is being offered via the internet directly to consumers. We discuss five reasons why these tests are not useful, namely: (1) the predictive ability is still limited; (2) the risk models used by the companies are based on assumptions that have not been verified; (3) the predicted risks keep changing when new variants are discovered and added to the test; (4) the tests do not consider non-genetic factors in the prediction of cardiovascular disease risk; and (5) the test results will not change recommendations of preventive interventions. Predictive genetic testing for multifactorial forms of cardiovascular disease clearly lacks benefits for the public. Prevention of disease should therefore remain focused on family history and on non-genetic risk factors as diet and physical activity that can have the strongest impact on disease risk, regardless of genetic susceptibility.

  6. Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease

    Science.gov (United States)

    Boelaert, Marleen; Verdonck, Kristien; Menten, Joris; Sunyoto, Temmy; van Griensven, Johan; Chappuis, Francois; Rijal, Suman

    2014-01-01

    Background The diagnosis of visceral leishmaniasis (VL) in patients with fever and a large spleen relies on showing Leishmania parasites in tissue samples and on serological tests. Parasitological techniques are invasive, require sophisticated laboratories, consume time, or lack accuracy. Recently, rapid diagnostic tests that are easy to perform have become available. Objectives To determine the diagnostic accuracy of rapid tests for diagnosing VL in patients with suspected disease presenting at health services in endemic areas. Search methods We searched MEDLINE, EMBASE, LILACS, CIDG SR, CENTRAL, SCI-expanded, Medion, Arif, CCT, and the WHO trials register on 3 December 2013, without applying language or date limits. Selection criteria This review includes original, phase III, diagnostic accuracy studies of rapid tests in patients clinically suspected to have VL. As reference standards, we accepted: (1) direct smear or culture of spleen aspirate; (2) composite reference standard based on one or more of the following: parasitology, serology, or response to treatment; and (3) latent class analysis. Data collection and analysis Two review authors independently extracted data and assessed quality of included studies using the QUADAS-2 tool. Discrepancies were resolved by a third author. We carried out a meta-analysis to estimate sensitivity and specificity of rapid tests, using a bivariate normal model with a complementary log-log link function. We analysed each index test separately. As possible sources of heterogeneity, we explored: geographical area, commercial brand of index test, type of reference standard, disease prevalence, study size, and risk of bias (QUADAS-2). We also undertook a sensitivity analysis to assess the influence of imperfect reference standards. Main results Twenty-four studies containing information about five index tests (rK39 immunochromatographic test (ICT), KAtex latex agglutination test in urine, FAST agglutination test, rK26 ICT, and r

  7. Genetic screens in Caenorhabditis elegans models for neurodegenerative diseases

    NARCIS (Netherlands)

    Alvarenga Fernandes Sin, Olga; Michels, Helen; Nollen, Ellen A. A.

    2014-01-01

    Caenorhabditis elegans comprises unique features that make it an attractive model organism in diverse fields of biology. Genetic screens are powerful to identify genes and C. elegans can be customized to forward or reverse genetic screens and to establish gene function. These genetic screens can be

  8. Evidence for a third genetic locus for autosomal dominant polycystic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Daoust, M.C.; Bichet, D.G. [Universite de Montreal, Quebec (Canada); Reynolds, D.M. [Albert Einstein College of Medicine, Bronx, NY (United States)] [and others

    1995-02-10

    Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disease with loci on chromosomes 16p and 4q. It has a moderately high spontaneous mutation rate, although the relative frequency of such mutations at each gene locus is unknown. In studying genetic heterogeneity in the French-Canadian population, we identified a family in which a classical clinical presentation of ADPKD resulted from a mutation at a locus genetically distinct from either of the previously described loci for this disease. This suggests the existence of a third genetic locus for ADPKD. 21 refs., 1 fig., 1 tab.

  9. The sense and nonsense of direct-to-consumer genetic testing for cardiovascular disease

    NARCIS (Netherlands)

    Janssens, A. C. J. W.; Wilde, A. A. M.; van Langen, I. M.

    2011-01-01

    Expectations are high that increasing knowledge of the genetic basis of cardiovascular disease will eventually lead to personalised medicine-to preventive and therapeutic interventions that are targeted to at-risk individuals on the basis of their genetic profiles. Most cardiovascular diseases are

  10. The sense and nonsense of direct-to-consumer genetic testing for cardiovascular disease

    NARCIS (Netherlands)

    Janssens, A. C. J. W.; Wilde, A. A. M.; van Langen, I. M.

    Expectations are high that increasing knowledge of the genetic basis of cardiovascular disease will eventually lead to personalised medicine-to preventive and therapeutic interventions that are targeted to at-risk individuals on the basis of their genetic profiles. Most cardiovascular diseases are

  11. The importance of genetics in the diagnosis of animal diseases - A ...

    African Journals Online (AJOL)

    Many animal genes have been mapped to chromosomes. A detailed genetic map has become of great value in the diagnosis of genetic diseases and in the development of potential cures through gene transfer therapy. In view of the emerging animal diseases like avian influenza, swine influenza among others with serious ...

  12. Context-specific effects of genetic variants associated with autoimmune disease.

    Science.gov (United States)

    Jonkers, Iris H; Wijmenga, Cisca

    2017-10-01

    Autoimmune diseases such as rheumatoid arthritis and coeliac disease are typical examples of complex genetic diseases caused by a combination of genetic and non-genetic risk factors. Insight into the genetic risk factors (single nucleotide polymorphisms (SNPs)) has increased since genome-wide association studies (GWAS) became possible in 2007 and, for individual diseases, SNPs can now explain some 15-50% of genetic risk. GWAS have also shown that some 50% of the genetic risk factors for individual autoimmune diseases overlap between different diseases. Thus, shared risk factors may converge to pathways that, when perturbed by genetic variation, predispose to autoimmunity in general. This raises the question of what determines disease specificity, and suggests that identical risk factors may have different effects in various autoimmune diseases. Addressing this question requires translation of genetic risk factors to causal genes and then to molecular and cellular pathways. Since >90% of the genetic risk factors are found in the non-coding part of the genome (i.e. outside the exons of protein-coding genes) and can have an impact on gene regulation, there is an urgent need to better understand the non-coding part of the genome. Here, we will outline the methods being used to unravel the gene regulatory networks perturbed in autoimmune diseases and the importance of doing this in the relevant cell types. We will highlight findings in coeliac disease, which manifests in the small intestine, to demonstrate how cell type and disease context can impact on the consequences of genetic risk factors. © The Author 2017. Published by Oxford University Press.

  13. Collective Genetic Interaction Effects and the Role of Antigen Presenting Cells in Autoimmune Diseases

    Science.gov (United States)

    2017-01-12

    information contained within genome-wide associa- tion studies to improve individual prediction of complex disease risk. Hum Mol Genet . 2009; 18 (18):3525–31...Rosenstiel P, Albrecht M, Stenzel A, et al. Sarcoidosis is associated with a truncating splice site mutation in BTNL2. Nat Genet . 2005; 37(4):357–64. Epub...RESEARCH ARTICLE Collective Genetic Interaction Effects and the Role of Antigen-Presenting Cells in Autoimmune Diseases Hyung Jun Woo*, Chenggang Yu

  14. Genetic Variation Underlying Traumatic Brain injury (TBI) and Late Onset Alzheimer’s Disease (LOAD)

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0588 TITLE: Genetic variation underlying traumatic brain injury (TBI) and Late Onset Alzheimer’s Disease (LOAD...14 Sep 2017 4. TITLE AND SUBTITLE Late-Onset Alzheimer’s Disease (LOAD) 5a. CONTRACT NUMBER Genetic variation underlying traumatic brain injury...accelerating individual’s memory decline and possibly accelerating LOAD like neuro-degeneration. In addition, genetic risk factors including non- coding and

  15. Rapid Communication: Large exploitable genetic variability exists to shorten age at slaughter in cattle.

    Science.gov (United States)

    Berry, D P; Cromie, A R; Judge, M M

    2017-10-01

    Apprehension among consumers is mounting on the efficiency by which cattle convert feedstuffs into human edible protein and energy as well as the consequential effects on the environment. Most (genetic) studies that attempt to address these issues have generally focused on efficiency metrics defined over a certain time period of an animal's life cycle, predominantly the period representing the linear phase of growth. The age at which an animal reaches the carcass specifications for slaughter, however, is also known to vary between breeds; less is known on the extent of the within-breed variability in age at slaughter. Therefore, the objective of the present study was to quantify the phenotypic and genetic variability in the age at which cattle reach a predefined carcass weight and subcutaneous fat cover. A novel trait, labeled here as the deviation in age at slaughter (DAGE), was represented by the unexplained variability from a statistical model, with age at slaughter as the dependent variable and with the fixed effects, among others, of carcass weight and fat score (scale 1 to 15 scored by video image analysis of the carcass at slaughter). Variance components for DAGE were estimated using either a 2-step approach (i.e., the DAGE phenotype derived first and then variance components estimated) or a 1-step approach (i.e., variance components for age at slaughter estimated directly in a mixed model that included the fixed effects of, among others, carcass weight and carcass fat score as well as a random direct additive genetic effect). The raw phenotypic SD in DAGE was 44.2 d. The genetic SD and heritability for DAGE estimated using the 1-step or 2-step models varied from 14.2 to 15.1 d and from 0.23 to 0.26 (SE 0.02), respectively. Assuming the (genetic) variability in the number of days from birth to reaching a desired carcass specifications can be exploited without any associated unfavorable repercussions, considerable potential exists to improve not only the

  16. Moyamoya disease and syndromes: from genetics to clinical management

    Science.gov (United States)

    Guey, Stéphanie; Tournier-Lasserve, Elisabeth; Hervé, Dominique; Kossorotoff, Manoelle

    2015-01-01

    Moyamoya angiopathy is characterized by a progressive stenosis of the terminal portion of the internal carotid arteries and the development of a network of abnormal collateral vessels. This chronic cerebral angiopathy is observed in children and adults. It mainly leads to brain ischemic events in children, and to ischemic and hemorrhagic events in adults. This is a rare condition, with a marked prevalence gradient between Asian countries and Western countries. Two main nosological entities are identified. On the one hand, moyamoya disease corresponds to isolated moyamoya angiopathy, defined as being “idiopathic” according to the Guidelines of the Research Committee on the Pathology and Treatment of Spontaneous Occlusion of the Circle of Willis. This entity is probably multifactorial and polygenic in most patients. On the other hand, moyamoya syndrome is a moyamoya angiopathy associated with an underlying condition and forms a very heterogeneous group with various clinical presentations, various modes of inheritance, and a variable penetrance of the cerebrovascular phenotype. Diagnostic and evaluation techniques rely on magnetic resonance imaging (MRI), magnetic resonance angiography (MRA) conventional angiography, and cerebral hemodynamics measurements. Revascularization surgery can be indicated, with several techniques. Characteristics of genetic moyamoya syndromes are presented, with a focus on recently reported mutations in BRCC3/MTCP1 and GUCY1A3 genes. Identification of the genes involved in moyamoya disease and several monogenic moyamoya syndromes unraveled different pathways involved in the development of this angiopathy. Studying genes and pathways involved in monogenic moyamoya syndromes may help to give insights into pathophysiological models and discover potential candidates for medical treatment strategies. PMID:25733922

  17. 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.

  18. Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies.

    Science.gov (United States)

    Oyrer, Julia; Maljevic, Snezana; Scheffer, Ingrid E; Berkovic, Samuel F; Petrou, Steven; Reid, Christopher A

    2018-01-01

    Epilepsy is a common and serious neurologic disease with a strong genetic component. Genetic studies have identified an increasing collection of disease-causing genes. The impact of these genetic discoveries is wide reaching-from precise diagnosis and classification of syndromes to the discovery and validation of new drug targets and the development of disease-targeted therapeutic strategies. About 25% of genes identified in epilepsy encode ion channels. Much of our understanding of disease mechanisms comes from work focused on this class of protein. In this study, we review the genetic, molecular, and physiologic evidence supporting the pathogenic role of a number of different voltage- and ligand-activated ion channels in genetic epilepsy. We also review proposed disease mechanisms for each ion channel and highlight targeted therapeutic strategies. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  19. Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors

    Science.gov (United States)

    Goldman, Jill S.; Hahn, Susan E.; Catania, Jennifer Williamson; LaRusse-Eckert, Susan; Butson, Melissa Barber; Rumbaugh, Malia; Strecker, Michelle N.; Roberts, J. Scott; Burke, Wylie; Mayeux, Richard; Bird, Thomas

    2012-01-01

    Alzheimer disease is the most common cause of dementia. It occurs worldwide and affects all ethnic groups. The incidence of Alzheimer disease is increasing due, in part, to increased life expectancy and the aging baby boomer generation. The average lifetime risk of developing Alzheimer disease is 10–12%. This risk at least doubles with the presence of a first-degree relative with the disorder. Despite its limited utility, patients express concern over their risk and, in some instances, request testing. Furthermore, research has demonstrated that testing individuals for apoli-poprotein E can be valuable and safe in certain contexts. However, because of the complicated genetic nature of the disorder, few clinicians are prepared to address the genetic risks of Alzheimer disease with their patients. Given the increased awareness in family history thanks to family history campaigns, the increasing incidence of Alzheimer disease, and the availability of direct to consumer testing, patient requests for information is increasing. This practice guideline provides clinicians with a framework for assessing their patients’ genetic risk for Alzheimer disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for AD. PMID:21577118

  20. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors.

    Science.gov (United States)

    Goldman, Jill S; Hahn, Susan E; Catania, Jennifer Williamson; LaRusse-Eckert, Susan; Butson, Melissa Barber; Rumbaugh, Malia; Strecker, Michelle N; Roberts, J Scott; Burke, Wylie; Mayeux, Richard; Bird, Thomas

    2011-06-01

    Alzheimer disease is the most common cause of dementia. It occurs worldwide and affects all ethnic groups. The incidence of Alzheimer disease is increasing due, in part, to increased life expectancy and the aging baby boomer generation. The average lifetime risk of developing Alzheimer disease is 10-12%. This risk at least doubles with the presence of a first-degree relative with the disorder. Despite its limited utility, patients express concern over their risk and, in some instances, request testing. Furthermore, research has demonstrated that testing individuals for apolipoprotein E can be valuable and safe in certain contexts. However, because of the complicated genetic nature of the disorder, few clinicians are prepared to address the genetic risks of Alzheimer disease with their patients. Given the increased awareness in family history thanks to family history campaigns, the increasing incidence of Alzheimer disease, and the availability of direct to consumer testing, patient requests for information is increasing. This practice guideline provides clinicians with a framework for assessing their patients' genetic risk for Alzheimer disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for AD.

  1. Patient with rapidly evolving neurological disease with neuropathological lesions of Creutzfeldt-Jakob disease, Lewy body dementia, chronic subcortical vascular encephalopathy and meningothelial meningioma.

    Science.gov (United States)

    Vita, Maria Gabriella; Tiple, Dorina; Bizzarro, Alessandra; Ladogana, Anna; Colaizzo, Elisa; Capellari, Sabina; Rossi, Marcello; Parchi, Piero; Masullo, Carlo; Pocchiari, Maurizio

    2017-04-01

    We report a case of rapidly evolving neurological disease in a patient with neuropathological lesions of Creutzfeldt-Jakob disease (CJD), Lewy body dementia (LBD), chronic subcortical vascular encephalopathy and meningothelial meningioma. The coexistence of severe multiple pathologies in a single patient strengthens the need to perform accurate clinical differential diagnoses in rapidly progressive dementias. © 2016 Japanese Society of Neuropathology.

  2. Premature birth and diseases in premature infants: common genetic background?

    Science.gov (United States)

    Hallman, Mikko

    2012-04-01

    It has been proposed that during human evolution, development of obligate bipedalism, narrow birth canal cross-sectional area and the large brain have forced an adjustment in duration of pregnancy (scaling of gestational age; Plunkett 2011). Children compared to other mammals are born with proportionally small brains (compared to adult brains), suggesting shortening of pregnancy duration during recent evolution. Prevalence of both obstructed delivery and premature birth is still exceptionally high. In near term infants, functional maturity and viability is high, and gene variants predisposing to respiratory distress syndrome (RDS) are rare. Advanced antenatal and neonatal treatment practices during the new era of medicine allowed survival of also very preterm infants (gestation premature birth. Specific genes associating with diseases in preterm infants may also contribute to the susceptibility to preterm birth. Understanding and applying the knowledge of genetic interactions in normal and abnormal perinatal-neonatal development requires large, well-structured population cohorts, studies involving the whole genome and international interdisciplinary collaboration.

  3. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    Heintz-Buschart, Anna; Pandey, Urvashi; Wicke, Tamara; Sixel-Döring, Friederike; Janzen, Annette; Sittig-Wiegand, Elisabeth; Trenkwalder, Claudia; Oertel, Wolfgang H; Mollenhauer, Brit; Wilmes, Paul

    2017-08-26

    Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD. To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals. Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed. Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms. Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement

  4. Joint modeling of genetically correlated diseases and functional annotations increases accuracy of polygenic risk prediction.

    Directory of Open Access Journals (Sweden)

    Yiming Hu

    2017-06-01

    Full Text Available Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes. In this work, we introduce PleioPred, a principled framework that leverages pleiotropy and functional annotations in genetic risk prediction for complex diseases. PleioPred uses GWAS summary statistics as its input, and jointly models multiple genetically correlated diseases and a variety of external information including linkage disequilibrium and diverse functional annotations to increase the accuracy of risk prediction. Through comprehensive simulations and real data analyses on Crohn's disease, celiac disease and type-II diabetes, we demonstrate that our approach can substantially increase the accuracy of polygenic risk prediction and risk population stratification, i.e. PleioPred can significantly better separate type-II diabetes patients with early and late onset ages, illustrating its potential clinical application. Furthermore, we show that the increment in prediction accuracy is significantly correlated with the genetic correlation between the predicted and jointly modeled diseases.

  5. Evidence that implicit assumptions of 'no evolution' of disease vectors in changing environments can be violated on a rapid timescale.

    Science.gov (United States)

    Egizi, Andrea; Fefferman, Nina H; Fonseca, Dina M

    2015-04-05

    Projected impacts of climate change on vector-borne disease dynamics must consider many variables relevant to hosts, vectors and pathogens, including how altered environmental characteristics might affect the spatial distributions of vector species. However, many predictive models for vector distributions consider their habitat requirements to be fixed over relevant time-scales, when they may actually be capable of rapid evolutionary change and even adaptation. We examine the genetic signature of a spatial expansion by an invasive vector into locations with novel temperature conditions compared to its native range as a proxy for how existing vector populations may respond to temporally changing habitat. Specifically, we compare invasions into different climate ranges and characterize the importance of selection from the invaded habitat. We demonstrate that vector species can exhibit evolutionary responses (altered allelic frequencies) to a temperature gradient in as little as 7-10 years even in the presence of high gene flow, and further, that this response varies depending on the strength of selection. We interpret these findings in the context of climate change predictions for vector populations and emphasize the importance of incorporating vector evolution into models of future vector-borne disease dynamics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  6. How will insights from genetics translate to clinical practice in inflammatory bowel disease?

    NARCIS (Netherlands)

    Festen, E. A. M.; Weersma, R. K.

    Inflammatory bowel disease, consisting of Crohn's disease and ulcerative colitis, is a chronic inflammatory disease of the gut, which arises through an excessive immune response to the normal gut flora in a genetically susceptible host. The disease affects predominantly young adults and due to its

  7. Rapid genetically modified organism (GMO screening of various food products and animal feeds using multiplex polymerase chain reaction (PCR

    Directory of Open Access Journals (Sweden)

    Lisha, V.

    2017-01-01

    Full Text Available modified crops which brought up a controversy on the safety usage of genetically modified organisms (GMOs. It has been implemented globally that all GMO products and its derived ingredients should have regulations on the usage and labelling. Thus, it is necessary to develop methods that allow rapid screening of GMO products to comply with the regulations. This study employed a reliable and flexible multiplex polymerase chain reaction (PCR method for the rapid detection of transgenic elements in genetically modified soy and maize along with the soybean LECTIN gene and maize ZEIN gene respectively. The selected four common transgenic elements were 35S promoter (35S; Agrobacterium tumefaciens nopaline synthase terminator (NOS; 5-enolypyruvylshikimate-3-phosphate synthase (epsps gene; and Cry1Ab delta-endotoxin (cry1Ab gene. Optimization of the multiplex PCR methods were carried out by using 1% Roundup ReadyTM Soybean (RRS as the certified reference material for soybean that produced fourplex PCR method detecting 35S promoter, NOS terminator, epsps gene and soybean LECTIN gene and by using 1% MON810 as the certified reference material for maize that produced triplex PCR method detecting 35S promoter, cry1Ab gene and maize ZEIN gene prior to screening of the GMO traits in various food products and animal feeds. 1/9 (11.1% of the animal feed contained maize and 1/15 (6.7% of the soybean food products showed positive results for the detection of GMO transgenic gene. None of the maize food products showed positive results for GMO transgenic gene. In total, approximately 4% of the food products and animal feed were positive as GMO. This indicated GMOs have not widely entered the food chain. However, it is necessary to have an appropriate screening method due to GMOs’ unknown potential risk to humans and to animals. This rapid screening method will provide leverage in terms of being economically wise, time saving and reliable.

  8. Using a new molecular genetic of genotype and liquid culture medium for rapid diagnosis tb

    Directory of Open Access Journals (Sweden)

    Ганна Іванівна Барбова

    2015-10-01

    Full Text Available This paper presents the results of molecular genetic test system GenoType multyresistentens MTBDRplus. It was established that the presence of mutations associated with resistance to isoniazid, only 93.1 % of cases of MBT to isoniazid during the test in a liquid medium. Work carried out under the National Programme to combat tuberculosisMaterials and methods. We investigated the clinical sputum samples from patients with pulmonary tuberculosis. The applied system GenoType. Principle DNA strip technology GenoType is that the DNA-coated strip specific test that are complementary to the derived PCR amplicon. After the single-stranded amplicon denaturation associated with tests on strip (hybridize, and visualized in a sequential enzymatic reaction with streptavydynom and alkaline phosphatase. Evaluation of hybridization is performed automatically. For culturing sputum liquid culture medium used - Middlebrook broth 7N9 VASTES MGIT system.Results and discussion. The results of molecular genetic studies of samples of sputum-concentrated and concentrated by a system GenoType not differed (P>0.05. Diagnostic value of two methods (molecular and genetic – system GenoType and phenotype – VASTES MGIT 960 system was very high (100%. Two systems have tested positive in the study 756 (95.5 % Mycobacterium strains that were identified in the system VASTES MGIT 960, formed Cord Factor and the results were positive identification test ID MTB MGIT they attributed to Mycobacterium tuberculosis complex. 36 (4.5 % samples from positive MGIT tubes were negative. As a result of molecular-genetic identification of nontuberculous mycobacteria complex it was found that 18 (2.3 % strains of mycobacteria belonging to the M. avium-intracellulare, 12 (1.5 % mycobacterial cultures were attributed to M. kansasii, 6 (0, 7 % cultures were identified as M. fortuitum. The results of the molecular study of MS on Mycobacterium resistance profile INN + RIF coincided in 95.5 % (894

  9. Comparative genetics of disease resistance within the solanaceae.

    Science.gov (United States)

    Grube, R C; Radwanski, E R; Jahn, M

    2000-06-01

    Genomic positions of phenotypically defined disease resistance genes (R genes) and R gene homologues were analyzed in three solanaceous crop genera, Lycopersicon (tomato), Solanum (potato), and Capsicum (pepper). R genes occurred at corresponding positions in two or more genomes more frequently than expected by chance; however, in only two cases, both involving Phytophthora spp., did genes at corresponding positions have specificity for closely related pathogen taxa. In contrast, resistances to Globodera spp., potato virus Y, tobacco mosaic virus, and tomato spotted wilt virus were mapped in two or more genera and did not occur in corresponding positions. Without exception, pepper homologues of the cloned R genes Sw-5, N, Pto, Prf, and I2 were found in syntenous positions in other solanaceous genomes and in some cases also mapped to additional positions near phenotypically defined solanaceous R genes. This detailed analysis and synthesis of all available data for solanaceous R genes suggests a working hypothesis regarding the evolution of R genes. Specifically, while the taxonomic specificity of host R genes may be evolving rapidly, general functions of R alleles (e.g., initiation of resistance response) may be conserved at homologous loci in related plant genera.

  10. Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis.

    Science.gov (United States)

    Egüez, Karina E; Alonso-Padilla, Julio; Terán, Carolina; Chipana, Zenobia; García, Wilson; Torrico, Faustino; Gascon, Joaquim; Lozano-Beltran, Daniel-Franz; Pinazo, María-Jesús

    2017-04-01

    Chagas disease is caused by the parasite Trypanosoma cruzi. It affects several million people, mainly in Latin America, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. Disease acute stage is mostly asymptomatic and infection goes undiagnosed. In the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like ELISA or indirect hemagglutination assays. Agreement in at least two tests must be obtained due to parasite wide antigenic variability. These techniques require equipped labs and trained personnel and are not available in distant regions. As a result, many infected people often remain undiagnosed until it is too late, as the two available chemotherapies show diminished efficacy in the advanced chronic stage. Easy-to-use rapid diagnostic tests have been developed to be implemented in remote areas as an alternative to conventional tests. They do not need electricity, nor cold chain, they can return results within an hour and some even work with whole blood as sample, like Chagas Stat-Pak (ChemBio Inc.) and Chagas Detect Plus (InBIOS Inc.). Nonetheless, in order to qualify a rapidly diagnosed positive patient for treatment, conventional serological confirmation is obligatory, which might risk its start. In this study two rapid tests based on distinct antigen sets were used in parallel as a way to obtain a fast and conclusive Chagas disease diagnosis using whole blood samples. Chagas Stat-Pak and Chagas Detect Plus were validated by comparison with three conventional tests yielding 100% sensitivity and 99.3% specificity over 342 patients seeking Chagas disease diagnosis in a reference centre in Sucre (Bolivia). Combined used of RDTs in distant regions could substitute laborious conventional serology, allowing immediate treatment and favouring better adhesion to it.

  11. Genetics Home Reference: glycogen storage disease type I

    Science.gov (United States)

    ... storage disease type I glycogen storage disease type I Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Glycogen storage disease type I (also known as GSDI or von Gierke disease) ...

  12. Clinical implications of shared genetics and pathogenesis in autoimmune diseases

    NARCIS (Netherlands)

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

    2013-01-01

    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the

  13. [Rapid first-tier genetic diagnosis in patients with Prader-Willi syndrome].

    Science.gov (United States)

    Ács, Orsolya Dóra; Péterfia, Bálint; Hollósi, Péter; Haltrich, Irén; Sallai, Ágnes; Luczay, Andrea; Buiting, Karin; Horsthemke, Bernhard; Török, Dóra; Szabó, András; Fekete, György

    2018-01-01

    According to the international literature, DNA methylation analysis of the promoter region of SNRPN locus is the most efficient way to start genetic investigation in patients with suspected Prader-Willi syndrome. Our aim was to develop a simple, reliable first-tier diagnosis to confirm Prader-Willi syndrome, therefore to compare our self-designed simple, cost-efficient high-resolution melting analysis and the most commonly used methylation-specific multiplex ligation-dependent probe amplification to confirm Prader-Willi syndrome. We studied 17 clinically suspected Prader-Willi syndrome children and their DNA samples. With self-designed primers, bisulfite-sensitive polymerase chain reaction, high-resolution melting analysis and, as a control, methylation-specific multiplex ligation-dependent probe amplification were performed. Prader-Willi syndrome was genetically confirmed in 6 out of 17 clinically suspected Prader-Willi syndrome patients. The results of high-resolution melting analysis and methylation-specific multiplex ligation-dependent probe amplification were equivalent in each case. Using our self-designed primers and altered bisulfite-specific PCR conditions, high-resolution melting analysis appears to be a simple, fast, reliable and effective method for primarily proving or excluding clinically suspected Prade-Willi syndrome cases. Orv Hetil. 2018; 159(2): 64-69.

  14. Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly.

    Science.gov (United States)

    Torella, Joseph P; Boehm, Christian R; Lienert, Florian; Chen, Jan-Hung; Way, Jeffrey C; Silver, Pamela A

    2014-01-01

    In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminator parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates.

  15. Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly

    Energy Technology Data Exchange (ETDEWEB)

    Torella, JP; Boehm, CR; Lienert, F; Chen, JH; Way, JC; Silver, PA

    2013-12-28

    In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminator parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates.

  16. Rise and fall of a wolf population: genetic diversity and structure during recovery, rapid expansion and drastic decline.

    Science.gov (United States)

    Jansson, E; Ruokonen, M; Kojola, I; Aspi, J

    2012-11-01

    The grey wolves (Canis lupus) of Finland have had a varied history, with a period of rapid population expansion after the mid-1990s followed by a decline with a current census size of about 140 wolves. Here, we investigate the impact of unstable population size and connectivity on genetic diversity and structure in a long-term genetic study of 298 Finnish wolves born in 1995-2009 and genotyped for 17 microsatellite loci. During the initial recovery and prior to population expansion, genetic diversity was high (1995-1997: LD-N(e)  = 67.2; H(o)  = 0.749; H(e)  = 0.709) despite a small census size and low number of breeders (N(c)  < 100; N(b)  < 10) likely reflecting the status of the Russian source population. Surprisingly, observed heterozygosity decreased significantly during the study period (t = -2.643, P = 0.021) despite population expansion, likely a result of an increase in inbreeding (F(IS)  = 0.108 in 2007-2009) owing to a low degree of connectivity with adjacent Russian wolf population (m = 0.016-0.090; F(ST)  = 0.086, P < 0.001) and population crash after 2006. However, population growth had a temporary positive impact on N(e) and number of family lines. This study shows that even strong population growth alone might not be adequate to retain genetic diversity, especially when accompanied with low amount of subsequent gene flow and population decline. © 2012 Blackwell Publishing Ltd.

  17. Rapid DNA extraction protocol from stool, suitable for molecular genetic diagnosis of colon cancer.

    Science.gov (United States)

    Abbaszadegan, Mohammad Reza; Velayati, Arash; Tavasoli, Alireza; Dadkhah, Ezzat

    2007-07-01

    Colorectal cancer (CRC) is one of the most common forms of cancers in the world and is curable if diagnosed at the early stage. Analysis of DNA extracted from stool specimens is a recent advantage to cancer diagnostics. Many protocols have been recommended for DNA extraction from stool, and almost all of them are difficult and time consuming, dealing with high amount of toxic materials like phenol. Their results vary due to sample collection method and further purification treatment. In this study, an easy and rapid method was optimized for isolating the human DNA with reduced PCR inhibitors present in stool. Fecal samples were collected from 10 colonoscopy-negative adult volunteers and 10 patients with CRC. Stool (1 g) was extracted using phenol/chloroform based protocol. The amplification of P53 exon 9 was examined to evaluate the extraction efficiency for human genomic targets and also compared its efficiency with Machiels et al. and Ito et al. protocols. The amplification of exon 9 of P53 from isolated fecal DNA was possible in most cases in 35 rounds of PCR using no additional purification procedure for elimination of the remaining inhibitors.inhibitors. A useful, rapid and easy protocol for routine extraction of DNA from stool was introduced and compared with two previous protocols.

  18. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

    OpenAIRE

    Hensman Moss, Davina J; Pardinas, Antonio; Langbehn, Douglas; Lo, Kitty; Leavitt, Blair R; Roos, Raymund; Durr, Alexandra; Mead, Simon; Holmans, Peter; Jones, Lesley; Tabrizi, Sarah J; Coleman, A; Santos, R Dar; Decolongon, J; Sturrock, A

    2017-01-01

    Background\\ud \\ud Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.\\ud \\ud Methods\\ud \\ud We generated a progression score on the basis of principal ...

  19. A method for identifying genetic heterogeneity within phenotypically defined disease subgroups.

    Science.gov (United States)

    Liley, James; Todd, John A; Wallace, Chris

    2017-02-01

    Many common diseases show wide phenotypic variation. We present a statistical method for determining whether phenotypically defined subgroups of disease cases represent different genetic architectures, in which disease-associated variants have different effect sizes in two subgroups. Our method models the genome-wide distributions of genetic association statistics with mixture Gaussians. We apply a global test without requiring explicit identification of disease-associated variants, thus maximizing power in comparison to standard variant-by-variant subgroup analysis. Where evidence for genetic subgrouping is found, we present methods for post hoc identification of the contributing genetic variants. We demonstrate the method on a range of simulated and test data sets, for which expected results are already known. We investigate subgroups of individuals with type 1 diabetes (T1D) defined by autoantibody positivity, establishing evidence for differential genetic architecture with positivity for thyroid-peroxidase-specific antibody, driven generally by variants in known T1D-associated genomic regions.

  20. Genetic Mutation Analysis of Parkinson's Disease Patients Using Multigene Next-Generation Sequencing Panels.

    Science.gov (United States)

    Gorostidi, Ana; Martí-Massó, José Félix; Bergareche, Alberto; Rodríguez-Oroz, Mari Cruz; López de Munain, Adolfo; Ruiz-Martínez, Javier

    2016-10-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of people. Genome-wide association studies (GWAS) have found >25 genetic risk factors and at least 15 loci directly associated with PD. Recent advances in new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent platform, make multigene sequencing cheaper, faster, and more reliable. Our objective was to test the power of this next-generation sequencing technology to analyze large samples by screening the majority of the most relevant PD-related genes known for single and compound mutations. To archive a rapid, robust, and cost-effective genetic analysis of a PD cohort, we designed a multiplex, polymerase chain reaction (PCR)-based primer panel to amplify and sequence coding exons of 15 PD-associated genes (SNCA, LRRK2, PARK2, PINK1, PARK7, GIGYF2, ATP13A2, UCHL1, PLA2G6, FBXO7, EIF4G1, VPS35, ACMSD, APOE, and GBA). We conducted parallel sequencing using the Ion Torrent Personal Genome Machine(®) system to detect mutations in 92 blood DNA samples from PD patients. After bioinformatics analysis and filtering, 95.13 % coverage of the targeted region was obtained at >40-fold mean coverage. The results revealed 44 previously documented variants in these 15 genes, with five revealed as pathogenic. We also discovered six novel variants, five of which had an in silico prediction of being pathogenic. Benchtop next-generation sequencing is a powerful method for genetic screening for PD. Our results indicated that it yielded a high frequency of discovery (66 %; n = 92) of variants in carriers from an enriched Spanish PD sample.

  1. Hope and major strides for genetic diseases of the eye

    Indian Academy of Sciences (India)

    2009-12-31

    Dec 31, 2009 ... erful molecular biology instrumentation and techniques, the completion of the human genome project, an increasing in- terest in the study of these ..... 2001 Update on the molecular genetics of retinitis pigmentosa. Ophthalmic Genet. 22, 133–154. Weiss J. S., Moller H. U., Lisch W., Kinoshita S., Aldave A. J.,.

  2. EDITORIAL Clinical issues in genetic testing for multifactorial diseases

    African Journals Online (AJOL)

    Technological advances in genomics are shifting the genetic testing paradigm, from testing targeted mutations in selected genes to testing whole genes and even whole genomes. These exciting developments raise numerous practical pitfalls and ethical issues. Two articles in this issue of the SAMJ address genetic testing ...

  3. genetic variability for tuber yield, quality, and virus disease complex ...

    African Journals Online (AJOL)

    Administrator

    Some cultivars e.g. Munyeera, New Kawogo, Silk and Sowola which showed high flowering ability failed to fertilise and set seed when crossed to specific cultivars. Preliminary genetic analysis for yield and quality following crossing elite 7 female and 6 male cultivars in a North Carolina 2 mating design showed wide genetic.

  4. The Role of Genetic Counseling in Pompe Disease After Patients Are Identified Through Newborn Screening.

    Science.gov (United States)

    Atherton, Andrea M; Day-Salvatore, Debra

    2017-07-01

    An important part of the coordinated care by experienced health care teams for all Pompe disease patients, whether diagnosed through newborn screening (NBS), clinical diagnosis, or prenatal diagnosis, is genetic counseling. Genetic counseling helps families better understand medical recommendations and options presented by the patient's health care team so they can make informed decisions. In addition to providing important information about the inheritance and genetic risks, genetic counseling also provides information about Pompe disease and available treatments and resources and should be offered to families with an affected child and all adults diagnosed with Pompe disease. Although the need for genetic counseling after a positive newborn screen for Pompe disease is recognized, the role that genetic counseling plays for both families of affected patients and health care teams is not fully understood. Consistent best genetic counseling practices also are lacking. The guidance in this article in the "Newborn Screening, Diagnosis, and Treatment for Pompe Disease" supplement is derived from expert consensus from the Pompe Disease Newborn Screening Working Group. It is intended to help guide genetic counseling efforts and provide a clear understanding of the role for families or carriers of Pompe disease identified through NBS; explain special considerations (eg, diagnosis of late-onset Pompe disease before the appearance of symptoms) and the impact and implications associated with a diagnosis (eg, determination of genetic risk and carrier status and preconception counseling); and provide health care teams caring for patients with a framework for a standardized approach to genetic counseling for patients and at-risk family members. Copyright © 2017 by the American Academy of Pediatrics.

  5. A Case of Sarcoidosis with Interstitial Lung Disease Mimicking Clinically Amyopathic Dermatomyositis and Rapidly Progressive Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Shinji Sato

    2014-01-01

    Full Text Available Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM with rapidly progressive interstitial lung disease (RP-ILD was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis.

  6. A Case of Sarcoidosis with Interstitial Lung Disease Mimicking Clinically Amyopathic Dermatomyositis and Rapidly Progressive Interstitial Lung Disease

    Science.gov (United States)

    Nogi, Shinichi; Sasaki, Noriko; Chinen, Naofumi; Honda, Kiri; Saito, Eiko; Wakabayashi, Takayuki; Yamada, Chiho; Suzuki, Yasuo

    2014-01-01

    Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD) was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM) from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis. PMID:25431723

  7. Emerging infectious disease leads to rapid population declines of common British birds.

    Directory of Open Access Journals (Sweden)

    Robert A Robinson

    Full Text Available Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period.

  8. Emerging Infectious Disease Leads to Rapid Population Declines of Common British Birds

    Science.gov (United States)

    Toms, Mike P.; Peck, Kirsi M.; Kirkwood, James K.; Chantrey, Julian; Clatworthy, Innes R.; Evans, Andy D.; Hughes, Laura A.; Hutchinson, Oliver C.; John, Shinto K.; Pennycott, Tom W.; Perkins, Matthew W.; Rowley, Peter S.; Simpson, Vic R.; Tyler, Kevin M.; Cunningham, Andrew A.

    2010-01-01

    Emerging infectious diseases are increasingly cited as threats to wildlife, livestock and humans alike. They can threaten geographically isolated or critically endangered wildlife populations; however, relatively few studies have clearly demonstrated the extent to which emerging diseases can impact populations of common wildlife species. Here, we report the impact of an emerging protozoal disease on British populations of greenfinch Carduelis chloris and chaffinch Fringilla coelebs, two of the most common birds in Britain. Morphological and molecular analyses showed this to be due to Trichomonas gallinae. Trichomonosis emerged as a novel fatal disease of finches in Britain in 2005 and rapidly became epidemic within greenfinch, and to a lesser extent chaffinch, populations in 2006. By 2007, breeding populations of greenfinches and chaffinches in the geographic region of highest disease incidence had decreased by 35% and 21% respectively, representing mortality in excess of half a million birds. In contrast, declines were less pronounced or absent in these species in regions where the disease was found in intermediate or low incidence. Also, populations of dunnock Prunella modularis, which similarly feeds in gardens, but in which T. gallinae was rarely recorded, did not decline. This is the first trichomonosis epidemic reported in the scientific literature to negatively impact populations of free-ranging non-columbiform species, and such levels of mortality and decline due to an emerging infectious disease are unprecedented in British wild bird populations. This disease emergence event demonstrates the potential for a protozoan parasite to jump avian host taxonomic groups with dramatic effect over a short time period. PMID:20805869

  9. Clinical usefulness of multiplex PCR lateral flow in MRSA detection: a novel, rapid genetic testing method.

    Science.gov (United States)

    Nihonyanagi, Shin; Kanoh, Yuhsaku; Okada, Kiyomi; Uozumi, Toshiki; Kazuyama, Yukumasa; Yamaguchi, Tokiko; Nakazaki, Nobuhiko; Sakurai, Keizou; Hirata, Yasuyoshi; Munekata, Shinichi; Ohtani, Shinichi; Takemoto, Tsuyoshi; Bandoh, Yuki; Akahoshi, Tohru

    2012-06-01

    Methicillin-resistant Staphylococcus aureus (MRSA) with exogenous cassette DNA containing the methicillin-resistant gene mecA (SCCmec) poses a problem as a drug-resistant bacterium responsible for hospital- and community-acquired infections. The frequency of MRSA detection has recently been increasing rapidly in Japan, and SCCmec has also been classified more diversely into types I-V. A rapid test is essential for early diagnosis and treatment of MRSA infections, but detection by conventional methods requires at least two days. The newly developed multiplex PCR lateral flow method allows specific amplification of femA to detect S. aureus, mecA to detect SCCmec, and kdpC to detect SCCmec type II; moreover, PCR products can be evaluated visually in about 3 h. In the present study, we developed a PCR lateral flow method for MRSA using this method and investigated its clinical usefulness in the detection of MRSA. The results showed a diagnostic concordance rate of 91.7% for MRSA and methicillin-susceptible S. aureus between bacteriological examination and PCR lateral flow, and a high level of specificity in PCR lateral flow. In addition, a higher detection rate for S. aureus using the same sample was observed for PCR lateral flow (70.2%) than for bacteriological tests (48.6%). The above results show that PCR lateral flow for MRSA detection has high sensitivity, specificity, and speed, and its clinical application as a method for early diagnosis of MRSA infections appears to be feasible.

  10. Rapid Genetic Adaptation during the First Four Months of Survival under Resource Exhaustion.

    Science.gov (United States)

    Avrani, Sarit; Bolotin, Evgeni; Katz, Sophia; Hershberg, Ruth

    2017-07-01

    Many bacteria, including the model bacterium Escherichia coli can survive for years within spent media, following resource exhaustion. We carried out evolutionary experiments, followed by whole genome sequencing of hundreds of evolved clones to study the dynamics by which E. coli adapts during the first 4 months of survival under resource exhaustion. Our results reveal that bacteria evolving under resource exhaustion are subject to intense selection, manifesting in rapid mutation accumulation, enrichment in functional mutation categories and extremely convergent adaptation. In the most striking example of convergent adaptation, we found that across five independent populations adaptation to conditions of resource exhaustion occurs through mutations to the three same specific positions of the RNA polymerase core enzyme. Mutations to these three sites are strongly antagonistically pleiotropic, in that they sharply reduce exponential growth rates in fresh media. Such antagonistically pleiotropic mutations, combined with the accumulation of additional mutations, severely reduce the ability of bacteria surviving under resource exhaustion to grow exponentially in fresh media. We further demonstrate that the three positions at which these resource exhaustion mutations occur are conserved for the ancestral E. coli allele, across bacterial phyla, with the exception of nonculturable bacteria that carry the resource exhaustion allele at one of these positions, at very high frequencies. Finally, our results demonstrate that adaptation to resource exhaustion is not limited by mutational input and that bacteria are able to rapidly adapt under resource exhaustion in a temporally precise manner through allele frequency fluctuations. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  11. Germline genetic variants with implications for disease risk and therapeutic outcomes.

    Science.gov (United States)

    Pasternak, Amy L; Ward, Kristen M; Luzum, Jasmine A; Ellingrod, Vicki L; Hertz, Daniel L

    2017-10-01

    Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics. The discussed relationships are diverse. Some of the agents are targeted for the disease-causing genetic variant, while others, although not targeted therapies, have implications for the disease they are used to treat. It is also possible that the disease implications of a genetic variant are unrelated to the pharmacogenomic implications. Some of these examples are considered clinically actionable pharmacogenes, with evidence-based, pharmacologic treatment recommendations, while others are still investigative as areas for additional research. It is important that clinicians are aware of both the disease and pharmacogenomic associations of these germline genetic variants to ensure patients are receiving comprehensive personalized care. Copyright © 2017 the American Physiological Society.

  12. Rapidly Progressive Encephalopathy: Initial Diagnosis of Creutzfeldt Jakob Disease in an Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Patrícia Afonso Mendes

    2017-01-01

    Full Text Available Creutzfeldt-Jakob disease (CJD is a rare, incurable and fatal condition that can only be confirmed through neuropathological investigation, such as brain biopsy or post-mortem study. However, a probable diagnosis can be made using clinical criteria. CJD manifests as rapidly progressive dementia with myoclonus and to a lesser extent visual impairment and cerebellar and pyramidal/extrapyramidal signs. We report the case of a previously independent adult male that met all the clinical criteria. Taken together, the investigation results suggested probable CJD.

  13. Ethical and social issues posed by genetic studies of cardiovascular disease.

    Science.gov (United States)

    Graham, J B

    Hereditary disorders of the cardiovascular system are caused by: 1) genetic change at a single locus (monogenic inheritance), 2) chromosomal abnormalities, and 3) a collection of genes which predispose to cardiovascular disease (polygenic inheritance). The types of genetic activity that create ethical and social problems are: 1) collection of family data, 2) screening of large populations for genetic defects, 3) gene therapy, 4) prenatal detection and selective abortion, and 5) genetic counseling. The types of genetic studies which are under way or in prospect are outlined.

  14. Ethical issues of genetic susceptibility testing for occupational diseases: opinions of trainees in a high-risk job

    NARCIS (Netherlands)

    Visser, M. J.; Rhebergen, M. D. F.; Kezic, S.; van Dijk, F. J. H.; Willems, D. L.; Verberk, M. M.

    2013-01-01

    Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are

  15. Genetic risk factors for the development of allergic disease identified by genome-wide association.

    Science.gov (United States)

    Portelli, M A; Hodge, E; Sayers, I

    2015-01-01

    An increasing proportion of the worldwide population is affected by allergic diseases such as allergic rhinitis (AR), atopic dermatitis (AD) and allergic asthma and improved treatment options are needed particularly for severe, refractory disease. Allergic diseases are complex and development involves both environmental and genetic factors. Although the existence of a genetic component for allergy was first described almost 100 years ago, progress in gene identification has been hindered by lack of high throughput technologies to investigate genetic variation in large numbers of subjects. The development of Genome-Wide Association Studies (GWAS), a hypothesis-free method of interrogating large numbers of common variants spanning the entire genome in disease and non-disease subjects has revolutionised our understanding of the genetics of allergic disease. Susceptibility genes for asthma, AR and AD have now been identified with confidence, suggesting there are common and distinct genetic loci associated with these diseases, providing novel insights into potential disease pathways and mechanisms. Genes involved in both adaptive and innate immune mechanisms have been identified, notably including multiple genes involved in epithelial function/secretion, suggesting that the airway epithelium may be particularly important in asthma. Interestingly, concordance/discordance between the genetic factors driving allergic traits such as IgE levels and disease states such as asthma have further supported the accumulating evidence for heterogeneity in these diseases. While GWAS have been useful and continue to identify novel genes for allergic diseases through increased sample sizes and phenotype refinement, future approaches will integrate analyses of rare variants, epigenetic mechanisms and eQTL approaches, leading to greater insight into the genetic basis of these diseases. Gene identification will improve our understanding of disease mechanisms and generate potential

  16. Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

    Science.gov (United States)

    Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

    2016-01-01

    Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for

  17. Nursing and genetic biobanks.

    Science.gov (United States)

    Sanner, Jennifer E; Yu, Erica; Udtha, Malini; Williams, Pamela Holtzclaw

    2013-12-01

    Biobanks function as vital components in genetic research, which often requires large disease-based or population-based biospecimens and clinical data to study complex or rare diseases. Genetic biobanks aim to provide resources for translational research focusing on rapidly moving scientific findings from the laboratory into health care practice. The nursing profession must evolve as genetic biobanking practices advance. Nursing involvement in genetic biobanking practices comes with a distinct set of educational, ethical, and practice competencies. In response to these growing competency standards, nursing science developed a conceptual framework and continues to study ethical considerations to guide genetic biobanking initiatives. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease.

    Science.gov (United States)

    Lang, B M; Biedermann, L; van Haaften, W T; de Vallière, C; Schuurmans, M; Begré, S; Zeitz, J; Scharl, M; Turina, M; Greuter, T; Schreiner, P; Heinrich, H; Kuntzen, T; Vavricka, S R; Rogler, G; Beerenwinkel, N; Misselwitz, B

    2017-10-20

    Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour. To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (PCrohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease. © 2017 John Wiley & Sons Ltd.

  19. Genetics Home Reference: Huntington disease-like syndrome

    Science.gov (United States)

    ... Twitter Home Health Conditions Huntington disease-like syndrome Huntington disease-like syndrome Printable PDF Open All Close ... collapse boxes. Description As its name suggests, a Huntington disease -like (HDL) syndrome is a condition that ...

  20. Genetics Home Reference: glycogen storage disease type VII

    Science.gov (United States)

    ... GSD) Disease InfoSearch: Phosphofructokinase Deficiency Johns Hopkins Medicine: Glycogen Storage Disease Merck Manual Consumer Version: Disorders of Carbohydrate Metabolism Muscular Dystrophy Association: Facts About Metabolic Diseases of ...