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Sample records for genetic screening study

  1. Prenatal screening and genetics

    DEFF Research Database (Denmark)

    Alderson, P; Aro, A R; Dragonas, T

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

  2. Prenatal screening and genetics

    NARCIS (Netherlands)

    Alderson, P.; Aro, A.R.; Dragonas, T.; Ettorre, E.; Hemminki, E.; Jalinoja, P.; Santalahti, P.; Tijmstra, T.

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we

  3. Prenatal screening and genetics

    NARCIS (Netherlands)

    Alderson, P.; Aro, A.R.; Dragonas, T.; Ettorre, E.; Hemminki, E.; Jalinoja, P.; Santalahti, P.; Tijmstra, T.

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we exami

  4. Prenatal screening and genetics

    DEFF Research Database (Denmark)

    Alderson, P; Aro, A R; Dragonas, T

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we ex...

  5. Prenatal Genetic Screening Tests

    Science.gov (United States)

    ... cells from the fetus or placenta obtained through amniocentesis or chorionic villus sampling (CVS) . FAQ164 “Prenatal Genetic ... should be followed by a diagnostic test with amniocentesis or CVS. The cell-free DNA screening test ...

  6. Testing for direct genetic effects using a screening step in family-based association studies

    Directory of Open Access Journals (Sweden)

    Sharon M Lutz

    2013-11-01

    Full Text Available In genome wide association studies (GWAS, families based studies tend to have less power to detect genetic associations than population based studies, such as case-control studies. This can be an issue when testing if genes in a family based GWAS have a direct effect on the phenotype of interest or if the genes act indirectly through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family based association test (FBAT approach similar to the conditional mean model approach in the VanSteen-algorithm [1]. Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.

  7. Optimal screening for genetic diseases.

    Science.gov (United States)

    Nævdal, Eric

    2014-12-01

    Screening for genetic diseases is performed in many regions and/or ethnic groups where there is a high prevalence of possibly malign genes. The propagation of such genes can be considered a dynamic externality. Given that many of these diseases are untreatable and give rise to truly tragic outcomes, they are a source of societal concern, and the screening process should perhaps be regulated. This paper incorporates a standard model of genetic propagation into an economic model of dynamic management to derive cost benefit rules for optimal screening. The highly non-linear nature of genetic dynamics gives rise to perhaps surprising results that include discontinuous controls and threshold effects. One insight is that any screening program that is in place for any amount of time should screen all individuals in a target population. The incorporation of genetic models may prove to be useful to several emerging fields in economics such as genoeconomics, neuroeconomics and paleoeconomics.

  8. Preliminary Study on Thalassemia Screening and Genetic Counseling in Selective Hmong People in Saraburi Province, Thailand

    Directory of Open Access Journals (Sweden)

    Pa Vang

    2008-01-01

    Full Text Available it can lead to the destruction of red blood cells. Studies have shown that there is a high prevalence of thalassemia in Southeast Asia. The Institute of Health Research, Chulalongkorn University developed a successful “Module” to screen for thalassemia in the Thai population, however, it has not been implemented in the minority population in Thailand. In this study, we investigated the feasibility of the newly developed educational and thalassemia screening program with the Hmong population. The primary aim of this study was to test this program. The secondary aim was to determine the prevalence of thalassemia in the Hmong and provide education. A third aim was to determine the reliability of two different screening methods in the Hmong population. A pre-test and post-test design was used; participants (N=12 were individuals residing in Thailand with the ability to read English and between the ages 18-50. The participants met twice with the researchers to complete the program. The first contact consisted of assessing participants’ knowledge about thalassemia, providing thalassemia information and education about genetic counseling, and drawing blood samples. The second contact consisted of assessing knowledge, providing a written report of individual blood sample results and counseling. The initial interview revealed that the majority of the participants (82% did not know anything about thalassemia prior to participation. The program was easy to understand by most participants (90%. Of the eleven Hmong participants, two tested positive for being a possible carrier for thalassemia. In order to reduce the prevalence of thalassemia, it is necessary to engage in risk reduction health services. The modified screening method proved to be as effective as the standard method. Therefore, the program can expand and be used in other regional populations with low cost.

  9. Judaism, genetic screening and genetic therapy.

    Science.gov (United States)

    Rosner, F

    1998-01-01

    Genetic screening, gene therapy and other applications of genetic engineering are permissible in Judaism when used for the treatment, cure, or prevention of disease. Such genetic manipulation is not considered to be a violation of God's natural law, but a legitimate implementation of the biblical mandate to heal. If Tay-Sachs disease, diabetes, hemophilia, cystic fibrosis, Huntington's disease or other genetic diseases can be cured or prevented by "gene surgery," then it is certainly permitted in Jewish law. Genetic premarital screening is encouraged in Judaism for the purpose of discouraging at-risk marriages for a fatal illness such as Tay-Sachs disease. Neonatal screening for treatable conditions such as phenylketonuria is certainly desirable and perhaps required in Jewish law. Preimplantation screening and the implantation of only "healthy" zygotes into the mother's womb to prevent the birth of an affected child are probably sanctioned in Jewish law. Whether or not these assisted reproduction techniques may be used to choose the sex of one's offspring, to prevent the birth of a child with a sex-linked disease such as hemophilia, has not yet been ruled on by modern rabbinic decisions. Prenatal screening with the specific intent of aborting an affected fetus is not allowed according to most rabbinic authorities, although a minority view permits it "for great need." Not to have children if both parents are carriers of genetic diseases such as Tay-Sachs is not a Jewish option. Preimplantation screening is preferable. All screening test results must remain confidential. Judaism does not permit the alteration or manipulation of physical traits and characteristics such as height, eye and hair color, facial features and the like, when such change provides no useful benefit to mankind. On the other hand, it is permissible to clone organisms and microorganisms to facilitate the production of insulin, growth hormone, and other agents intended to benefit mankind and to

  10. Genetic studies of Polish migraine patients: screening for causative mutations in four migraine-associated genes.

    Science.gov (United States)

    Domitrz, Izabela; Kosiorek, Michalina; Żekanowski, Cezary; Kamińska, Anna

    2016-01-08

    Migraine is the most common neurological disorder, affecting approximately 12 % of the adult population worldwide, caused by both environmental and genetic factors. Three causative genes have been identified in familial hemiplegic migraine (FHM) families: CACNA1A, ATP1A2, and SCNA1A. Recently, several mutations in KCNK18 have also been found as causative factors in migraine development. The aim of our study was to identify the genetic background of migraine in the Polish population. Sixty patients with migraine without aura (MO) or with different types of migraine with aura (MA), including sporadic hemiplegic, familial hemiplegic, and probable familial hemiplegic, were screened for mutations in the four genes previously linked with different types of migraine (ATP1A2, CACNA1A, SCN1A, and KCNK18). Two missense mutations were found. One novel mutation in SCN1A, encoding α subunit of sodium channel, causing amino acid change M1500V localized to a region encoding inactivation loop between transmembrane domains III and IV of the channel, was detected in a female FHM patient. The M1500V mutation was absent in a group of 62 controls, as well as in the ExAC database. The second, already known missense mutation S231P in KCNK18 was found in a female MA patient. Additionally, a novel intronic polymorphism possibly affecting alternative splicing of SCN1A, at chr2:16685249, g.77659T>C, and c.4581+32A>G, located between exons 24 and 25, in a region encoding the inactivation loop of the sodium channel was found in a female MO patient. No mutations in ATP1A2 or CACNA1A were found in the study group. The presence of SCN1A mutations and absence of mutations in ATP1A2 or CACNA1A suggest that the Polish patients represent FHM type 3. On the other hand, the presence of KCNK18 mutation indicated another FHM subtype. It could be speculated that contrary to other European populations, the genetic basis of migraine in the Polish population involves mutations in genes not included in the

  11. Newborn genetic screening: blessing or curse?

    Science.gov (United States)

    Kenner, C; Amlung, S

    1999-10-01

    Newly discovered genes and advances in genetic screening programs prompt many questions reflecting the kinds of ethical dilemmas that go hand in hand with life-changing discoveries. Neonatal genetic screening has been a standard of care for some time, but as our knowledge in the field of genetics expands, should we continue with the same approach? What newborn genetic screening tests should be mandatory, and what are the long-range consequences associated with testing? This article reviews genetic modes of inheritance, outlines and explains the most common newborn screening tests, and enumerates the ethical issues associated with these screening procedures. The role of the neonatal nurse in the newborn genetic screening process is discussed.

  12. Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies

    Science.gov (United States)

    Carreño, Oriel; Corominas, Roser; Serra, Selma Angèlica; Sintas, Cèlia; Fernández-Castillo, Noèlia; Vila-Pueyo, Marta; Toma, Claudio; Gené, Gemma G; Pons, Roser; Llaneza, Miguel; Sobrido, María-Jesús; Grinberg, Daniel; Valverde, Miguel Ángel; Fernández-Fernández, José Manuel; Macaya, Alfons; Cormand, Bru

    2013-01-01

    Hemiplegic migraine (HM) is a rare and severe subtype of autosomal dominant migraine, characterized by a complex aura including some degree of motor weakness. Mutations in four genes (CACNA1A, ATP1A2, SCN1A and PRRT2) have been detected in familial and in sporadic cases. This genetically and clinically heterogeneous disorder is often accompanied by permanent ataxia, epileptic seizures, mental retardation, and chronic progressive cerebellar atrophy. Here we report a mutation screening in the CACNA1A and ATP1A2 genes in 18 patients with HM. Furthermore, intragenic copy number variant (CNV) analysis was performed in CACNA1A using quantitative approaches. We identified four previously described missense CACNA1A mutations (p.Ser218Leu, p.Thr501Met, p.Arg583Gln, and p.Thr666Met) and two missense changes in the ATP1A2 gene, the previously described p.Ala606Thr and the novel variant p.Glu825Lys. No structural variants were found. This genetic screening allowed the identification of more than 30% of the disease alleles, all present in a heterozygous state. Functional consequences of the CACNA1A-p.Thr501Met mutation, previously described only in association with episodic ataxia, and ATP1A2-p.Glu825Lys, were investigated by means of electrophysiological studies, cell viability assays or Western blot analysis. Our data suggest that both these variants are disease-causing. PMID:24498617

  13. Genetical studies of resistance to Phytophthora porri in Allium porrum, using a new early screening method.

    NARCIS (Netherlands)

    Smilde, W.D.; Nes, van M.; Reinink, K.; Kik, C.

    1997-01-01

    A new screening method was developed to evaluate resistance of leek (Allium porrum) to Phytophthora porri, based on inoculation by 24 h-immersion of leek plantlets in the 3–6 leaf stage in a suspension of ca. 100 zoospores.ml-1. The immersion test was used for identifying new sources of resistance a

  14. Culture and genetic screening in Africa.

    Science.gov (United States)

    Jegede, Ayodele S

    2009-12-01

    Africa is a continent in transition amidst a revival of cultural practices. Over previous years the continent was robbed of the benefits of medical advances by unfounded cultural practices surrounding its cultural heritage. In a fast moving field like genetic screening, discussions of social and policy aspects frequently need to take place at an early stage to avoid the dilemma encountered by Western medicine. This paper, examines the potential challenges to genetic screening in Africa. It discusses how cultural practices may affect genetic screening. It views genomics science as a culture which is trying to diffuse into another one. It argues that understanding the existing culture will help the diffusion process. The paper emphasizes the importance of genetic screening for Africa, by assessing the current level of burden of diseases in the continent and shows its role in reducing disease prevalence. The paper identifies and discusses the cultural challenges that are likely to confront genetic screening on the continent, such as the worldview, rituals and taboos, polygyny, culture of son preference and so on. It also discusses cultural practices that may promote the science such as inheritance practices, spouse selection practices and naming patterns. Factors driving the cultural challenges are identified and discussed, such as socialization process, patriarchy, gender, belief system and so on. Finally, the paper discusses the way forward and highlights the ethical considerations of doing genetic screening on the continent. However, the paper also recognizes that African culture is not monolithic and therefore makes a case for exceptions.

  15. The art and design of genetic screens: maize.

    Science.gov (United States)

    Candela, Héctor; Hake, Sarah

    2008-03-01

    Maize (Zea mays) is an excellent model for basic research. Genetic screens have informed our understanding of developmental processes, meiosis, epigenetics and biochemical pathways--not only in maize but also in other cereal crops. We discuss the forward and reverse genetic screens that are possible in this organism, and emphasize the available tools. Screens exploit the well-studied behaviour of transposon systems, and the distinctive chromosomes allow an integration of cytogenetics into mutagenesis screens and analyses. The imminent completion of the maize genome sequence provides the essential resource to move seamlessly from gene to phenotype and back.

  16. BIOCHEMICAL GENETIC STUDIES ON CUTTLEFISH SEPIELLA MAINDRONI (CEPHALOPODA: SEPIIDAE)- ACTIVE LOCI SCREENING OF ISOZYME

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Screening of 46 putative enzyme-coding loci and 4 different kinds of tissues of Sepiella maindroni de Rochebrone, 1884 for enzymatic activities using starch gel electrophoretic technique proved that the 21 enzymes such as AAT, AK, ALP, AP, CK, DIA, ES, FBP, G3PDH, GPI, GRS,IDH, LDH, MDH, MEP, MPI, NP, PGDH, PGM, SOD and XO* , were active to Sepiella maindroni after being stained. The tissue exhibiting stable and clear bands was also determined. Among tissues tested, mantle muscle tissue was the best for electrophoretic survey of isozymes. Buccal bulb muscle, eye and liver were fairly good for some special enzymes, such as DIA, ES, MPI, NP, etc.

  17. Antenatal screening and the gendering of genetic responsibility

    Directory of Open Access Journals (Sweden)

    Reed Kate

    2007-09-01

    Full Text Available Abstract Background The objective of this study is to explore men's and women's perceptions of antenatal blood screening. The study will assess the impact of these perceptions on decision-making regarding diagnostic testing and selective abortion, and on parental feelings of genetic responsibility. By exploring gender and antenatal screening in this way, the research aims to contribute to our understanding of lay perceptions of genetic screening and increase our knowledge of the decision-making process in screening. Research design This qualitative study will be based on semi-structured interviews with twenty pregnant women and twenty male partners in the post-industrial city of Sheffield, UK. All interviews will be taped, transcribed and analysed thematically using NVIVO, a qualitative software package. Discussion The findings of this study have relevance to existing debates on the social and ethical implications of reproductive genetics. A better understanding of male and female perceptions of the screening process could improve guidance and practice in antenatal screening and genetic counselling. It will also inform and contribute to the development of theory on gender and genetic screening.

  18. Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens

    DEFF Research Database (Denmark)

    Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.

    2016-01-01

    The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, we...... compare the efficacy of genome-wide CRISPR/Cas9-mediated forward genetic screens versus gene-trap mutagenesis screens in haploid human cells, which represent the existing ‘gold standard’ method. This head-to-head comparison aimed to identify genes required for the endoplasmic reticulum....../3-associated disulphide reductase. Genome-wide CRISPR/Cas9-mediated screens together with haploid genetic screens provide a powerful addition to the forward genetic toolbox....

  19. Genetic screening and democracy: lessons from debating genetic screening criteria in the Netherlands.

    Science.gov (United States)

    van El, Carla Geertruida; Pieters, Toine; Cornel, Martina

    2012-04-01

    Recent decades have witnessed increasing possibilities for genetic testing and screening. In clinical genetics, the doctor's office defined a secluded space for discussion of sensitive reproductive options in cases of elevated risk for genetic disorders in individuals or their offspring. When prenatal screening for all pregnant women became conceivable, the potential increase in scale made social and ethical concerns relevant for the whole of society. Whereas genetic testing in clinical genetic practice was widely accepted, prenatal screening at a population level met with unease. Concerns were raised regarding social pressure to screen: the sum of individual choice might result in a 'collective eugenics'. The government's involvement also raised suspicion: actively offering screening evoked associations with eugenic population policies from the first half of the 20th century. By reconstructing elements of policy and public debate on prenatal screening in the Netherlands from the past 30 years, this article discusses how the government has gradually changed its role in balancing the interest of the individual and the collective on genetic reproductive issues. Against a background of increasing knowledge about and demand for prenatal screening among the population, governmental policy changed from focusing on protection by banning screening toward facilitating screening in a careful and ethically sound way by providing adequate information, decision aids and quality assessment instruments. In the meanwhile, invigorating democracy in public debate may entail discussing concepts of 'the good life' in relation to living with or without impairments and dealing with genetic information about oneself or one's offspring.

  20. Genetic screening services provided in Turkey.

    Science.gov (United States)

    Erdem, Yurdagül; Tekşen, Fulya

    2013-12-01

    In Turkey, the rate of consanguineous marriage is quite high (22-24 %) and as a result, the incidence of autosomal recessive diseases and congenital anomalies is also very high and gives rise to a serious public health problem. In the last three decades, great effort has been made to avoid increases in the prevalence of these hereditary diseases. For this purpose, population-based premarital, prenatal, neonatal and adult genetic screening programs are performed in various centers such as Community Health Centers, Early Diagnosis of Cancer and Education Centers (KETEM), Prenatal and Neonatal Departments of Universities and State Hospitals and Thalessemia Screening Centers. Such centers are staffed by health professionals including physicians, family physicians, nurses, midwives, biologists and medical geneticists. Genetic counseling is also provided to patients attending these centers after screening tests are performed. Since there are no specialized training programs for genetic counselors, genetic counseling is generally provided by doctors or medical geneticists. The aim of this paper is to give an overview of the genetic screening services provided in Turkey, the prevalence of genetic diseases and the design of intensive educational programs for health professionals.

  1. Pragmatic approaches to genetic screening.

    NARCIS (Netherlands)

    Mallia, P.; Have, H.A.M.J. ten

    2005-01-01

    Pragmatic approaches to genetic testing are discussed and appraised. Whilst there are various schools of pragmatism, the Deweyan approach seems to be the most appreciated in bioethics as it allows a historical approach indebted to Hegel. This in turn allows the pragmatist to specify and balance prin

  2. Studies of Resurgent Bed Bugs: Population Genetic Structure, Impact of Aggregation on Development and Molecular Screening for Bartonella

    Science.gov (United States)

    Saenz, Virna Lisa

    The recent resurgence of bed bugs (Cimex lectularius L.) has created an unprecedented demand for research on its biology. The main objectives of this dissertation research were to investigate several aspects of bed bug biology: infestation and dispersal dynamics at a large and small geographical scale using molecular markers, to determine the impact of aggregation on bed bug development and to screen bed bug populations for a re-emergent pathogen. First, we studied the infestation and dispersal dynamics of bed bugs at large geographical scale (e.g., across cities, states). Although bed bug infestations are on the rise, there is a poor understanding of their dispersal patterns and sources of infestation. We conducted a genetic study of 21 bed bug infestations from the eastern United States. We genotyped samples comprised of 8 - 10 individuals per infestation at nine polymorphic microsatellite loci. Despite high genetic diversity across all infestations, with 5 -- 17 alleles per locus (mean = 10.3), we found low genetic diversity (1 -- 4 alleles per locus) within all but one of the infestations. These results suggest that nearly all the studied infestations were started by a small propagule possibly consisting of a singly mated female and/or her progeny. All infestations were strongly genetically differentiated from each other (mean pairwise FST between populations = 0.68) and we did not find strong evidence of a geographic pattern of structuring. The high level of genetic diversity across infestations from the eastern United States together with the lack of geographically organized structure is consistent with multiple introductions into the United States from foreign sources. This work is described in Chapter 2 and was published in the Journal of Medical Entomology in 2012. Second, we investigated dispersal and infestation dynamics of bed bugs at a fine geographical scale within three multistory apartment buildings: one from Raleigh, NC and two from Jersey City, NJ

  3. Genetic risk factors for cerebrovascular disease in children with sickle cell disease: design of a case-control association study and genomewide screen

    Directory of Open Access Journals (Sweden)

    Brambilla Donald

    2003-07-01

    Full Text Available Abstract Background The phenotypic heterogeneity of sickle cell disease is likely the result of multiple genetic factors and their interaction with the sickle mutation. High transcranial doppler (TCD velocities define a subgroup of children with sickle cell disease who are at increased risk for developing ischemic stroke. The genetic factors leading to the development of a high TCD velocity (i.e. cerebrovascular disease and ultimately to stroke are not well characterized. Methods We have designed a case-control association study to elucidate the role of genetic polymorphisms as risk factors for cerebrovascular disease as measured by a high TCD velocity in children with sickle cell disease. The study will consist of two parts: a candidate gene study and a genomewide screen and will be performed in 230 cases and 400 controls. Cases will include 130 patients (TCD ≥ 200 cm/s randomized in the Stroke Prevention Trial in Sickle Cell Anemia (STOP study as well as 100 other patients found to have high TCD in STOP II screening. Four hundred sickle cell disease patients with a normal TCD velocity (TCD Discussion It is expected that this study will yield important information on genetic risk factors for the cerebrovascular disease phenotype in sickle cell disease by clarifying the role of candidate genes in the development of high TCD. The genomewide screen for a large number of SNPs may uncover the association of novel polymorphisms with cerebrovascular disease and stroke in sickle cell disease.

  4. In vitro fertilization with preimplantation genetic screening

    NARCIS (Netherlands)

    Mastenbroek, Sebastiaan; Twisk, Moniek; van Echten-Arends, Jannie; Sikkema-Raddatz, Birgit; Korevaar, Johanna C.; Verhoeve, Harold R.; Vogel, Niels E. A.; Arts, Eus G. J. M.; de Vries, Jan W. A.; Bossuyt, Patrick M.; Buys, Charles H. C. M.; Heineman, Maas Jan; Repping, Sjoerd; van der Veen, Fulco

    2007-01-01

    BACKGROUND: Pregnancy rates in women of advanced maternal age undergoing in vitro fertilization (IVF) are disappointingly low. It has been suggested that the use of preimplantation genetic screening of cleavage-stage embryos for aneuploidies may improve the effectiveness of IVF in these women.

  5. Genetic dissection of mammalian ERAD through comparative haploid and CRISPR forward genetic screens

    DEFF Research Database (Denmark)

    Timms, Richard T.; Menzies, Sam A.; Tchasovnikarova, Iva A.;

    2016-01-01

    The application of forward genetic screens to cultured human cells represents a powerful method to study gene function. The repurposing of the bacterial CRISPR/Cas9 system provides an effective method to disrupt gene function in mammalian cells, and has been applied to genome-wide screens. Here, ...

  6. 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

  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. Sources of Error in Mammalian Genetic Screens

    Directory of Open Access Journals (Sweden)

    Laura Magill Sack

    2016-09-01

    Full Text Available Genetic screens are invaluable tools for dissection of biological phenomena. Optimization of such screens to enhance discovery of candidate genes and minimize false positives is thus a critical aim. Here, we report several sources of error common to pooled genetic screening techniques used in mammalian cell culture systems, and demonstrate methods to eliminate these errors. We find that reverse transcriptase-mediated recombination during retroviral replication can lead to uncoupling of molecular tags, such as DNA barcodes (BCs, from their associated library elements, leading to chimeric proviral genomes in which BCs are paired to incorrect ORFs, shRNAs, etc. This effect depends on the length of homologous sequence between unique elements, and can be minimized with careful vector design. Furthermore, we report that residual plasmid DNA from viral packaging procedures can contaminate transduced cells. These plasmids serve as additional copies of the PCR template during library amplification, resulting in substantial inaccuracies in measurement of initial reference populations for screen normalization. The overabundance of template in some samples causes an imbalance between PCR cycles of contaminated and uncontaminated samples, which results in a systematic artifactual depletion of GC-rich library elements. Elimination of contaminating plasmid DNA using the bacterial endonuclease Benzonase can restore faithful measurements of template abundance and minimize GC bias.

  9. GAMPMS: Genetic algorithm managed peptide mutant screening.

    Science.gov (United States)

    Long, Thomas; McDougal, Owen M; Andersen, Tim

    2015-06-30

    The prominence of endogenous peptide ligands targeted to receptors makes peptides with the desired binding activity good molecular scaffolds for drug development. Minor modifications to a peptide's primary sequence can significantly alter its binding properties with a receptor, and screening collections of peptide mutants is a useful technique for probing the receptor-ligand binding domain. Unfortunately, the combinatorial growth of such collections can limit the number of mutations which can be explored using structure-based molecular docking techniques. Genetic algorithm managed peptide mutant screening (GAMPMS) uses a genetic algorithm to conduct a heuristic search of the peptide's mutation space for peptides with optimal binding activity, significantly reducing the computational requirements of the virtual screening. The GAMPMS procedure was implemented and used to explore the binding domain of the nicotinic acetylcholine receptor (nAChR) α3β2-isoform with a library of 64,000 α-conotoxin (α-CTx) MII peptide mutants. To assess GAMPMS's performance, it was compared with a virtual screening procedure that used AutoDock to predict the binding affinity of each of the α-CTx MII peptide mutants with the α3β2-nAChR. The GAMPMS implementation performed AutoDock simulations for as few as 1140 of the 64,000 α-CTx MII peptide mutants and could consistently identify a set of 10 peptides with an aggregated binding energy that was at least 98% of the aggregated binding energy of the 10 top peptides from the exhaustive AutoDock screening.

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

    Science.gov (United States)

    Lundin, Knut E A; Wijmenga, Cisca

    2015-09-01

    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 have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening-and subsequent treatment if coeliac disease is detected-could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed.

  11. MRI screening for breast cancer in women with familial or genetic predisposition : design of the Dutch National Study (MRISC)

    NARCIS (Netherlands)

    Kriege, M; Brekelmans, C T; Boetes, C; Rutgers, E J; Oosterwijk, J C; Tollenaar, R A; Manoliu, R A; Holland, R; de Koning, H J; Klijn, J G

    2001-01-01

    Mammography screening of women aged 50-70 years for breast cancer has proven to be effective in reducing breast cancer mortality. There is no consensus about the value of breast cancer screening in women aged 40-49 years. Five to ten per cent of all breast cancers are hereditary. One of the options

  12. Genetic Screening for Familial Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Oliveira Carla

    2004-05-01

    Full Text Available Abstract Approximately 10% of gastric cancer cases show familial clustering but only 1-3% of gastric carcinomas arise as a result of inherited gastric cancer predisposition syndromes. Direct proof that Hereditary Gastric Cancer a genetic disease with a germline gene defect has come from the demonstration of co-segregation of germline E-cadherin (CDH1 mutations with early onset diffuse gastric cancer in families with an autosomal dominant pattern of inheritance (HDGC. E-cadherin is a transmembrane calcium-dependent cell-adhesion molecule involved in cell-junction formation and the maintenance of epithelial integrity. In this review, we describe frequency and type of CDH1 mutations in sporadic and familial gastric cancer. Further we demonstrate the functional significance of some CDH1 germline missense mutations found in HDGC. We also discuss the CDH1 polymorphisms that have been associated to gastric cancer. We report other types of malignancies associated to HDGC, besides diffuse gastric cancer. Moreover, we review the data available on putative alternative candidate genes screened in familial gastric cancer. Finally, we briefly discuss the role of low-penetrance genes and Helicobacter pylori in gastric cancer. This knowledge is a fundamental step towards accurate genetic counselling, in which a highly specialised pre-symptomatic therapeutic intervention should be offered.

  13. Combination of hearing screening and genetic screening for deafness-susceptibility genes in newborns.

    Science.gov (United States)

    Yao, Gen-Dong; Li, Shou-Xia; Chen, Ding-Li; Feng, Hai-Qin; Zhao, Su-Bin; Liu, Yong-Jie; Guo, Li-Li; Yang, Zhi-Ming; Zhang, Xiao-Fang; Sun, Cai-Xia; Wang, Ze-Hui; Zhang, Wei-Yong

    2014-01-01

    The aim of this study was to determine the clinical significance of the results of screening of newborn hearing and the incidence of deafness-susceptibility genes. One thousand newborn babies in the Handan Center Hospital (Handan, China) underwent screening of hearing and deafness-susceptibility genes. The first screening test was carried out using otoacoustic emissions (OAEs). Babies with hearing loss who failed to pass the initial screening were scheduled for rescreening at 42 days after birth. Cord blood was used for the screening of deafness-susceptibility genes, namely the GJB2, SLC26A4 and mitochondrial 12S rRNA (MTRNR1) genes. Among the 1,000 neonates that underwent the first hearing screening, 25 exhibited left-sided hearing loss, 21 exhibited right-sided hearing loss and 15 cases had binaural hearing loss. After rescreening 42 days later, only one of the initial 61 cases exhibited hearing loss under OAE testing. The neonatal deafness gene tests showed two cases with 1555A>G mutation and two cases with 1494C>T mutation of the MTRNR1 gene. In the SLC26A4 gene screening, four cases exhibited the heterozygous IVS7-2A>G mutation and one case exhibited heterozygous 1226G>A mutation. In the GJB2 gene screening, two cases exhibited the homozygous 427C>T mutation and 10 exhibited the heterozygous 235delC mutation. The genetic screening revealed 21 newborns with mutations in the three deafness-susceptibility genes. The overall carrier rate was 2.1% (21/1,000). The association of hearing and gene screening may be the promising screening strategy for the diagnosis of hearing loss.

  14. RET and EDNRB mutation screening in patients with Hirschsprung disease: Functional studies and its implications for genetic counseling.

    Science.gov (United States)

    Widowati, Titis; Melhem, Shamiram; Patria, Suryono Y; de Graaf, Bianca M; Sinke, Richard J; Viel, Martijn; Dijkhuis, Jos; Sadewa, Ahmad H; Purwohardjono, Rochadi; Soenarto, Yati; Hofstra, Robert Mw; Sribudiani, Yunia

    2016-06-01

    Hirschsprung disease (HSCR) is a major cause of chronic constipation in children. HSCR can be caused by germline mutations in RET and EDNRB. Defining causality of the mutations identified is difficult and almost exclusively based on in silico predictions. Therefore, the reported frequency of pathogenic mutations might be overestimated. We combined mutation analysis with functional assays to determine the frequencies of proven pathogenic RET and EDNRB mutations in HSCR. We sequenced RET and EDNRB in 57 HSCR patients. The identified RET-coding variants were introduced into RET constructs and these were transfected into HEK293 cells to determine RET phosphorylation and activation via ERK. An exon trap experiment was performed to check a possible splice-site mutation. We identified eight rare RET-coding variants, one possible splice-site variant, but no rare EDNRB variants. Western blotting showed that three coding variants p.(Pr270Leu), p.(Ala756Val) and p.(Tyr1062Cys) resulted in lower activation of RET. Moreover, only two RET variants (p.(Ala756Val) and p.(Tyr1062Cys)) resulted in reduced ERK activation. Splice-site assays on c.1880-11A>G could not confirm its pathogenicity. Our data suggest that indeed almost half of the identified rare variants are proven pathogenic and that, hence, functional studies are essential for proper genetic counseling.

  15. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases

    Science.gov (United States)

    Lanoiselée, Hélène-Marie; Nicolas, Gaël; Wallon, David; Rovelet-Lecrux, Anne; Lacour, Morgane; Rousseau, Stéphane; Richard, Anne-Claire; Pasquier, Florence; Rollin-Sillaire, Adeline; Martinaud, Olivier; Quillard-Muraine, Muriel; de la Sayette, Vincent; Boutoleau-Bretonniere, Claire; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Sarazin, Marie; le Ber, Isabelle; Epelbaum, Stéphane; Jonveaux, Thérèse; Rouaud, Olivier; Ceccaldi, Mathieu; Félician, Olivier; Godefroy, Olivier; Formaglio, Maite; Croisile, Bernard; Auriacombe, Sophie; Chamard, Ludivine; Vincent, Jean-Louis; Sauvée, Mathilde; Marelli-Tosi, Cecilia; Gabelle, Audrey; Ozsancak, Canan; Pariente, Jérémie; Paquet, Claire; Hannequin, Didier; Campion, Dominique

    2017-01-01

    Background Amyloid protein precursor (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) mutations cause autosomal dominant forms of early-onset Alzheimer disease (AD-EOAD). Although these genes were identified in the 1990s, variant classification remains a challenge, highlighting the need to colligate mutations from large series. Methods and findings We report here a novel update (2012–2016) of the genetic screening of the large AD-EOAD series ascertained across 28 French hospitals from 1993 onwards, bringing the total number of families with identified mutations to n = 170. Families were included when at least two first-degree relatives suffered from early-onset Alzheimer disease (EOAD) with an age of onset (AOO) ≤65 y in two generations. Furthermore, we also screened 129 sporadic cases of Alzheimer disease with an AOO below age 51 (44% males, mean AOO = 45 ± 2 y). APP, PSEN1, or PSEN2 mutations were identified in 53 novel AD-EOAD families. Of the 129 sporadic cases screened, 17 carried a PSEN1 mutation and 1 carried an APP duplication (13%). Parental DNA was available for 10 sporadic mutation carriers, allowing us to show that the mutation had occurred de novo in each case. Thirteen mutations (12 in PSEN1 and 1 in PSEN2) identified either in familial or in sporadic cases were previously unreported. Of the 53 mutation carriers with available cerebrospinal fluid (CSF) biomarkers, 46 (87%) had all three CSF biomarkers—total tau protein (Tau), phospho-tau protein (P-Tau), and amyloid β (Aβ)42—in abnormal ranges. No mutation carrier had the three biomarkers in normal ranges. One limitation of this study is the absence of functional assessment of the possibly and probably pathogenic variants, which should help their classification. Conclusions Our findings suggest that a nonnegligible fraction of PSEN1 mutations occurs de novo, which is of high importance for genetic counseling, as PSEN1 mutational screening is currently performed in familial cases only

  16. Moving up the slippery slope: mandated genetic screening on Cyprus.

    Science.gov (United States)

    Cowan, Ruth Schwartz

    2009-02-15

    Many social scientists and bioethicists have argued that genetic screening is a new form of eugenics. Examination of the development of the quasi-mandated screening program for beta-thalassemia in the Republic of Cyprus (1970-1984) demonstrates that there is nothing eugenic about modern genetic screening practices. The Cypriot screening program involves mandated premarital carrier screening, voluntary prenatal diagnosis (originally through fetoscopy, now through CVS), and voluntary termination of afflicted pregnancies-all at public expense. In the Republic of Cyprus, the mandating agency for genetic screening is the established church, so this examination also demonstrates that religious authorities with profound objections to abortion can balance that moral precept against others, such as the imperative to reduce suffering that sometimes conflict with it. (c) 2009 Wiley-Liss, Inc.

  17. BIOCHEMICAL GENETIC STUDIES ON CUTYLEFISH SEPIELLA MAINDRONI (CEPHALOPODA: SEPIIDAE)——ACTIVE LOCI SCREENING OF ISOZYME

    Institute of Scientific and Technical Information of China (English)

    郑小东; YutakaNatsukari; 王如才; 王昭萍; 李云

    2001-01-01

    Screening of 46 putative enzyme-coding loci and 4 different kinds of tissues of Sepiella maindroni de Rochebrone, 1884 for enzymatic activities using starch gel electrophoretic technique proved that the 21 enzymes such as AAT, AK, ALP, AP, CK, DIA, ES, FBP, G3PDH, GPI, GRS,IDH, LDH, MDH, MEP, MPI, NP, PGDH, PGM, SOD and XO* , were active to Sepiella maindroni after being stained. The tissue exhibiting stable and clear bands was also determined. Among tissues tested, mantle muscle tissue was the best for electrophoretic survey of isozymes. Buccal bulb muscle, eye and liver were fairly good for some special enzymes, such as DIA, ES, MPI, NT, etc.

  18. Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study.

    Science.gov (United States)

    Djarmati, Ana; Schneider, Susanne A; Lohmann, Katja; Winkler, Susen; Pawlack, Heike; Hagenah, Johann; Brüggemann, Norbert; Zittel, Simone; Fuchs, Tania; Raković, Aleksandar; Schmidt, Alexander; Jabusch, Hans-Christian; Wilcox, Robert; Kostić, Vladimir S; Siebner, Hartwig; Altenmüller, Eckart; Münchau, Alexander; Ozelius, Laurie J; Klein, Christine

    2009-05-01

    DYT6 is a primary, early-onset torsion dystonia; however, unlike in DYT1 dystonia, the symptoms of DYT6 dystonia frequently involve the craniocervical region. Recently, two mutations in THAP1, the gene that encodes THAP (thanatos-associated protein) domain-containing apoptosis-associated protein 1 (THAP1), have been identified as a cause of DYT6 dystonia. We screened THAP1 by sequence analysis and quantitative real-time polymerase chain reaction (PCR) in 160 white patients of European ancestry who had dystonia with an early age at onset (n=64), generalised dystonia (n=35), a positive family history of dystonia (n=56), or facial or laryngeal dystonia. Another 160 patients with dystonia were screened for reported and novel variants in THAP1. 280 neurologically healthy controls were screened for the newly identified and previously reported changes in THAP1 and these and an additional 75 controls were screened for a rare non-coding mutation. We identified two mutations in THAP1 (388_389delTC and 474delA), respectively, in two (1%) German patients from the 160 patients with dystonia. Both mutation carriers had laryngeal dystonia that started in childhood and both went on to develop generalised dystonia. Thus, two of three patients with early-onset generalised dystonia with orobulbar involvement had mutations in THAP1. One of the identified patients with DYT6 dystonia had two family members with subtle motor signs who also carried the same mutation. A rare substitution in the 5'untranslated region (-236_235GA-->TT) was found in 20 of 320 patients and in seven of 355 controls (p=0.0054). Although mutations in THAP1 might have only a minor role in patients with different, but mainly focal, forms of dystonia, they do seem to be associated with early-onset generalised dystonia with spasmodic dysphonia. This combination of symptoms might be a characteristic feature of DYT6 dystonia and could be useful in the differential diagnosis of DYT1, DYT4, DYT12, and DYT17 dystonia. In

  19. Empirical study of supervised gene screening

    Directory of Open Access Journals (Sweden)

    Ma Shuangge

    2006-12-01

    Full Text Available Abstract Background Microarray studies provide a way of linking variations of phenotypes with their genetic causations. Constructing predictive models using high dimensional microarray measurements usually consists of three steps: (1 unsupervised gene screening; (2 supervised gene screening; and (3 statistical model building. Supervised gene screening based on marginal gene ranking is commonly used to reduce the number of genes in the model building. Various simple statistics, such as t-statistic or signal to noise ratio, have been used to rank genes in the supervised screening. Despite of its extensive usage, statistical study of supervised gene screening remains scarce. Our study is partly motivated by the differences in gene discovery results caused by using different supervised gene screening methods. Results We investigate concordance and reproducibility of supervised gene screening based on eight commonly used marginal statistics. Concordance is assessed by the relative fractions of overlaps between top ranked genes screened using different marginal statistics. We propose a Bootstrap Reproducibility Index, which measures reproducibility of individual genes under the supervised screening. Empirical studies are based on four public microarray data. We consider the cases where the top 20%, 40% and 60% genes are screened. Conclusion From a gene discovery point of view, the effect of supervised gene screening based on different marginal statistics cannot be ignored. Empirical studies show that (1 genes passed different supervised screenings may be considerably different; (2 concordance may vary, depending on the underlying data structure and percentage of selected genes; (3 evaluated with the Bootstrap Reproducibility Index, genes passed supervised screenings are only moderately reproducible; and (4 concordance cannot be improved by supervised screening based on reproducibility.

  20. Studies in genetic discrimination. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  1. Private and public eugenics: genetic and screening in India

    NARCIS (Netherlands)

    Gupta, J.A.

    2007-01-01

    Epidemiologists and geneticists claim that genetics has an increasing role to play in public health policies and programs in the future. Within this perspective, genetic testing and screening are instrumental in avoiding the birth of children with serious, costly or untreatable disorders. This paper

  2. Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study.

    Science.gov (United States)

    Fostira, Florentia; Tsitlaidou, Marianthi; Papadimitriou, Christos; Pertesi, Maroulio; Timotheadou, Eleni; Stavropoulou, Alexandra V; Glentis, Stavros; Bournakis, Evangelos; Bobos, Mattheos; Pectasides, Dimitrios; Papakostas, Pavlos; Pentheroudakis, George; Gogas, Helen; Skarlos, Pantelis; Samantas, Epaminontas; Bafaloukos, Dimitrios; Kosmidis, Paris A; Koutras, Angelos; Yannoukakos, Drakoulis; Konstantopoulou, Irene; Fountzilas, George

    2012-07-01

    In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations. Median age at diagnosis was 50 years (range 20-83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8%. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24-77% of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16%). Median age of onset for mutation carriers was 39 years. Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36%) had a BRCA1 mutation, while 27% of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48% (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer. It is noteworthy, however, that of the 65 carriers, 15 (23%) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98%). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer.

  3. The art and design of genetic screens: mouse.

    Science.gov (United States)

    Kile, Benjamin T; Hilton, Douglas J

    2005-07-01

    Humans are mammals, not bacteria or plants, yeast or nematodes, insects or fish. Mice are also mammals, but unlike gorilla and goat, fox and ferret, giraffe and jackal, they are suited perfectly to the laboratory environment and genetic experimentation. In this review, we will summarize the tools, tricks and techniques for executing forward genetic screens in the mouse and argue that this approach is now accessible to most biologists, rather than being the sole domain of large national facilities and specialized genetics laboratories.

  4. Technical Update: Preimplantation Genetic Diagnosis and Screening.

    Science.gov (United States)

    Dahdouh, Elias M; Balayla, Jacques; Audibert, François; Wilson, R Douglas; Audibert, François; Brock, Jo-Ann; Campagnolo, Carla; Carroll, June; Chong, Karen; Gagnon, Alain; Johnson, Jo-Ann; MacDonald, William; Okun, Nanette; Pastuck, Melanie; Vallée-Pouliot, Karine

    2015-05-01

    Objectif : Mettre à jour et passer en revue les techniques et les indications du diagnostic génétique préimplantatoire et du dépistage génétique préimplantatoire. Options : Discussion au sujet des aspects techniques et génétiques des techniques génésiques préimplantatoires, particulièrement en ce qui concerne celles qui font appel aux nouvelles technologies cytogénétiques et à la biopsie au stade de l’embryon. Issues : Les issues cliniques obtenues par les techniques génésiques à la suite du recours au diagnostic génétique préimplantatoire et au dépistage génétique préimplantatoire sont incluses. La présente mise à jour ne traite pas en détail des issues indésirables qui ont été signalées en association avec les technologies de procréation assistée. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans Medline et The Cochrane Library en avril 2014 au moyen d’un vocabulaire contrôlé (« aneuploidy », « blastocyst/physiology », « genetic diseases », « preimplantation diagnosis/methods », « fertilization in vitro ») et de mots clés (p. ex. « preimplantation genetic diagnosis », « preimplantation genetic screening », « comprehensive chromosome screening », « aCGH », « SNP microarray », « qPCR » et « embryo selection ») appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais entre 1990 et avril 2014. Aucune restriction n’a été imposée en matière de langue. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu’en janvier 2015. Des publications additionnelles ont été identifiées à partir des bibliographies des articles récupérés. La littérature grise (non publiée) a été identifiée par l’intermédiaire de

  5. Big screens with small RNAs : loss of function genetic screens to identify novel cancer genes

    NARCIS (Netherlands)

    Mullenders, J.

    2009-01-01

    This thesis described the construction and screening of one of the first large scale RNAi libraries for use in human cells. Functional genetic screens with this library have led to the identification of novel cancer genes. These cancer genes function in several pathways including the p53 tumor suppr

  6. Stakeholder perspectives on the implementation of genetic carrier screening in a changing landscape.

    Science.gov (United States)

    Holtkamp, Kim C A; Vos, Evelien M; Rigter, Tessel; Lakeman, Phillis; Henneman, Lidewij; Cornel, Martina C

    2017-02-16

    In most countries, genetic carrier screening is neither offered, nor embedded in mainstream healthcare. Technological developments have triggered a two-fold transition in carrier screening: the expansion from screening one single disorder to many disorders simultaneously, and offering screening universally, regardless of ancestry. This study aims to identify general and population-specific barriers and needs reflected by stakeholders regarding the implementation of carrier screening in a changing landscape. Seventeen semi-structured interviews were conducted with Dutch key stakeholders working in the practical and scientific field of carrier screening. The constellation approach was used to categorise barriers and needs into three levels: culture, structure and practice. Barriers on a cultural level include: undecidedness about the desirability of carrier screening, and a lack of priority of screening in mainstream healthcare. On a structural level barriers included: need for organisational structures in healthcare for embedding carrier screening, need for guidelines, financial structures, practical tools for overcoming challenges during counselling, and a need for training and education of both professionals and the public. A lack of demand for screening by the public, and a need for a division of responsibilities were barriers on a practical level. The absence of a collective sense of urgency for genetic carrier screening, a lack of organisational structures, and uncertainty or even disagreement about the responsibilities seem to be important barriers in the implementation of carrier screening. Stakeholders therefore suggest that change agents should be formally acknowledged to strategically plan broadening of current initiatives and attune different stakeholders.

  7. Genetic counseling, prenatal screening and diagnosis of Down syndrome in the second trimester in women of advanced maternal age: a prospective study

    Institute of Scientific and Technical Information of China (English)

    QI Qing-wei; JIANG Yu-lin; ZHOU Xi-ya; LIU Jun-tao; YIN Jie; BIAN Xu-ming

    2013-01-01

    Background The incidence of autosomal trisomy in livebirths is strongly dependent on maternal age.Special consideration is given to the provision of prenatal screening and cytogenetic testing to women of advanced maternal age (AMA).The aim of this study was to evaluate the effectiveness of second trimester prenatal screening and amniocentesis for Down syndrome (DS) and compare the trends of choice of screening and amniocentesis among AMAwomen.Methods A total of 5404 AMA patients with natural singleton pregnancy were recruited for this prospective study from January 2008 to December 2010.The gestational weeks were from 15 weeks to 20+6 weeks.The patients referred were grouped into a screening group (2107 cases) and an amniocentesis group (3297 cases) by their own decision.The prevalence of DS was compared between the two groups by chi-square test.Choice rates for each maternal age with trends were compared by regression analysis.Results There were 18 cases of fetal DS detected in the screening group with a prevalence of 8.54‰ (18/2107).Twentyfive cases of fetal DS were diagnosed in the amniocentesis group with a prevalence of 7.58‰ (25/3297).No statistical difference was observed in the prevalence of DS between the screening and amniocentesis group (P=0.928).The invasive testing rate for DS in the amniocentesis group was 5.54 times higher than that of the screening group (1/131.88 vs.1/23.78).With the increase of the maternal age,the choice of amniocentesis increased while the choice of the screening showed an opposite trend.The choice of the AMA women between the screening and amniocantesis was significantly age relevant (P=0.012).Conclusions The second trimester serum screening in combination with maternal age was more effective than maternal age alone to screen for DS.We suggest educating the patients by recommending AMA women be informed of both screening and amniocentesis options.

  8. Medical and lay attitudes towards genetic screening and testing in Finland

    DEFF Research Database (Denmark)

    Toiviainen, Hanna; Jallinoja, Piia; Aro, Arja R

    2003-01-01

    The purpose of this study was to compare physicians', midwives' and lay people's attitudes towards genetic screening and testing to find out whether medical education and experience influence attitudes of genetic screening and testing. The study was based on comparison of answers to joint questions...... referred to as midwives in the following; n=800, response rate 79%), and lay people (n=2000, response rate 62%). Midwives were more worried about the consequences of genetic testing and stressed the autonomy of the customer more strongly than lay people did. Furthermore, professionals considered that lay...

  9. Coupled mutagenesis screens and genetic mapping in zebrafish.

    Science.gov (United States)

    Rawls, John F; Frieda, Matthew R; McAdow, Anthony R; Gross, Jason P; Clayton, Chad M; Heyen, Candy K; Johnson, Stephen L

    2003-01-01

    Forward genetic analysis is one of the principal advantages of the zebrafish model system. However, managing zebrafish mutant lines derived from mutagenesis screens and mapping the corresponding mutations and integrating them into the larger collection of mutations remain arduous tasks. To simplify and focus these endeavors, we developed an approach that facilitates the rapid mapping of new zebrafish mutations as they are generated through mutagenesis screens. We selected a minimal panel of 149 simple sequence length polymorphism markers for a first-pass genome scan in crosses involving C32 and SJD inbred lines. We also conducted a small chemical mutagenesis screen that identified several new mutations affecting zebrafish embryonic melanocyte development. Using our first-pass marker panel in bulked-segregant analysis, we were able to identify the genetic map positions of these mutations as they were isolated in our screen. Rapid mapping of the mutations facilitated stock management, helped direct allelism tests, and should accelerate identification of the affected genes. These results demonstrate the efficacy of coupling mutagenesis screens with genetic mapping. PMID:12663538

  10. NELSON lung cancer screening study

    NARCIS (Netherlands)

    Y. Zhao (Yingru); X. Xie (Xueqian); H.J. de Koning (Harry); W.P. Mali (Willem); R. Vliegenthart (Rozemarijn); M. Oudkerk (Matthijs)

    2011-01-01

    textabstractThe Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON study) was designed to investigate whether screening for lung cancer by low-dose multidetector computed tomography (CT) in high-risk subjects will lead to a decrease in 10-year lung cancer mortality of at

  11. A comprehensive platform for highly multiplexed mammalian functional genetic screens

    Directory of Open Access Journals (Sweden)

    Cheung-Ong Kahlin

    2011-05-01

    Full Text Available Abstract Background Genome-wide screening in human and mouse cells using RNA interference and open reading frame over-expression libraries is rapidly becoming a viable experimental approach for many research labs. There are a variety of gene expression modulation libraries commercially available, however, detailed and validated protocols as well as the reagents necessary for deconvolving genome-scale gene screens using these libraries are lacking. As a solution, we designed a comprehensive platform for highly multiplexed functional genetic screens in human, mouse and yeast cells using popular, commercially available gene modulation libraries. The Gene Modulation Array Platform (GMAP is a single microarray-based detection solution for deconvolution of loss and gain-of-function pooled screens. Results Experiments with specially constructed lentiviral-based plasmid pools containing ~78,000 shRNAs demonstrated that the GMAP is capable of deconvolving genome-wide shRNA "dropout" screens. Further experiments with a larger, ~90,000 shRNA pool demonstrate that equivalent results are obtained from plasmid pools and from genomic DNA derived from lentivirus infected cells. Parallel testing of large shRNA pools using GMAP and next-generation sequencing methods revealed that the two methods provide valid and complementary approaches to deconvolution of genome-wide shRNA screens. Additional experiments demonstrated that GMAP is equivalent to similar microarray-based products when used for deconvolution of open reading frame over-expression screens. Conclusion Herein, we demonstrate four major applications for the GMAP resource, including deconvolution of pooled RNAi screens in cells with at least 90,000 distinct shRNAs. We also provide detailed methodologies for pooled shRNA screen readout using GMAP and compare next-generation sequencing to GMAP (i.e. microarray based deconvolution methods.

  12. Moderating effects of autism on parent views of genetic screening for aggression.

    Science.gov (United States)

    May, Michael E; Brandt, Rachel C; Bohannan, Joseph K

    2012-10-01

    Advances in gene-environment interaction research have revealed genes that are associated with aggression. However, little is known about parent perceptions of genetic screening for behavioral symptoms like aggression as opposed to diagnosing disabilities. These perceptions may influence future research endeavors involving genetic linkage studies to behavior, including proactive approaches for parents to avoid events leading to aggression. The purpose of this study was to solicit the perspectives of parents who have children with autism about screening for genes associated with aggression, compared to responses from those who have children without disabilities and those planning to have children. Parents of children with autism were more likely to support screening and the use of the results to seek treatment if necessary. Results are discussed in the context of surveillance screening and systematic early intervention for behavioral symptoms related to autism. The results may provide insight for clincians, researchers, policymakers, and advocacy groups related to diagnosing and treating aggression in people with autism.

  13. Genetic screening for infertility: When should it be done?

    Directory of Open Access Journals (Sweden)

    Elda Kara

    2010-07-01

    Primary amenorrhea should be investigated by karyotype analysis and selected mutation screening according to the patient's clinical features. Karyotype analyses and FMR1 gene screening is recommended in cases of POF. At present the infertility of patients with POF cannot be restored if the diagnosis is made after complete follicular depletion, but in some cases, early diagnosis by genetic investigation may instead lead to the advice of early conception or oocyte harvesting and preservation. In addition, the accumulation and annotation of array comparative genomic hybridization data might, in the near future, lead to the identification of pathogenetic copy number variations and genes involved in POF. Karyotype analysis of both partners is recommended in all couples with recurrent pregnancy loss. No routine genetic test can be recommended so far in patients with PCOS.

  14. Forward genetic screen for auxin-deficient mutants by cytokinin.

    Science.gov (United States)

    Wu, Lei; Luo, Pan; Di, Dong-Wei; Wang, Li; Wang, Ming; Lu, Cheng-Kai; Wei, Shao-Dong; Zhang, Li; Zhang, Tian-Zi; Amakorová, Petra; Strnad, Miroslav; Novák, Ondřej; Guo, Guang-Qin

    2015-07-06

    Identification of mutants with impairments in auxin biosynthesis and dynamics by forward genetic screening is hindered by the complexity, redundancy and necessity of the pathways involved. Furthermore, although a few auxin-deficient mutants have been recently identified by screening for altered responses to shade, ethylene, N-1-naphthylphthalamic acid (NPA) or cytokinin (CK), there is still a lack of robust markers for systematically isolating such mutants. We hypothesized that a potentially suitable phenotypic marker is root curling induced by CK, as observed in the auxin biosynthesis mutant CK-induced root curling 1 / tryptophan aminotransferase of Arabidopsis 1 (ckrc1/taa1). Phenotypic observations, genetic analyses and biochemical complementation tests of Arabidopsis seedlings displaying the trait in large-scale genetic screens showed that it can facilitate isolation of mutants with perturbations in auxin biosynthesis, transport and signaling. However, unlike transport/signaling mutants, the curled (or wavy) root phenotypes of auxin-deficient mutants were significantly induced by CKs and could be rescued by exogenous auxins. Mutants allelic to several known auxin biosynthesis mutants were re-isolated, but several new classes of auxin-deficient mutants were also isolated. The findings show that CK-induced root curling provides an effective marker for discovering genes involved in auxin biosynthesis or homeostasis.

  15. Pathways and barriers to genetic testing and screening: Molecular genetics meets the high-risk family. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Duster, T.

    1998-11-01

    The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.

  16. Neurological Condition of Infants Born After In Vitro Fertilization With Preimplantation Genetic Screening

    NARCIS (Netherlands)

    Middelburg, Karin J.; Heineman, Maas J.; Haadsma, Maaike L.; Bos, Arend F.; Kok, Joke H.; Hadders-Algra, Mijna

    2010-01-01

    Aim of this study was to evaluate the effect of preimplantation genetic screening (PGS) on neurodevelopmental outcome in children. We conducted a prospective follow-up Study of children born to women randomly assigned to in vitro fertilization with or without PGS. Primary outcome was adverse neurolo

  17. Effect of screening for cystic-fibrosis on the influence of genetic-counseling

    NARCIS (Netherlands)

    Dankert-Roelse, J E; te Meerman, G J; Knol, K; ten Kate, L P

    1987-01-01

    We studied the influence of genetic counseling for cystic fibrosis on family planning, using neonatal screening, family size at time of diagnosis, and maternal age as possible determinants for reproductive behaviour. The expected number of children born to mothers of equal age and parity in the same

  18. 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

  19. CRISPR-Cas9 for medical genetic screens: applications and future perspectives.

    Science.gov (United States)

    Xue, Hui-Ying; Ji, Li-Juan; Gao, Ai-Mei; Liu, Ping; He, Jing-Dong; Lu, Xiao-Jie

    2016-02-01

    CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) systems have emerged as versatile and convenient (epi)genome editing tools and have become an important player in medical genetic research. CRISPR-Cas9 and its variants such as catalytically inactivated Cas9 (dead Cas9, dCas9) and scaffold-incorporating single guide sgRNA (scRNA) have been applied in various genomic screen studies. CRISPR screens enable high-throughput interrogation of gene functions in health and diseases. Compared with conventional RNAi screens, CRISPR screens incur less off-target effects and are more versatile in that they can be used in multiple formats such as knockout, knockdown and activation screens, and can target coding and non-coding regions throughout the genome. This powerful screen platform holds the potential of revolutionising functional genomic studies in the near future. Herein, we introduce the mechanisms of (epi)genome editing mediated by CRISPR-Cas9 and its variants, introduce the procedures and applications of CRISPR screen in functional genomics, compare it with conventional screen tools and at last discuss current challenges and opportunities and propose future directions.

  20. Global burden of genetic disease and the role of genetic screening.

    Science.gov (United States)

    Verma, I C; Puri, R D

    2015-10-01

    It is estimated that 5.3% of newborns will suffer from a genetic disorder, when followed up until the age of 25 years. In developing, as compared to western countries, hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency have a higher incidence due to severe falciparum malaria in the distant past, and autosomal recessive disorders have a higher frequency due to greater proportion of consanguineous marriages. Chromosomal disorders have a combined frequency of 1 in 153 births, therefore screening for chromosomal disorders is essential, using biochemical markers, ultrasonography, and recently by non-invasive prenatal diagnosis based on cell-free fetal DNA in maternal plasma. Preconceptional counseling should be encouraged. For genetic disorders screening should be carried out, ideally after marriage, but before pregnancy. The disorders to be screened depend upon ethnicity. Metabolic disorders have a high incidence in developing countries due to greater rate of consanguineous marriages. Newborn screening is recommended to reduce the burden of these disorders, as many metabolic disorders can be treated. Hearing and critical congenital heart disease should both be screened in the newborn period.

  1. Screening for oral precancer with noninvasive genetic cytology

    NARCIS (Netherlands)

    Bremmer, J.F.; Graveland, A.P.; Brink, A.; Braakhuis, B.J.M.; Kuik, D.J.; Leemans, C.R.; Bloemena, E.; van der Waal, I.; Brakenhoff, R.H.

    2009-01-01

    Oral squamous cell carcinomas develop in precancerous fields consisting of genetically altered mucosal epithelial cells. These precancerous fields may appear as clinically visible lesions, in particular, oral leukoplakia, but the large majority remains clinically undetectable. The aim of this study

  2. Pooled-matrix protein interaction screens using Barcode Fusion Genetics.

    Science.gov (United States)

    Yachie, Nozomu; Petsalaki, Evangelia; Mellor, Joseph C; Weile, Jochen; Jacob, Yves; Verby, Marta; Ozturk, Sedide B; Li, Siyang; Cote, Atina G; Mosca, Roberto; Knapp, Jennifer J; Ko, Minjeong; Yu, Analyn; Gebbia, Marinella; Sahni, Nidhi; Yi, Song; Tyagi, Tanya; Sheykhkarimli, Dayag; Roth, Jonathan F; Wong, Cassandra; Musa, Louai; Snider, Jamie; Liu, Yi-Chun; Yu, Haiyuan; Braun, Pascal; Stagljar, Igor; Hao, Tong; Calderwood, Michael A; Pelletier, Laurence; Aloy, Patrick; Hill, David E; Vidal, Marc; Roth, Frederick P

    2016-04-22

    High-throughput binary protein interaction mapping is continuing to extend our understanding of cellular function and disease mechanisms. However, we remain one or two orders of magnitude away from a complete interaction map for humans and other major model organisms. Completion will require screening at substantially larger scales with many complementary assays, requiring further efficiency gains in proteome-scale interaction mapping. Here, we report Barcode Fusion Genetics-Yeast Two-Hybrid (BFG-Y2H), by which a full matrix of protein pairs can be screened in a single multiplexed strain pool. BFG-Y2H uses Cre recombination to fuse DNA barcodes from distinct plasmids, generating chimeric protein-pair barcodes that can be quantified via next-generation sequencing. We applied BFG-Y2H to four different matrices ranging in scale from ~25 K to 2.5 M protein pairs. The results show that BFG-Y2H increases the efficiency of protein matrix screening, with quality that is on par with state-of-the-art Y2H methods.

  3. Frequency of chromosomal aneuploidy in high quality embryos from young couples using preimplantation genetic screening

    Directory of Open Access Journals (Sweden)

    Farzaneh Fesahat

    2017-09-01

    Full Text Available Background: Selection of the best embryo for transfer is very important in assisted reproductive technology (ART. Using morphological assessment for this selection demonstrated that the correlation between embryo morphology and implantation potential is relatively weak. On the other hand, aneuploidy is a key genetic factor that can influence human reproductive success in ART. Objective: The aim of this lab trial study was to evaluate the incidence of aneuploidies in five chromosomes in the morphologically high-quality embryos from young patients undergoing ART for sex selection. Materials and Methods: A total of 97 high quality embryos from 23 women at the age of 37or younger years that had previously undergone preimplantation genetic screening for sex selection were included in this study. After washing, the slides of blastomeres from embryos of patients were reanalyzed by fluorescence in-situ hybridization for chromosomes 13, 18 and 21. Results: There was a significant rate of aneuploidy determination in the embryos using preimplantation genetic screening for both sex and three evaluated autosomal chromosomes compared to preimplantation genetic screening for only sex chromosomes (62.9% vs. 24.7%, p=0.000. The most frequent detected chromosomal aneuploidy was trisomy or monosomy of chromosome 13. Conclusion: There is considerable numbers of chromosomal abnormalities in embryos generated in vitro which cause in vitro fertilization failure and it seems that morphological characterization of embryos is not a suitable method for choosing the embryos without these abnormalities

  4. Applying theological developments to bioethical issues such as genetic screening.

    Science.gov (United States)

    Mallia, Pierre; ten Have, Henk

    2005-01-01

    Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic screening and testing. It is important therefore to analyse the philosophical implications of this approach onto the bioethical world, where much disagreement occurs on fundamental issues. It is Catholic basic teaching to recognize and see God's hand in plurality, not merely as a cliche and then doing what we feel is right, but to recognize how to live in a pluralistic world. We recognize, in agreement with these theologians, that in order for a Trinitarian mode of understanding to be used by those doing bioethical debate, there is a need to depart from fundamentalism.

  5. Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells

    OpenAIRE

    Forment, Josep V.; Herzog, Mareike; Coates, Julia; Konopka, Tomasz; Gapp, Bianca V.; Nijman, Sebastian M.; Adams, David J; Keane, Thomas M.; Jackson, Stephen P.

    2016-01-01

    This is the author accepted manuscript. In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mut...

  6. Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors.

    Science.gov (United States)

    Bennett, Robin L; Motulsky, Arno G; Bittles, Alan; Hudgins, Louanne; Uhrich, Stefanie; Doyle, Debra Lochner; Silvey, Kerry; Scott, C Ronald; Cheng, Edith; McGillivray, Barbara; Steiner, Robert D; Olson, Debra

    2002-04-01

    The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.

  7. PRENATAL DIAGNOSIS AND SCREENING OF GENETIC ABNORMALITIES IN EARLY PREGNANCY

    Directory of Open Access Journals (Sweden)

    Jyothi Kiran Kohli

    2016-11-01

    Full Text Available BACKGROUND Genetic diseases are one of the major causes of hospital admissions due to disability and mortality particularly among children (1:5 children of hospital admission either partially/completely as distribution of genetic diseases is not related to socioeconomic background, which implies that developing world has a large number of genetic diseases largely left uncared for, i.e. overall incidence of foetal/neonatal loss due to genetic/genetic environmental causes are as follows: 1:50 newborns have major congenital abnormality, 1:100 have a unifactorial disorder, 1:200 have a major chromosomal abnormality before birth. Diagnosis of chromosomal anomalies in foetus is one of the most important challenges in modern perinatology as invasive or noninvasive methods. The aim of the study is to review on cytogenetic evaluation of CVS obtained (transcervically during first trimester of pregnancy by direct karyotyping of tissue. MATERIALS AND METHODS This study was conducted in 2001 in Department of Anatomy along with Obstetrics and Gynaecology Department, LNJP Hospital. 37 healthy cases with 6-12 weeks of gestational age coming for medical termination of pregnancy were included in the study. After written informed consent for procedure, ultrasound-guided transcervical chorionic villus sampling was done (Brambati’s method. Tissue procured was then processed for direct karyotyping and studied. Metaphase spreads were photographed and karyotypes prepared and studied. RESULTS Out of 37 pregnant females, 30 samples were successfully prepared and processed by Direct method out of which 23 were normal female (46, XX and 7 were normal male (46, XY. No normal anomaly was detected. Best biopsies were obtained with 8-12 weeks gestation. G Banding could not be performed as chromosome obtained were found to be resistant to banding. CONCLUSIONS To summarise chromosome preparations obtained from CVS by Direct method has advantage of providing sufficient number

  8. Screening of herbal extracts influencing hematopoiesis and their chemical genetic effects in embryonic zebrafish

    Institute of Scientific and Technical Information of China (English)

    Rajaretinam Rajesh Kannan; Samuel Gnana Prakash Vincent

    2012-01-01

    Objective: To screen the herbal extracts influencing the hematopoietic stem cells (HSC) in zebrafish embryos and their chemical genetic effects. Methods: The herbals used in this study had been widely applicable in Siddha medicines in South India. Herbal extracts were treated in zebrafish embryos at 4 d post fertilization and the extracts inducing the HSC were enumerated in hemocytometer. The biocompatibility and the organogenesis of the screened extracts were assessed in the zebrafish embryos for their chemical genetic effects. The LC50 values were calculated with their parallel control. The blood cells were enumerated. Results: The level of RBC was found increased in the Bergera koenigii (B. koenigii) at 15 μg/mL (P<0.05), Mimosa pudica (M. pudica) at 20 μg/mL (P<0.05) and Solanum trilobatum (S. trilobatum) at 25 μg/mL (P<0.05) and decreased RBC level was found in Phyllanthus niruri (P. niruri) at 30 μg/mL (P<0.05). The WBC count was found increased in S. trilobatum at 20 μg/mL (P<0.05) and Annona muricata (Annona muricata) at 15 μg/mL (P<0.05) and the Vitis quadrangularis (V. quadrangularis) at 20 μg/mL (P<0.05) decreased the WBC level. There were no notable effects in heart beats and the chemical genetic effects were observed at higher concentration of the extract resulting in Pericardial bulging, trunk tail flexure with heart edema, fin fold deformities etc. Conclusions: This in vivo based screening of Hematopoiesis is an inexpensive assay to screen herbal compounds and found that S. trilobatum extract influenced embryonic HSC in zebrafish, which could be a therapeutic for blood related disorders.

  9. Identification of common genetic modifiers of neurodegenerative diseases from an integrative analysis of diverse genetic screens in model organisms

    Directory of Open Access Journals (Sweden)

    Chen Xi

    2012-02-01

    Full Text Available Abstract Background An array of experimental models have been developed in the small model organisms C. elegans, S. cerevisiae and D. melanogaster for the study of various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and expanded polyglutamine diseases as exemplified by Huntington's disease (HD and related ataxias. Genetic approaches to determine the nature of regulators of the disease phenotypes have ranged from small scale to essentially whole genome screens. The published data covers distinct models in all three organisms and one important question is the extent to which shared genetic factors can be uncovered that affect several or all disease models. Surprisingly it has appeared that there may be relatively little overlap and that many of the regulators may be organism or disease-specific. There is, however, a need for a fully integrated analysis of the available genetic data based on careful comparison of orthologues across the species to determine the real extent of overlap. Results We carried out an integrated analysis using C. elegans as the baseline model organism since this is the most widely studied in this context. Combination of data from 28 published studies using small to large scale screens in all three small model organisms gave a total of 950 identifications of genetic regulators. Of these 624 were separate genes with orthologues in C. elegans. In addition, 34 of these genes, which all had human orthologues, were found to overlap across studies. Of the common genetic regulators some such as chaperones, ubiquitin-related enzymes (including the E3 ligase CHIP which directly links the two pathways and histone deacetylases were involved in expected pathways whereas others such as the peroxisomal acyl CoA-oxidase suggest novel targets for neurodegenerative disease therapy Conclusions We identified a significant number of overlapping regulators of neurodegenerative disease models. Since the diseases

  10. A genetic screen to isolate Toxoplasma gondii host-cell egress mutants.

    Science.gov (United States)

    Coleman, Bradley I; Gubbels, Marc-Jan

    2012-02-08

    The widespread, obligate intracellular, protozoan parasite Toxoplasma gondii causes opportunistic disease in immuno-compromised patients and causes birth defects upon congenital infection. The lytic replication cycle is characterized by three stages: 1. active invasion of a nucleated host cell; 2. replication inside the host cell; 3. active egress from the host cell. The mechanism of egress is increasingly being appreciated as a unique, highly regulated process, which is still poorly understood at the molecular level. The signaling pathways underlying egress have been characterized through the use of pharmacological agents acting on different aspects of the pathways. As such, several independent triggers of egress have been identified which all converge on the release of intracellular Ca(2+), a signal that is also critical for host cell invasion. This insight informed a candidate gene approach which led to the identification of plant like calcium dependent protein kinase (CDPK) involved in egress. In addition, several recent breakthroughs in understanding egress have been made using (chemical) genetic approaches. To combine the wealth of pharmacological information with the increasing genetic accessibility of Toxoplasma we recently established a screen permitting the enrichment for parasite mutants with a defect in host cell egress. Although chemical mutagenesis using N-ethyl-N-nitrosourea (ENU) or ethyl methanesulfonate (EMS) has been used for decades in the study of Toxoplasma biology, only recently has genetic mapping of mutations underlying the phenotypes become routine. Furthermore, by generating temperature-sensitive mutants, essential processes can be dissected and the underlying genes directly identified. These mutants behave as wild-type under the permissive temperature (35 °C), but fail to proliferate at the restrictive temperature (40 °C) as a result of the mutation in question. Here we illustrate a new phenotypic screening method to isolate mutants

  11. Genetic synthetic lethality screen at the single gene level in cultured human cells

    OpenAIRE

    Simons, Arnold H.; Dafni, Naomi; Dotan, Iris; Oron, Yoram; Canaani, Dan

    2001-01-01

    Recently, we demonstrated the feasibility of a chemical synthetic lethality screen in cultured human cells. We now demonstrate the principles for a genetic synthetic lethality screen. The technology employs both an immortalized human cell line deficient in the gene of interest, which is complemented by an episomal survival plasmid expressing the wild-type cDNA for the gene of interest, and the use of a novel GFP-based double-label fluorescence system. Dominant negative genetic suppressor elem...

  12. Large-Scale Forward Genetic Screening Analysis of Development of Hematopoiesis in Zebrafish

    Institute of Scientific and Technical Information of China (English)

    Kun Wang; Ning Ma; Yiyue Zhang; Wenqing Zhang; Zhibin Huang; Lingfeng Zhao; Wei Liu; Xiaohui Chen; Ping Meng; Qing Lin; Yali Chi; Mengchang Xu

    2012-01-01

    Zebrafish is a powerful model for the investigation of hematopoiesis.In order to isolate novel mutants with hematopoietic defects,large-scale mutagenesis screening of zebrafish was performed.By scoring specific hematopoietic markers,52 mutants were identified and then classified into four types based on specific phenotypic traits.Each mutant represented a putative mutation of a gene regulating the relevant aspect of hematopoiesis,including early macrophage development,early granulopoiesis,embryonic myelopoiesis,and definitive erythropoiesis/lymphopoiesis.Our method should be applicable for other types of genetic screening in zebrafish.In addition,further study of the mutants we identified may help to unveil the molecular basis of hematopoiesis.

  13. Systematic genetic screening in a prospective group of Danish patients with pheochromocytoma

    DEFF Research Database (Denmark)

    Hansen, Morten Steen Svarer; Jacobsen, Niels; Frederiksen, Anja Lisbeth

    2017-01-01

    Recent guidelines recommend consideration of genetic screening in all newly diagnosed patients with pheochromocytoma. Patients diagnosed with pheochromocytoma in the Region of Southern Denmark during 2006-2013 without previously recognized monogenetic etiology were offered genetic screening...... for mutations in the VHL, RET, SDHB, SDHC, and SDHD genes. A total of 41 patients were included, and genetic data were available in 35. In four of the 35 patients, a pathogenic variant was identified prior to the diagnosis of pheochromocytoma (von Hippel-Lindau disease, n=2; neurofibromatosis type 1, n=2......). The patients carrying a genetic mutation were all younger than 45 years at time of diagnosis of pheochromocytoma, two patients presented with bilateral tumors, and one patient had a positive family history of pheochromocytoma. Genetic screening of the remaining 31 patients did not identify any mutations...

  14. Chemical genetics and drug screening in Drosophila cancer models

    Institute of Scientific and Technical Information of China (English)

    Mara Gladstone; Tin Tin Su

    2011-01-01

    Drug candidates often fail in preclinical and clinical testing because of reasons of efficacy and/or safety.It would be time- and cost-efficient to have screening models that reduce the rate of such false positive candidates that appear promising at first but fail later.In this regard,it would be particularly useful to have a rapid and inexpensive whole animal model that can pre-select hits from high-throughput screens but before testing in costly rodent assays.Drosophila melanogaster has emerged as a potential whole animal model for drug screening.Of particular interest have been drugs that must act in the context of multi-cellularity such as those for neurological disorders and cancer.A recent review provides a comprehensive summary of drug screening in Drosophila,but with an emphasis on neurodegenerative disorders.Here,we review Drosophila screens in the literature aimed at cancer therapeutics.

  15. GAPscreener: An automatic tool for screening human genetic association literature in PubMed using the support vector machine technique

    Directory of Open Access Journals (Sweden)

    Khoury Muin J

    2008-04-01

    Full Text Available Abstract Background Synthesis of data from published human genetic association studies is a critical step in the translation of human genome discoveries into health applications. Although genetic association studies account for a substantial proportion of the abstracts in PubMed, identifying them with standard queries is not always accurate or efficient. Further automating the literature-screening process can reduce the burden of a labor-intensive and time-consuming traditional literature search. The Support Vector Machine (SVM, a well-established machine learning technique, has been successful in classifying text, including biomedical literature. The GAPscreener, a free SVM-based software tool, can be used to assist in screening PubMed abstracts for human genetic association studies. Results The data source for this research was the HuGE Navigator, formerly known as the HuGE Pub Lit database. Weighted SVM feature selection based on a keyword list obtained by the two-way z score method demonstrated the best screening performance, achieving 97.5% recall, 98.3% specificity and 31.9% precision in performance testing. Compared with the traditional screening process based on a complex PubMed query, the SVM tool reduced by about 90% the number of abstracts requiring individual review by the database curator. The tool also ascertained 47 articles that were missed by the traditional literature screening process during the 4-week test period. We examined the literature on genetic associations with preterm birth as an example. Compared with the traditional, manual process, the GAPscreener both reduced effort and improved accuracy. Conclusion GAPscreener is the first free SVM-based application available for screening the human genetic association literature in PubMed with high recall and specificity. The user-friendly graphical user interface makes this a practical, stand-alone application. The software can be downloaded at no charge.

  16. Genetical Genomics for Evolutionary Studies

    NARCIS (Netherlands)

    Prins, J.C.P.; Smant, G.; Jansen, R.C.

    2012-01-01

    enetical genomics combines acquired high-throughput genomic data with genetic analysis. In this chapter, we discuss the application of genetical genomics for evolutionary studies, where new high-throughput molecular technologies are combined with mapping quantitative trait loci (QTL) on the genome

  17. Defining asthma in genetic studies

    NARCIS (Netherlands)

    Koppelman, GH; Postma, DS; Meijer, G.

    1999-01-01

    Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define

  18. Defining asthma in genetic studies

    NARCIS (Netherlands)

    Koppelman, GH; Postma, DS; Meijer, G.

    1999-01-01

    Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define

  19. Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire: development and testing of a screening questionnaire for use in clinical cancer genetics

    NARCIS (Netherlands)

    Eijzenga, W.; Bleiker, E.M.A.; Hahn, D.E.E.; Kluijt, I.; Sidharta, G.N.; Gundy, C.; Aaronson, N.K.

    2014-01-01

    Background: Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific psych

  20. Molecular and genetic characterization, clinical evaluation and pilot study to assess the feasibility of a carrier screening for Crisponi syndrome in Sardinia

    OpenAIRE

    Piras, Roberta

    2013-01-01

    Crisponi syndrome (CS) and cold-induced sweating syndrome type 1 (CISS1) share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis and cold-induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia, associated with death in most cases in the first years of life. Functional and clinical studies supported the fact that they represent manifestations of the same autosomal recessive disorder caused by mutations in the...

  1. Quick genetic screening using targeted next-generation sequencing in patients with tuberous sclerosis.

    Science.gov (United States)

    Liu, Qing; Huang, Yan; Zhang, Mingrong; Wang, Lian Qing; Guo, Xia Nan; Si, Nuo; Qi, Zhan; Zhou, Xiang Qin; Cui, Li-ying

    2015-04-01

    Tuberous sclerosis complex is an autosomal dominant disorder characterized by hamartomas in multiple organ systems. Mutations in the 2 large genes TSC1 and TSC2 have been demonstrated to be associated with tuberous sclerosis complex by various mutation screening methods. Targeted next-generation sequencing for genetic analysis is performed in the current study and is proved to be less cost, labor, and time consuming compared with Sanger sequencing. Two de novo and 1 recurrent TSC2 mutation in patients with tuberous sclerosis complex were revealed. Clinical details of patients were described and the underlying mechanism of the 2 novel TSC2 mutations, c.245G>A(p.W82X) and c.5405_5408dupACTT(p.P1803Lfs*25), were discussed. These results added to variability of TSC mutation spectrum and suggest that targeted next-generation sequencing could be the primary choice over Sanger sequencing in future tuberous sclerosis complex genetic counseling.

  2. Genetic and Phenotypic Screening of Mannose-Binding Lectin in Relation to Risk of Recurrent Vulvovaginal Infections in Women of North India: A Prospective Cohort Study

    Science.gov (United States)

    Kalia, Namarta; Singh, Jatinder; Sharma, Sujata; Arora, Hardesh; Kaur, Manpreet

    2017-01-01

    Recurrent Vulvovaginal Infections (RVVI) is common problem associated with women of reproductive age. The function and deleterious effect of Mannose Binding Lectin 2 (MBL2) common polymorphisms are reported to be associated with various diseases. However, the role of MBL2 promoter gene polymorphisms and their combined effect with structural variant along with Serum Mannose Binding Lectin (sMBL) levels in RVVI has not been investigated. The study included 258 RVVI cases and 203 age matched healthy controls. These were investigated for the distribution of MBL2 codon 54 and promoter polymorphisms by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). sMBL levels were quantified by Enzyme Linked Immnosorbent Assay (ELISA). The frequency of X allele and its genotypes was significantly high in cases than controls conferring risk toward RVVI and its types (p Vulvovaginal Candidiasis (VVC), and MI cases compared to controls (p < 0.05). VVC patient showed significantly low sMBL levels than RVVI and MI cases (p < 0.05). The mean sMBL levels segregated based on MBL2 genotypes and haplotypes showed significant difference in different cases groups with controls. The findings of the present study suggested that MBL2 Y/X polymorphism and low sMBL levels were associated with susceptibility to RVVI either it is BV, VVC, or MI. Thus MBL deficiency in women with RVVI may contribute to decreased efficiency in clearing of pathogens. Hence, specific measures like administration of purified or recombinant MBL might decrease the incidence of vaginal infections recurrences and more-effective treatment. PMID:28197138

  3. Genetic Screening of Couples with Recurrent Spontaneous Abortion

    Directory of Open Access Journals (Sweden)

    M. Nail Alp

    2006-01-01

    Full Text Available The aim of this study was to determine the chromosomal abberations and their incidence in non-consanguineous couples with a history of two or more than two spontaneous abortion. In the study, we carried out cytogenetic analysis on 434 couples. Patients detected with chromosome abnormality were evaluated according to their pedigree analysis, and also patients’ relatives were screened for the same abnormality. Peripheral blood were taken from patients, then performed with lymphocyte culture and stained by binded using Giemsa-banding method. For each individual, 20-30-cells chromosomes were counted and around 5-10 well-binded metaphase chromosomes were karyotyped for numerical and structural chromosomal aberrations. Of 434 couples investigated, 30 (6.91% were found to have chromosomal abnormality, in one of couples partners. In 13 of couples (2.99%, one of partners was found to be balanced translocation carrier. Of these, 7 (1.61%were found to be reciprocal carrier, while 6 (1.38% Robertsonian-type balanced translocation carrier. Gonadal mosaicism was found in 3 couples (0.69%, pericentric 9 inversion in 8 couples (1.85 %, while 6 couples showed different chromosomal structure from each other. These chromosomal aberrations may cause of abortion due to high incidence in general population.

  4. A recessive genetic screen for components of the RNA interference pathway in mouse embryonic stem cells.

    Science.gov (United States)

    Trombly, Melanie I; Wang, Xiaozhong

    2010-01-01

    Several key components of the RNA interference (RNAi) pathway were identified in genetic screens performed in nonmammalian model organisms. To identify components of the mammalian RNAi pathway, we developed a recessive genetic screen in mouse embryonic stem (ES) cells. Recessive genetic screens are feasible in ES cells that are Bloom-syndrome protein (Blm-) deficient. Therefore, we constructed a reporter cell line in Blm-deficient ES cells to isolate RNAi mutants through a simple drug-selection scheme. This chapter describes how we used retroviral gene traps to mutagenize the reporter cell line and select for RNAi mutants. Putative RNAi mutants were confirmed using a separate functional assay. The location of the gene trap was then identified using molecular techniques such as Splinkerette PCR. Our screening strategy successfully isolated several mutant clones of Argonaute2, a vital component of the RNAi pathway.

  5. Patients' ratings of genetic conditions validate a taxonomy to simplify decisions about preconception carrier screening via genome sequencing.

    Science.gov (United States)

    Leo, Michael C; McMullen, Carmit; Wilfond, Benjamin S; Lynch, Frances L; Reiss, Jacob A; Gilmore, Marian J; Himes, Patricia; Kauffman, Tia L; Davis, James V; Jarvik, Gail P; Berg, Jonathan S; Harding, Cary; Kennedy, Kathleen A; Simpson, Dana Kostiner; Quigley, Denise I; Richards, C Sue; Rope, Alan F; Goddard, Katrina A B

    2016-03-01

    Advances in genome sequencing and gene discovery have created opportunities to efficiently assess more genetic conditions than ever before. Given the large number of conditions that can be screened, the implementation of expanded carrier screening using genome sequencing will require practical methods of simplifying decisions about the conditions for which patients want to be screened. One method to simplify decision making is to generate a taxonomy based on expert judgment. However, expert perceptions of condition attributes used to classify these conditions may differ from those used by patients. To understand whether expert and patient perceptions differ, we asked women who had received preconception genetic carrier screening in the last 3 years to fill out a survey to rate the attributes (predictability, controllability, visibility, and severity) of several autosomal recessive or X-linked genetic conditions. These conditions were classified into one of five taxonomy categories developed by subject experts (significantly shortened lifespan, serious medical problems, mild medical problems, unpredictable medical outcomes, and adult-onset conditions). A total of 193 women provided 739 usable ratings across 20 conditions. The mean ratings and correlations demonstrated that participants made distinctions across both attributes and categories. Aggregated mean attribute ratings across categories demonstrated logical consistency between the key features of each attribute and category, although participants perceived little difference between the mild and serious categories. This study provides empirical evidence for the validity of our proposed taxonomy, which will simplify patient decisions for results they would like to receive from preconception carrier screening via genome sequencing.

  6. Applying theological developments to bioethical issues such as genetic screening.

    NARCIS (Netherlands)

    Mallia, P.; Have, H.A.M.J. ten

    2005-01-01

    Catholic movements within the centre of Roman Catholic doctrine recently have discussed Trinitarian theology as applied to sciences, arts, economics, health and other social areas. We explore the possibilities Trinitarian theology offers to bioethical debate, concentrating particularly on genetic sc

  7. A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia.

    Science.gov (United States)

    Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

    2014-06-01

    In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia.

  8. Genetic screening and evaluation for chromosomal abnormalities of infertile males in Jilin Province, China.

    Science.gov (United States)

    Zhang, M; Fan, H-T; Zhang, Q-S; Wang, X-Y; Yang, X; Tian, W-J; Li, R-W

    2015-12-08

    Chromosomal abnormality is the most common genetic cause of male infertility, particularly in cases of azoospermia, oligozoospermia, and recurrent spontaneous abortion. Chromosomal rearrangement may interrupt an important gene or exert position effects. The functionality of genes at specific breakpoints, perhaps with a specific role in spermatogenesis, may be altered by such rearrangements. Structural chromosome abnormalities are furthermore known to increase the risk of pregnancy loss. In this study, we aimed to assess chromosomal defects in infertile men from Jilin Province, China, by genetic screening and to evaluate the relationship between structural chromosome abnormalities and male infertility. The prevalence of chromosomal abnormalities among the study participants (receiving genetic counseling in Jilin Province, China) was 10.55%. The most common chromosome abnormality was Klinefelter syndrome, and the study findings suggested that azoospermia and oligospermia may result from structural chromosomal abnormalities. Chromosome 1 was shown to be most commonly involved in male infertility and balanced chromosomal translocation was identified as one of the causes of recurrent spontaneous abortion. Chromosomes 4, 7, and 10 were the most commonly involved chromosomes in male partners of women experiencing repeated abortion.

  9. Pre-marital screening for sickle cell haemoglobin and genetic counseling: awareness and acceptability among undergraduate students of a Nigerian University

    OpenAIRE

    Ugwu N.I.

    2016-01-01

    Background: Sickle cell disease (SCD) is a genetic disease which is more prevalent in developing countries. Pre-marital screening for sickle cell disorder is helpful in the prevention and control of the condition. Aim: The aim of this study was to assess the level of awareness and acceptability of premarital genetic counseling and screening for sickle cell haemoglobin among undergraduate students of Ebonyi State University Abakaliki, South eastern, Nigeria. Methods: A cross-sectio...

  10. 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.

  11. 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.

  12. Screening for Outliers in Multiple Trait Genetic Evaluarion

    DEFF Research Database (Denmark)

    Madsen, Per; Pösa, Jukka; Pedersen, Jørn

    2012-01-01

    genetic evaluation in dairy cattle. Application of such is simple to implement and increased the accuracy of predicted breeding values for animals that has one or more records edited. Potential biases in evaluations for contemporary animals were also reduced. Optimum editing rules can be determined using......Use of multivariate models in genetic evaluation requires a multivariate method for detecting erroneous outliers that cannot be detected using univariate methods. A simple rule for detecting outliers based on an approximated Mahanalobis distance was applied to Jersey data from the routine Nordic...

  13. No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy

    NARCIS (Netherlands)

    Twisk, Moniek; Mastenbroek, Sebastiaan; Hoek, Annemieke; Heineman, Maas-Jan; van der Veen, Fulco; Bossuyt, Patrick M.; Repping, Sjoerd; Korevaar, Johanna C.

    2008-01-01

    Human preimplantation embryos generated through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments show a variable rate of numerical chromosome abnormalities or aneuploidies. Preimplantation genetic screening (PGS) has been designed to screen for aneuploidies in high

  14. No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy

    NARCIS (Netherlands)

    Twisk, Moniek; Mastenbroek, Sebastiaan; Hoek, Annemieke; Heineman, Maas-Jan; van der Veen, Fulco; Bossuyt, Patrick M.; Repping, Sjoerd; Korevaar, Johanna C.

    2008-01-01

    Human preimplantation embryos generated through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments show a variable rate of numerical chromosome abnormalities or aneuploidies. Preimplantation genetic screening (PGS) has been designed to screen for aneuploidies in high

  15. Designer babies on tap? Medical students' attitudes to pre-implantation genetic screening.

    Science.gov (United States)

    Meisenberg, Gerhard

    2009-03-01

    This paper describes two studies about the determinants of attitudes to pre-implantation genetic screening in a multicultural sample of medical students from the United States. Sample sizes were 292 in study 1 and 1464 in study 2. Attitudes were of an undifferentiated nature, but respondents did make a major distinction between use for disease prevention and use for enhancement. No strong distinctions were made between embryo selection and germ line gene manipulations, and between somatic gene therapy and germ line gene manipulations. Religiosity was negatively associated with acceptance of "designer baby" technology for Christians and Muslims but not Hindus. However, the strongest and most consistent influence was an apparently moralistic stance against active and aggressive interference with natural processes in general. Trust in individuals and institutions was unrelated to acceptance of the technology, indicating that fear of abuse by irresponsible individuals and corporations is not an important determinant of opposition.

  16. A genetic screen for components of the mammalian RNA interference pathway in Bloom-deficient mouse embryonic stem cells

    OpenAIRE

    2009-01-01

    Genetic screens performed in model organisms have helped identify key components of the RNA interference (RNAi) pathway. Recessive genetic screens have recently become feasible through the use of mouse embryonic stem (ES) cells that are Bloom's syndrome protein (Blm) deficient. Here, we developed and performed a recessive genetic screen to identify components of the mammalian RNAi pathway in Blm-deficient ES cells. Genome-wide mutagenesis using a retroviral gene trap strategy resulted in the ...

  17. Screening of spontaneous castor bean accesses for genetic ...

    African Journals Online (AJOL)

    Tuoyo Aghomotsegin

    2016-10-05

    Oct 5, 2016 ... 1Department of Agricultural Engineering, Federal University of Campina Grande ... sizing the consequences of human actions in the ... significant increase in the literature of the use of ... genetic improvement programs of this culture in Brazil, ... subsequent selection according to color pattern, weight, health,.

  18. Genetic studies in alcohol research

    Energy Technology Data Exchange (ETDEWEB)

    Karp, R.W. [National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (United States)

    1994-12-15

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

  19. Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review

    Science.gov (United States)

    Prince, Anya E R; Cadigan, R Jean; Henderson, Gail E; Evans, James P; Adams, Michael; Coker-Schwimmer, Emmanuel; Penn, Dolly C; Van Riper, Marcia; Corbie-Smith, Giselle; Jonas, Daniel E

    2017-01-01

    Background The emerging dual imperatives of personalized medicine and technologic advances make population screening for preventable conditions resulting from genetic alterations a realistic possibility. Lynch syndrome is a potential screening target due to its prevalence, penetrance, and the availability of well-established, preventive interventions. However, while population screening may lower incidence of preventable conditions, implementation without evidence may lead to unintentional harms. We examined the literature to determine whether evidence exists that screening for Lynch-associated mismatch repair (MMR) gene mutations leads to improved overall survival, cancer-specific survival, or quality of life. Documenting evidence and gaps is critical to implementing genomic approaches in public health and guiding future research. Materials and methods Our 2014–2015 systematic review identified studies comparing screening with no screening in the general population, and controlled studies assessing analytic validity of targeted next-generation sequencing, and benefits or harms of interventions or screening. We conducted meta-analyses for the association between early or more frequent colonoscopies and health outcomes. Results Twelve studies met our eligibility criteria. No adequate evidence directly addressed the main question or the harms of screening in the general population. Meta-analyses found relative reductions of 68% for colorectal cancer incidence (relative risk: 0.32, 95% confidence interval: 0.23–0.43, three cohort studies, 590 participants) and 78% for all-cause mortality (relative risk: 0.22, 95% confidence interval: 0.09–0.56, three cohort studies, 590 participants) for early or more frequent colonoscopies among family members of people with cancer who also had an associated MMR gene mutation. Conclusion Inadequate evidence exists examining harms and benefits of population-based screening for Lynch syndrome. Lack of evidence highlights the need

  20. Functional Genetic Screen to Identify Interneurons Governing Behaviorally Distinct Aspects of Drosophila Larval Motor Programs

    Directory of Open Access Journals (Sweden)

    Matt Q. Clark

    2016-07-01

    Full Text Available Drosophila larval crawling is an attractive system to study rhythmic motor output at the level of animal behavior. Larval crawling consists of waves of muscle contractions generating forward or reverse locomotion. In addition, larvae undergo additional behaviors, including head casts, turning, and feeding. It is likely that some neurons (e.g., motor neurons are used in all these behaviors, but the identity (or even existence of neurons dedicated to specific aspects of behavior is unclear. To identify neurons that regulate specific aspects of larval locomotion, we performed a genetic screen to identify neurons that, when activated, could elicit distinct motor programs. We used 165 Janelia CRM-Gal4 lines—chosen for sparse neuronal expression—to ectopically express the warmth-inducible neuronal activator TrpA1, and screened for locomotor defects. The primary screen measured forward locomotion velocity, and we identified 63 lines that had locomotion velocities significantly slower than controls following TrpA1 activation (28°. A secondary screen was performed on these lines, revealing multiple discrete behavioral phenotypes, including slow forward locomotion, excessive reverse locomotion, excessive turning, excessive feeding, immobile, rigid paralysis, and delayed paralysis. While many of the Gal4 lines had motor, sensory, or muscle expression that may account for some or all of the phenotype, some lines showed specific expression in a sparse pattern of interneurons. Our results show that distinct motor programs utilize distinct subsets of interneurons, and provide an entry point for characterizing interneurons governing different elements of the larval motor program.

  1. The future role of genetic screening to detect newborns at risk of childhood-onset hearing loss

    Science.gov (United States)

    2013-01-01

    Objective: To explore the future potential of genetic screening to detect newborns at risk of childhood-onset hearing loss. Design: An expert led discussion of current and future developments in genetic technology and the knowledge base of genetic hearing loss to determine the viability of genetic screening and the implications for screening policy. Results and Discussion: Despite increasing pressure to adopt genetic technologies, a major barrier for genetic screening in hearing loss is the uncertain clinical significance of the identified mutations and their interactions. Only when a reliable estimate of the future risk of hearing loss can be made at a reasonable cost, will genetic screening become viable. Given the speed of technological advancement this may be within the next 10 years. Decision-makers should start to consider how genetic screening could augment current screening programmes as well as the associated data processing and storage requirements. Conclusion: In the interim, we suggest that decision makers consider the benefits of (1) genetically testing all newborns and children with hearing loss, to determine aetiology and to increase knowledge of the genetic causes of hearing loss, and (2) consider screening pregnant women for the m.1555A> G mutation to reduce the risk of aminoglycoside antibiotic-associated hearing loss. PMID:23131088

  2. Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers.

    Science.gov (United States)

    Li, J; Holm, J; Bergh, J; Eriksson, M; Darabi, H; Lindström, L S; Törnberg, S; Hall, P; Czene, K

    2015-03-01

    Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. A 77 single-nucleotide polymorphism polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. PRS weighted by breast cancer overall estimates was found to be differentially associated with 1865 screen-detected and 782 interval cancers in the LIBRO-1 study {age-adjusted odds ratio (OR)perSD [95% confidence interval (CI)] 0.91 [0.83-0.99], P = 0.023}. The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates [ORperSD = 0.90 (0.82-0.98), P = 0.011]. This result was corroborated by two independent studies [combined ORperSD = 0.87 (0.76-1.00), P = 0.058] with no evidence of heterogeneity. When enriched for 'true' interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced [ORperSD = 0.74 (0.62-0.89), P = 0.001], with a significant interaction effect between PRS and mammographic density (Pinteraction = 0.017). To our knowledge, this is the first report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: a systematic review of randomized controlled trials.

    Science.gov (United States)

    Dahdouh, Elias M; Balayla, Jacques; García-Velasco, Juan Antonio

    2015-03-01

    Embryonic aneuploidy is highly prevalent in IVF cycles and contributes to decreased implantation rates, IVF cycle failure and early pregnancy loss. Preimplantation genetic screening (PGS) selects the most competent (euploid) embryos for transfer, and has been proposed to improve IVF outcomes. Use of PGS with fluorescence-in-situ hybridization technology after day 3 embryo biopsy (PGS-v1) significantly lowers live birth rates and is not recommended for use. Comprehensive chromosome screening technology, which assesses the whole chromosome complement, can be achieved using different genetic platforms. Whether PGS using comprehensive chromosome screening after blastocyst biopsy (PGS-v2) improves IVF outcomes remains to be determined. A systematic review of randomized controlled trials was conducted on PGS-v2. Three trials met full inclusion criteria, comparing PGS-v2 and routine IVF care. PGS-v2 is associated with higher clinical implantation rates, and higher ongoing pregnancy rates when the same number of embryos is transferred in both PGS and control groups. Additionally, PGS-v2 improves embryo selection in eSET practice, maintaining the same ongoing pregnancy rates between PGS and control groups, while sharply decreasing multiple pregnancy rates. These results stem from good-prognosis patients undergoing IVF. Whether these findings can be extrapolated to poor-prognosis patients with decreased ovarian reserve remains to be determined. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  4. Clinical and genetic aspects of bicuspid aortic valve: a proposed model for family screening based on a review of literature

    Directory of Open Access Journals (Sweden)

    Hubert Baars

    2015-04-01

    Full Text Available Bicuspid aortic valve (BAV is the most common congenital cardiac defect causing serious morbidity including valvular dysfunction and thoracic aortic aneurysms (TAA in around 30% of BAV patients. Cardiological screening of first-degree relatives is advised in recent guidelines given the observed familial clustering of BAV. However, guidelines regarding screening of family members and DNA testing are not unequivocal. The aim of this review is to provide an overview of the literature on echocardiographic screening in first-degree relatives of BAV patients and to propose a model for family screening. In addition, we provide a flowchart for DNA testing. We performed a PubMed search and included studies providing data on echocardiographic screening in asymptomatic relatives of BAV patients. Nine studies were included. In 5.8-47.4% of the families BAV was shown to be familial. Of the screened first-degree relatives 1.8-11% was found to be affected with BAV. Results regarding a potential risk of TAA in first-degree relatives with a tricuspid aortic valve (TAV were conflicting. The reported familial clustering of BAV underlines the importance of cardiological screening in relatives. After reviewing the available family history, patient characteristics and the results of cardiological screening in relatives, follow-up in relatives with a TAV and/or DNA testing may be advised in a subset of families. In this study we propose a model for the clinical and genetic work-up in BAV families, based on the most extensive literature review on family screening performed until now.

  5. The minisequencing method: a simple strategy for genetic screening of MEN 2 families

    Directory of Open Access Journals (Sweden)

    Domingues Rita

    2002-05-01

    Full Text Available Abstract Background Multiple endocrine neoplasia type 2 is an autosomal dominant disorder. MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism; MEN 2B by medullary thyroid carcinoma, pheochromocytoma and characteristic stigmata. Activating germline mutations of the RET proto oncogene are responsible for this hereditary syndrome. Codon 634 mutations are the most common mutations occurring in MEN 2A families whereas a specific mutation at codon 918 is observed in the great majority of MEN 2B families. Analysis of these codons will provide a final diagnosis in the great majority of affected families making unnecessary further studies. To specifically study the codons 634 and 918 we used a minisequencing method as an alternative method to complete sequencing. Results Using this mutation detection method we were able to reproduce in all cases, representative of 7 families, the information previously obtained by direct sequencing of PCR products. Depending on the number of primers used in the minisequencing reaction, we were able to interrogate either only one nucleotide of the target codon or the three nucleotides simultaneously. Conclusions This technique appears as a simple, rapid and efficient method for genetic screening of MEN 2 families. It can be utilized to seek for unknown mutations at specific codons or to screen for previously identified mutations and is therefore of interest to study index cases or individuals at risk. Results suggest that complete sequencing is unnecessary.

  6. A Forward Genetic Screening for Prostate Cancer Progression Genes

    Science.gov (United States)

    2012-10-01

    melanoma. Nature 436, 117‐122 (2005). 26. J.C. Cronin et al. Frequent mutations in the MITF pathway in melanoma.  Pigment   Cell Melanoma Res. 22, 435‐444... bacterial genetics. J Mol Biol 116: 125–159. 3. Ding S, Wu X, Li G, Han M, Zhuang Y, et al. (2005) Efficient transposition of the piggyBac (PB) transposon

  7. Screening of genetic parameters for soluble protein expression in Escherichia coli

    DEFF Research Database (Denmark)

    Vernet, Erik; Kotzsch, Alexander; Voldborg, Bjørn

    2011-01-01

    . Here we present a screening strategy for expression of biomedically relevant proteins in Escherichia coli using a panel of six different genetic variations. These include engineered strains for rare codon supplementation, increased disulfide bond formation in the cytoplasm and novel vectors...

  8. Incidental findings, genetic screening and the challenge of personalisation

    Directory of Open Access Journals (Sweden)

    Carlo Petrini

    2014-12-01

    Full Text Available Genetic tests frequently produce more information than is initially expected. Several documents have addressed this issue and offer suggestions regarding how this information should be managed and, in particular, concerning the expedience of revealing (or not revealing it to the persons concerned. While the approaches to the management of these incidental findings (IFs vary, it is usually recommended that the information be disclosed if there is confirmed clinical utility and the possibility of treatment or prevention. However, this leaves unsolved some fundamental issues such as the different ways of interpreting "clinical utility", countless sources of uncertainty and varying ways of defining the notion of "incidental". Guidelines and other reference documents can offer indications to those responsible for managing IFs but should not be allowed to relieve researchers and healthcare professionals of their responsibilities.

  9. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men.

    Science.gov (United States)

    Fu, Li; Xiong, Da-Ke; Ding, Xian-Ping; Li, Chuang; Zhang, Li-Yuan; Ding, Min; Nie, Shuang-Shuang; Quan, Qiang

    2012-06-01

    To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men. This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reaction(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia. Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls. There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.

  10. Genetic screening of the inherited Ichtyosis causative mutation in Chianina cattle

    Directory of Open Access Journals (Sweden)

    Luciano Molteni

    2010-01-01

    Full Text Available Inherited Ichthyosis, Chianina, Causative mutation, Genetic screening.Inherited Ichthyosis is a genetic disorder reported in both humans and animals, including bovines. Two inherited forms were reported in cattle and both are transmitted in an autosomal recessive manner: Ichthyosis Fetalis (IF and Ichthyosis Congenita (IC. A causative mutation of IF in Chianina cattle was recently indentified in the ABC12 gene. This work reports the first genetic screening using this recently available genetic test on Chianina cattle. Tests were performed on both the population of farm breeding selected young bulls (131 samples randomly chosen and high breeding value sires (16 samples. Results confirm a low total prevalence of carriers in the selected sire population (2/131; 1.5% and the presence of the disease allele among the high value selected sires (1/16; 6.3%. This result strengthens the importance to continue the genetic screening program, particularly in performance tested bulls approved for use in AI or natural service.

  11. A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans

    Science.gov (United States)

    Li, Shiwei; Xu, Shibin; Ma, Yanli; Wu, Shuang; Feng, Yu; Cui, Qingpo; Chen, Lifeng; Zhou, Shuang; Kong, Yuanyuan; Zhang, Xiaoyu; Yu, Jialei; Wu, Mengdi; Zhang, Shaobing O.

    2016-01-01

    To identify genes that regulate the dynamics of lipid droplet (LD) size, we have used the genetically tractable model organism Caenorhabditis elegans, whose wild-type LD population displays a steady state of size with an upper limit of 3 μm in diameter. From a saturated forward genetic screen of 6.7 × 105 mutagenized haploid genomes, we isolated 118 mutants with supersized intestinal LDs often reaching 10 μm. These mutants define nine novel complementation groups, in addition to four known genes (maoc-1, dhs-28, daf-22, and prx-10). The nine groups are named drop (lipid droplet abnormal) and categorized into four classes. Class I mutants drop-5 and drop-9, similar to prx-10, are up-regulated in ACS-22-DGAT-2-dependent LD growth, resistant to LD hydrolysis, and defective in peroxisome import. Class II mutants drop-2, drop-3, drop-6, and drop-7 are up-regulated in LD growth, are resistant to LD hydrolysis, but are not defective in peroxisome import. Class III mutants drop-1 and drop-8 are neither up-regulated in LD growth nor resistant to LD hydrolysis, but seemingly up-regulated in LD fusion. Class IV mutant drop-4 is cloned as sams-1 and, different to the other three classes, is ACS-22-independent and hydrolysis-resistant. These four classes of supersized LD mutants should be valuable for mechanistic studies of LD cellular processes including growth, hydrolysis, and fusion. PMID:27261001

  12. A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Shiwei Li

    2016-08-01

    Full Text Available To identify genes that regulate the dynamics of lipid droplet (LD size, we have used the genetically tractable model organism Caenorhabditis elegans, whose wild-type LD population displays a steady state of size with an upper limit of 3 μm in diameter. From a saturated forward genetic screen of 6.7 × 105 mutagenized haploid genomes, we isolated 118 mutants with supersized intestinal LDs often reaching 10 μm. These mutants define nine novel complementation groups, in addition to four known genes (maoc-1, dhs-28, daf-22, and prx-10. The nine groups are named drop (lipid droplet abnormal and categorized into four classes. Class I mutants drop-5 and drop-9, similar to prx-10, are up-regulated in ACS-22-DGAT-2-dependent LD growth, resistant to LD hydrolysis, and defective in peroxisome import. Class II mutants drop-2, drop-3, drop-6, and drop-7 are up-regulated in LD growth, are resistant to LD hydrolysis, but are not defective in peroxisome import. Class III mutants drop-1 and drop-8 are neither up-regulated in LD growth nor resistant to LD hydrolysis, but seemingly up-regulated in LD fusion. Class IV mutant drop-4 is cloned as sams-1 and, different to the other three classes, is ACS-22-independent and hydrolysis-resistant. These four classes of supersized LD mutants should be valuable for mechanistic studies of LD cellular processes including growth, hydrolysis, and fusion.

  13. A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer.

    Science.gov (United States)

    Rad, Roland; Rad, Lena; Wang, Wei; Strong, Alexander; Ponstingl, Hannes; Bronner, Iraad F; Mayho, Matthew; Steiger, Katja; Weber, Julia; Hieber, Maren; Veltkamp, Christian; Eser, Stefan; Geumann, Ulf; Öllinger, Rupert; Zukowska, Magdalena; Barenboim, Maxim; Maresch, Roman; Cadiñanos, Juan; Friedrich, Mathias; Varela, Ignacio; Constantino-Casas, Fernando; Sarver, Aaron; Ten Hoeve, Jelle; Prosser, Haydn; Seidler, Barbara; Bauer, Judith; Heikenwälder, Mathias; Metzakopian, Emmanouil; Krug, Anne; Ehmer, Ursula; Schneider, Günter; Knösel, Thomas; Rümmele, Petra; Aust, Daniela; Grützmann, Robert; Pilarsky, Christian; Ning, Zemin; Wessels, Lodewyk; Schmid, Roland M; Quail, Michael A; Vassiliou, George; Esposito, Irene; Liu, Pentao; Saur, Dieter; Bradley, Allan

    2015-01-01

    Here we describe a conditional piggyBac transposition system in mice and report the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen. We identify Foxp1 as an oncogenic transcription factor that drives pancreatic cancer invasion and spread in a mouse model and correlates with lymph node metastasis in human patients with pancreatic cancer. The propensity of piggyBac for open chromatin also enabled genome-wide screening for cancer-relevant noncoding DNA, which pinpointed a Cdkn2a cis-regulatory region. Histologically, we observed different tumor subentities and discovered associated genetic events, including Fign insertions in hepatoid pancreatic cancer. Our studies demonstrate the power of genetic screening to discover cancer drivers that are difficult to identify by other approaches to cancer genome analysis, such as downstream targets of commonly mutated human cancer genes. These piggyBac resources are universally applicable in any tissue context and provide unique experimental access to the genetic complexity of cancer.

  14. Screening for Iron Overload: Lessons from the HEmochromatosis and IRon Overload Screening (HEIRS Study

    Directory of Open Access Journals (Sweden)

    Paul C Adams

    2009-01-01

    Full Text Available BACKGROUND: The HEmochromatosis and IRon Overload Screening (HEIRS Study provided data on a racially, ethnically and geographically diverse cohort of participants in North America screened from primary care populations.

  15. [Large-scale population-based genetic screening and prenatal diagnosis for thalassemias in Zhuhai City of Guangdong Province].

    Science.gov (United States)

    Zhou, Yu-qiu; Shang, Xuan; Yin, Bao-min; Xiong, Fu; Xiao, Qi-zhi; Zhou, Wan-jun; Zhang, Yong-liang; Xu, Xiang-min

    2012-02-01

    were voluntarily terminated. In Zhuhai City, the average annual birth rate of fetuses with severe thalassemia was declined by 32.9% (49/149). This study has reduced effectively birth rate of perinatal infants with severe thalassemias in Zhuhai City by genetic screening and prenatal diagnosis of thalassemia in the large population of 13 years. Our summary comes out of technical proposals for prenatal screening and diagnosis, which could be take example by preventative control of thalassemia in other regions of China where are prevalent.

  16. A post-developmental genetic screen for zebrafish models of inherited liver disease.

    Directory of Open Access Journals (Sweden)

    Seok-Hyung Kim

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH, cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization, we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease.

  17. A post-developmental genetic screen for zebrafish models of inherited liver disease.

    Science.gov (United States)

    Kim, Seok-Hyung; Wu, Shu-Yu; Baek, Jeong-In; Choi, Soo Young; Su, Yanhui; Flynn, Charles R; Gamse, Joshua T; Ess, Kevin C; Hardiman, Gary; Lipschutz, Joshua H; Abumrad, Naji N; Rockey, Don C

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease such as simple steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis and fibrosis. However, the molecular pathogenesis and genetic variations causing NAFLD are poorly understood. The high prevalence and incidence of NAFLD suggests that genetic variations on a large number of genes might be involved in NAFLD. To identify genetic variants causing inherited liver disease, we used zebrafish as a model system for a large-scale mutant screen, and adopted a whole genome sequencing approach for rapid identification of mutated genes found in our screen. Here, we report on a forward genetic screen of ENU mutagenized zebrafish. From 250 F2 lines of ENU mutagenized zebrafish during post-developmental stages (5 to 8 days post fertilization), we identified 19 unique mutant zebrafish lines displaying visual evidence of hepatomegaly and/or steatosis with no developmental defects. Histological analysis of mutants revealed several specific phenotypes, including common steatosis, micro/macrovesicular steatosis, hepatomegaly, ballooning, and acute hepatocellular necrosis. This work has identified multiple post-developmental mutants and establishes zebrafish as a novel animal model for post-developmental inherited liver disease.

  18. Space mutagenesis of genetically engineered bacteria expressing recombinant human interferon α1b and screening of higher yielding strains.

    Science.gov (United States)

    Wang, Junfeng; Liu, Changting; Liu, Jinyi; Fang, Xiangqun; Xu, Chen; Guo, Yinghua; Chang, De; Su, Longxiang

    2014-03-01

    The aim of this study was to investigate the space mutagenesis of genetically engineered bacteria expressing recombinant human interferon α1b. The genetically engineered bacteria expressing the recombinant interferon α1b were sent into outer space on the Chinese Shenzhou VIII spacecraft. After the 17 day space flight, mutant strains that highly expressed the target gene were identified. After a series of screening of spaceflight-treated bacteria and the quantitative comparison of the mutant strains and original strain, we found five strains that showed a significantly higher production of target proteins, compared with the original strain. Our results support the notion that the outer space environment has unique effects on the mutation breeding of microorganisms, including genetically engineered strains. Mutant strains that highly express the target protein could be obtained through spaceflight-induced mutagenesis.

  19. Performance Studies on Distributed Virtual Screening

    Directory of Open Access Journals (Sweden)

    Jens Krüger

    2014-01-01

    Full Text Available Virtual high-throughput screening (vHTS is an invaluable method in modern drug discovery. It permits screening large datasets or databases of chemical structures for those structures binding possibly to a drug target. Virtual screening is typically performed by docking code, which often runs sequentially. Processing of huge vHTS datasets can be parallelized by chunking the data because individual docking runs are independent of each other. The goal of this work is to find an optimal splitting maximizing the speedup while considering overhead and available cores on Distributed Computing Infrastructures (DCIs. We have conducted thorough performance studies accounting not only for the runtime of the docking itself, but also for structure preparation. Performance studies were conducted via the workflow-enabled science gateway MoSGrid (Molecular Simulation Grid. As input we used benchmark datasets for protein kinases. Our performance studies show that docking workflows can be made to scale almost linearly up to 500 concurrent processes distributed even over large DCIs, thus accelerating vHTS campaigns significantly.

  20. Hospital malnutrition: a 33-hospital screening study.

    Science.gov (United States)

    Kamath, S K; Lawler, M; Smith, A E; Kalat, T; Olson, R

    1986-02-01

    A collaborative study involving nutrition screening of 3,047 patients (excluding 125 pregnant women) at admission to 33 hospitals in and around the greater Chicago area was carried out to identify patients at nutritional risk. Information on sex, age, admitting diagnosis, serum albumin, hemoglobin, total lymphocyte count, and height and weight was collected from the medical chart within 48 hours of admission. Nutrition screening could not be completed for a larger number of patients (60%) because data at admission were not available. Of the remaining 40% of patients, more than 50% had below normal values for one or more of the variables studied: serum albumin, hemoglobin, and total lymphocyte count. A large number of the patients (40%) also were considered at nutritional risk as judged by the criteria of weight/height (measured only). Early nutrition intervention for high-risk patients cannot be implemented, nor can the efficacy of nutrition services be evaluated, unless nutrition screening is carried out on patients at admission.

  1. Preimplantation Genetic Screening: An Effective Testing for Infertile and Repeated Miscarriage Patients?

    Directory of Open Access Journals (Sweden)

    Ning Wang

    2010-01-01

    Full Text Available Aneuploidy in pregnancy is known to increase with advanced maternal age (AMA and associate with repeated implantation failure (RIF, and repeated miscarriage (RM. Preimplantation genetic screening (PGS has been introduced into clinical practice, screening, and eliminating aneuploidy embryos, which can improve the chance of conceptions for infertility cases with poor prognosis. These patients are a good target group to assess the possible benefit of aneuploidy screening. Although practiced widely throughout the world, there still exist some doubts about the efficacy of this technique. Recent randomized trials were not as desirable as we expected, suggesting that PGS needs to be reconsidered. The aim of this review is to discuss the efficacy of PGS.

  2. Statement of The American Society of Human Genetics on cystic fibrosis carrier screening

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-01

    The identification in 1989 of the cystic fibrosis (CF) gene and its most common mutation immediately raised the possibility of CF carrier detection by DNA analysis. The American Society of Human Genetics (ASHG) issued a statement recommending that CF carrier testing should be made available to individuals with a family history of CF. It was also stated that screening of individuals or couples in the general population should not be offered until the rate of CF carrier detection improves. An additional prerequisite emphasized the need for the establishment of effective educational and counseling programs consistent with previous widely accepted principles. An NIH workshop reached similar conclusions. ASHG recommendations are that screening be limited to individuals with a family history of CF, testing should be accompanied by education and counseling, screening should be voluntary and confidential with appropriate laboratory quality controls, and efforts should be expanded to educate health care providers and the public.

  3. Evaluation of a novel electronic genetic screening and clinical decision support tool in prenatal clinical settings.

    Science.gov (United States)

    Edelman, Emily A; Lin, Bruce K; Doksum, Teresa; Drohan, Brian; Edelson, Vaughn; Dolan, Siobhan M; Hughes, Kevin; O'Leary, James; Vasquez, Lisa; Copeland, Sara; Galvin, Shelley L; DeGroat, Nicole; Pardanani, Setul; Gregory Feero, W; Adams, Claire; Jones, Renee; Scott, Joan

    2014-07-01

    "The Pregnancy and Health Profile" (PHP) is a free prenatal genetic screening and clinical decision support (CDS) software tool for prenatal providers. PHP collects family health history (FHH) during intake and provides point-of-care risk assessment for providers and education for patients. This pilot study evaluated patient and provider responses to PHP and effects of using PHP in practice. PHP was implemented in four clinics. Surveys assessed provider confidence and knowledge and patient and provider satisfaction with PHP. Data on the implementation process were obtained through semi-structured interviews with administrators. Quantitative survey data were analyzed using Chi square test, Fisher's exact test, paired t tests, and multivariate logistic regression. Open-ended survey questions and interviews were analyzed using qualitative thematic analysis. Of the 83% (513/618) of patients that provided feedback, 97% felt PHP was easy to use and 98% easy to understand. Thirty percent (21/71) of participating physicians completed both pre- and post-implementation feedback surveys [13 obstetricians (OBs) and 8 family medicine physicians (FPs)]. Confidence in managing genetic risks significantly improved for OBs on 2/6 measures (p values ≤0.001) but not for FPs. Physician knowledge did not significantly change. Providers reported value in added patient engagement and reported mixed feedback about the CDS report. We identified key steps, resources, and staff support required to implement PHP in a clinical setting. To our knowledge, this study is the first to report on the integration of patient-completed, electronically captured and CDS-enabled FHH software into primary prenatal practice. PHP is acceptable to patients and providers. Key to successful implementation in the future will be customization options and interoperability with electronic health records.

  4. [Biochemical screening and genetic diagnosis of thalassemia in children from Kunming].

    Science.gov (United States)

    Wen, Bai-Ping; Fan, Mao; Dai, Hong-Jian; Zhuang, Yu; Liu, Hong-Ling; Yang, Jun-Yi; Yang, Xiao-Hong; Deng, Wen-Guo

    2011-02-01

    To investigate the types and frequency of gene mutations in children with thalassemia in Kunming, Yunan Province. A biochemical screening for thalassemia was performed by testing RBC fragility, MCV and hemoglobin electrophoresis on 1338 children from Kunming, Yunnan Province. Genetic diagnosis was performed on the children with α-thalassemia by gap-PCR and on the children with β-thalassemia by PCR-RDB. The positive rate of the biochemical screening for thalassemia was 11.36% (152 cases). The positive rate of genetic diagnosis was 8.59% (115 cases). Of the 115 cases, α-thalassemia was found in 43 cases, β-thalassemia in 68 cases and α-combined-β thalassemia in 4 cases.--SEA/αα accounted for 47%, -α4.2/αα accounted for 21%, and HbH disease accounted for 14%. Six genotypes were found in 68 cases of β-thalassemia and the mutation frequency of βE was the highest (32%), followed by CD41-42 (24%), CD17 (23%), IVS-II654 (10%), CD71-72 (10%), and -28 (1%). The frequency of gene mutations for thalassemia is high in children from Kunming, Yunnan Province. Premarital and prenatal screenings and genetic diagnosis for thalassemia should be carried out in this area.

  5. Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS).

    Science.gov (United States)

    Gleicher, Norbert; Weghofer, Andrea; Barad, David H

    2010-11-10

    Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR), and to reduce miscarriage rates by 50-80%. Such an effect is mathematically inconceivable without beneficial effects on embryo ploidy. This study, therefore, assesses effects of DHEA on embryo aneuploidy. In a 1:2, matched case control study 22 consecutive women with DOR, supplemented with DHEA, underwent preimplantation genetic screening (PGS) of embryos during in vitro fertilization (IVF) cycles. Each was matched by patient age and time period of IVF with two control IVF cycles without DHEA supplementation (n = 44). PGS was performed for chromosomes X, Y, 13, 16, 18, 21 and 22, and involved determination of numbers and percentages of aneuploid embryos. DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P DHEA effects on DOR patients, at least partially, are the likely consequence of lower embryo aneuploidy. DHEA supplementation also deserves investigation in older fertile women, attempting to conceive, where a similar effect, potentially, could positively affect public health.

  6. Practical experiences with an extended screening strategy for genetically modified organisms (GMOs) in real-life samples.

    Science.gov (United States)

    Scholtens, Ingrid; Laurensse, Emile; Molenaar, Bonnie; Zaaijer, Stephanie; Gaballo, Heidi; Boleij, Peter; Bak, Arno; Kok, Esther

    2013-09-25

    Nowadays most animal feed products imported into Europe have a GMO (genetically modified organism) label. This means that they contain European Union (EU)-authorized GMOs. For enforcement of these labeling requirements, it is necessary, with the rising number of EU-authorized GMOs, to perform an increasing number of analyses. In addition to this, it is necessary to test products for the potential presence of EU-unauthorized GMOs. Analysis for EU-authorized and -unauthorized GMOs in animal feed has thus become laborious and expensive. Initial screening steps may reduce the number of GMO identification methods that need to be applied, but with the increasing diversity also screening with GMO elements has become more complex. For the present study, the application of an informative detailed 24-element screening and subsequent identification strategy was applied in 50 animal feed samples. Almost all feed samples were labeled as containing GMO-derived materials. The main goal of the study was therefore to investigate if a detailed screening strategy would reduce the number of subsequent identification analyses. An additional goal was to test the samples in this way for the potential presence of EU-unauthorized GMOs. Finally, to test the robustness of the approach, eight of the samples were tested in a concise interlaboratory study. No significant differences were found between the results of the two laboratories.

  7. The conditional nature of genetic interactions: the consequences of wild-type backgrounds on mutational interactions in a genome-wide modifier screen.

    Directory of Open Access Journals (Sweden)

    Sudarshan Chari

    Full Text Available The phenotypic outcome of a mutation cannot be simply mapped onto the underlying DNA variant. Instead, the phenotype is a function of the allele, the genetic background in which it occurs and the environment where the mutational effects are expressed. While the influence of genetic background on the expressivity of individual mutations is recognized, its consequences on the interactions between genes, or the genetic network they form, is largely unknown. The description of genetic networks is essential for much of biology; yet if, and how, the topologies of such networks are influenced by background is unknown. Furthermore, a comprehensive examination of the background dependent nature of genetic interactions may lead to identification of novel modifiers of biological processes. Previous work in Drosophila melanogaster demonstrated that wild-type genetic background influences the effects of an allele of scalloped (sd, with respect to both its principal consequence on wing development and its interactions with a mutation in optomotor blind. In this study we address whether the background dependence of mutational interactions is a general property of genetic systems by performing a genome wide dominant modifier screen of the sd(E3 allele in two wild-type genetic backgrounds using molecularly defined deletions. We demonstrate that ~74% of all modifiers of the sd(E3 phenotype are background-dependent due in part to differential sensitivity to genetic perturbation. These background dependent interactions include some with qualitative differences in the phenotypic outcome, as well as instances of sign epistasis. This suggests that genetic interactions are often contingent on genetic background, with flexibility in genetic networks due to segregating variation in populations. Such background dependent effects can substantially alter conclusions about how genes influence biological processes, the potential for genetic screens in alternative wild

  8. A Genetic Screen To Assess Dopamine Receptor (DopR1 Dependent Sleep Regulation in Drosophila

    Directory of Open Access Journals (Sweden)

    Yiqin Jiang

    2016-12-01

    Full Text Available Sleep is an essential behavioral state of rest that is regulated by homeostatic drives to ensure a balance of sleep and activity, as well as independent arousal mechanisms in the central brain. Dopamine has been identified as a critical regulator of both sleep behavior and arousal. Here, we present results of a genetic screen that selectively restored the Dopamine Receptor (DopR/DopR1/dumb to specific neuroanatomical regions of the adult Drosophila brain to assess requirements for DopR in sleep behavior. We have identified subsets of the mushroom body that utilizes DopR in daytime sleep regulation. These data are supported by multiple examples of spatially restricted genetic rescue data in discrete circuits of the mushroom body, as well as immunohistochemistry that corroborates the localization of DopR protein within mushroom body circuits. Independent loss of function data using an inducible RNAi construct in the same specific circuits also supports a requirement for DopR in daytime sleep. Additional circuit activation of discrete DopR+ mushroom body neurons also suggests roles for these subpopulations in sleep behavior. These conclusions support a new separable function for DopR in daytime sleep regulation within the mushroom body. This daytime regulation is independent of the known role of DopR in nighttime sleep, which is regulated within the Fan-Shaped Body (FSB. This study provides new neuroanatomical loci for exploration of dopaminergic sleep functions in Drosophila, and expands our understanding of sleep regulation during the day vs. night.

  9. Large genetic screens for gynogenesis and androgenesis haploid inducers in Arabidopsis thaliana failed to identify mutants

    Directory of Open Access Journals (Sweden)

    Virginie ePortemer

    2015-03-01

    Full Text Available Gynogenesis is a process in which the embryo genome originates exclusively from female origin, following embryogenesis stimulation by a male gamete. In contrast, androgenesis is the development of embryos that contain only the male nuclear genetic background. Both phenomena are of great interest in plant breeding as haploidisation is an efficient tool to reduce the length of breeding schemes to create varieties. Although few inducer lines have been described, the genetic control of these phenomena is poorly understood. We developed genetic screens to identify mutations that would induce gynogenesis or androgenesis in Arabidopsis thaliana. The ability of mutant pollen to induce either gynogenesis or androgenesis was tested by crossing mutagenized plants as males. Seedlings from these crosses were screened with recessive phenotypic markers, one genetically controlled by the female genome and another by the male genome. Positive and negative controls confirmed the unambiguous detection of both gynogenesis and androgenesis events. This strategy was applied to 1,666 EMS-mutagenised lines and 47 distant Arabidopsis strains. While an internal control suggested that the mutagenesis reached saturation, no gynogenesis or androgenesis inducer was found. However, spontaneous gynogenesis was observed at a frequency of 1/10,800. Altogether, these results suggest that no simple EMS-induced mutation in the male genome is able to induce gynogenesis or androgenesis in Arabidopsis.

  10. SYBR® Green qPCR Screening Methods for Detection of Anti-herbicide Genes in Genetically Modiifed Processed Products

    Institute of Scientific and Technical Information of China (English)

    Zhen Zhen; Lv Wei; Tang Zhi-fen; Liu Ying; Ao Jin-xia; Yuan Xiao-han; Zhang Ming-hui; Qiu You-wen; Gao Xue-jun

    2016-01-01

    The use of genetically modified organisms (GMOs) as food products becomes more and more widespread. The European Union has implemented a set of very strict procedures for the approval to grow, import and/or utilize GMOs as food or food ingredients. Thus, analytical methods for detection of GMOs are necessary in order to verify compliance with labelling requirements. There are few effective screening methods for processed GM (genetically modified) products. Three anti-herbicide genes (CP4-EPSPS,BAR andPAT) are common exogenous genes used in commercialized transgenic soybean, maize and rice. In the present study, a new SYBR® Green qPCR screening method was developed to simultaneously detect the three exogenous anti-herbicide genes and one endogenous gene in a run. We tested seven samples of representative processed products (soya lecithin, soya protein powder, chocolate beverage, infant rice cereal, maize protein powder, maize starch, and maize jam) using the developed method, and amplicons of endogenous gene and transgenic fragments were obtained from all the processed products, and the sensitivity was 0.1%. These results indicated that SYBR® Green qPCR screening method was appropriate for qualitative detection of transgenic soybean, maize and rice in processed products.

  11. A genetic screen in Drosophila reveals novel cytoprotective functions of the autophagy-lysosome pathway.

    Directory of Open Access Journals (Sweden)

    Andrew M Arsham

    Full Text Available The highly conserved autophagy-lysosome pathway is the primary mechanism for breakdown and recycling of macromolecular and organellar cargo in the eukaryotic cell. Autophagy has recently been implicated in protection against cancer, neurodegeneration, and infection, and interest is increasing in additional roles of autophagy in human health, disease, and aging. To search for novel cytoprotective features of this pathway, we carried out a genetic mosaic screen for mutations causing increased lysosomal and/or autophagic activity in the Drosophila melanogaster larval fat body. By combining Drosophila genetics with live-cell imaging of the fluorescent dye LysoTracker Red and fixed-cell imaging of autophagy-specific fluorescent protein markers, the screen was designed to identify essential metazoan genes whose disruption causes increased flux through the autophagy-lysosome pathway. The screen identified a large number of genes associated with the protein synthesis and ER-secretory pathways (e.g. aminoacyl tRNA synthetases, Oligosaccharyl transferase, Sec61alpha, and with mitochondrial function and dynamics (e.g. Rieske iron-sulfur protein, Dynamin-related protein 1. We also observed that increased lysosomal and autophagic activity were consistently associated with decreased cell size. Our work demonstrates that disruption of the synthesis, transport, folding, or glycosylation of ER-targeted proteins at any of multiple steps leads to autophagy induction. In addition to illuminating cytoprotective features of autophagy in response to cellular damage, this screen establishes a genetic methodology for investigating cell biological phenotypes in live cells, in the context of viable wild type organisms.

  12. Genome-wide screening for genetic loci associated with noise-induced hearing loss.

    Science.gov (United States)

    White, Cory H; Ohmen, Jeffrey D; Sheth, Sonal; Zebboudj, Amina F; McHugh, Richard K; Hoffman, Larry F; Lusis, Aldons J; Davis, Richard C; Friedman, Rick A

    2009-04-01

    Noise-induced hearing loss (NIHL) is one of the more common sources of environmentally induced hearing loss in adults. In a mouse model, Castaneous (CAST/Ei) is an inbred strain that is resistant to NIHL, while the C57BL/6J strain is susceptible. We have used the genome-tagged mice (GTM) library of congenic strains, carrying defined segments of the CAST/Ei genome introgressed onto the C57BL/6J background, to search for loci modifying the noise-induced damage seen in the C57BL/6J strain. NIHL was induced by exposing 6-8-week old mice to 108 dB SPL intensity noise. We tested the hearing of each mouse strain up to 23 days after noise exposure using auditory brainstem response (ABR). This study identifies a number of genetic loci that modify the initial response to damaging noise, as well as long-term recovery. The data suggest that multiple alleles within the CAST/Ei genome modify the pathogenesis of NIHL and that screening congenic libraries for loci that underlie traits of interest can be easily carried out in a high-throughput fashion.

  13. Data on screening and identification of genetically modified papaya in food supplements.

    Science.gov (United States)

    Prins, Theo W; Scholtens, Ingrid M J; Bak, Arno W; van Dijk, Jeroen P; Voorhuijzen, Marleen M; Laurensse, Emile J; Kok, Esther J

    2016-12-01

    This article contains data related to the research article entitled "A case study to determine the geographical origin of unknown GM papaya in routine food sample analysis, followed by identification of papaya events 16-0-1 and 18-2-4" (Prins et al., 2016) [1]. Quantitative real-time PCR (qPCR) with targets that are putatively present in genetically modified (GM) papaya was used as a first screening to narrow down the vast array of candidates. The combination of elements P-nos and nptII was further confirmed by amplification and subsequent sequencing of the P-nos/nptII construct. Next, presence of the candidate GM papayas 16-0-1 and 18-2-4 were investigated by amplification and sequencing of event-spanning regions on the left and right border. This data article reports the Cq values for GM elements, the nucleotide sequence of the P-nos/nptII construct and the presence of GM papaya events 18-2-4 and/or 16-0-1 in five samples that were randomly sampled to be analysed in the framework of the official Dutch GMO monitoring program for food.

  14. Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review

    Science.gov (United States)

    2014-01-01

    Only a few years ago the American Society of Assisted Reproductive Medicine (ASRM), the European Society for Human Reproduction and Embryology (ESHRE) and the British Fertility Society declared preimplantation genetic screening (PGS#1) ineffective in improving in vitro fertilization (IVF) pregnancy rates and in reducing miscarriage rates. A presumably upgraded form of the procedure (PGS#2) has recently been reintroduced, and is here assessed in a systematic review. PGS#2 in comparison to PGS#1 is characterized by: (i) trophectoderm biopsy on day 5/6 embryos in place of day-3 embryo biopsy; and (ii) fluorescence in-situ hybridization (FISH) of limited chromosome numbers is replaced by techniques, allowing aneuploidy assessments of all 24 chromosome pairs. Reviewing the literature, we were unable to identify properly conducted prospective clinical trials in which IVF outcomes were assessed based on “intent to treat”. Whether PGS#2 improves IVF outcomes can, therefore, not be determined. Reassessments of data, alleged to support the efficacy of PGS#2, indeed, suggest the opposite. Like with PGS#1, the introduction of PGS#2 into unrestricted IVF practice again appears premature, and threatens to repeat the PGS#1 experience, when thousands of women experienced reductions in IVF pregnancy chances, while expecting improvements. PGS#2 is an unproven and still experimental procedure, which, until evidence suggests otherwise, should only be offered under study conditions, and with appropriate informed consents. PMID:24628895

  15. Hamartomatous polyps - a clinical and molecular genetic study

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie

    2016-01-01

    the knowledge on clinical course and molecular genetics in patients with HPs and HPS, and to investigate research participants' attitude towards the results of extensive genetic testing. Paper I: In the first paper we investigated the occurrence, anatomic distribution, and other demographics of juvenile polyps......-Jeghers syndrome, and the PTEN hamartoma tumour syndrome. Currently, the HPS diagnoses are based on clinical criteria and are often assisted with genetic testing as candidate genes have been described for each syndrome. This thesis is based on six scientific papers. The overall aim of the studies was to expand......% fulfilled to diagnostic criteria of JPS. The majority of patients had a single juvenile polyp. Paper II: In this paper we conducted a review of the HPS based on the current literature. Paper III: We investigated the hypothesis that patients with one or few HPs may have a HPS based on genetic screening. We...

  16. Maine Coon renal screening: ultrasonographical characterisation and preliminary genetic analysis for common genes in cats with renal cysts.

    Science.gov (United States)

    Gendron, Karine; Owczarek-Lipska, Marta; Lang, Johann; Leeb, Tosso

    2013-12-01

    The objective of this study was to assess the prevalence of renal cysts and other renal abnormalities in purebred Maine Coon cats, and to characterise these through genetic typing. Voluntary pre-breeding screening programmes for polycystic kidney disease (PKD) are offered for this breed throughout Switzerland, Germany and other northern European countries. We performed a retrospective evaluation of Maine Coon screening for renal disease at one institution over an 8-year period. Renal ultrasonography was performed in 187 healthy Maine Coon cats. Renal changes were observed in 27 of these cats. Renal cysts were found in seven cats, and were mostly single and unilateral (6/7, 85.7%), small (mean 3.6 mm) and located at the corticomedullary junction (4/6, 66.7%). Sonographical changes indicating chronic kidney disease (CKD) were observed in 10/187 (5.3%) cats and changes of unknown significance were documented in 11/187 (5.9%) cats. All six cats genetically tested for PKD1 were negative for the mutation, and gene sequencing of these cats did not demonstrate any common genetic sequences. Cystic renal disease occurs with a low prevalence in Maine Coons and is unrelated to the PKD observed in Persians and related breeds. Ultrasonographical findings compatible with CKD are not uncommon in juvenile Maine Coons.

  17. Study of Screen Design Principles for Visualizing Medical Records.

    Science.gov (United States)

    Fujita, Kenichiro; Takemura, Tadamasa; Kuroda, Tomohiro

    2015-01-01

    To improve UX of EMR/EHR, the screen design principles for the visualization are required. Through the study of common attributes of medical records, we present four principles and show three screen designs by applying them.

  18. Newborn screening for lysosomal diseases: current status and potential interface with population medical genetics in Latin America.

    Science.gov (United States)

    Giugliani, Roberto

    2012-09-01

    with a comprehensive coverage in terms of number of diseases and number of births. Population medical genetics is the area of medical genetics that aims at the study and medical care of the population, and not of the family, which is the case for clinical or medical genetics itself. It combines different aspects of genetics: clinical genetics; human population genetics, which investigates populations according to micro-evolutionary parameters; epidemiological genetics, traditionally involved in the study of common chronic diseases of polygenic etiology, except for Mendelian diseases; and sanitary or community genetics, which stands at the interface with public health, giving support to preventive health measures. Taking into account that several LSDs were identified in a higher frequency in selected areas and/or populations, the population medical genetics approach could help to introduce the NBS for LSDs in the region, with identification of areas with higher risk for selected diseases and design of customized screening program to address specific needs. As an example of the potential of this approach, a pilot program of NBS for MPS VI was implemented in a community from North East Brazil where 13 cases of MPS VI were identified in an area with 50,000 inhabitants. This program, which will enable not only identification and early treatment of affected newborns but also carrier detection, and which would allow genetic counseling for at-risk couples, could be an alternative model for a customized NBS of LSDs to be carried out in selected regions.

  19. Pregnancy outcome after preimplantation genetic screening or natural conception in couples with unexplained recurrent miscarriage: a systematic review of the best available evidence.

    NARCIS (Netherlands)

    Musters, A.M.; Repping, S.; Korevaar, J.C.; Mastenbroek, S.; Limpens, J.; Veen, F. van der; Goddijn, M.

    2011-01-01

    The objective of this systematic review was to assess live birth rates and miscarriage rates after preimplantation genetic screening or natural conception for unexplained recurrent miscarriage. There were no randomized controlled trials or comparative studies found on this topic. Until data from ran

  20. Pre-implantation genetic screening using fluorescence in situ hybridization in couples of Indian ethnicity: Is there a scope?

    Directory of Open Access Journals (Sweden)

    Shailaja Gada Saxena

    2014-01-01

    Full Text Available Context: There is a high incidence of numerical chromosomal aberration in couples with repeated in vitro fertilization (IVF failure, advanced maternal age, repeated unexplained abortions, severe male factor infertility and unexplained infertility. Pre-implantation genetic screening (PGS, a variant of pre-implantation genetic diagnosis, screens numerical chromosomal aberrations in couples with normal karyotype, experiencing poor reproductive outcome. The present study includes the results of the initial pilot study on 9 couples who underwent 10 PGS cycles. Aim: The aim of the present study was to evaluate the beneficial effects of PGS in couples with poor reproductive outcome. Settings and Design: Data of initial 9 couples who underwent 10 PGS for various indications was evaluated. Subjects and Methods: Blastomere biopsy was performed on cleavage stage embryos and subjected to two round fluorescence in situ hybridization (FISH testing for chromosomes 13, 18, 21, X and Y as a two-step procedure. Results: Six of the 9 couples (10 PGS cycles conceived, including a twin pregnancy in a couple with male factor infertility, singleton pregnancies in a couple with secondary infertility, in three couples with adverse obstetric outcome in earlier pregnancies and in one couple with repeated IVF failure. Conclusion: In the absence of availability of array-comparative genomic hybridization in diagnostic clinical scenario for PGS and promising results with FISH based PGS as evident from the current pilot study, it is imperative to offer the best available services in the present scenario for better pregnancy outcome for patients.

  1. Neonatal Screening: Some Ethical Issues of Expanding Spectrum for Genetically Determined Diseases

    Directory of Open Access Journals (Sweden)

    S. S. Deryabina

    2015-01-01

    Full Text Available The article considers philosophical questions of neonatal screening technology. The main focus is on ethical and methodological issues that inevitably arise when expanding the number of scanned nosologies and applying genetic research methods. Questions concerning the existing discrepancy between technical capacity and the practical level of healthcare delivery and the probabilistic nature of results obtained by molecular testing are analyzed in terms of methodology. Access to information about the DNA-testing of newborns and the linkage between neonatal screening and prenatal diagnostics are among the most topical ethical problems raised within this article. One of the purposes of this article is to draw the attention of the public — especially it concerns current and prospective parents and volunteer organizations — to these contemporary problems.

  2. Genetic screens and functional genomics using CRISPR/Cas9 technology.

    Science.gov (United States)

    Hartenian, Ella; Doench, John G

    2015-04-01

    Functional genomics attempts to understand the genome by perturbing the flow of information from DNA to RNA to protein, in order to learn how gene dysfunction leads to disease. CRISPR/Cas9 technology is the newest tool in the geneticist's toolbox, allowing researchers to edit DNA with unprecedented ease, speed and accuracy, and representing a novel means to perform genome-wide genetic screens to discover gene function. In this review, we first summarize the discovery and characterization of CRISPR/Cas9, and then compare it to other genome engineering technologies. We discuss its initial use in screening applications, with a focus on optimizing on-target activity and minimizing off-target effects. Finally, we comment on future challenges and opportunities afforded by this technology.

  3. Genetic Screening for Bacterial Mutants in Liquid Growth Media By Fluorescence-Activated Cell Sorting

    Science.gov (United States)

    Abuaita, Basel H.; Withey, Jeffrey H.

    2010-01-01

    Many bacterial pathogens have defined in vitro virulence inducing conditions in liquid media which lead to production of virulence factors important during an infection. Identifying mutants that no longer respond to virulence inducing conditions will increase our understanding of bacterial pathogenesis. However, traditional genetic screens require growth on solid media. Bacteria in a single colony are in every phase of the growth curve, which complicates the analysis and make screens for growth phase-specific mutants problematic. Here, we utilize fluorescence-activated cell sorting in conjunction with random transposon mutagenesis to isolate bacteria grown in liquid media that are defective in virulence activation. This method permits analysis of an entire bacterial population in real time and selection of individual bacterial mutants with the desired gene expression profile at any time point after induction. We have used this method to identify Vibrio cholerae mutants defective in virulence induction. PMID:21094189

  4. Screening Out Controversy: Human Genetics, Emerging Techniques of Diagnosis, and the Origins of the Social Issues Committee of the American Society of Human Genetics, 1964-1973.

    Science.gov (United States)

    Mitchell, M X

    2017-05-01

    In the years following World War II, and increasingly during the 1960s and 1970s, professional scientific societies developed internal sub-committees to address the social implications of their scientific expertise (Moore, Disrupting Science: Social Movements, American Scientists, and the Politics of the Military, 1945-1975. Princeton: Princeton University Press, 2008). This article explores the early years of one such committee, the American Society of Human Genetics' "Social Issues Committee," founded in 1967. Although the committee's name might suggest it was founded to increase the ASHG's public and policy engagement, exploration of the committee's early years reveals a more complicated reality. Affronted by legislators' recent unwillingness to seek the expert advice of human geneticists before adopting widespread neonatal screening programs for phenylketonuria (PKU), and feeling pressed to establish their relevance in an increasingly resource-scarce funding environment, committee members sought to increase the discipline's expert authority. Painfully aware of controversy over abortion rights and haunted by the taint of the discipline's eugenic past, however, the committee proceeded with great caution. Seeking to harness interest in and assert professional control over emerging techniques of genetic diagnosis, the committee strove to protect the society's image by relegating ethical and policy questions about their use to the individual consciences of member scientists. It was not until 1973, after the committee's modest success in organizing support for a retrospective public health study of PKU screening and following the legalization of abortion on demand, that the committee decided to take a more publicly engaged stance.

  5. Descriptive epidemiology of screen and non-screen sedentary time in adolescents: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Ridley Kate

    2010-12-01

    Full Text Available Abstract Background Much attention has been paid to adolescents' screen time, however very few studies have examined non-screen sedentary time (NSST. This study aimed to (1 describe the magnitude and composition of screen sedentary time (SST and NSST in Australian adolescents, (2 describe the socio-demographic correlates of SST and NSST, and (3 determine whether screen time is an adequate surrogate for total sedentary behaviour in this population. Methods 2200 9-16 year old Australians provided detailed use of time data for four days. Non-screen sedentary time (NSST included time spent participating in activities expected to elicit Results Adolescents spent a mean (SD of 345 (105 minutes/day in NSST, which constituted 60% of total sedentary time. School activities contributed 42% of NSST, socialising 19%, self-care (mainly eating 16%, and passive transport 15%. Screen time and NSST showed opposite patterns in relation to key socio-demographic characteristics, including sex, age, weight status, household income, parental education and day type. Because screen time was negatively correlated with NSST (r = -0.58, and exhibited a moderate correlation (r = 0.53 with total sedentary time, screen time was only a moderately effective surrogate for total sedentary time. Conclusions To capture a complete picture of young people's sedentary time, studies should endeavour to measure both screen time and NSST.

  6. Breast density and outcome of mammography screening: a cohort study

    DEFF Research Database (Denmark)

    Olsen, A H; Bihrmann, K; Jensen, M-B

    2009-01-01

    The purpose of this study was to investigate the effect of breast density on breast cancer (BC) mortality in a mammography screening programme. The cohort included 48 052 women participating in mammography screening in Copenhagen, Denmark, where biennial screening is offered to women aged 50-69 y...

  7. The role of experiential knowledge within attitudes towards genetic carrier screening: A comparison of people with and without experience of spinal muscular atrophy.

    Science.gov (United States)

    Boardman, Felicity K; Young, Philip J; Warren, Oliver; Griffiths, Frances E

    2017-07-13

    Autosomal recessive conditions, while individually rare, are a significant health burden with limited treatment options. Population carrier screening has been suggested as a means of tackling them. Little is known, however, about the attitudes of the general public towards such carrier screening and still less about the views of people living with candidate genetic diseases. Here, we focus on the role that such experience has on screening attitudes by comparing views towards screening of people with and without prior experience of the monogenetic disorder, Spinal Muscular Atrophy. An exploratory sequential mixed methods design was adopted. In-depth qualitative interviews were used to develop two surveys. The surveys addressed attitudes towards carrier screening (pre-conceptual and prenatal) for SMA. 337 participants with SMA experience completed the SMA Screening Survey (UK) and 336 participants with no prior experience of SMA completed the UK GenPop Survey, an amended version of the SMA Screening Survey (UK). The majority of both cohorts were in favour of pre-conception and prenatal carrier screening, however people with experience of type II SMA were least likely to support either. Key differences emerged around perceptions of SMA, with those without SMA experience taking a dimmer view of the condition than those with. This study underscores the significance of prior experience with the condition to screening attitudes. It highlights the need for accurate and high-quality educational resources to support any future carrier screening programmes, that particularly in relation to rare genetic disorders like SMA that will fall outside the remit of everyday experience for the majority of the population. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

  8. Gene set analysis for interpreting genetic studies

    DEFF Research Database (Denmark)

    Pers, Tune H

    2016-01-01

    Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways and func......Interpretation of genome-wide association study (GWAS) results is lacking behind the discovery of new genetic associations. Consequently, there is an urgent need for data-driven methods for interpreting genetic association studies. Gene set analysis (GSA) can identify aetiologic pathways...

  9. A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion

    Directory of Open Access Journals (Sweden)

    Alexandre Picard

    2016-11-01

    Full Text Available The counterregulatory response to hypoglycemia, which restores normal blood glucose levels to ensure sufficient provision of glucose to the brain, is critical for survival. To discover underlying brain regulatory systems, we performed a genetic screen in recombinant inbred mice for quantitative trait loci (QTL controlling glucagon secretion in response to neuroglucopenia. We identified a QTL on the distal part of chromosome 7 and combined this genetic information with transcriptomic analysis of hypothalami. This revealed Fgf15 as the strongest candidate to control the glucagon response. Fgf15 was expressed by neurons of the dorsomedial hypothalamus and the perifornical area. Intracerebroventricular injection of FGF19, the human ortholog of Fgf15, reduced activation by neuroglucopenia of dorsal vagal complex neurons, of the parasympathetic nerve, and lowered glucagon secretion. In contrast, silencing Fgf15 in the dorsomedial hypothalamus increased neuroglucopenia-induced glucagon secretion. These data identify hypothalamic Fgf15 as a regulator of glucagon secretion.

  10. New Advances of Preimplantation and Prenatal Genetic Screening and Noninvasive Testing as a Potential Predictor of Health Status of Babies

    Directory of Open Access Journals (Sweden)

    Tanya Milachich

    2014-01-01

    Full Text Available The current morphologically based selection of human embryos for transfer cannot detect chromosome aneuploidies. So far, only biopsy techniques have been able to screen for chromosomal aneuploidies in the in vitro fertilization (IVF embryos. Preimplantation genetic diagnosis (PGD or screening (PGS involves the biopsy of oocyte polar bodies or embryonic cells and has become a routine clinical procedure in many IVF clinics worldwide, including recent development of comprehensive chromosome screening of all 23 pairs of chromosomes by microarrays for aneuploidy screening. The routine preimplantation and prenatal genetic diagnosis (PND require testing in an aggressive manner. These procedures may be invasive to the growing embryo and fetus and potentially could compromise the clinical outcome. Therefore the aim of this review is to summarize not only the new knowledge on preimplantation and prenatal genetic diagnosis in humans, but also on the development of potential noninvasive embryo and fetal testing that might play an important role in the future.

  11. Breast cancer screening: An outpatient clinic study

    Directory of Open Access Journals (Sweden)

    Mustafa Girgin

    2017-03-01

    Conclusion: A multidisciplinary cancer screening program should be maintained. With such a process, the aim is to reduce the morbidity and mortality of the disease without adversely affecting the health conditions of asymptomatic individuals based on the screening. Success is brought about by the combination of individual features. [Arch Clin Exp Surg 2017; 6(1.000: 23-27

  12. Establishment of a system based on universal multiplex-PCR for screening genetically modified crops.

    Science.gov (United States)

    Lu, I-Jen; Lin, Chih-Hui; Pan, Tzu-Ming

    2010-03-01

    The rapid development of many genetically modified (GM) crops in the past two decades makes it necessary to introduce an alternative strategy for routine screening and identification. In this study, we established a universal multiplex PCR detection system which will effectively reduce the number of reactions needed for sample identification. The PCR targets of this system include the six most frequently used transgenic elements: cauliflower mosaic virus (CaMV) 35S promoter, Agrobacterium tumefaciens nopaline synthase (nos) promoter, Agrobacterium tumefaciens nopaline synthase (nos) terminator, the neomycin phosphotransferase II (nptII) gene, the 5-enolpyruvylshikimate-3-phosphate synthase (CP4 epsps) gene of Agrobacterium tumefaciens strain CP4, and the phosphinothricin N-acetyltransferase (pat) gene. According to the AGBIOS database, the coverage of this detection system is 93% of commercial GM crops. This detection system could detect all certified reference materials (CRMs) at the 1.0% level. The correct combination of all the CRM amplicon patterns proved the specificity of this multiplex PCR system. Furthermore, the amplicon patterns of this multiplex PCR detection system could be used as an index of classification which will narrow the range of possible GM products. The simulation result of this multiplex PCR detection system on all commercialized 139 GM products in the AGBIOS database showed that the maximum number of PCR reactions needed to identify an unknown sample can be reduced to 13. In this study, we established a high-throughput multiplex PCR detection system with feasible sensitivity, specificity, and cost. By incorporating this detection system, the routine GM crop-detection process will meet the challenges resulting from a rapid increase in the number of GM crops in the future.

  13. Genetic study of Kelp"901"strain

    Institute of Scientific and Technical Information of China (English)

    XIA Peng; WANG Xiuliang; LI Xiaojie; ZHAO Yushan; YAO Lin; DUAN Delin

    2005-01-01

    Based on DNA extraction and optimization of random amplified reaction (RAPD) to the gametophytes and sporophytes of Kelp"901"strain,genetic study on variation was conducted to its parents and offsprings of F6,F7,F8,and F9 generation.RAPD results have shown that among 30 selected primers for gametophytes,297 loci ranging from 200 to 3 000 bp were obtained in the average of 9.9 loci for each primer.This indicated a high polymorphic rate with RAPD detection.UPGMA(unweighted pair-group method arithmetic average)analysis showed that each male and female gametophyte of a generation could be clustered into one pair separately.The genetic distances of the Kelp 901 generation were 0.321 2-0.476 7,and the maximum was between F7and F8 (0.476 7).Identityanalysis showed that F6 generation was more close to the female parent(0.659 3),and F7 generation was more close to the male parent(0.578 8).To the sporophytes study in 24 selected primers for RAPD amplification,191 loci ranging from 230-2 800 bp were obtained,in the average to each primer of 8.0 loci.The heterozygosity to six populations were male parent(0.223 9),female parent(0.107 2),F6(0.216 4),F7(0.228 6),F8 (0.229 6)and F9 (0.317 2).The nearest genetic distance was 0.083 5(F8,F9).Total heterozygosity (HT)ofF6,F7,F8and F9 generations was 0.318 6,the average heterozygosity(Hs) for F6,F7,F8 and F9 generations was 0.248 0,and deduced coefficient of population differentiation (Gst) was 22.2%.Six sequence characterized amplified regions (SCAR) were preliminary screened through RAPD analysis.It needed to be verified in detail as they are significant for molecular marker assistance in breeding and selecting Laminaria.

  14. Quantitative genetic studies of antisocial behaviour.

    Science.gov (United States)

    Viding, Essi; Larsson, Henrik; Jones, Alice P

    2008-08-12

    This paper will broadly review the currently available twin and adoption data on antisocial behaviour (AB). It is argued that quantitative genetic research can make a significant contribution to further the understanding of how AB develops. Genetically informative study designs are particularly useful for investigating several important questions such as whether: the heritability estimates vary as a function of assessment method or gender; the relative importance of genetic and environmental influences varies for different types of AB; the environmental risk factors are truly environmental; and genetic vulnerability influences susceptibility to environmental risk. While the current data are not yet directly translatable for prevention and treatment programmes, quantitative genetic research has concrete translational potential. Quantitative genetic research can supplement neuroscience research in informing about different subtypes of AB, such as AB coupled with callous-unemotional traits. Quantitative genetic research is also important in advancing the understanding of the mechanisms by which environmental risk operates.

  15. Decoding directional genetic dependencies through orthogonal CRISPR/Cas screens | Office of Cancer Genomics

    Science.gov (United States)

    Genetic interaction studies are a powerful approach to identify functional interactions between genes. This approach can reveal networks of regulatory hubs and connect uncharacterized genes to well-studied pathways. However, this approach has previously been limited to simple gene inactivation studies. Here, we present an orthogonal CRISPR/Cas-mediated genetic interaction approach that allows the systematic activation of one gene while simultaneously knocking out a second gene in the same cell.

  16. Human genetics in rheumatoid arthritis guides a high-throughput drug screen of the CD40 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Gang Li

    2013-05-01

    Full Text Available Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA, there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10(-9. Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10(-9, a finding corroborated by expression quantitative trait loci (eQTL analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2 and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65, a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L and conduct an HTS of 1,982 chemical compounds and FDA-approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel

  17. Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway

    Science.gov (United States)

    Li, Gang; Diogo, Dorothée; Wu, Di; Spoonamore, Jim; Dancik, Vlado; Franke, Lude; Kurreeman, Fina; Rossin, Elizabeth J.; Duclos, Grant; Hartland, Cathy; Zhou, Xuezhong; Li, Kejie; Liu, Jun; De Jager, Philip L.; Siminovitch, Katherine A.; Zhernakova, Alexandra; Raychaudhuri, Soumya; Bowes, John; Eyre, Steve; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Gupta, Namrata; Clemons, Paul A.; Stahl, Eli; Tolliday, Nicola; Plenge, Robert M.

    2013-01-01

    Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant in RA discovered by a previous genome-wide association study (GWAS) and to perform a high-throughput drug screen for modulators of CD40 signaling based on human genetic findings. First, we fine-map the CD40 risk locus in 7,222 seropositive RA patients and 15,870 controls, together with deep sequencing of CD40 coding exons in 500 RA cases and 650 controls, to identify a single SNP that explains the entire signal of association (rs4810485, P = 1.4×10−9). Second, we demonstrate that subjects homozygous for the RA risk allele have ∼33% more CD40 on the surface of primary human CD19+ B lymphocytes than subjects homozygous for the non-risk allele (P = 10−9), a finding corroborated by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells from 1,469 healthy control individuals. Third, we use retroviral shRNA infection to perturb the amount of CD40 on the surface of a human B lymphocyte cell line (BL2) and observe a direct correlation between amount of CD40 protein and phosphorylation of RelA (p65), a subunit of the NF-κB transcription factor. Finally, we develop a high-throughput NF-κB luciferase reporter assay in BL2 cells activated with trimerized CD40 ligand (tCD40L) and conduct an HTS of 1,982 chemical compounds and FDA–approved drugs. After a series of counter-screens and testing in primary human CD19+ B cells, we identify 2 novel chemical inhibitors not previously implicated in inflammation or CD40-mediated NF-κB signaling. Our study demonstrates proof-of-concept that human genetics can be used to guide the development of phenotype-based, high-throughput small-molecule screens to identify potential novel therapies in

  18. Review:Aluminium tolerance in barley (Hordeum vulgare L.): physiological mechanisms, genetics and screening methods

    Institute of Scientific and Technical Information of China (English)

    WANG Jun-ping; RAMAN Harsh; ZHANG Guo-ping; MENDHAM Neville; ZHOU Mei-xue

    2006-01-01

    Aluminium (Al) toxicity is one of the major limiting factors for barley production on acid soils. It inhibits root cell division and elongation, thus reducing water and nutrient uptake, consequently resulting in poor plant growth and yield. Plants tolerate Al either through external resistance mechanisms, by which Al is excluded from plant tissues or internal tolerance mechanisms, conferring the ability of plants to tolerate Al ion in the plant symplasm where Al that has permeated the plasmalemma is sequestered or converted into an innocuous form. Barley is considered to be most sensitive to Al toxicity among cereal species. Al tolerance in barley has been assessed by several methods, such as nutrient solution culture, soil bioassay and field screening. Genetic and molecular mapping research has shown that Al tolerance in barley is controlled by a single locus which is located on chromosome 4H. Molecular markers linked with Al tolerance loci have been identified and validated in a range of diverse populations. This paper reviews the (1) screening methods for evaluating Al tolerance, (2) genetics and (3) mechanisms underlying Al tolerance in barley.

  19. Multiplicity of experimental approaches to therapy for genetic muscle diseases and necessity for population screening.

    Science.gov (United States)

    Laing, Nigel G

    2008-01-01

    Currently a multiplicity of experimental approaches to therapy for genetic muscle diseases is being investigated. These include replacement of the missing gene, manipulation of the gene message, repair of the mutation, upregulation of an alternative gene and pharmacological interventions targeting a number of systems. A number of these approaches are in current clinical trials. There is considerable anticipation that perhaps more than one of the approaches will finally prove of clinical benefit, but there are many voices of caution. No matter which approaches might ultimately prove effective, there is a consensus that for most benefit to the patients it will be necessary to start treatment as early as possible. A consensus is also developing that the only way to do this is to implement population-based newborn screening to identify affected children shortly after birth. Population-based newborn screening is currently practised in very few places in the world and it brings with it implications for prevention rather than cure of genetic muscle diseases.

  20. Generation of Mouse Haploid Somatic Cells by Small Molecules for Genome-wide Genetic Screening

    Directory of Open Access Journals (Sweden)

    Zheng-Quan He

    2017-08-01

    Full Text Available The recent success of derivation of mammalian haploid embryonic stem cells (haESCs has provided a powerful tool for large-scale functional analysis of the mammalian genome. However, haESCs rapidly become diploidized after differentiation, posing challenges for genetic analysis. Here, we show that the spontaneous diploidization of haESCs happens in metaphase due to mitotic slippage. Diploidization can be suppressed by small-molecule-mediated inhibition of CDK1 and ROCK. Through ROCK inhibition, we can generate haploid somatic cells of all three germ layers from haESCs, including terminally differentiated neurons. Using piggyBac transposon-based insertional mutagenesis, we generated a haploid neural cell library harboring genome-wide mutations for genetic screening. As a proof of concept, we screened for Mn2+-mediated toxicity and identified the Park2 gene. Our findings expand the applications of mouse haploid cell technology to somatic cell types and may also shed light on the mechanisms of ploidy maintenance.

  1. A genetic epidemiologic study of hemochromatosis

    NARCIS (Netherlands)

    O.T. Njajou (Omer)

    2002-01-01

    textabstractThe goal of genetic epidemiology is to study the genetic etiology of diseases. There were t\\vo main aims for the present thesis. The first aim was to study the effects of the hemochromatosis gene (HFE) mutations on serum iron levels and disease associated conditions. Secondly, we aimed a

  2. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  3. Quantitative genetic studies of antisocial behaviour

    OpenAIRE

    Viding, Essi; Larsson, Henrik; Jones, Alice P.

    2008-01-01

    This paper will broadly review the currently available twin and adoption data on antisocial behaviour (AB). It is argued that quantitative genetic research can make a significant contribution to further the understanding of how AB develops. Genetically informative study designs are particularly useful for investigating several important questions such as whether: the heritability estimates vary as a function of assessment method or gender; the relative importance of genetic and environmental ...

  4. Flow Cytometry Enables Multiplexed Measurements of Genetically Encoded Intramolecular FRET Sensors Suitable for Screening.

    Science.gov (United States)

    Doucette, Jaimee; Zhao, Ziyan; Geyer, Rory J; Barra, Melanie M; Balunas, Marcy J; Zweifach, Adam

    2016-07-01

    Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)-activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections.

  5. Genetic analysis and SOD1 mutation screening in Iranian amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Alavi, Afagh; Nafissi, Shahriar; Rohani, Mohammad; Zamani, Babak; Sedighi, Behnaz; Shamshiri, Hosein; Fan, Jian-Bing; Ronaghi, Mostafa; Elahi, Elahe

    2013-05-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, and the most common in European populations. Results of genetic analysis and mutation screening of SOD1 in a cohort of 60 Iranian ALS patients are here reported. Initially, linkage analysis in 4 families identified a disease-linked locus that included the known ALS gene, SOD1. Screening of SOD1 identified homozygous p.Asp90Ala causing mutations in all the linked families. Haplotype analysis suggests that the p.Asp90Ala alleles in the Iranian patients might share a common founder with the renowned Scandinavian recessive p.Asp90Ala allele. Subsequent screening in all the patients resulted in identification of 3 other mutations in SOD1, including p.Leu84Phe in the homozygous state. Phenotypic features of the mutation-bearing patients are presented. SOD1 mutations were found in 11.7% of the cohort, 38.5% of the familial ALS probands, and 4.25% of the sporadic ALS cases. SOD1 mutations contribute significantly to ALS among Iranians.

  6. A genetic screen for components of the mammalian RNA interference pathway in Bloom-deficient mouse embryonic stem cells.

    Science.gov (United States)

    Trombly, Melanie I; Su, Hong; Wang, Xiaozhong

    2009-03-01

    Genetic screens performed in model organisms have helped identify key components of the RNA interference (RNAi) pathway. Recessive genetic screens have recently become feasible through the use of mouse embryonic stem (ES) cells that are Bloom's syndrome protein (Blm) deficient. Here, we developed and performed a recessive genetic screen to identify components of the mammalian RNAi pathway in Blm-deficient ES cells. Genome-wide mutagenesis using a retroviral gene trap strategy resulted in the isolation of putative homozygous RNAi mutant cells. Candidate clones were confirmed by an independent RNAi-based reporter assay and the causative gene trap integration site was identified using molecular techniques. Our screen identified multiple mutant cell lines of Argonaute 2 (Ago2), a known essential component of the RNAi pathway. This result demonstrates that true RNAi components can be isolated by this screening strategy. Furthermore, Ago2 homozygous mutant ES cells provide a null genetic background to perform mutational analyses of the Ago2 protein. Using genetic rescue, we resolve an important controversy regarding the role of two phenylalanine residues in Ago2 activity.

  7. Genetic Variance for Autism Screening Items in an Unselected Sample of Toddler-Age Twins

    Science.gov (United States)

    Stilp, Rebecca L. H.; Gernsbacher, Morton Ann; Schweigert, Emily K.; Arneson, Carrie L.; Goldsmith, H. Hill

    2010-01-01

    Objective: Twin and family studies of autistic traits and of cases diagnosed with autism suggest high heritability; however, the heritability of autistic traits in toddlers has not been investigated. Therefore, this study's goals were (1) to screen a statewide twin population using items similar to the six critical social and communication items…

  8. Focal congenital hyperinsulinism managed by medical treatment: a diagnostic algorithm based on molecular genetic screening.

    Science.gov (United States)

    Maiorana, Arianna; Barbetti, Fabrizio; Boiani, Arianna; Rufini, Vittoria; Pizzoferro, Milena; Francalanci, Paola; Faletra, Flavio; Nichols, Colin G; Grimaldi, Chiara; de Ville de Goyet, Jean; Rahier, Jacques; Henquin, Jean-Claude; Dionisi-Vici, Carlo

    2014-11-01

    Congenital hyperinsulinism (CHI) requires rapid diagnosis and treatment to avoid irreversible neurological sequelae due to hypoglycaemia. Aetiological diagnosis is instrumental in directing the appropriate therapy. Current diagnostic algorithms provide a complete set of diagnostic tools including (i) biochemical assays, (ii) genetic facility and (iii) state-of-the-art imaging. They consider the response to a therapeutic diazoxide trial an early, crucial step before proceeding (or not) to specific genetic testing and eventually imaging, aimed at distinguishing diffuse vs focal CHI. However, interpretation of the diazoxide test is not trivial and can vary between research groups, which may lead to inappropriate decisions. Objective of this report is proposing a new algorithm in which early genetic screening, rather than diazoxide trial, dictates subsequent clinical decisions. Two CHI patients weaned from parenteral glucose infusion and glucagon after starting diazoxide. No hypoglycaemia was registered during a 72-h continuous glucose monitoring (CGMS), or hypoglycaemic episodes were present for no longer than 3% of 72-h. Normoglycaemia was obtained by low-medium dose diazoxide combined with frequent carbohydrate feeds for several years. We identified monoallelic, paternally inherited mutations in KATP channel genes, and (18) F-DOPA PET-CT revealed a focal lesion that was surgically resected, resulting in complete remission of hypoglycaemia. Although rare, some patients with focal lesions may be responsive to diazoxide. As a consequence, we propose an algorithm that is not based on a 'formal' diazoxide response but on genetic testing, in which patients carrying paternally inherited ABCC8 or KCNJ11 mutations should always be subjected to (18) F-DOPA PET-CT. © 2014 John Wiley & Sons Ltd.

  9. Familial Mediterranean fever without cardinal symptoms and role of genetic screening.

    Science.gov (United States)

    Ulas, T; Buyukhatipoglu, H; Bes, C; Dal, M S; Hacıbekiroglu, I; Apucu, H G; Borlu, F

    2012-07-19

    Familial Mediterranean fever is an autosomal recessive disorder characterized by paroxysmal episodes of fever and serosal inflammation. The classical presentation is fever and severe recurrent abdominal pain due to serositis that lasts for one to three days and the resolves spontaneously. Between the episodes patients are asymptomatic. Ninety-five percent of patients with familial mediterranean fever have painful episodes localized to the abdomen, which is usually the dominant manifestation of the disease. Herein, we present a case of 34-year-old man with incomplete abdominal pain episode of familial mediterranean fever limited to the epigastrum and had no cardinals symptoms of this disease. The diagnosis was made by genetic screening. Successful treatment response was achieved by colchicine.

  10. Familial Mediterranean fever without cardinal symptoms and role of genetic screening

    Directory of Open Access Journals (Sweden)

    I. Hacıbekiroglu

    2012-07-01

    Full Text Available Familial mediterranean fever is an autosomal recessive disorder characterized by paroxysmal episodes of fever and serosal inflammation. The classical presentation is fever and severe recurrent abdominal pain due to serositis that lasts for one to three days and the resolves spontaneously. Between the episodes patients are asymptomatic. Ninety-five percent of patients with familial mediterranean fever have painful episodes localized to the abdomen, which is usually the dominant manifestation of the disease. Herein, we present a case of 34-year-old man with incomplete abdominal pain episode of familial mediterranean fever limited to the epigastrum and had no cardinals symptoms of this disease. The diagnosis was made by genetic screening. Succesful treatment response was achieved by colchicine.

  11. Cerebral cavernous malformations: clinical insights from genetic studies.

    Science.gov (United States)

    Mindea, Stefan A; Yang, Benson P; Shenkar, Robert; Bendok, Bernard; Batjer, H Hunt; Awad, Issam A

    2006-07-15

    Familial disease is responsible for one third to one half of cerebral cavernous malformation (CCM) cases presenting to clinical attention. Much has been learned in the past decade about the genetics of these cases, which are all inherited in an autosomal dominant pattern, at three known chromosome loci. Unique features of inherited CCMs in Hispanic-Americans of Mexican descent have been described. The respective genes for each locus have been identified and preliminary observations on disease pathways and mechanisms are coming to light, including possible explanations for selectivity of neural milieu and relationships to endothelial layer abnormalities. Mechanisms of lesion genesis in cases of genetic predisposition are being investigated, with evidence to support a two-hit model emerging from somatic mutation screening of the lesions themselves and from lesion formation in transgenic murine models of the disease. Other information on potential inflammatory factors has emerged from differential gene expression studies. Unique phenotypic features of solitary versus familial cases have emerged: different associations with venous developmental anomaly and the exceptionally high penetrance rates that are found in inherited cases when high-sensitivity screening is performed with gradient echo magnetic resonance imaging. This information has changed the landscape of screening and counseling for patients and their families, and promises to lead to the development of new tools for predicting, explaining, and modifying disease behavior.

  12. A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria.

    Science.gov (United States)

    Jen, Freda E-C; Djoko, Karrera Y; Bent, Stephen J; Day, Christopher J; McEwan, Alastair G; Jennings, Michael P

    2015-09-01

    Under conditions of low oxygen availability, Neisseria meningitidis and Neisseria gonorrhoeae are able to respire via a partial denitrification pathway in which nitrite is converted to nitrous oxide. In this process, nitrite reductase (AniA), a copper (Cu)-containing protein converts nitrite to NO, and this product is converted to nitrous oxide by nitric oxide reductase (NorB). NorB also confers protection against toxic NO, and so we devised a conditional lethal screen, using a norB mutant, to identify mutants that were resistant to nitrite-dependent killing. After random-deletion mutagenesis of N. meningitidis, this genetic screen identified a gene encoding a Cu chaperone that is essential for AniA function, AccA. Purified AccA binds one Cu (I) ion and also possesses a second binding site for Cu (II). This novel periplasmic Cu chaperone (AccA) appears to be essential for provision of Cu ions to AniA of pathogenic Neisseria to generate an active nitrite reductase. Apart from the Neisseria genus, AccA is distributed across a wide range of environmental Proteobacteria species. © FASEB.

  13. Genetic modifier screens reveal new components that interact with the Drosophila dystroglycan-dystrophin complex.

    Directory of Open Access Journals (Sweden)

    Mariya M Kucherenko

    Full Text Available The Dystroglycan-Dystrophin (Dg-Dys complex has a capacity to transmit information from the extracellular matrix to the cytoskeleton inside the cell. It is proposed that this interaction is under tight regulation; however the signaling/regulatory components of Dg-Dys complex remain elusive. Understanding the regulation of the complex is critical since defects in this complex cause muscular dystrophy in humans. To reveal new regulators of the Dg-Dys complex, we used a model organism Drosophila melanogaster and performed genetic interaction screens to identify modifiers of Dg and Dys mutants in Drosophila wing veins. These mutant screens revealed that the Dg-Dys complex interacts with genes involved in muscle function and components of Notch, TGF-beta and EGFR signaling pathways. In addition, components of pathways that are required for cellular and/or axonal migration through cytoskeletal regulation, such as Semaphorin-Plexin, Frazzled-Netrin and Slit-Robo pathways show interactions with Dys and/or Dg. These data suggest that the Dg-Dys complex and the other pathways regulating extracellular information transfer to the cytoskeletal dynamics are more intercalated than previously thought.

  14. Study of the Active Screen Plasma Nitriding

    Institute of Scientific and Technical Information of China (English)

    Zhao Cheng; C. X. Li; H. Dong; T. Bell

    2004-01-01

    Active screen plasma nitriding (ASPN) is a novel nitriding process, which overcomes many of the practical problems associated with the conventional DC plasma nitriding (DCPN). Experimental results showed that the metallurgical characteristics and hardening effect of 722M24 steel nitrided by ASPN at both floating potential and anodic (zero) potential were similar to those nitrided by DCPN. XRD and high-resolution SEM analysis indicated that iron nitride particles with sizes in sub-micron scale were deposited on the specimen surface in AS plasma nitriding. These indicate that the neutral iron nitride particles, which are sputtered from the active screen and transferred through plasma to specimen surface, are considered to be the dominant nitrogen carder in ASPN. The OES results show that NH could not be a critical species in plasma nitriding.

  15. Randomized studies of PSA screening: an opinion

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor

    2011-01-01

    @@ The issue of prostate cancer screening with prostate-specific antigen (PSA) has been contentious for nearly two decades due to lack of data from randomized trials, but that has now changed.A brief review of the available data is warranted as there is finally some clarity on this critically important topic.Knowing what to ignore, as well as what to focus on, is critical for understanding the current data.

  16. Screening of Tag SNPs and prediction of their potential function in genetic studies of complex diseases%复杂性疾病遗传研究中Tag SNP的筛选及其潜在功能预测

    Institute of Scientific and Technical Information of China (English)

    朱益民; 许玉洋; 凌洁

    2011-01-01

    利用公共数据库筛选与复杂性疾病相关的单核苷酸多态性(single nucleotide polymorphism,SNP).运用FastSNP、SNP Function Prediction、F-SNP等多种SNP功能预测软件筛选有潜在功能的SNPs;通过HapMap等数据库筛选Tag SNP;综合比较各软件结果.以IGFBP 7基因为例,筛选转录因子结合位点SNPs 11个,内含子增强子31个,内含子增强子和转录因子结合位点4个,剪接位点1个,共47个SNPs.%We applied public databases of single nucleotide polymorphism (SNP) to screen complex disease-related SNPs and assessed the potential functions of selected SNPs through SNP function prediction software, including FastSNP, SNP Function Prediction, F-SNP. We selected Tag SNP in HapMap database and compared all results with above software. With above strategies we screened IGFBP7 gene and obtained total 47 SNPs, including 11 TFBS SNPs,31 intronic enhancer SNPs,4 intronic enhancer and TFBS SNPs and 1 splicing sites SNPs.

  17. Interlaboratory validation of quantitative duplex real-time PCR method for screening analysis of genetically modified maize.

    Science.gov (United States)

    Takabatake, Reona; Koiwa, Tomohiro; Kasahara, Masaki; Takashima, Kaori; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Oguchi, Taichi; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi

    2011-01-01

    To reduce the cost and time required to routinely perform the genetically modified organism (GMO) test, we developed a duplex quantitative real-time PCR method for a screening analysis simultaneously targeting an event-specific segment for GA21 and Cauliflower Mosaic Virus 35S promoter (P35S) segment [Oguchi et al., J. Food Hyg. Soc. Japan, 50, 117-125 (2009)]. To confirm the validity of the method, an interlaboratory collaborative study was conducted. In the collaborative study, conversion factors (Cfs), which are required to calculate the GMO amount (%), were first determined for two real-time PCR instruments, the ABI PRISM 7900HT and the ABI PRISM 7500. A blind test was then conducted. The limit of quantitation for both GA21 and P35S was estimated to be 0.5% or less. The trueness and precision were evaluated as the bias and reproducibility of the relative standard deviation (RSD(R)). The determined bias and RSD(R) were each less than 25%. We believe the developed method would be useful for the practical screening analysis of GM maize.

  18. A highly sensitive and specific method for the screening detection of genetically modified organisms based on digital PCR without pretreatment.

    Science.gov (United States)

    Fu, Wei; Zhu, Pengyu; Wang, Chenguang; Huang, Kunlun; Du, Zhixin; Tian, Wenying; Wang, Qin; Wang, Huiyu; Xu, Wentao; Zhu, Shuifang

    2015-08-04

    Digital PCR has developed rapidly since it was first reported in the 1990 s. It was recently reported that an improved method facilitated the detection of genetically modified organisms (GMOs). However, to use this improved method, the samples must be pretreated, which could introduce inaccuracy into the results. In our study, we explored a pretreatment-free digital PCR detection method for the screening for GMOs. We chose the CaMV35s promoter and the NOS terminator as the templates in our assay. To determine the specificity of our method, 9 events of GMOs were collected, including MON810, MON863, TC1507, MIR604, MIR162, GA21, T25, NK603 and Bt176. Moreover, the sensitivity, intra-laboratory and inter-laboratory reproducibility of our detection method were assessed. The results showed that the limit of detection of our method was 0.1%, which was lower than the labeling threshold level of the EU. The specificity and stability among the 9 events were consistent, respectively. The intra-laboratory and inter-laboratory reproducibility were both good. Finally, the perfect fitness for the detection of eight double-blind samples indicated the good practicability of our method. In conclusion, the method in our study would allow more sensitive, specific and stable screening detection of the GMO content of international trading products.

  19. Validation of a semiconductor next-generation sequencing assay for the clinical genetic screening of CFTR.

    Science.gov (United States)

    Trujillano, Daniel; Weiss, Maximilian E R; Köster, Julia; Papachristos, Efstathios B; Werber, Martin; Kandaswamy, Krishna Kumar; Marais, Anett; Eichler, Sabrina; Creed, Jenny; Baysal, Erol; Jaber, Iqbal Yousuf; Mehaney, Dina Ahmed; Farra, Chantal; Rolfs, Arndt

    2015-09-01

    Genetic testing for cystic fibrosis and CFTR-related disorders mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the CFTR gene. We have explored a more efficient genetic screening strategy based on next-generation sequencing (NGS) of the CFTR gene. We validated this approach in a cohort of 177 patients with previously known CFTR mutations and polymorphisms. Genomic DNA was amplified using the Ion AmpliSeq™ CFTR panel. The DNA libraries were pooled, barcoded, and sequenced using an Ion Torrent PGM sequencer. The combination of different robust bioinformatics tools allowed us to detect previously known pathogenic mutations and polymorphisms in the 177 samples, without detecting spurious pathogenic calls. In summary, the assay achieves a sensitivity of 94.45% (95% CI: 92% to 96.9%), with a specificity of detecting nonvariant sites from the CFTR reference sequence of 100% (95% CI: 100% to 100%), a positive predictive value of 100% (95% CI: 100% to 100%), and a negative predictive value of 99.99% (95% CI: 99.99% to 100%). In addition, we describe the observed allelic frequencies of 94 unique definitely and likely pathogenic, uncertain, and neutral CFTR variants, some of them not previously annotated in the public databases. Strikingly, a seven exon spanning deletion as well as several more technically challenging variants such as pathogenic poly-thymidine-guanine and poly-thymidine (poly-TG-T) tracts were also detected. Targeted NGS is ready to substitute classical molecular methods to perform genetic testing on the CFTR gene.

  20. A genetic screen of the mutations in the Korean patients with early-onset Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    An SS

    2016-12-01

    Full Text Available Seong Soo An,1,* Sun Ah Park,2,* Eva Bagyinszky,1 Sun Oh Bae,1 Yoon-Jeong Kim,2 Ji Young Im,2 Kyung Won Park,3 Kee Hyung Park,4 Eun-Joo Kim,5 Jee Hyang Jeong,6 Jong Hun Kim,7 Hyun Jeong Han,8 Seong Hye Choi,9 SangYun Kim10 1Department of Bionano Technology, Gachon University, Seongnam-si, 2Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, 3Department of Neurology, Dong-A University College of Medicine and Institute of Convergence Bio-Health, Busan, 4Department of Neurology, Gachon University Gil Medical Center, Incheon, 5Department of Neurology, Pusan National University Hospital, Busan, 6Department of Neurology, Ewha Womans University Mokdong Hospital, Seoul, 7Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, 8Department of Neurology, Myongii Hospital, Goyang, 9Department of Neurology, Inha University School of Medicine, Incheon, 10Department of Neurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea *These authors contributed equally to this work Abstract: Early-onset Alzheimer’s disease (EOAD has distinct clinical characteristics in comparison to late-onset Alzheimer’s disease (LOAD. The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer’s disease (AD

  1. 小耳畸形家系的基因定位及候选基因筛查初步研究%Preliminary study of genetic basis of congenital microtia with gene mapping and candidate gene screening approach

    Institute of Scientific and Technical Information of China (English)

    林琳; 潘博; 蒋海越; 赵延勇; 韩娟

    2013-01-01

    Objective:To map and to identify the causative genes for congenital microtia in a Chinese family.Methods:Linkage analysis with microsatellite markers spanning the whole human-genome was performed in ZX07 family.Direct sequence analysis of the candidate genes was carried out.Results:The position of the causal gene did not be excluded from chromosome11 and chromosome4.Based on the functions of the genes,three genes were chosen as candidate genes including FGF3,FGFR3 and HMX1,nearby D11S4191,D4S419,D4S412,respectively.No mutation of these genes had been identified in this family.Conclusion:FGF3,FGFR3 and HMX1 genes were not the causative genes of ZX07 family.Further investigation should be needed.This study provided insight into the genetic basis of congenital microtia.%目的小耳畸形致病基因的定位克隆及其候选基因筛查的初步研究.方法针对收集的先天性小耳畸形家系(ZX07家系)通过STR标记进行全基因组扫描和连锁分析;在可疑的连锁区域选择与小耳畸形相关的候选基因进行筛查研究.结果全基因组扫描连锁分析发现15、11、4、12、16、2号条染色体有存在致病基因的可能,在NCBI网站上查询并选择杂合度较高的位点设计STR引物,通过精细定位排除了15、16、12、2号染色体连锁的可能.在11号和4号染色体D11S4191、D4S419、D4S412三个位点附近选择与小耳畸形相关的FGF3、FGFR3和HMX1基因进行筛查,未发现上述基因的突变.结论ZX07小耳畸形家系为常染色体显性遗传,初步的基因筛查排除了FGF3、FGFR3和HMX1基因突变,为进一步研究小耳畸形的致病基因奠定了基础.

  2. In vitro fertilization with preimplantation genetic screening improves implantation and live birth in women age 40 through 43.

    Science.gov (United States)

    Lee, Hsiao-Ling; McCulloh, David H; Hodes-Wertz, Brooke; Adler, Alexis; McCaffrey, Caroline; Grifo, James A

    2015-03-01

    In Vitro Fertilization is an effective treatment for infertility; however, it has relatively low success in women of advanced maternal age (>37) who have a high risk of producing aneuploid embryos, resulting in implantation failure, a higher rate of miscarriage or birth of a child with chromosome abnormalities. The purpose of this study was to compare the implantation, miscarriage and live birth rates with and without preimplantation genetic screening (PGS) of embryos from patients aged 40 through 43 years. This is a retrospective cohort study, comparing embryos screened for ploidy using trophectoderm biopsy and array comparative genomic hybridization to embryos that were not screened. We compared pregnancy outcomes for traditional fresh IVF cycles with day 5 embryo transfers, Frozen Embryo Transfer (FET) cycles without PGS and PGS-FET (FET of only euploid embryos) cycles of patients with maternal ages ranging from 40 to 43 years, undergoing oocyte retrievals during the period between 1/1/2011 and 12/31/2012. The implantation rate of euploid embryos transferred in FET cycles (50.9%) was significantly greater than for unscreened embryos transferred in either fresh (23.8%) or FET (25.4%) cycles. The incidence of live birth per transferred embryo for PGS-FET (45.5%) was significantly greater than for No PGS fresh (15.8%) or No PGS FET (19.0 %) cycles. The incidences of live birth per implanted sac for PGS FET cycles (89.3%), No PGS fresh cycles (66.7%) and No PGS FET cycles (75.0%) were not significantly different. The present data provides evidence of the benefits of PGS with regard to improved implantation and live birth rate per embryo transferred.

  3. Use of the Photoactic Ability of a Bacterium to Teach the Genetic Principles of Random Mutagenesis & Mutant Screening

    Science.gov (United States)

    Din, Neena; Bird, Terry H.; Berleman, James E.

    2007-01-01

    In this article, the authors present a laboratory activity that relies on the use of a very versatile bacterial system to introduce the concept of how mutagenesis can be used for molecular and genetic analysis of living organisms. They have used the techniques of random mutagenesis and selection/screening to obtain strains of the organism "R.…

  4. Multiplex PCR-based simultaneous amplification of selectable marker and reporter genes for the screening of genetically modified crops.

    Science.gov (United States)

    Randhawa, Gurinder Jit; Chhabra, Rashmi; Singh, Monika

    2009-06-24

    The development and commercialization of genetically modified (GM) crops with enhanced insect and herbicide resistance, abiotic stress tolerance, and improved nutritional quality has expanded dramatically. Notwithstanding the huge potential benefits of GM crops, the perceived environmental risks associated with these crops need to be addressed in proper perspective. One critical concern is the adventitious presence or unintentional mixing of GM seed in non-GM seed lots, which can seriously affect the global seed market. It would therefore be necessary though a challenging task to develop reliable, efficient, and economical assays for GM detection, identification, and quantification in non-GM seed lots. This can be systematically undertaken by preliminary screening for control elements and selectable or scorable (reporter) marker genes. In this study, simplex and multiplex polymerase chain reaction (PCR) assays individually as well as simultaneously amplifying the commonly used selectable marker genes, i.e., aadA, bar, hpt, nptII, pat encoding, respectively, for aminoglycoside-3'-adenyltransferase, Streptococcus viridochromogenes phosphinothricin-N-acetyltransferase, hygromycin phosphotransferase, neomycin phosphotransferase, Streptococcus hygroscopicus phosphinothricin-N-acetyltransferase, and a reporter gene uidA encoding beta-d-glucuronidase, were developed as a reliable tool for qualitative screening of GM crops. The efficiency of the assays was also standardized in the test samples prepared by artificial mixing of transgenic seed samples in different proportions. The developed multiplex PCR assays will be useful in verifying the GM status of a sample irrespective of the crop and GM trait.

  5. Alcohol screening in people with cognitive impairment: an exploratory study.

    Science.gov (United States)

    Randall-James, James; Wadd, Sarah; Edwards, Kim; Thake, Anna

    2015-01-01

    Alcohol misuse can coexist with and/or contribute to the development of cognitive impairment in the older adult population but continues to be underestimated and undetected in older people. This study aimed to examine the feasibility and acceptability of routine screening for alcohol misuse in a small sample of older people with cognitive impairment receiving services in memory clinics. This study employed a qualitative and exploratory design, using a convenience sample of individuals attending a memory clinic in England. Ten service users older than 65 with a diagnosis of cognitive impairment (i.e., mild cognitive impairment or dementia) took part in the study. Individuals who met inclusion criteria were invited to take part in an hour-long interview, which included the interviewer administering the alcohol screening tools. Interview transcripts were analyzed using thematic analysis. Participants were able to engage with the screening tools and could, with assistance, complete them in a collaborative and timely manner without distress. All participants reported that these tools were acceptable as part of the clinic assessment. Administering the screening tools was not time-consuming or difficult, making their use feasible within the memory clinic setting. While there were some challenges (e.g., arithmetic, recall, language problems), these challenges could be overcome with the aid of the person administering the screening tool using standardized techniques for assessment administration. Routine screening for alcohol misuse in older people with cognitive impairment receiving services in memory clinics is feasible and acceptable. The process of completing alcohol screening tools with older adults receiving services at memory clinics may increase awareness of the potential impact of alcohol on cognitive functioning and provide practitioners with an opportunity to educate service users about the ways that their drinking is affecting their memory. Several techniques to

  6. Programmatic screening for colorectal cancer: the COLONPREV study.

    Science.gov (United States)

    Castells, Antoni; Quintero, Enrique

    2015-03-01

    The COLONPREV study is an ongoing multicenter, nationwide, randomized controlled trial aimed at evaluating the efficacy of once-only colonoscopy and biennial fecal immunochemical testing with respect to the reduction of CRC-related mortality at 10 years in average-risk colorectal cancer screening population. Following a pragmatic approach, this study may contribute to establishing the most cost-effective strategy in a programmatic, population-based setting. In this review, we report the results obtained at the first screening round, as well as others achieved in nested evaluations using the COLONPREV dataset with the aim of clarifying some controversial issues on the different strategies of colorectal cancer screening.

  7. Development of quantitative duplex real-time PCR method for screening analysis of genetically modified maize.

    Science.gov (United States)

    Oguchi, Taichi; Onishi, Mari; Minegishi, Yasutaka; Kurosawa, Yasunori; Kasahara, Masaki; Akiyama, Hiroshi; Teshima, Reiko; Futo, Satoshi; Furui, Satoshi; Hino, Akihiro; Kitta, Kazumi

    2009-06-01

    A duplex real-time PCR method was developed for quantitative screening analysis of GM maize. The duplex real-time PCR simultaneously detected two GM-specific segments, namely the cauliflower mosaic virus (CaMV) 35S promoter (P35S) segment and an event-specific segment for GA21 maize which does not contain P35S. Calibration was performed with a plasmid calibrant specially designed for the duplex PCR. The result of an in-house evaluation suggested that the analytical precision of the developed method was almost equivalent to those of simplex real-time PCR methods, which have been adopted as ISO standard methods for the analysis of GMOs in foodstuffs and have also been employed for the analysis of GMOs in Japan. In addition, this method will reduce both the cost and time requirement of routine GMO analysis by half. The high analytical performance demonstrated in the current study would be useful for the quantitative screening analysis of GM maize. We believe the developed method will be useful for practical screening analysis of GM maize, although interlaboratory collaborative studies should be conducted to confirm this.

  8. [Genetics in the study of HIV infection].

    Science.gov (United States)

    Amoroso, Antonio; Savoldi, Silvana

    2012-01-01

    Thirty years after the discovery of the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS), no effective vaccines are available and there is no cure for the disease. The susceptibility to HIV infection shows a considerable degree of individual heterogeneity, which may be largely due to the genetic variability of the host. In an effort to find the host factors required for viral replication, to identify the crucial pathogenetic pathways, and reveal the full armament of host defenses, there has been a shift from candidate-gene studies to unbiased genomewide genetic and functional studies. Nevertheless, the number of established genetic factors involved in the susceptibility to diseases caused by HIV infection remains small, explaining only 15-20% of the observed heterogeneity, most of which is attributable to polymorphisms of human leukocyte antigens (HLA). Genetic studies, however, have allowed to clarify which genetic variations underlie the adverse response to some antiretroviral drugs (such as HLA-B*5701 in the treatment with abacavir) or the occurrence of renal complications as the disease progresses. The results of these studies already have a possible impact on healthcare practice.

  9. The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen.

    Science.gov (United States)

    Chataway, J; Feakes, R; Coraddu, F; Gray, J; Deans, J; Fraser, M; Robertson, N; Broadley, S; Jones, H; Clayton, D; Goodfellow, P; Sawcer, S; Compston, A

    1998-10-01

    Genetic susceptibility to multiple sclerosis is implicated on the basis of classical family studies and phenotype analyses. The only reproducible legacy from the candidate gene approach has been the discovery of population associations with alleles of the major histocompatibility complex. Systematic genome scanning has since been applied using a panel of anonymous markers to identify areas of linkage in co-affected siblings. Here, we describe the principles of genome screening and update the UK survey of multiple sclerosis. This identified 20 regions of potential interest, but in none was there unequivocal linkage. In theory, attempting to replicate these findings in a second set of sibling pair families is the most appropriate way to distinguish true from false positives, but unfortunately the number of families required to do this reliably is prohibitively large. We used three approaches to increase the definition achieved by the screen: (i) the number of sibling pairs typed in an identified region of potential linkage was extended; (ii) the information extraction was increased in an identified region; and (iii) a search was made for missed regions of potential linkage. Each of these approaches has considerable limitations. A chromosome-by-chromosome account is given to direct future searches. Although an additional marker placed distal to the 'hit' on chromosome 14q increased linkage in this area, and typing extra sibling pairs increased linkage on chromosomes 6p and 17q, evidence for linkage was more commonly reduced and no additional regions of interest were found. A further refinement of the genome screen was undertaken by conditioning for the presence of HLA-DR15. This produced a surprising degree of segregation among the regions of interest, which divided into two distinct groups depending on DR15 sharing: the DR15-sharing cohort comprised loci on chromosomal areas 1p, 17q and X; and the DR15-non-sharing cohort was made up of loci on 1cen, 3p, 7p, 14q and

  10. Barriers to colorectal cancer screening: A case-control study

    Institute of Scientific and Technical Information of China (English)

    Shan-Rong Cai; Su-Zhan Zhang; Shu Zheng; Hong-Hong Zhu

    2009-01-01

    AIM:To investigate barriers to colorectal cancer (CRC) screening in a community population. METHODS:We conducted a community-based case-control study in an urban Chinese population by questionnaire. Cases were selected from those completing both a fecal occult blood test (FOBT) case and colonoscopy in a CRC screening program in 2004. Control groups were matched by gender, age group and community. Control 1 included those having a positive FOBT but refusing a colonoscopy. Control 2 included those who refused both an FOBT and colonoscopy. RESULTS:The impact of occupation on willingness to attend a colorectal screening program differed by gender. P for heterogeneity was 0.009 for case vs control group 1, 0.01 for case versus control group 2, and 0.80 for control group 1 vs 2. Poor awareness of CRC and its screening program, characteristics of screening tests, and lack of time affected the screening rate. Financial support, fear of pain and bowel preparation were barriers to a colonoscopy as a screening test. Eighty-two percent of control group 1 and 87.1% of control group 2 were willing attend if the colonoscopy was free, but only 56.3% and 53.1%,respectively, if it was self-paid. Multivariate odds ratios for case vs control group 1 were 0.10 among those unwilling to attend a free colonoscopy and 0.50 among those unwilling to attend a self-paid colonoscopy. CONCLUSION:Raising the public awareness of CRC and its screening, integrating CRC screening into the health care system, and using a painless colonoscopy would increase its screening rate.

  11. Screening Genetic Resources of Capsicum Peppers in Their Primary Center of Diversity in Bolivia and Peru.

    Directory of Open Access Journals (Sweden)

    Maarten van Zonneveld

    Full Text Available For most crops, like Capsicum, their diversity remains under-researched for traits of interest for food, nutrition and other purposes. A small investment in screening this diversity for a wide range of traits is likely to reveal many traditional varieties with distinguished values. One objective of this study was to demonstrate, with Capsicum as model crop, the application of indicators of phenotypic and geographic diversity as effective criteria for selecting promising genebank accessions for multiple uses from crop centers of diversity. A second objective was to evaluate the expression of biochemical and agromorphological properties of the selected Capsicum accessions in different conditions. Four steps were involved: 1 Develop the necessary diversity by expanding genebank collections in Bolivia and Peru; 2 Establish representative subsets of ~100 accessions for biochemical screening of Capsicum fruits; 3 Select promising accessions for different uses after screening; and 4 Examine how these promising accessions express biochemical and agromorphological properties when grown in different environmental conditions. The Peruvian Capsicum collection now contains 712 accessions encompassing all five domesticated species (C. annuum, C. chinense, C. frutescens, C. baccatum, and C. pubescens. The collection in Bolivia now contains 487 accessions, representing all five domesticates plus four wild taxa (C. baccatum var. baccatum, C. caballeroi, C. cardenasii, and C. eximium. Following the biochemical screening, 44 Bolivian and 39 Peruvian accessions were selected as promising, representing wide variation in levels of antioxidant capacity, capsaicinoids, fat, flavonoids, polyphenols, quercetins, tocopherols, and color. In Peru, 23 promising accessions performed well in different environments, while each of the promising Bolivian accessions only performed well in a certain environment. Differences in Capsicum diversity and local contexts led to distinct

  12. Screening Genetic Resources of Capsicum Peppers in Their Primary Center of Diversity in Bolivia and Peru.

    Science.gov (United States)

    van Zonneveld, Maarten; Ramirez, Marleni; Williams, David E; Petz, Michael; Meckelmann, Sven; Avila, Teresa; Bejarano, Carlos; Ríos, Llermé; Peña, Karla; Jäger, Matthias; Libreros, Dimary; Amaya, Karen; Scheldeman, Xavier

    2015-01-01

    For most crops, like Capsicum, their diversity remains under-researched for traits of interest for food, nutrition and other purposes. A small investment in screening this diversity for a wide range of traits is likely to reveal many traditional varieties with distinguished values. One objective of this study was to demonstrate, with Capsicum as model crop, the application of indicators of phenotypic and geographic diversity as effective criteria for selecting promising genebank accessions for multiple uses from crop centers of diversity. A second objective was to evaluate the expression of biochemical and agromorphological properties of the selected Capsicum accessions in different conditions. Four steps were involved: 1) Develop the necessary diversity by expanding genebank collections in Bolivia and Peru; 2) Establish representative subsets of ~100 accessions for biochemical screening of Capsicum fruits; 3) Select promising accessions for different uses after screening; and 4) Examine how these promising accessions express biochemical and agromorphological properties when grown in different environmental conditions. The Peruvian Capsicum collection now contains 712 accessions encompassing all five domesticated species (C. annuum, C. chinense, C. frutescens, C. baccatum, and C. pubescens). The collection in Bolivia now contains 487 accessions, representing all five domesticates plus four wild taxa (C. baccatum var. baccatum, C. caballeroi, C. cardenasii, and C. eximium). Following the biochemical screening, 44 Bolivian and 39 Peruvian accessions were selected as promising, representing wide variation in levels of antioxidant capacity, capsaicinoids, fat, flavonoids, polyphenols, quercetins, tocopherols, and color. In Peru, 23 promising accessions performed well in different environments, while each of the promising Bolivian accessions only performed well in a certain environment. Differences in Capsicum diversity and local contexts led to distinct outcomes in

  13. Screening and genetic manipulation of green organisms for establishment of biological life support systems in space.

    Science.gov (United States)

    Saei, Amir Ata; Omidi, Amir Ali; Barzegari, Abolfazl

    2013-01-01

    Curiosity has driven humankind to explore and conquer space. However, today, space research is not a means to relieve this curiosity anymore, but instead has turned into a need. To support the crew in distant expeditions, supplies should either be delivered from the Earth, or prepared for short durations through physiochemical methods aboard the space station. Thus, research continues to devise reliable regenerative systems. Biological life support systems may be the only answer to human autonomy in outposts beyond Earth. For construction of an artificial extraterrestrial ecosystem, it is necessary to search for highly adaptable super-organisms capable of growth in harsh space environments. Indeed, a number of organisms have been proposed for cultivation in space. Meanwhile, some manipulations can be done to increase their photosynthetic potential and stress tolerance. Genetic manipulation and screening of plants, microalgae and cyanobacteria is currently a fascinating topic in space bioengineering. In this commentary, we will provide a viewpoint on the realities, limitations and promises in designing biological life support system based on engineered and/or selected green organism. Special focus will be devoted to the engineering of key photosynthetic enzymes in pioneer green organisms and their potential use in establishment of transgenic photobioreactors in space.

  14. Successful birth of South India's first twins after preimplantation genetic screening of embryos

    Directory of Open Access Journals (Sweden)

    Priya Selvaraj

    2016-01-01

    Full Text Available We report the first documented successful birth of twins following preimplantation genetic screening (PGS of cleavage stage embryos by array comparative genomic hybridization (CGH technology, in South India. The case was a 28-year-old woman with the previous history of preclinical pregnancy and a miscarriage in two attempted in vitro fertilization cycles. Day 3 cleavage stage embryos were generated by conventional long protocol with the use of a gonadotropin-releasing hormone analog and a combination of recombinant folliculotropins and human menopausal gonadotropins. Intracytoplasmic sperm injection of oocytes thus obtained was performed, and 10 selected embryos underwent PGS using the array CGH technique. Two normal blastocysts were transferred to the patient, and she conceived twins. She delivered at 35 weeks of gestation by elective cesarean on November 19, 2014. She delivered a healthy male and female baby weighing 2.19 kg and 2.26 kg, respectively. Postnatal evaluation of babies was also normal, and the hospital course was uneventful. PGS has a definitive indication in assisted reproductive technology programs and can be utilized to improve pregnancy rates significantly.

  15. A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans

    Science.gov (United States)

    Neal, Scott J.; Park, JiSoo; DiTirro, Danielle; Yoon, Jason; Shibuya, Mayumi; Choi, Woochan; Schroeder, Frank C.; Butcher, Rebecca A.; Kim, Kyuhyung; Sengupta, Piali

    2016-01-01

    Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation. PMID:26976437

  16. A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis

    Science.gov (United States)

    Moriarity, Branden S; Otto, George M; Rahrmann, Eric P; Rathe, Susan K; Wolf, Natalie K; Weg, Madison T; Manlove, Luke A; LaRue, Rebecca S; Temiz, Nuri A; Molyneux, Sam D; Choi, Kwangmin; Holly, Kevin J; Sarver, Aaron L; Scott, Milcah C; Forster, Colleen L; Modiano, Jaime F; Khanna, Chand; Hewitt, Stephen M; Khokha, Rama; Yang, Yi; Gorlick, Richard; Dyer, Michael A; Largaespada, David A

    2016-01-01

    Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma. PMID:25961939

  17. Screening genetically modified organisms using multiplex-PCR coupled with oligonucleotide microarray.

    Science.gov (United States)

    Xu, Jia; Miao, Haizhen; Wu, Houfei; Huang, Wensheng; Tang, Rong; Qiu, Minyan; Wen, Jianguo; Zhu, Shuifang; Li, Yao

    2006-07-15

    In this research, we developed a multiplex polymerase chain reaction (multiplex-PCR) coupled with a DNA microarray system simultaneously aiming at many targets in a consecutive reaction to detect a genetically modified organism (GMO). There are a total of 20 probes for detecting a GMO in a DNA microarray which can be classified into three categories according to their purpose: the first for screening GMO from un-transgenic plants based on the common elements such as promoter, reporter and terminator genes; the second for specific gene confirmation based on the target gene sequences such as herbicide-resistance or insect-resistance genes; the third for species-specific genes which the sequences are unique for different plant species. To ensure the reliability of this method, different kinds of positive and negative controls were used in DNA microarray. Commercial GM soybean, maize, rapeseed and cotton were identified by means of this method and further confirmed by PCR analysis and sequencing. The results indicate that this method discriminates between the GMOs very quickly and in a cost-saving and more time efficient way. It can detect more than 95% of currently commercial GMO plants and the limits of detection are 0.5% for soybean and 1% for maize. This method is proved to be a new method for routine analysis of GMOs.

  18. A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Scott J. Neal

    2016-05-01

    Full Text Available Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation.

  19. A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans.

    Science.gov (United States)

    Neal, Scott J; Park, JiSoo; DiTirro, Danielle; Yoon, Jason; Shibuya, Mayumi; Choi, Woochan; Schroeder, Frank C; Butcher, Rebecca A; Kim, Kyuhyung; Sengupta, Piali

    2016-05-03

    Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation.

  20. Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

    Science.gov (United States)

    Bancroft, Elizabeth K.; Page, Elizabeth C.; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S.; Mitchell, Gillian; Drew, Kate; Mæhle, Lovise; Axcrona, Karol; Evans, D. Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A.; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J.; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A.; Oosterwijk, Jan C.; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J.; Buys, Saundra; Conner, Tom; Ausems, Margreet G.; Ong, Kai-ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R.; Maia, Sofia; Foulkes, William D.; Taherian, Nassim; Ruijs, Marielle; den Enden, Apollonia T. Helderman-van; Izatt, Louise; Davidson, Rosemarie; Adank, Muriel A.; Walker, Lisa; Schmutzler, Rita; Tucker, Kathy; Kirk, Judy; Hodgson, Shirley; Harris, Marion; Douglas, Fiona; Lindeman, Geoffrey J.; Zgajnar, Janez; Tischkowitz, Marc; Clowes, Virginia E.; Susman, Rachel; Ramón y Cajal, Teresa; Patcher, Nicholas; Gadea, Neus; Spigelman, Allan; van Os, Theo; Liljegren, Annelie; Side, Lucy; Brewer, Carole; Brady, Angela F.; Donaldson, Alan; Stefansdottir, Vigdis; Friedman, Eitan; Chen-Shtoyerman, Rakefet; Amor, David J.; Copakova, Lucia; Barwell, Julian; Giri, Veda N.; Murthy, Vedang; Nicolai, Nicola; Teo, Soo-Hwang; Greenhalgh, Lynn; Strom, Sara; Henderson, Alex; McGrath, John; Gallagher, David; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Dearnaley, David; Costello, Philandra; Eyfjord, Jorunn; Rothwell, Jeanette; Falconer, Alison; Gronberg, Henrik; Hamdy, Freddie C.; Johannsson, Oskar; Khoo, Vincent; Kote-Jarai, Zsofia; Lubinski, Jan; Axcrona, Ulrika; Melia, Jane; McKinley, Joanne; Mitra, Anita V.; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Wilson, Penny; Killick, Emma; Moss, Sue; Eeles, Rosalind A.

    2014-01-01

    Background Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective To report the first year's screening results for all men at enrolment in the study. Design, setting and participants We recruited men aged 40–69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%—double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. Conclusions The IMPACT screening network will be useful

  1. Characterization of new bacterial catabolic genes and mobile genetic elements by high throughput genetic screening of a soil metagenomic library.

    Science.gov (United States)

    Jacquiod, Samuel; Demanèche, Sandrine; Franqueville, Laure; Ausec, Luka; Xu, Zhuofei; Delmont, Tom O; Dunon, Vincent; Cagnon, Christine; Mandic-Mulec, Ines; Vogel, Timothy M; Simonet, Pascal

    2014-11-20

    A mix of oligonucleotide probes was used to hybridize soil metagenomic DNA from a fosmid clone library spotted on high density membranes. The pooled radio-labeled probes were designed to target genes encoding glycoside hydrolases GH18, dehalogenases, bacterial laccases and mobile genetic elements (integrases from integrons and insertion sequences). Positive hybridizing spots were affiliated to the corresponding clones in the library and the metagenomic inserts were sequenced. After assembly and annotation, new coding DNA sequences related to genes of interest were identified with low protein similarity against the closest hits in databases. This work highlights the sensitivity of DNA/DNA hybridization techniques as an effective and complementary way to recover novel genes from large metagenomic clone libraries. This study also supports that some of the identified catabolic genes might be associated with horizontal transfer events.

  2. The Ischemic Stroke Genetics Study (ISGS Protocol

    Directory of Open Access Journals (Sweden)

    Rich Stephen S

    2003-07-01

    Full Text Available Abstract Background The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. Methods/Design The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes β-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. Discussion The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes.

  3. Screening and cervical cancer cure: population based cohort study

    OpenAIRE

    Andrae, B.; Andersson, T. M.-L.; Lambert, P C; Kemetli, L.; Silfverdal, L.; Strander, B.; Ryd, W.; Dillner, J.; Tornberg, S.; Sparen, P.

    2012-01-01

    Objective To determine whether detection of invasive cervical cancer by screening results in better prognosis or merely increases the lead time until death. Design Nationwide population based cohort study. Setting Sweden. Participants All 1230 women with cervical cancer diagnosed during 1999-2001 in Sweden prospectively followed up for an average of 8.5 years. Main outcome measures Cure proportions and five year relative survival ratios, stratified by screening history, mode of detection, age...

  4. Genetic studies of the Roma (Gypsies: a review

    Directory of Open Access Journals (Sweden)

    Gresham David

    2001-04-01

    Full Text Available Abstract Background Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Results Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups. Conclusion Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.

  5. Studying Extrachromosomal Genetic Elements in Sulfolobus

    DEFF Research Database (Denmark)

    Guannan, Liu

    facilitated the characterization of viruses, plasmids and membrane vesicles. Studying the interactions between Sulfolobus and extrachromosomal genetic elements has provided many new insights into basic molecular processes. Secreted membrane vesicle seems to be a common characteristic for Sulfolobus. In order...... of random chromosomal fragments, including IS elements. The results suggest that membrane vesicles could serve as vehicles for the inter-cellular transport of genetic material. A variant of ATV, ATV2, was isolated that infected a newly isolated Sulfolobus solfataricus P3 strain. Comparative genomics......, whereas the deactivation of pKEF9 in S. solfataricus was caused by mobile elements after it had integrated into the host genome....

  6. Studying Extrachromosomal Genetic Elements in Sulfolobus

    DEFF Research Database (Denmark)

    Guannan, Liu

    facilitated the characterization of viruses, plasmids and membrane vesicles. Studying the interactions between Sulfolobus and extrachromosomal genetic elements has provided many new insights into basic molecular processes. Secreted membrane vesicle seems to be a common characteristic for Sulfolobus. In order...... of random chromosomal fragments, including IS elements. The results suggest that membrane vesicles could serve as vehicles for the inter-cellular transport of genetic material. A variant of ATV, ATV2, was isolated that infected a newly isolated Sulfolobus solfataricus P3 strain. Comparative genomics......, whereas the deactivation of pKEF9 in S. solfataricus was caused by mobile elements after it had integrated into the host genome....

  7. [Rare diseases: specific ethical and legal aspects of genetic counseling and screening].

    Science.gov (United States)

    Sánchez-Caro, Javier

    2011-01-01

    This article analyses the specific rights of patients with rare diseases from a dual perspective. On the one hand, they concern a new generation of patients' rights that arise once the consolidation of basic rights has occurred, fundamentally after the application of Law 41/2002 (on Regulating Patient Autonomy and Rights and Obligations in the Field of Health Documentation and Information) and its development by the autonomous communities. On the other hand, the fundamental question raises a serious issue related to these patients, which involves the principles of equality, equity, non-discrimination and solidarity. This is aimed at promoting legislative measures to protect patients' equality of access to health and social services, with the ultimate aim of improving their quality of life. The author has given special relevance in his study to the treatment of rare diseases that are genetic in origin, and to the importance of adequate genetic counseling.

  8. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of the

  9. Understanding Salesforce Behavior using Genetic Association Studies

    NARCIS (Netherlands)

    W.E. van den Berg (Wouter)

    2014-01-01

    markdownabstract__Abstract__ Using genetic association studies, this thesis aims to investigate the drivers of successful customer-salesperson interactions in a context where knowledge development has become crucial to the value creation process. Central to this thesis is the developing role of the

  10. A genetic screen for replication initiation defective (rid mutants in Schizosaccharomyces pombe

    Directory of Open Access Journals (Sweden)

    Locovei Alexandra M

    2010-08-01

    Full Text Available Abstract In fission yeast the intra-S phase and DNA damage checkpoints are activated in response to inhibition of DNA replication or DNA damage, respectively. The intra-S phase checkpoint responds to stalled replication forks leading to the activation of the Cds1 kinase that both delays cell cycle progression and stabilizes DNA replication forks. The DNA damage checkpoint, that operates during the G2 phase of the cell cycle delays mitotic progression through activation of the checkpoint kinase, Chk1. Delay of the cell cycle is believed to be essential to allow time for either replication restart (in S phase or DNA damage repair (in G2. Previously, our laboratory showed that fission yeast cells deleted for the N-terminal half of DNA polymerase ε (Cdc20 are delayed in S phase, but surprisingly require Chk1 rather than Cds1 to maintain cell viability. Several additional DNA replication mutants were then tested for their dependency on Chk1 or Cds1 when grown under semi-permissive temperatures. We discovered that mutants defective in DNA replication initiation are sensitive only to loss of Chk1, whilst mutations that inhibit DNA replication elongation are sensitive to loss of both Cds1 and Chk1. To confirm that the Chk1-sensitive, Cds1-insensitive phenotype (rid phenotype is specific to mutants defective in DNA replication initiation, we completed a genetic screen for cell cycle mutants that require Chk1, but not Cds1 to maintain cell viability when grown at semi-permissive temperatures. Our screen identified two mutants, rid1-1 and rid2-1, that are defective in Orc1 and Mcm4, respectively. Both mutants show defects in DNA replication initiation consistent with our hypothesis that the rid phenotype is replication initiation specific. In the case of Mcm4, the mutation has been mapped to a highly conserved region of the protein that appears to be required for DNA replication initiation, but not elongation. Therefore, we conclude that the cellular

  11. Presymptomatic studies in genetic frontotemporal dementia.

    Science.gov (United States)

    Rohrer, J D; Warren, J D; Fox, N C; Rossor, M N

    2013-10-01

    Approximately 20% of patients with the neurodegenerative disorder frontotemporal dementia (FTD) have an autosomal dominant pattern of inheritance. Genetic FTD is caused by mutations in three genes in most cases (progranulin, microtubule-associated protein tau and chromosome 9 open reading frame 72) although a number of other genes are rare causes. Studies of other neurodegenerative diseases have shown imaging and biomarker evidence of disease onset many years prior to the development of symptoms. Similar studies in genetic FTD are now revealing evidence of a series of presymptomatic changes, initially in plasma biomarkers followed by MR imaging abnormalities of functional and structural connectivity and then grey matter atrophy. Lastly, neuropsychometric tests become abnormal in proximity to the onset of symptoms. Such studies have been relatively small until now but research centres with an expertise in genetic FTD are now forming consortia such as the Genetic Frontotemporal Dementia Initiative (GenFI) to create larger cohorts that can form the basis of future clinical trials. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. piggyBac transposon somatic mutagenesis with an activated reporter and tracker (PB-SMART for genetic screens in mice.

    Directory of Open Access Journals (Sweden)

    Sean F Landrette

    Full Text Available Somatic forward genetic screens have the power to interrogate thousands of genes in a single animal. Retroviral and transposon mutagenesis systems in mice have been designed and deployed in somatic tissues for surveying hematopoietic and solid tumor formation. In the context of cancer, the ability to visually mark mutant cells would present tremendous advantages for identifying tumor formation, monitoring tumor growth over time, and tracking tumor infiltrations and metastases into wild-type tissues. Furthermore, locating mutant clones is a prerequisite for screening and analyzing most other somatic phenotypes. For this purpose, we developed a system using the piggyBac (PB transposon for somatic mutagenesis with an activated reporter and tracker, called PB-SMART. The PB-SMART mouse genetic screening system can simultaneously induce somatic mutations and mark mutated cells using bioluminescence or fluorescence. The marking of mutant cells enable analyses that are not possible with current somatic mutagenesis systems, such as tracking cell proliferation and tumor growth, detecting tumor cell infiltrations, and reporting tissue mutagenesis levels by a simple ex vivo visual readout. We demonstrate that PB-SMART is highly mutagenic, capable of tumor induction with low copy transposons, which facilitates the mapping and identification of causative insertions. We further integrated a conditional transposase with the PB-SMART system, permitting tissue-specific mutagenesis with a single cross to any available Cre line. Targeting the germline, the system could also be used to conduct F1 screens. With these features, PB-SMART provides an integrated platform for individual investigators to harness the power of somatic mutagenesis and phenotypic screens to decipher the genetic basis of mammalian biology and disease.

  13. A Sleeping Beauty DNA transposon-based genetic sensor for functional screening of vitamin D3 analogues

    DEFF Research Database (Denmark)

    Staunstrup, Nicklas Heine; Sharma, Nynne; Bak, Rasmus Otkjær;

    2011-01-01

    Analogues of vitamin D3 are extensively used in the treatment of various illnesses, such as osteoporosis, inflammatory skin diseases, and cancer. Functional testing of new vitamin D3 analogues and formulations for improved systemic and topical administration is supported by sensitive screening me...... analogues. The tri-cistronic genetic sensor encodes a drug-sensoring protein, a reporter protein expressed from an activated sensor-responsive promoter, and a resistance marker....

  14. [Genetic screening of patients with familial hypercholesterolemia and insurability for life insurance policies and disability cover policies].

    Science.gov (United States)

    Homsma, S J; Lansberg, P J; Kastelein, J J

    2004-03-01

    In the Netherlands, people with familial hypercholesterolaemia (FH) have been actively screened since 1994 by means of DNA analysis. Recently, the Stichting Opsporing Erfelijke Hypercholesterolemie (Foundation for the Detection of Familial Hypercholesterolaemia) initiated a large scale-screening programme aimed at finding all 40,000 people. The Dutch ministry of Health, Welfare and Sport is providing the financial support. Genetic screening has social implications and raises questions on insurability. The Dutch Medical Examination Act prohibits insurers from posing questions about untreatable, serious inheritable conditions for insured sums under a certain value: for life-insurance policies policies insurers can request information for the purpose of an accurate risk classification. Insurance contracts can be accepted at normal rates if the target value of LDL-cholesterol < 4 mmol/l and additional risk factors such as smoking and an abnormal BMI are absent; the risk is determined by the phenotype and clinical factors and not by the genotype.

  15. Electrochemical sensor for multiplex screening of genetically modified DNA: identification of biotech crops by logic-based biomolecular analysis.

    Science.gov (United States)

    Liao, Wei-Ching; Chuang, Min-Chieh; Ho, Ja-An Annie

    2013-12-15

    Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Diabetic Retinopathy Screening Using Telemedicine Tools: Pilot Study in Hungary

    Science.gov (United States)

    Eszes, Dóra J.; Szabó, Dóra J.; Russell, Greg; Kirby, Phil; Paulik, Edit; Nagymajtényi, László

    2016-01-01

    Introduction. Diabetic retinopathy (DR) is a sight-threatening complication of diabetes. Telemedicine tools can prevent blindness. We aimed to investigate the patients' satisfaction when using such tools (fundus camera examination) and the effect of demographic and socioeconomic factors on participation in screening. Methods. Pilot study involving fundus camera screening and self-administered questionnaire on participants' experience during fundus examination (comfort, reliability, and future interest in participation), as well as demographic and socioeconomic factors was performed on 89 patients with known diabetes in Csongrád County, a southeastern region of Hungary. Results. Thirty percent of the patients had never participated in any ophthalmological screening, while 25.7% had DR of some grade based upon a standard fundus camera examination and UK-based DR grading protocol (Spectra™ software). Large majority of the patients were satisfied with the screening and found it reliable and acceptable to undertake examination under pupil dilation; 67.3% were willing to undergo nonmydriatic fundus camera examination again. There was a statistically significant relationship between economic activity, education and marital status, and future interest in participation. Discussion. Participants found digital retinal screening to be reliable and satisfactory. Telemedicine can be a strong tool, supporting eye care professionals and allowing for faster and more comfortable DR screening. PMID:28078306

  17. Diabetic Retinopathy Screening Using Telemedicine Tools: Pilot Study in Hungary

    Directory of Open Access Journals (Sweden)

    Dóra J. Eszes

    2016-01-01

    Full Text Available Introduction. Diabetic retinopathy (DR is a sight-threatening complication of diabetes. Telemedicine tools can prevent blindness. We aimed to investigate the patients’ satisfaction when using such tools (fundus camera examination and the effect of demographic and socioeconomic factors on participation in screening. Methods. Pilot study involving fundus camera screening and self-administered questionnaire on participants’ experience during fundus examination (comfort, reliability, and future interest in participation, as well as demographic and socioeconomic factors was performed on 89 patients with known diabetes in Csongrád County, a southeastern region of Hungary. Results. Thirty percent of the patients had never participated in any ophthalmological screening, while 25.7% had DR of some grade based upon a standard fundus camera examination and UK-based DR grading protocol (Spectra™ software. Large majority of the patients were satisfied with the screening and found it reliable and acceptable to undertake examination under pupil dilation; 67.3% were willing to undergo nonmydriatic fundus camera examination again. There was a statistically significant relationship between economic activity, education and marital status, and future interest in participation. Discussion. Participants found digital retinal screening to be reliable and satisfactory. Telemedicine can be a strong tool, supporting eye care professionals and allowing for faster and more comfortable DR screening.

  18. Automated, quantitative cognitive/behavioral screening of mice: for genetics, pharmacology, animal cognition and undergraduate instruction.

    Science.gov (United States)

    Gallistel, C R; Balci, Fuat; Freestone, David; Kheifets, Aaron; King, Adam

    2014-02-26

    We describe a high-throughput, high-volume, fully automated, live-in 24/7 behavioral testing system for assessing the effects of genetic and pharmacological manipulations on basic mechanisms of cognition and learning in mice. A standard polypropylene mouse housing tub is connected through an acrylic tube to a standard commercial mouse test box. The test box has 3 hoppers, 2 of which are connected to pellet feeders. All are internally illuminable with an LED and monitored for head entries by infrared (IR) beams. Mice live in the environment, which eliminates handling during screening. They obtain their food during two or more daily feeding periods by performing in operant (instrumental) and Pavlovian (classical) protocols, for which we have written protocol-control software and quasi-real-time data analysis and graphing software. The data analysis and graphing routines are written in a MATLAB-based language created to simplify greatly the analysis of large time-stamped behavioral and physiological event records and to preserve a full data trail from raw data through all intermediate analyses to the published graphs and statistics within a single data structure. The data-analysis code harvests the data several times a day and subjects it to statistical and graphical analyses, which are automatically stored in the "cloud" and on in-lab computers. Thus, the progress of individual mice is visualized and quantified daily. The data-analysis code talks to the protocol-control code, permitting the automated advance from protocol to protocol of individual subjects. The behavioral protocols implemented are matching, autoshaping, timed hopper-switching, risk assessment in timed hopper-switching, impulsivity measurement, and the circadian anticipation of food availability. Open-source protocol-control and data-analysis code makes the addition of new protocols simple. Eight test environments fit in a 48 in x 24 in x 78 in cabinet; two such cabinets (16 environments) may be

  19. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    Science.gov (United States)

    DiTommaso, Tia; Jones, Lynelle K; Cottle, Denny L; Gerdin, Anna-Karin; Vancollie, Valerie E; Watt, Fiona M; Ramirez-Solis, Ramiro; Bradley, Allan; Steel, Karen P; Sundberg, John P; White, Jacqueline K; Smyth, Ian M

    2014-10-01

    The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  20. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    Directory of Open Access Journals (Sweden)

    Tia DiTommaso

    2014-10-01

    Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  1. Comparative Haploid Genetic Screens Reveal Divergent Pathways in the Biogenesis and Trafficking of Glycophosphatidylinositol-Anchored Proteins

    Directory of Open Access Journals (Sweden)

    Eric M. Davis

    2015-06-01

    Full Text Available Glycophosphatidylinositol-anchored proteins (GPI-APs play essential roles in physiology, but their biogenesis and trafficking have not been systematically characterized. Here, we took advantage of the recently available haploid genetics approach to dissect GPI-AP pathways in human cells using prion protein (PrP and CD59 as model molecules. Our screens recovered a large number of common and unexpectedly specialized factors in the GPI-AP pathways. PIGN, PGAP2, and PIGF, which encode GPI anchor-modifying enzymes, were selectively isolated in the CD59 screen, suggesting that GPI anchor composition significantly influences the biogenesis of GPI-APs in a substrate-dependent manner. SEC62 and SEC63, which encode components of the ER-targeting machinery, were selectively recovered in the PrP screen, indicating that they do not constitute a universal route for the biogenesis of mammalian GPI-APs. Together, these comparative haploid genetic screens demonstrate that, despite their similarity in overall architecture and subcellular localization, GPI-APs follow markedly distinct biosynthetic and trafficking pathways.

  2. A screen for genetic suppressor elements of hepatitis C virus identifies a supercharged protein inhibitor of viral replication.

    Science.gov (United States)

    Simeon, Rudo L; Chen, Zhilei

    2013-01-01

    Genetic suppressor elements (GSEs) are biomolecules derived from a gene or genome of interest that act as transdominant inhibitors of biological functions presumably by disruption of critical biological interfaces. We exploited a cell death reporter cell line for hepatitis C virus (HCV) infection, n4mBid, to develop an iterative selection/enrichment strategy for the identification of anti-HCV GSEs. Using this approach, a library of fragments of an HCV genome was screened for sequences that suppress HCV infection. A 244 amino acid gene fragment, B1, was strongly enriched after 5 rounds of selection. B1 derives from a single-base frameshift of the enhanced green fluorescent protein (eGFP) which was used as a filler during fragment cloning. B1 has a very high net positive charge of 43 at neutral pH and a high charge-to-mass (kDa) ratio of 1.5. We show that B1 expression specifically inhibits HCV replication. In addition, five highly positively charged B1 fragments produced from progressive truncation at the C-terminus all retain the ability to inhibit HCV, suggesting that a high positive charge, rather than a particular motif in B1, likely accounts for B1's anti-HCV activity. Another supercharged protein, +36GFP, was also found to strongly inhibit HCV replication when added to cells at the time of infection. This study reports a new methodology for HCV inhibitor screening and points to the anti-HCV potential of positively charged proteins/peptides.

  3. IronMaking Process Alternatives Screening Study

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2000-10-01

    This study by Lockwood Greene evaluates a number ironmaking processes. The appendices provide greater detail and further exploration of the ironmaking processes, including components, relative costs, and comparisons.

  4. Problems and Limitations in Studies on Screening for Language Delay

    Science.gov (United States)

    Eriksson, Marten; Westerlund, Monica; Miniscalco, Carmela

    2010-01-01

    This study discusses six common methodological limitations in screening for language delay (LD) as illustrated in 11 recent studies. The limitations are (1) whether the studies define a target population, (2) whether the recruitment procedure is unbiased, (3) attrition, (4) verification bias, (5) small sample size and (6) inconsistencies in choice…

  5. Premarital Screening and Genetic Counseling program: knowledge, attitude, and satisfaction of attendees of governmental outpatient clinics in Jeddah.

    Science.gov (United States)

    Ibrahim, Nahla Khamis; Bashawri, Jamel; Al Bar, Hussein; Al Ahmadi, Jawaher; Al Bar, Adnan; Qadi, Mahdi; Milaat, Waleed; Feda, Hashim

    2013-02-01

    Premarital care (PMC) is a worldwide activity that aims to diagnose and treat unrecognized disorders and reduce the transmission of diseases to couples and children. To assess the knowledge and attitude of individuals attending governmental outpatient clinics regarding the Premarital Screening and Genetic Counseling (PMSGC) programs, to identify predictors of high knowledge scores and to determine the satisfaction and recommendations of clients of the program. A cross-sectional study was conducted from January to April 2009. Individuals who attended three governmental hospital outpatient clinics on the day of the interview and agreed to participate in the study were recruited. The three hospitals were the two hospitals in Jeddah that offer the PMSGC programs and the King Abdulaziz University Hospital. Ethical considerations were followed and data were collected through an interview questionnaire that had been constructed for the study. The questionnaire asked for personal and socio-demographic data and for responses, on a 5-point Likert scale, to 30 knowledge items and 14 attitude statements. Individuals who participated in the PMSGC program were asked questions regarding the services and activities of the program to ascertain their satisfaction with the program and their recommendations for program improvement. The statistical analysis was performed using SPSS version 16 (SPSS Inc., Chicago, IL). The sample included 655 participants, of whom 38.8% completed the PMSGC program. The participants' knowledge about the program was generally low. Education was the first predictor of a high knowledge score; individuals having ≥ university degree obtained a higher score (aOR=2.73; 95% CI: 1.77-4.20). The second predictor was the nationality of the participants, with Saudis gaining a higher score (aOR=2.04; 95% CI: 1.002-4.16). The third predictor was monthly income. Regarding attitudes, the vast majority of participants (96.0%) strongly agreed on the importance of the

  6. Infrastructure and Educational Needs of Newborn Screening Short-Term Follow-Up Programs within the Southeast Regional Newborn Screening & Genetics Collaborative: A Pilot Survey

    Directory of Open Access Journals (Sweden)

    Cecelia A. Bellcross

    2015-10-01

    Full Text Available Newborn screening (NBS follow-up protocols vary significantly by state, and there is a need to better understand the infrastructure and communication flow of NBS programs. In addition, assessment of the educational needs of families and providers with regard to the implications of NBS results is required to inform the development of appropriate informational resources and training opportunities. To begin to address these issues, we administered a web-based survey to state NBS coordinators within the Southeast Regional Newborn Screening & Genetics Collaborative (SERC. Fourteen coordinators responded to the survey, including at least one from each of the 10 SERC states/territories. Over one-third of respondents had never received formal training regarding the metabolic conditions identified on NBS. Most communicated results via telephone or fax, though two centers indicated use of a web-based platform. Only two programs were involved in directly reporting results to the family. Four programs reported a long-term follow-up protocol. Deficits were noted for primary care provider (PCP knowledge of metabolic disorders identified on NBS, and how to inform parents of abnormal results. Close to half indicated that the adequacy of the number of genetic counselors, dietitians, and medical/biochemical geneticists was minimal to insufficient. Respondents uniformly recognized the importance of providing additional educational and informational resources in multiple categories to NBS staff, PCPs, and families.

  7. Genetic Screen Reveals the Role of Purine Metabolism in Staphylococcus aureus Persistence to Rifampicin

    Directory of Open Access Journals (Sweden)

    Rebecca Yee

    2015-12-01

    Full Text Available Chronic infections with Staphylococcus aureus such as septicemia, osteomyelitis, endocarditis, and biofilm infections are difficult to treat because of persisters. Despite many efforts in understanding bacterial persistence, the mechanisms of persister formation in S. aureus remain elusive. Here, we performed a genome-wide screen of a transposon mutant library to study the molecular mechanisms involved in persistence of community-acquired S. aureus. Screening of the library for mutants defective in persistence or tolerance to rifampicin revealed many genes involved in metabolic pathways that are important for antibiotic persistence. In particular, the identified mutants belonged to metabolic pathways involved in carbohydrate, amino acid, lipid, vitamin and purine biosynthesis. Five mutants played a role in purine biosynthesis and two mutants, purB, an adenylosuccinate lyase, and purM, a phosphoribosylaminoimidazole synthetase, were selected for further confirmation. Mutants purB and purM showed defective persistence compared to the parental strain USA300 in multiple stress conditions including various antibiotics, low pH, and heat stress. The defect in persistence was restored by complementation with the wildtype purB and purM gene in the respective mutants. These findings provide new insights into the mechanisms of persistence in S. aureus and provide novel therapeutic targets for developing more effective treatment for persistent infections due to S. aureus.

  8. A Novel Genetic Screen Identifies Modifiers of Age-Dependent Amyloid β Toxicity in the Drosophila Brain

    Science.gov (United States)

    Belfiori-Carrasco, Lautaro F.; Marcora, María S.; Bocai, Nadia I.; Ceriani, M. Fernanda; Morelli, Laura; Castaño, Eduardo M.

    2017-01-01

    The accumulation of amyloid β peptide (Aβ) in the brain of Alzheimer’s disease (AD) patients begins many years before clinical onset. Such process has been proposed to be pathogenic through the toxicity of Aβ soluble oligomers leading to synaptic dysfunction, phospho-tau aggregation and neuronal loss. Yet, a massive accumulation of Aβ can be found in approximately 30% of aged individuals with preserved cognitive function. Therefore, within the frame of the “amyloid hypothesis”, compensatory mechanisms and/or additional neurotoxic or protective factors need to be considered and investigated. Here we describe a modifier genetic screen in Drosophila designed to identify genes that modulate toxicity of Aβ42 in the CNS. The expression of Aβ42 led to its accumulation in the brain and a moderate impairment of negative geotaxis at 18 days post-eclosion (d.p.e) as compared with genetic or parental controls. These flies were mated with a collection of lines carrying chromosomal deletions and negative geotaxis was assessed at 5 and 18 d.p.e. Our screen is the first to take into account all of the following features, relevant to sporadic AD: (1) pan-neuronal expression of wild-type Aβ42; (2) a quantifiable complex behavior; (3) Aβ neurotoxicity associated with progressive accumulation of the peptide; and (4) improvement or worsening of climbing ability only evident in aged animals. One hundred and ninety-nine deficiency (Df) lines accounting for ~6300 genes were analyzed. Six lines, including the deletion of 52 Drosophila genes with human orthologs, significantly modified Aβ42 neurotoxicity in 18-day-old flies. So far, we have validated CG11796 and identified CG17249 as a strong candidate (whose human orthologs are HPD and PRCC, respectively) by using RNAi or mutant hemizygous lines. PRCC encodes proline-rich protein PRCC (ppPRCC) of unknown function associated with papillary renal cell carcinoma. HPD encodes 4-hydroxyphenylpyruvate dioxygenase (HPPD), a key

  9. Integrated screening concept in women with genetic predisposition for breast cancer; Integriertes Frueherkennungskonzept bei Frauen mit genetischer Praedisposition fuer Brustkrebs

    Energy Technology Data Exchange (ETDEWEB)

    Bick, U. [Muenster Univ. (Germany). Inst. fuer Klinische Radiologie

    1997-08-01

    Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.) [Deutsch] Mammakarzinome sind in etwa 5% auf eine genetische Disposition zurueckzufuehren. Am haeufigsten finden sich Mutationen im Bereich der Gene BRCA1 und BRCA2. Frauen mit einer genetischen Disposition erkranken in etwa 70-90% im Laufe ihres Lebens an einem Mammakarzinom. Das Erkrankungsalter bei diesen Frauen liegt in der Regel deutlich niedriger als bei den spontanen Formen des Mammakarzinoms, so dass vorhandene Frueherkennungskonzepte auf der Basis eines Mammographiescrennings nicht ohne weiteres auf dieses Hochrisikokollektiv uebertragbar sind. Im folgenden wird ein integriertes Konzept zur Frueherkennung bei Frauen mit genetischer Praedisposition fuer ein Mammakarzinom auf der Basis von Brustselbstuntersuchung, klinischer Untersuchung, Sonographie, Mammographie und Magnetresonanztomographie vorgestellt. (orig.)

  10. Impact of gene patents and licensing practices on access to genetic testing and carrier screening for Tay-Sachs and Canavan disease.

    Science.gov (United States)

    Colaianni, Alessandra; Chandrasekharan, Subhashini; Cook-Deegan, Robert

    2010-04-01

    Genetic testing for Tay-Sachs and Canavan disease is particularly important for Ashkenazi Jews, because both conditions are more frequent in that population. This comparative case study was possible because of different patenting and licensing practices. The role of DNA testing differs between Tay-Sachs and Canavan diseases. The first-line screening test for Tay-Sachs remains an enzyme activity test rather than genotyping. Genotyping is used for preimplantation diagnosis and confirmatory testing. In contrast, DNA-based testing is the basis for Canavan screening and diagnosis. The HEXA gene for Tay-Sachs was cloned at the National Institutes of Health, and the gene was patented but has not been licensed. The ASPA gene for Canavan disease was cloned and patented by Miami Children's Hospital. Miami Children's Hospital did not inform family members and patient groups that had contributed to the gene discovery that it was applying for a patent, and pursued restrictive licensing practices when a patent issued in 1997. This led to intense controversy, litigation, and a sealed, nonpublic 2003 settlement that apparently allowed for nonexclusive licensing. A survey of laboratories revealed a possible price premium for ASPA testing, with per-unit costs higher than for other genetic tests in the Secretary's Advisory Committee on Genetics, Health, and Society case studies. The main conclusion from comparing genetic testing for Tay-Sachs and Canavan diseases, however, is that patenting and licensing conducted without communication with patients and advocates cause mistrust and can lead to controversy and litigation, a negative model to contrast with the positive model of patenting and licensing for genetic testing of cystic fibrosis.

  11. Early blight resistance in tomato: screening and genetic study

    NARCIS (Netherlands)

    Chaerani, R.

    2006-01-01

    Tomato early blight (EB) caused by the fungus Alternaria solani is a field disease with a worldwide distribution, including Indonesia. The disease is currently controlled using frequent applications of fungicides. The use of resistant cultivar would be an attractive way to reduce fungicide applicati

  12. A genetic screen reveals Arabidopsis stomatal and/or apoplastic defenses against Pseudomonas syringae pv. tomato DC3000.

    Directory of Open Access Journals (Sweden)

    Weiqing Zeng

    2011-10-01

    Full Text Available Bacterial infection of plants often begins with colonization of the plant surface, followed by entry into the plant through wounds and natural openings (such as stomata, multiplication in the intercellular space (apoplast of the infected tissues, and dissemination of bacteria to other plants. Historically, most studies assess bacterial infection based on final outcomes of disease and/or pathogen growth using whole infected tissues; few studies have genetically distinguished the contribution of different host cell types in response to an infection. The phytotoxin coronatine (COR is produced by several pathovars of Pseudomonas syringae. COR-deficient mutants of P. s. tomato (Pst DC3000 are severely compromised in virulence, especially when inoculated onto the plant surface. We report here a genetic screen to identify Arabidopsis mutants that could rescue the virulence of COR-deficient mutant bacteria. Among the susceptible to coronatine-deficient Pst DC3000 (scord mutants were two that were defective in stomatal closure response, two that were defective in apoplast defense, and four that were defective in both stomatal and apoplast defense. Isolation of these three classes of mutants suggests that stomatal and apoplastic defenses are integrated in plants, but are genetically separable, and that COR is important for Pst DC3000 to overcome both stomatal guard cell- and apoplastic mesophyll cell-based defenses. Of the six mutants defective in bacterium-triggered stomatal closure, three are defective in salicylic acid (SA-induced stomatal closure, but exhibit normal stomatal closure in response to abscisic acid (ABA, and scord7 is compromised in both SA- and ABA-induced stomatal closure. We have cloned SCORD3, which is required for salicylic acid (SA biosynthesis, and SCORD5, which encodes an ATP-binding cassette (ABC protein, AtGCN20/AtABCF3, predicted to be involved in stress-associated protein translation control. Identification of SCORD5 begins to

  13. A Screening Study on Dermatoses in Pregnancy

    Science.gov (United States)

    Tharini, GK

    2017-01-01

    Introduction Pregnancy produces many cutaneous changes, some of which are specifically related to pregnancy (dermatoses of pregnancy), some are modifiable by pregnancy and others that are common are named physiologic. These physiologic skin changes, usually do not impair the health of the mother or the fetus but some of them can be cosmetically significant and of importance to the dermatologist. Aim The present study was undertaken to find out the prevalence of the physiological and pathological skin changes in pregnancy, and to correlate the prevalence of the major cutaneous changes and diseases in relation to different trimesters of pregnancy and with gravidity. Materials and Methods A cross-sectional study was conducted during the period of August 2008 to August 2010. Ethical clearance was sought from Institutional Ethical Committee. Five hundred pregnant women were randomly selected, irrespective of the duration of pregnancy and gravidity. Detailed history and complete dermatological examination was done. Results were tabulated and analysed. Statistical analysis was done by Fisher’s exact test and Chi square test. Results Physiological skin changes were seen in 94.8% of cases, with pigmentary changes being more common (90.8%). Specific dermatoses of pregnancy were observed in 14% of cases with pruritus gravidarum being the most common (10.4%). Prevalence of infection was found to 30.8% with fungal infection being the most common (23.8%). Exacerbations of systemic lupus erythematosus and neurofibromatosis was observed. Pigmentary changes, striae gravidarum and specific dermatoses of pregnancy were observed in statistically significant proportion in primigravidas and during third trimester. Conclusion This study emphasizes that the prevalence of physiological skin changes (94.8%) was much higher than specific dermatoses (14%), stressing the fact that in most instances, the skin problems during pregnancy needs only reassurance. But meticulous observation and

  14. Six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and β-thalassemia in Saudi Arabia

    National Research Council Canada - National Science Library

    Memish, Ziad Ahmed; Saeedi, Mohammad Y

    2011-01-01

    Saudi Arabia has a high prevalence of hereditary hemoglobin disorders. Data has been collected by the Saudi Premarital Screening and Genetic Counseling Program on the prevalence of sickle cell disease and β...

  15. Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients

    Science.gov (United States)

    Gonçalves, Maria J.; Mourão, Ana F.; Martinho, António; Simões, Olívia; Melo-Gomes, José; Salgado, Manuel; Estanqueiro, Paula; Ribeiro, Célia; Brito, Iva; Fonseca, João E.; Canhão, Helena

    2017-01-01

    Fabry’s disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No “classic” pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292). PMID:28299312

  16. Thermodynamic Studies for Drug Design and Screening

    Science.gov (United States)

    Garbett, Nichola C.; Chaires, Jonathan B.

    2012-01-01

    Introduction A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. Areas covered This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 – 2011 using the Science Citation Index and PUBMED and the keywords listed below. Expert opinion The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically-driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development towards an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. PMID:22458502

  17. Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer.

    Science.gov (United States)

    Fawdar, Shameem; Trotter, Eleanor W; Li, Yaoyong; Stephenson, Natalie L; Hanke, Franziska; Marusiak, Anna A; Edwards, Zoe C; Ientile, Sara; Waszkowycz, Bohdan; Miller, Crispin J; Brognard, John

    2013-07-23

    Approximately 70% of patients with non-small-cell lung cancer present with late-stage disease and have limited treatment options, so there is a pressing need to develop efficacious targeted therapies for these patients. This remains a major challenge as the underlying genetic causes of ~50% of non-small-cell lung cancers remain unknown. Here we demonstrate that a targeted genetic dependency screen is an efficient approach to identify somatic cancer alterations that are functionally important. By using this approach, we have identified three kinases with gain-of-function mutations in lung cancer, namely FGFR4, MAP3K9, and PAK5. Mutations in these kinases are activating toward the ERK pathway, and targeted depletion of the mutated kinases inhibits proliferation, suppresses constitutive activation of downstream signaling pathways, and results in specific killing of the lung cancer cells. Genomic profiling of patients with lung cancer is ushering in an era of personalized medicine; however, lack of actionable mutations presents a significant hurdle. Our study indicates that targeted genetic dependency screens will be an effective strategy to elucidate somatic variants that are essential for lung cancer cell viability.

  18. Impact of human genome initiative-derived technology on genetic testing, screening and counseling: Cultural, ethical and legal issues

    Energy Technology Data Exchange (ETDEWEB)

    Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. (Morehouse Coll., Atlanta, GA (United States). School of Medicine); Crandall, L.A.; Moseley, R.E.; Armotrading, D. (Florida Univ., Gainesville, FL (United States). Coll. of Medicine)

    1993-01-01

    Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia's system of Children's Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.

  19. Ironmaking Process Alternative Screening Study, Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    Lockwood Greene, . .

    2005-01-06

    Iron in the United States is largely produced from iron ore mined in the United States or imported from Canada or South America. The iron ore is typically smelted in Blast Furnaces that use primarily iron ore, iron concentrate pellets metallurgical coke, limestone and lime as the raw materials. Under current operating scenarios, the iron produced from these Blast Furnaces is relatively inexpensive as compared to current alternative iron sources, e.g. direct iron reduction, imported pig iron, etc. The primary problem the Blast Furnace Ironmaking approach is that many of these Blast furnaces are relatively small, as compared to the newer, larger Blast Furnaces; thus are relatively costly and inefficient to operate. An additional problem is also that supplies of high-grade metallurgical grade coke are becoming increasingly in short supply and costs are also increasing. In part this is due to the short supply and costs of high-grade metallurgical coals, but also this is due to the increasing necessity for environmental controls for coke production. After year 2003 new regulations for coke product environmental requirement will likely be promulgated. It is likely that this also will either increase the cost of high-quality coke production or will reduce the available domestic U.S. supply. Therefore, iron production in the United States utilizing the current, predominant Blast Furnace process will be more costly and would likely be curtailed due to a coke shortage. Therefore, there is a significant need to develop or extend the economic viability of Alternate Ironmaking Processes to at least partially replace current and declining blast furnace iron sources and to provide incentives for new capacity expansion. The primary conclusions of this comparative Study of Alternative Ironmaking Process scenarios are: (1) The processes with the best combined economics (CAPEX and OPEX impacts in the I.R.R. calculation) can be grouped into those Fine Ore based processes with no scrap

  20. Study of Siberian forest genetic resources

    Directory of Open Access Journals (Sweden)

    L. I. Milyutin

    2016-06-01

    Full Text Available Forest genetic resources are the aggregate of genofonds of native and cultivar populations of forest woody plants, valuable really or potential for specific territory (A brief dictionary… 2014. Forest genetic resources are studied in practice in most cases on example of forest-forming woody plants. It is necessary to consider of study of these resources in two positions: taxonomic and geographic. Forest forming coniferous species are studied best of all from the taxonomic point of view taking into account biodiversity. Genetic polymorphism is studied most in detail with such species as Pinus sylvestris, Pinus sibirica, Larix sibirica, Larix sukaczevii, Picea obovata, Abies sibirica. Populations of Larix gmelinii, Larix cajanderi, Picea ajanensis are studied considerable worse. Materials about genetic polymorphism of forest forming foliage species – representative of genera Betula and Populus are absent. Caryological polymorphism is studied sufficiently well in all Siberian conifer species. It should be noted especially attached to examination of this problem, that individuals with B-chromosome were discovered first by gymnosperms as an example Picea obovata. Discovery in Siberia of triploid asp deserve special attention. Geographic variability is shown most broadly in the investigations of Pinus sylvestris, Pinus sibirica, Larix sibirica. These investigations were conducted both in natural populations and in provenance trials. Such investigations of another conifer and foliage species either are shown by separate fragments or are absent at all Geographic variability is shown in a large measure in the operative forest seed sources regionalization. Numerous investigations directed to the analysis of morphological variability are conducted by all forest forming species in the first place by conifers. Questions of hereditary determination of either signs remain in this problem. Similar questions concern the variability of other signs

  1. High-Throughput Genetic Screening of 51 Pediatric Cataract Genes Identifies Causative Mutations in Inherited Pediatric Cataract in South Eastern Australia

    Directory of Open Access Journals (Sweden)

    Shari Javadiyan

    2017-10-01

    Full Text Available Pediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of pediatric cataract in Australian families by screening known disease-associated genes using massively parallel sequencing technology. We sequenced 51 previously reported pediatric cataract genes in 33 affected individuals with a family history (cases with previously known or published mutations were excluded using the Ion Torrent Personal Genome Machine. Variants were prioritized for validation if they were predicted to alter the protein sequence and were absent or rare with minor allele frequency 60% of familial pediatric cataract in Australia, indicating that still more causative genes remain to be identified.

  2. Register-based studies of cancer screening effects

    DEFF Research Database (Denmark)

    Von Euler-Chelpin, My; Lynge, Elsebeth; Rebolj, Matejka

    2011-01-01

    INTRODUCTION: There are two organised cancer screening programmes in Denmark, against cervical and breast cancers. The aim with this study was to give an overview of the available register-based research regarding these two programmes, to demonstrate the usefulness of data from the national regis...

  3. Investigating the viability of genetic screening/testing for RA susceptibility using combinations of five confirmed risk loci

    Science.gov (United States)

    McClure, Annie; Lunt, Mark; Eyre, Steve; Ke, Xiayi; Thomson, Wendy; Hinks, Anne; Bowes, John; Gibbons, Laura; Plant, Darren; Wilson, Anthony G.; Marinou, Ioanna; Morgan, Ann W.; Emery, Paul; Steer, Sophia; Hocking, Lynne J.; Reid, David M.; Wordsworth, Paul; Harrison, Pille; Worthington, Jane

    2009-01-01

    Objective. Five loci—the shared epitope (SE) of HLA-DRB1, the PTPN22 gene, a locus on 6q23, the STAT4 gene and a locus mapping to the TRAF1/C5 genetic region—have now been unequivocally confirmed as conferring susceptibility to RA. The largest single effect is conferred by SE. We hypothesized that combinations of susceptibility alleles may increase risk over and above that of any individual locus alone. Methods. We analysed data from 4238 RA cases and 1811 controls, for which genotypes were available at all five loci. Results. Statistical analysis identified eight high-risk combinations conferring an odds ratio >6 compared with carriage of no susceptibility variants and, interestingly, 10% population controls carried a combination conferring high risk. All high-risk combinations included SE, and all but one contained PTPN22. Statistical modelling showed that a model containing only these two loci could achieve comparable sensitivity and specificity to a model including all five. Furthermore, replacing SE (which requires full subtyping at the HLA-DRB1 gene) with DRB1*1/4/10 carriage resulted in little further loss of information (correlation coefficient between models = 0.93). Conclusions. This represents the first exploration of the viability of population screening for RA and identifies several high-risk genetic combinations. However, given the population incidence of RA, genetic screening based on these loci alone is neither sufficiently sensitive nor specific at the current time. PMID:19741008

  4. Quantitative genome-wide genetic interaction screens reveal global epistatic relationships of protein complexes in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Mohan Babu

    2014-02-01

    Full Text Available Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes, but not their functional organization into biological pathways and processes. Conversely, genetic interaction (GI screens can provide insights into the biological role(s of individual gene and higher order associations. Combining the information from both approaches should elucidate how complexes and pathways intersect functionally at a systems level. However, such integrative analysis has been hindered due to the lack of relevant GI data. Here we present a systematic, unbiased, and quantitative synthetic genetic array screen in E. coli describing the genetic dependencies and functional cross-talk among over 600,000 digenic mutant combinations. Combining this epistasis information with putative functional modules derived from previous proteomic data and genomic context-based methods revealed unexpected associations, including new components required for the biogenesis of iron-sulphur and ribosome integrity, and the interplay between molecular chaperones and proteases. We find that functionally-linked genes co-conserved among γ-proteobacteria are far more likely to have correlated GI profiles than genes with divergent patterns of evolution. Overall, examining bacterial GIs in the context of protein complexes provides avenues for a deeper mechanistic understanding of core microbial systems.

  5. Cultural Concerns when Counseling Orthodox Jewish Couples for Genetic Screening and PGD.

    Science.gov (United States)

    Grazi, Richard V; Wolowelsky, Joel B

    2015-12-01

    There is a spectrum of attitudes within the Orthodox Jewish community towards genetic testing and PGD. Increased understanding of the belief systems of the Orthodox Jewish population will enhance the genetic counselors' ability to better serve this unique group of patients. By improving cultural competence, genetic counselors can help patients choose the testing options that they deem appropriate, while simultaneously respecting the patient's belief system.

  6. Genetic screening for Krabbe disease: learning from the past and looking to the future.

    Science.gov (United States)

    Macarov, Michal; Zlotogora, Joel; Meiner, Vardiella; Khatib, Zinab; Sury, Vivi; Mengistu, Getu; Bargal, Ruth; Shmueli, Esther; Meidan, Bela; Zeigler, Marsha

    2011-03-01

    In Israel, Krabbe disease is frequent in two Moslem Arab villages in the Jerusalem area. In this paper we present our experience of almost four decades with diagnosis of Krabbe disease, carrier screening and prenatal diagnosis. The screening program is well accepted by the community, and there is a clear trend towards premarital testing. The screening program and prenatal diagnosis have led to a decrease in the incidence of Krabbe disease from 1.6 per 1,000 live births to 0.82 per 1,000. Copyright © 2011 Wiley-Liss, Inc.

  7. Automated screening versus manual screening: a comparison of the ThinPrep imaging system and manual screening in a time study

    DEFF Research Database (Denmark)

    Schledermann, Doris; Hyldebrandt, Tina; Ejersbo, Dorthe;

    2007-01-01

    The ThinPrep Imaging System (TIS) is an automated system that assists cytotechnologists in the primary screening of ThinPrep liquid based cervical samples. Between June 1, 2004, and April 1, 2005, four experienced cytotechnologists participated in the study in which the duration of the screening ...

  8. Representing genetic variation as continuous surfaces: An approach for identifying spatial dependency in landscape genetic studies

    Science.gov (United States)

    Melanie A. Murphy; Jeffrey S. Evans; Samuel A. Cushman; Andrew Storfer

    2008-01-01

    Landscape genetics, an emerging field integrating landscape ecology and population genetics, has great potential to influence our understanding of habitat connectivity and distribution of organisms. Whereas typical population genetics studies summarize gene flow as pairwise measures between sampling localities, landscape characteristics that influence population...

  9. A Novel Frizzled-Based Screening Tool Identifies Genetic Modifiers of Planar Cell Polarity in Drosophila Wings

    Directory of Open Access Journals (Sweden)

    Jose Maria Carvajal-Gonzalez

    2016-12-01

    Full Text Available Most mutant alleles in the Fz-PCP pathway genes were discovered in classic Drosophila screens looking for recessive loss-of-function (LOF mutations. Nonetheless, although Fz-PCP signaling is sensitive to increased doses of PCP gene products, not many screens have been performed in the wing under genetically engineered Fz overexpression conditions, mostly because the Fz phenotypes were strong and/or not easy to score and quantify. Here, we present a screen based on an unexpected mild Frizzled gain-of-function (GOF phenotype. The leakiness of a chimeric Frizzled protein designed to be accumulated in the endoplasmic reticulum (ER generated a reproducible Frizzled GOF phenotype in Drosophila wings. Using this genotype, we first screened a genome-wide collection of large deficiencies and found 16 strongly interacting genomic regions. Next, we narrowed down seven of those regions to finally test 116 candidate genes. We were, thus, able to identify eight new loci with a potential function in the PCP context. We further analyzed and confirmed krasavietz and its interactor short-stop as new genes acting during planar cell polarity establishment with a function related to actin and microtubule dynamics.

  10. Improving toxicity screening and drug development by using genetically defined strains.

    Science.gov (United States)

    Festing, Michael F W

    2010-01-01

    According to the US Food and Drugs Administration (Food and Drug Administration (2004) Challenge and opportunity on the critical path to new medical products.) "The inability to better assess and predict product safety leads to failures during clinical development and, occasionally, after marketing". This increases the cost of new drugs as clinical trials are even more expensive than pre-clinical testing.One relatively easy way of improving toxicity testing is to improve the design of animal experiments. A fundamental principle when designing an experiment is to control all variables except the one of interest: the treatment. Toxicologist and pharmacologists have widely ignored this principle by using genetically heterogeneous "outbred" rats and mice, increasing the chance of false-negative results. By using isogenic (inbred or F1 hybrid, see Note 1) rats and mice instead of outbred stocks the signal/noise ratio and the power of the experiments can be increased at little extra cost whilst using no more animals. Moreover, the power of the experiment can be further increased by using more than one strain, as this reduces the chance of selecting one which is resistant to the test chemical. This can also be done without increasing the total number of animals by using a factorial experimental design, e.g. if the ten outbred animals per treatment group in a 28-day toxicity test were replaced by two animals of each of five strains (still ten animals per treatment group) selected to be as genetically diverse as possible, this would increase the signal/noise ratio and power of the experiment. This would allow safety to be assessed using the most sensitive strain.Toxicologists should also consider making more use of the mouse instead of the rat. They are less costly to maintain, use less test substance, there are many inbred and genetically modified strains, and it is easier to identify gene loci controlling variation in response to xenobiotics in this species.We demonstrate

  11. Screening study on new tumor marker periplakin for lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shuqin Dai; Wei Li; Mian Kong; Yuzhen Zheng; Shuying Chen; Junye Wang; Linquan Zang

    2013-01-01

    Objective: The aim of this study was to use lung cancer targeting binding polypeptide ZS-9 to screen cDNA library of human lung cancer and obtain ZS-9 specific ligand to confirm tumor marker of non small-cell lung cancer. Methods: Artificially synthesize biotin labeled peptide ZS-9, anchored ZS-9 in the enzyme label plate coupled by avidin, used ZS-9 as probe to screen cDNA library of human lung cancer, after screening, obtained bacteriophage clone specifically binding with anchored polypeptide ZS-9. Extracted plasmid of bacteriophage and performed sequencing after amplified by PCR. Results: It was demonstrated by bioinformatic analysis on the sequence of ligand binded by lung cancer specific peptide ZS-9 that the ligand was the cytoskeletal protein periplakin on the surface of lung cancer cells, suggesting that periplakin might be a new marker for non-small-cell lung cancer in lung cancer. Conclusion: Use specific lung cancer binding peptide to screen new tumor marker periplakin in lung cancer and further studies on its biologic functions in genesis and development of lung cancer are still needed.

  12. [The significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis].

    Science.gov (United States)

    Zhang, J; Wang, Y N; Wang, J S; Wu, L; Wei, N; Fu, L; Gao, Z; Chen, J H; Pei, R J; Wang, Z

    2016-07-01

    To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH). Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations. The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a). Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.

  13. A Genetic Study on Myasthenia Gravis

    Institute of Scientific and Technical Information of China (English)

    Lu Chuan-Zhen; Zhou Zhigang; Wu Yongqin

    2000-01-01

    @@Myasthenia Gravis is considered as an autoimmune disease caused by circulating ant:bodies against acetylcholine receptor(AchR) at neuromuscular junctions. Although thousands of studies in the field of function of AchR, activation passway of immune response on MG, genetic control of o-subunit of AchR have been done in the world since 1970's, it is still unclear what is the initial factor of autoimmune response and what hind of genes control are in MG patients.

  14. Genetic screening and functional characterization of PDGFRB mutations associated with Basal Ganglia Calcification of Unknown Etiology

    Science.gov (United States)

    Sanchez-Contreras, Monica; Baker, Matthew C.; Finch, NiCole A.; Nicholson, Alexandra; Wojtas, Aleksandra; Wszolek, Zbigniew K.; Ross, Owen A.; Dickson, Dennis W.; Rademakers, Rosa

    2014-01-01

    Three causal genes for Idiopathic Basal Ganglia Calcification (IBGC) have been identified. Most recently, mutations in PDGFRB, encoding a member of the platelet-derived growth factor receptor family type β, and PDGFB, encoding PDGF-B, the specific ligand of PDGFRβ, were found implicating the PDGF-B/PDGFRβ pathway in abnormal brain calcification. In this study we aimed to identify and study mutations in PDGFRB and PDGFB in a series of 26 patients from the Mayo Clinic Florida Brain Bank with moderate to severe basal ganglia calcification (BCG) of unknown etiology. No mutations in PDGFB were found. However, we identified one mutation in PDGFRB, p.R695C located in the tyrosine kinase domain, in one BGC patient. We further studied the function of p.R695C mutant PDGFRβ and two previously reported mutants, p.L658P and p.R987W PDGFRβ in cell culture. We show that, in response to PDGF-BB stimulation, the p.L658P mutation completely suppresses PDGFRβ autophosphorylation whereas the p.R695C mutation results in partial loss of autophosphorylation. For the p.R987W mutation, our data suggest a different mechanism involving reduced protein levels. These genetic and functional studies provide the first insight into the pathogenic mechanisms associated with PDGFRB mutations and provide further support for a pathogenic role of PDGFRB mutations in BGC. PMID:24796542

  15. Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway

    NARCIS (Netherlands)

    Li, Gang; Diogo, Dorothee; Wu, Di; Spoonamore, Jim; Dancik, Vlado; Franke, Lude; Kurreeman, Fina; Rossin, Elizabeth J.; Duclos, Grant; Hartland, Cathy; Zhou, Xuezhong; Li, Kejie; Liu, Jun; De Jager, Philip L.; Siminovitch, Katherine A.; Zhernakova, Alexandra; Raychaudhuri, Soumya; Bowes, John; Eyre, Steve; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Gupta, Namrata; Clemons, Paul A.; Stahl, Eli; Tolliday, Nicola; Plenge, Robert M.

    2013-01-01

    Although genetic and non-genetic studies in mouse and human implicate the CD40 pathway in rheumatoid arthritis (RA), there are no approved drugs that inhibit CD40 signaling for clinical care in RA or any other disease. Here, we sought to understand the biological consequences of a CD40 risk variant

  16. Scintillating screens study for LEIR/LHC heavy ion beams

    CERN Document Server

    Bal, C; Lefèvre, T; Scrivens, R; Taborelli, M

    2005-01-01

    It has been observed on different machines that scintillating ceramic screens (like chromium doped alumina) are quickly damaged by low energy ion beams. These particles are completely stopped on the surface of the screens, inducing both a high local temperature increase and the electrical charging of the material. A study has been initiated to understand the limiting factors and the damage mechanisms. Several materials, ZrO2, BN and Al2O3, have been tested at CERN on LINAC3 with 4.2MeV/u lead ions. Alumina (Al2O3) is used as the reference material as it is extensively used in beam imaging systems. Boron nitride (BN) has better thermal properties than Alumina and Zirconium oxide (ZrO2). BN has in fact the advantage of increasing its electrical conductivity when heated. This contribution presents the results of the beam tests, including the post-mortem analysis of the screens and the outlook for further measurements. The strategy for the choice of the screens for the Low Energy Ion Ring (LEIR), currently under ...

  17. A Genetic Epidemiological Study of Behavioral Traits

    NARCIS (Netherlands)

    N. Amin (Najaf)

    2011-01-01

    textabstractHuman behavioural genetics aims to unravel the genetic and environmental contributions to variations in human behaviour. Behaviour is a complex trait, involving multiple genes that are affected by a variety of other factors. Genetic epidemiological research of behaviour goes back to Sir

  18. Reporting genetic results in research studies: summary and recommendations of an NHLBI working group.

    Science.gov (United States)

    Bookman, Ebony B; Langehorne, Aleisha A; Eckfeldt, John H; Glass, Kathleen C; Jarvik, Gail P; Klag, Michael; Koski, Greg; Motulsky, Arno; Wilfond, Benjamin; Manolio, Teri A; Fabsitz, Richard R; Luepker, Russell V

    2006-05-15

    Prospective epidemiologic studies aid in identifying genetic variants associated with diseases, health risks, and physiologic traits. These genetic variants may eventually be measured clinically for purposes of diagnosis, prognosis, and treatment. As evidence of the potential clinical value of such information accrues, research studies face growing pressure to report these results to study participants or their physicians, even before sufficient evidence is available to support widespread screening of asymptomatic persons. There is thus a need to begin to develop consensus on whether and when genetic findings should be reported to participants in research studies. The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group on Reporting Genetic Results in Research Studies to discuss if, when, and how genetic information should be reported to study participants. The Working Group concluded that genetic test results should be reported to study participants when the associated risk for the disease is significant; the disease has important health implications such as premature death or substantial morbidity or has significant reproductive implications; and proven therapeutic or preventive interventions are available. Finally, the Working Group recommended procedures for reporting genetic research results and encouraged increased efforts to create uniform guidelines for this activity.

  19. An ergonomics study of thumb movements on smartphone touch screen.

    Science.gov (United States)

    Xiong, Jinghong; Muraki, Satoshi

    2014-01-01

    This study investigated the relationships between thumb muscle activity and thumb operating tasks on a smartphone touch screen with one-hand posture. Six muscles in the right thumb and forearm were targeted in this study, namely adductor pollicis, flexor pollicis brevis, abductor pollicis brevis (APB), abductor pollicis longus, first dorsal interosseous (FDI) and extensor digitorum. The performance measures showed that the thumb developed fatigue rapidly when tapping on smaller buttons (diameter: 9 mm compared with 3 mm), and moved more slowly in flexion-extension than in adduction-abduction orientation. Meanwhile, the electromyography and perceived exertion values of FDI significantly increased in small button and flexion-extension tasks, while those of APB were greater in the adduction-abduction task. This study reveals that muscle effort among thumb muscles on a touch screen smartphone varies according to the task, and suggests that the use of small touch buttons should be minimised for better thumb performance.

  20. Targeted sequencing identifies a novel SH2D1A pathogenic variant in a Chinese family: Carrier screening and prenatal genetic testing

    Science.gov (United States)

    Chen, Yi-Yao; Li, Shu-Yuan; Zhang, Lan-Lan; Shen, Ying-Hua; Chang, Chun-Xin; Xiang, Yu-Qian; Huang, He-Feng; Xu, Chen-Ming

    2017-01-01

    X-linked lymphoproliferative disease type 1 (XLP1) is a rare primary immunodeficiency characterized by a clinical triad consisting of severe EBV-induced hemophagocytic lymphohistiocytosis, B-cell lymphoma, and dysgammaglobulinemia. Mutations in SH2D1A gene have been revealed as the cause of XLP1. In this study, a pregnant woman with recurrence history of birthing immunodeficiency was screened for pathogenic variant because the proband sample was unavailable. We aimed to clarify the genetic diagnosis and provide prenatal testing for the family. Next-generation sequencing (NGS)-based multigene panel was used in carrier screening of the pregnant woman. Variants of immunodeficiency related genes were analyzed and prioritized. Candidate variant was verified by using Sanger sequencing. The possible influence of the identified variant was evaluated through RNA assay. Amniocentesis, karyotyping, and Sanger sequencing were performed for prenatal testing. We identified a novel de novo frameshift SH2D1A pathogenic variant (c.251_255delTTTCA) in the pregnant carrier. Peripheral blood RNA assay indicated that the mutant transcript could escape nonsense-mediated mRNA decay (NMD) and might encode a C-terminal truncated protein. Information of the variant led to success prenatal diagnosis of the fetus. In conclusion, our study clarified the genetic diagnosis and altered disease prevention for a pregnant carrier of XLP1. PMID:28231257

  1. Regret on choice of colorectal cancer screening modality was associated with poorer screening compliance: a 4-year prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Martin C S Wong

    Full Text Available Very few studies examined the issue of regret on choosing colorectal cancer (CRC screening tests. We evaluated the determinants of regret and tested the hypothesis that regret over screening choices was associated with poorer screening compliance.A bowel cancer screening centre invited all Hong Kong citizens aged 50-70 years who were asymptomatic of CRC to participate in free-of-charge screening programmes. Upon attendance they attended health seminars on CRC and its screening, and were offered an option to choose yearly faecal immunochemical test (FIT for up to four years vs. one direct colonoscopy. They were not allowed to switch the screening option after decision. A self-administered, four-item validated survey was used to assess whether they regretted over their choice (> 2 = regretful from a scale of 0 [no regret]-5 [extreme regret]. A binary logistic regression model evaluated if initial regret over their choice was associated with poorer programme compliance.From 4,341 screening participants who have chosen FIT or colonoscopy, 120 (2.8% regretted over their decision and 1,029 (23.7% were non-compliant with the screening programme. Younger subjects and people who felt pressure when making their decision were associated with regret. People who regretted their decision were 2.189 (95% C.I. 1.361-3.521, p = 0.001 times more likely to be non-compliant with the programme.This study is the first to show that regret over the initial CRC screening choice was associated with later non-compliance. Screening participants who expressed regret over their choice should receive additional reminders to improve their programmatic compliance.

  2. Screening for periodontal disease in research dogs - a methodology study

    DEFF Research Database (Denmark)

    Kortegaard, Hanne E; Eriksen, Thomas; Bælum, Vibeke

    2014-01-01

    BackgroundIt has been shown that the prevalence of both clinical attachment loss (CAL) >1 mm and pocket probing depth (PPD) >4 mm is relatively high even in younger dogs, but also that only a minority of the dogs have such clinical signs of periodontal disease (PD) in more than a few teeth. Hence...... is the central variable in assessing PD extent and severity while PPD is the central variable used in treatment planning which make these two variables obvious in a screening protocol with the dual aim of disease identification and treatment planning. The main purpose of the present study in 98 laboratory Beagle.......2% of all teeth positive for CAL ¿1mm. The results presented here only pertain to the present study population.ConclusionsThis screening protocol is suitable for examination of larger groups of laboratory Beagle dogs for PD and our findings indicate that diseased dogs are identified with a high degree...

  3. Characterization of pellicle inhibition in Gluconacetobacter xylinus 53582 by a small molecule, pellicin, identified by a chemical genetics screen.

    Directory of Open Access Journals (Sweden)

    Janice L Strap

    Full Text Available Pellicin ([2E]-3-phenyl-1-[2,3,4,5-tetrahydro-1,6-benzodioxocin-8-yl]prop-2-en-1-one was identified in a chemical genetics screen of 10,000 small molecules for its ability to completely abolish pellicle production in Gluconacetobacter xylinus. Cells grown in the presence of pellicin grew 1.5 times faster than untreated cells. Interestingly, growth in pellicin also caused G. xylinus cells to elongate. Measurement of cellulose synthesis in vitro showed that cellulose synthase activity was not directly inhibited by pellicin. Rather, when cellulose synthase activity was measured in cells that were pre-treated with the compound, the rate of cellulose synthesis increased eight-fold over that observed for untreated cells. This phenomenon was also apparent in the rapid production of cellulose when cells grown in the presence of pellicin were washed and transferred to media lacking the inhibitor. The rate at which cellulose was produced could not be accounted for by growth of the organism. Pellicin was not detected when intracellular contents were analyzed. Furthermore, it was found that pellicin exerts its effect extracellularly by interfering with the crystallization of pre-cellulosic tactoidal aggregates. This interference of the crystallization process resulted in enhanced production of cellulose II as evidenced by the ratio of acid insoluble to acid soluble product in in vitro assays and confirmed in vivo by scanning electron microscopy and powder X-ray diffraction. The relative crystallinity index, RCI, of pellicle produced by untreated G. xylinus cultures was 70% while pellicin-grown cultures had RCI of 38%. Mercerized pellicle of untreated cells had RCI of 42%, which further confirms the mechanism of action of pellicin as an inhibitor of the cellulose I crystallization process. Pellicin is a useful tool for the study of cellulose biosynthesis in G. xylinus.

  4. Effects of genetic mutations and chemical exposures on Caenorhabditis elegans feeding: evaluation of a novel, high-throughput screening assay.

    Directory of Open Access Journals (Sweden)

    Windy A Boyd

    environmental agents. This assay may also be applicable to large scale genetic or RNAi screens used to identify genes that are necessary for the development or function of the pharynx or other neuromuscular systems.

  5. High acceptance of an early dyslexia screening test involving genetic analyses in Germany

    National Research Council Canada - National Science Library

    Wilcke, Arndt; Müller, Bent; Schaadt, Gesa; Kirsten, Holger; Boltze, Johannes

    2016-01-01

    ... the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics...

  6. Colorectal cancer screening

    Directory of Open Access Journals (Sweden)

    Almeida Frederico Ferreira Novaes de

    2000-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in the world, and mortality has remained the same for the past 50 years, despite advances in diagnosis and treatment. Because significant numbers of patients present with advanced or incurable stages, patients with pre-malignant lesions (adenomatous polyps that occur as result of genetic inheritance or age should be screened, and patients with long-standing inflammatory bowel disease should undergo surveillance. There are different risk groups for CRC, as well as different screening strategies. It remains to be determined which screening protocol is the most cost-effective for each risk catagory. The objective of screening is to reduce morbidity and mortality in a target population. The purpose of this review is to analyze the results of the published CRC screening studies, with regard to the measured reduction of morbidity and mortality, due to CRC in the studied populations, following various screening procedures. The main screening techniques, used in combination or alone, include fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy. Evidence from the published literature on screening methods for specific risk groups is scanty and frequently does not arise from controlled studies. Nevertheless, data from these studies, combined with recent advances in molecular genetics, certainly lead the way to greater efficacy and lower cost of CRC screening.

  7. RNA sequencing of Sleeping Beauty transposon-induced tumors detects transposon-RNA fusions in forward genetic cancer screens

    Science.gov (United States)

    Temiz, Nuri A.; Moriarity, Branden S.; Wolf, Natalie K.; Riordan, Jesse D.; Dupuy, Adam J.; Largaespada, David A.; Sarver, Aaron L.

    2016-01-01

    Forward genetic screens using Sleeping Beauty (SB)-mobilized T2/Onc transposons have been used to identify common insertion sites (CISs) associated with tumor formation. Recurrent sites of transposon insertion are commonly identified using ligation-mediated PCR (LM-PCR). Here, we use RNA sequencing (RNA-seq) data to directly identify transcriptional events mediated by T2/Onc. Surprisingly, the majority (∼80%) of LM-PCR identified junction fragments do not lead to observable changes in RNA transcripts. However, in CIS regions, direct transcriptional effects of transposon insertions are observed. We developed an automated method to systematically identify T2/Onc-genome RNA fusion sequences in RNA-seq data. RNA fusion-based CISs were identified corresponding to both DNA-based CISs (Cdkn2a, Mycl1, Nf2, Pten, Sema6d, and Rere) and additional regions strongly associated with cancer that were not observed by LM-PCR (Myc, Akt1, Pth, Csf1r, Fgfr2, Wisp1, Map3k5, and Map4k3). In addition to calculating recurrent CISs, we also present complementary methods to identify potential driver events via determination of strongly supported fusions and fusions with large transcript level changes in the absence of multitumor recurrence. These methods independently identify CIS regions and also point to cancer-associated genes like Braf. We anticipate RNA-seq analyses of tumors from forward genetic screens will become an efficient tool to identify causal events. PMID:26553456

  8. RNA sequencing of Sleeping Beauty transposon-induced tumors detects transposon-RNA fusions in forward genetic cancer screens.

    Science.gov (United States)

    Temiz, Nuri A; Moriarity, Branden S; Wolf, Natalie K; Riordan, Jesse D; Dupuy, Adam J; Largaespada, David A; Sarver, Aaron L

    2016-01-01

    Forward genetic screens using Sleeping Beauty (SB)-mobilized T2/Onc transposons have been used to identify common insertion sites (CISs) associated with tumor formation. Recurrent sites of transposon insertion are commonly identified using ligation-mediated PCR (LM-PCR). Here, we use RNA sequencing (RNA-seq) data to directly identify transcriptional events mediated by T2/Onc. Surprisingly, the majority (∼80%) of LM-PCR identified junction fragments do not lead to observable changes in RNA transcripts. However, in CIS regions, direct transcriptional effects of transposon insertions are observed. We developed an automated method to systematically identify T2/Onc-genome RNA fusion sequences in RNA-seq data. RNA fusion-based CISs were identified corresponding to both DNA-based CISs (Cdkn2a, Mycl1, Nf2, Pten, Sema6d, and Rere) and additional regions strongly associated with cancer that were not observed by LM-PCR (Myc, Akt1, Pth, Csf1r, Fgfr2, Wisp1, Map3k5, and Map4k3). In addition to calculating recurrent CISs, we also present complementary methods to identify potential driver events via determination of strongly supported fusions and fusions with large transcript level changes in the absence of multitumor recurrence. These methods independently identify CIS regions and also point to cancer-associated genes like Braf. We anticipate RNA-seq analyses of tumors from forward genetic screens will become an efficient tool to identify causal events.

  9. A microarray-based genetic screen for yeast chronological aging factors.

    Directory of Open Access Journals (Sweden)

    Mirela Matecic

    2010-04-01

    Full Text Available Model organisms have played an important role in the elucidation of multiple genes and cellular processes that regulate aging. In this study we utilized the budding yeast, Saccharomyces cerevisiae, in a large-scale screen for genes that function in the regulation of chronological lifespan, which is defined by the number of days that non-dividing cells remain viable. A pooled collection of viable haploid gene deletion mutants, each tagged with unique identifying DNA "bar-code" sequences was chronologically aged in liquid culture. Viable mutants in the aging population were selected at several time points and then detected using a microarray DNA hybridization technique that quantifies abundance of the barcode tags. Multiple short- and long-lived mutants were identified using this approach. Among the confirmed short-lived mutants were those defective for autophagy, indicating a key requirement for the recycling of cellular organelles in longevity. Defects in autophagy also prevented lifespan extension induced by limitation of amino acids in the growth media. Among the confirmed long-lived mutants were those defective in the highly conserved de novo purine biosynthesis pathway (the ADE genes, which ultimately produces IMP and AMP. Blocking this pathway extended lifespan to the same degree as calorie (glucose restriction. A recently discovered cell-extrinsic mechanism of chronological aging involving acetic acid secretion and toxicity was suppressed in a long-lived ade4Delta mutant and exacerbated by a short-lived atg16Delta autophagy mutant. The identification of multiple novel effectors of yeast chronological lifespan will greatly aid in the elucidation of mechanisms that cells and organisms utilize in slowing down the aging process.

  10. Screening a core collection of citrus genetic resources for resistance to Fusarium solani (Mart) Sacc

    Science.gov (United States)

    A causal agent for Dry root rot (DRR) of citrus has not been definitively identified, but the organism most consistently associated with DRR is Fusarium solani (Mart.) Sacc. To efficiently screen a citrus germplasm collection for resistance to F. solani, a core subset of the collection was evaluated...

  11. Effects and Costs of Breast Cancer screening in women with a familial or genetic predisposition

    NARCIS (Netherlands)

    A.J. Rijnsburger (Rian)

    2005-01-01

    textabstract"Women with a BRCA1 or BRCA2 mutation, who have a considerable increased risk of developing breast cancer, now face the choice of intensive screening, prophylactic surgery or chemoprevention. The efficacy of the various medical options and the durability of its effects are of major

  12. Differences between first and subsequent rounds of the MRISC breast cancer screening program for women with a familial or genetic predisposition

    NARCIS (Netherlands)

    Kriege, M; Brekelmans, CTM; Boetes, C; Muller, SH; Zonderland, HM; Obdeijn, IM; Manoliu, RA; Kok, T; Rutgers, EJT; de Koning, HJ; Klijn, JGM

    2006-01-01

    BACKGROUND. within the Dutch MRI Screening (MRISC) study, a Dutch multicenter screening study for hereditary breast cancer, the authors investigated whether previously reported increased diagnostic accuracy of magnetic resonance imaging (MRI) compared with mammography would be maintained during subs

  13. Development of a qualitative, multiplex real-time PCR kit for screening of genetically modified organisms (GMOs).

    Science.gov (United States)

    Dörries, Hans-Henno; Remus, Ivonne; Grönewald, Astrid; Grönewald, Cordt; Berghof-Jäger, Kornelia

    2010-03-01

    The number of commercially available genetically modified organisms (GMOs) and therefore the diversity of possible target sequences for molecular detection techniques are constantly increasing. As a result, GMO laboratories and the food production industry currently are forced to apply many different methods to reliably test raw material and complex processed food products. Screening methods have become more and more relevant to minimize the analytical effort and to make a preselection for further analysis (e.g., specific identification or quantification of the GMO). A multiplex real-time PCR kit was developed to detect the 35S promoter of the cauliflower mosaic virus, the terminator of the nopaline synthase gene of Agrobacterium tumefaciens, the 35S promoter from the figwort mosaic virus, and the bar gene of the soil bacterium Streptomyces hygroscopicus as the most widely used sequences in GMOs. The kit contains a second assay for the detection of plant-derived DNA to control the quality of the often processed and refined sample material. Additionally, the plant-specific assay comprises a homologous internal amplification control for inhibition control. The determined limits of detection for the five assays were 10 target copies/reaction. No amplification products were observed with DNAs of 26 bacterial species, 25 yeasts, 13 molds, and 41 not genetically modified plants. The specificity of the assays was further demonstrated to be 100% by the specific amplification of DNA derived from reference material from 22 genetically modified crops. The applicability of the kit in routine laboratory use was verified by testing of 50 spiked and unspiked food products. The herein described kit represents a simple and sensitive GMO screening method for the reliable detection of multiple GMO-specific target sequences in a multiplex real-time PCR reaction.

  14. DRD2 genetic variation in relation to smoking and obesity in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

    Science.gov (United States)

    Morton, Lindsay M; Wang, Sophia S; Bergen, Andrew W; Chatterjee, Nilanjan; Kvale, Paul; Welch, Robert; Yeager, Meredith; Hayes, Richard B; Chanock, Stephen J; Caporaso, Neil E

    2006-12-01

    Cigarette smoking is the leading cause of morbidity and mortality worldwide. We investigated the association between smoking behavior and genetic variations in the D2 dopamine receptor (DRD2), which mediates nicotine dependence. To assess the specificity of genetic effects, we also investigated other reward-motivated characteristics (obesity, alcohol consumption). Four single nucleotide polymorphisms in DRD2 were genotyped in 2374 participants selected randomly from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. Single nucleotide polymorphism and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals derived from conditional logistic regression models, adjusted for race/ethnicity. DRD2 polymorphisms were associated with the risk of remaining a current smoker and obesity. Current smokers were more likely than former smokers to possess the variant TaqIA allele (rsmusical sharp1800497) in a dose-dependent model (ORCT=1.2, ORTT=1.5, P for linear trend=0.007). The DRD2 haplotype T-C-T-A [TaqIA(C/T)-957(T/C)-IVS6-83(G/T)- -50977(A/G)] was more common among current than former smokers (OR=1.3, P=0.006), particularly among heavy smokers (21+ cigarettes per day; OR=1.6, P=0.006), and was more common among obese than normal weight individuals (OR=1.4, P=0.02). Genetic variation in DRD2 is a modifier of the reward-motivated characteristics, smoking and obesity. As fewer than 15% of smokers who attempt to quit are able to maintain abstinence for greater than 3 months, our results support that DRD2 is an appropriate molecular target for smoking cessation treatments. Our results further support evaluation of DRD2 antagonists for obesity therapies.

  15. Molecular genetic studies in flax (Linum usitatissimum L.)

    NARCIS (Netherlands)

    Vromans, J.

    2006-01-01

    In this thesis five molecular genetic studies on flax ( Linum usitatissimum L.) are described, of which two chapters aim to characterize the genetic structure and the amount of genetic diversity in the primary and secondary gene pool of the crop species. Three chapters describe the development of

  16. The potential harms of primary human papillomavirus screening in over-screened women: a microsimulation study

    NARCIS (Netherlands)

    S.K. Naber (Steffie); I.M.C.M. de Kok (Inge); S.M. Matthijsse (Suzette); M. van Ballegooijen (Marjolein)

    2016-01-01

    textabstractBackground: It is well acknowledged that HPV testing should not be performed at young age and at short intervals. Cytological screening practices have shown that over-screening, i.e., from a younger age and at shorter intervals than recommended, is hard to avoid. We quantified the conseq

  17. Genome-wide association study of coronary and aortic calcification in lung cancer screening CT

    Science.gov (United States)

    de Vos, Bob D.; van Setten, Jessica; de Jong, Pim A.; Mali, Willem P.; Oudkerk, Matthijs; Viergever, Max A.; Išgum, Ivana

    2016-03-01

    Arterial calcification has been related to cardiovascular disease (CVD) and osteoporosis. However, little is known about the role of genetics and exact pathways leading to arterial calcification and its relation to bone density changes indicating osteoporosis. In this study, we conducted a genome-wide association study of arterial calcification burden, followed by a look-up of known single nucleotide polymorphisms (SNPs) for coronary artery disease (CAD) and myocardial infarction (MI), and bone mineral density (BMD) to test for a shared genetic basis between the traits. The study included a subcohort of the Dutch-Belgian lung cancer screening trial comprised of 2,561 participants. Participants underwent baseline CT screening in one of two hospitals participating in the trial. Low-dose chest CT images were acquired without contrast enhancement and without ECG-synchronization. In these images coronary and aortic calcifications were identified automatically. Subsequently, the detected calcifications were quantified using coronary artery calcium Agatston and volume scores. Genotype data was available for these participants. A genome-wide association study was conducted on 10,220,814 SNPs using a linear regression model. To reduce multiple testing burden, known CAD/MI and BMD SNPs were specifically tested (45 SNPs from the CARDIoGRAMplusC4D consortium and 60 SNPS from the GEFOS consortium). No novel significant SNPs were found. Significant enrichment for CAD/MI SNPs was observed in testing Agatston and coronary artery calcium volume scores. Moreover, a significant enrichment of BMD SNPs was shown in aortic calcium volume scores. This may indicate genetic relation of BMD SNPs and arterial calcification burden.

  18. Polar body biopsy: a viable alternative to preimplantation genetic diagnosis and screening.

    Science.gov (United States)

    Montag, M; van der Ven, K; Rösing, B; van der Ven, H

    2009-01-01

    Polar body diagnosis (PBD) is a diagnostic method for the indirect genetic analysis of oocytes. Polar bodies are by-products of the meiotic cell cycle, which have no influence on further embryo development. The biopsy of polar bodies can be accomplished either by zona drilling or laser drilling within a very short time period. However, the paternal contribution to the genetic constitution of the developing embryo cannot be diagnosed by PBD. The major application of PBD is the detection of maternally derived chromosomal aneuploidies and translocations in oocytes. For these indications, PBD may offer a viable alternative to blastomere biopsy as the embryo's integrity remains unaffected, in contrast to preimplantation genetic diagnosis (PGD) by blastomere biopsy. The rapid pace of developments in the field of molecular diagnostics will also influence the advantages of PBD, and probably allow more general diagnostic applications in the future.

  19. Metabolic and Genetic Screening of Electromagnetic Hypersensitive Subjects as a Feasible Tool for Diagnostics and Intervention

    Directory of Open Access Journals (Sweden)

    Chiara De Luca

    2014-01-01

    Full Text Available Growing numbers of “electromagnetic hypersensitive” (EHS people worldwide self-report severely disabling, multiorgan, non-specific symptoms when exposed to low-dose electromagnetic radiations, often associated with symptoms of multiple chemical sensitivity (MCS and/or other environmental “sensitivity-related illnesses” (SRI. This cluster of chronic inflammatory disorders still lacks validated pathogenetic mechanism, diagnostic biomarkers, and management guidelines. We hypothesized that SRI, not being merely psychogenic, may share organic determinants of impaired detoxification of common physic-chemical stressors. Based on our previous MCS studies, we tested a panel of 12 metabolic blood redox-related parameters and of selected drug-metabolizing-enzyme gene polymorphisms, on 153 EHS, 147 MCS, and 132 control Italians, confirming MCS altered (P<0.05–0.0001 glutathione-(GSH, GSH-peroxidase/S-transferase, and catalase erythrocyte activities. We first described comparable—though milder—metabolic pro-oxidant/proinflammatory alterations in EHS with distinctively increased plasma coenzyme-Q10 oxidation ratio. Severe depletion of erythrocyte membrane polyunsaturated fatty acids with increased ω6/ω3 ratio was confirmed in MCS, but not in EHS. We also identified significantly (P=0.003 altered distribution-versus-control of the CYP2C19*1/*2 SNP variants in EHS, and a 9.7-fold increased risk (OR: 95% C.I.=1.3–74.5 of developing EHS for the haplotype (nullGSTT1 + (nullGSTM1 variants. Altogether, results on MCS and EHS strengthen our proposal to adopt this blood metabolic/genetic biomarkers’ panel as suitable diagnostic tool for SRI.

  20. 'Smoking genes': a genetic association study.

    Directory of Open Access Journals (Sweden)

    Zoraida Verde

    Full Text Available Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A [rs1801272], CYP2A6*9 (-48T>G [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T [rs8192789], CYP2A13*3 (7520C>G, CYP2A13*4 (579G>A, CYP2A13*7 (578C>T [rs72552266], CYP2B6*4 (785A>G, CYP2B6*9 (516G>T, CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126 and ethnically matched never smokers (controls, N = 80. The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both PA (Taq1A polymorphisms was 3.60 (95%CI: 1.75, 7.44 and 2.63 (95%CI: 1.41, 4.89 respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65. We found a significant genotype effect (all P≤0.017 for the following smoking-related phenotypes: (i cigarettes smoked per day and CYP2A13*3; (ii pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A; (iii nicotine dependence (assessed with the Fagestrom test and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5, serotoninergic (HTR2A, opioid (OPRM1 or cannabinoid receptors (CNR1.

  1. Hamartomatous polyps - a clinical and molecular genetic study

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie

    2016-01-01

    are typically removed concurrently with endoscopy when located in the colon, rectum, or stomach, whereas polyps in the small bowel are removed during push-enteroscopy, device-assisted enteroscopy, or by surgery. HPs can be classified as juvenile polyps or Peutz-Jeghers polyps based on their histopathological......% fulfilled to diagnostic criteria of JPS. The majority of patients had a single juvenile polyp. Paper II: In this paper we conducted a review of the HPS based on the current literature. Paper III: We investigated the hypothesis that patients with one or few HPs may have a HPS based on genetic screening. We...... reported previously none could be classified as definitely pathogenic or likely pathogenic according to our variant classification scheme and thus we concluded that genetic screening of patients with one or few JPs are not indicated. Paper IV: In Paper IV we investigated one of the ethical aspects of next...

  2. Integrating empirical data and population genetic simulations to study the genetic architecture of type 2 diabetes

    OpenAIRE

    Agarwala, Vineeta

    2013-01-01

    Most common diseases have substantial heritable components but are characterized by complex inheritance patterns implicating numerous genetic and environmental factors. A longstanding goal of human genetics research is to delineate the genetic architecture of these traits - the number, frequencies, and effect sizes of disease-causing alleles - to inform mapping studies, elucidate mechanisms of disease, and guide development of targeted clinical therapies and diagnostics. Although vast empir...

  3. High acceptance of an early dyslexia screening test involving genetic analyses in Germany.

    Science.gov (United States)

    Wilcke, Arndt; Müller, Bent; Schaadt, Gesa; Kirsten, Holger; Boltze, Johannes

    2016-02-01

    Dyslexia is a developmental disorder characterized by severe problems in the acquisition of reading and writing skills. It has a strong neurobiological basis. Genetic influence is estimated at 50-70%. One of the central problems with dyslexia is its late diagnosis, normally not before the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics. Our aim was to determine the acceptance of such a future test among parents. We conducted a representative survey in Germany with 1000 parents of children aged 3-7 years, with and without experience of dyslexia. 88.7% of the parents supported the introduction of an early test for dyslexia based on EEG and genetics; 82.8% would have their own children tested, and 57.9% were willing to pay for the test if health insurance did not cover the costs. Test acceptance was significantly higher if parents had prior experience with dyslexia. The perceived benefits of such a test were early recognition and remediation and, preventing deficits. Concerns regarded the precision of the test, its potentially stigmatizing effect and its costs. The high overall support for the test leads to the conclusion that parents would accept a test for dyslexia based on EEG and genetics.

  4. High acceptance of an early dyslexia screening test involving genetic analyses in Germany

    Science.gov (United States)

    Wilcke, Arndt; Müller, Bent; Schaadt, Gesa; Kirsten, Holger; Boltze, Johannes; Angela, h c; Friederici, D; Emmrich, Frank; Brauer, Jens; Wilcke, Arndt; Neef, Nicole; Boltze, Johannes; Skeide, Michael; Kirsten, Holger; Schaadt, Gesa; Müller, Bent; Kraft, Indra; Czepezauer, Ivonne; Bobovnikov, Nadin

    2016-01-01

    Dyslexia is a developmental disorder characterized by severe problems in the acquisition of reading and writing skills. It has a strong neurobiological basis. Genetic influence is estimated at 50–70%. One of the central problems with dyslexia is its late diagnosis, normally not before the end of the 2nd grade, resulting in the loss of several years for early therapy. Currently, research is focusing on the development of early tests for dyslexia, which may be based on EEG and genetics. Our aim was to determine the acceptance of such a future test among parents. We conducted a representative survey in Germany with 1000 parents of children aged 3–7 years, with and without experience of dyslexia. 88.7% of the parents supported the introduction of an early test for dyslexia based on EEG and genetics; 82.8% would have their own children tested, and 57.9% were willing to pay for the test if health insurance did not cover the costs. Test acceptance was significantly higher if parents had prior experience with dyslexia. The perceived benefits of such a test were early recognition and remediation and, preventing deficits. Concerns regarded the precision of the test, its potentially stigmatizing effect and its costs. The high overall support for the test leads to the conclusion that parents would accept a test for dyslexia based on EEG and genetics. PMID:26036858

  5. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing

    NARCIS (Netherlands)

    Domingo, E; Laiho, P; Ollikainen, M; Pinto, M; Wang, L; French, AJ; Westra, J.; Frebourg, T; Espin, E; Armengol, M; Hamelin, R; Yamamoto, H; Hofstra, RMW; Seruca, R; Lindblom, A; Peltomaki, P; Thibodeau, SN; Aaltonen, LA; Schwartz, S

    2004-01-01

    Background: According to the international criteria for hereditary non-polyposis colorectal cancer (HNPCC) diagnostics, cancer patients with a family history or early onset of colorectal tumours showing high microsatellite instability (MSI-H) should receive genetic counselling and be offered testing

  6. The promises of genomic screening: building a governance infrastructure. Special issue: genetics and democracy.

    Science.gov (United States)

    Cornel, Martina C; van El, Carla G; Dondorp, Wybo J

    2012-04-01

    New screening possibilities become available at a high rate, both useful and unsound possibilities. All screening programmes do harm, and only few have more advantages than disadvantages at reasonable cost. Horizon scanning is needed to identify those few possibilities with more pros than cons. Attunement is needed between actors involved: scientists developing new high-throughput screening techniques and treatment, health care workers, patients and consumers and governmental agencies. The product of a process of attunement may be a quality mark as a norm for professional conduct, rather than legal measures, as the field is moving fast. As actors may have varying perspectives, a governance structure is needed to develop an agenda that is agreed upon by all or most actors involved. A standing committee might oversee the evaluation of benefits and disadvantages in an integrated approach, taking evidence, economics and ethics into account. A proactive role of governmental agencies is needed to facilitate agenda setting and attunement. Policy making has to be transparent and open to stakeholder engagement.

  7. Zagreb Amblyopia Preschool Screening Study: near and distance visual acuity testing increase the diagnostic accuracy of screening for amblyopia

    OpenAIRE

    Bušić, Mladen; Bjeloš, Mirjana; Petrovečki, Mladen; Kuzmanović Elabjer, Biljana; Bosnar, Damir; Ramić, Senad; Miletić, Daliborka; Andrijašević, Lidija; Kondža Krstonijević, Edita; Jakovljević, Vid; Bišćan Tvrdi, Ana; Predović, Jurica; Kokot, Antonio; Bišćan, Filip; Kovačević Ljubić, Mirna

    2016-01-01

    Aim To present and evaluate a new screening protocol for amblyopia in preschool children. Methods Zagreb Amblyopia Preschool Screening (ZAPS) study protocol performed screening for amblyopia by near and distance visual acuity (VA) testing of 15 648 children aged 48-54 months attending kindergartens in the City of Zagreb County between September 2011 and June 2014 using Lea Symbols in lines test. If VA in either eye was >0.1 logMAR, the child was re-tested, if failed at re-test, the child was ...

  8. Automated screening versus manual screening: a comparison of the ThinPrep imaging system and manual screening in a time study.

    Science.gov (United States)

    Schledermann, Doris; Hyldebrandt, Tina; Ejersbo, Dorthe; Hoelund, Berit

    2007-06-01

    The ThinPrep Imaging System (TIS) is an automated system that assists cytotechnologists in the primary screening of ThinPrep liquid based cervical samples. Between June 1, 2004, and April 1, 2005, four experienced cytotechnologists participated in the study in which the duration of the screening procedure was timed for each of the 11,354 slides included. In every slide 22 fields of view were reviewed, and the samples that contained potentially abnormal cells were fully screened. The screening time was reduced by 42% (mean) (p < 0.001). By manual rescreening of the negative TIS samples, abnormal cells were found in 10 samples (false negative rate 0.14%). In every case the abnormal cells had been identified by the scanner, but misinterpreted by the cytotechnologist. These findings stressed the importance of carefulness in the interpretation of the marked fields and beyond that helped the cytotechnologists and pathologists to have more confidence in the automated system.

  9. Analysis of mutants from a genetic screening reveals the control of intestine and liver development by many common genes in zebrafish.

    Science.gov (United States)

    Jiang, Faming; Chen, Jiehui; Ma, Xirui; Huang, Chao; Zhu, Shicheng; Wang, Fei; Li, Li; Luo, Lingfei; Ruan, Hua; Huang, Honghui

    2015-05-01

    Both the intestine and liver develop from the endoderm, yet little is known how these two digestive organs share and differ in their developmental programs, at the molecular level. A classical forward genetic screen, with no gene bias, is an effective way to address this question by examining the defects of the intestine and liver in obtained mutants to assess mutated genes responsible for the development of either organ or both. We report here such a screen in zebrafish. ENU was used as the mutagen because of its high mutagenic efficiency and no site preference. Embryos were collected at 3.5 dpf for RNA whole mount in situ hybridization with a cocktail probe of the intestine marker ifabp and the liver marker lfabp to check phenotypes and determine their parental heterozygosis. A total of 52 F2 putative mutants were identified, and those with general developmental defects were aborted. To rule out non-inheritable phenotypes caused by high mutation background, F2 putative mutants were outcrossed with wild type fish and a re-screen in F3 generations was performed. After complementation tests between F3 mutants with similar phenotypes originating from the same F2 families, a total of 37 F3 mutant lines originated from 22 F2 families were identified after screening 78 mutagenized genomes. Classification of mutant phenotypes indicated that 31 out of the 37 mutants showed defects in both the intestine and liver. In addition, four "intestine specific mutants" and two "liver specific mutants" showed selectively more severe phenotype in the intestine and liver respectively. These results suggested that the intestine and liver share a substantial number of essential genes during both organs development in zebrafish. Further studies of the mutants are likely to shed more insights into the molecular basis of the digestive system development in the zebrafish and vertebrate.

  10. Zagreb Amblyopia Preschool Screening Study: near and distance visual acuity testing increase the diagnostic accuracy of screening for amblyopia.

    Science.gov (United States)

    Bušić, Mladen; Bjeloš, Mirjana; Petrovečki, Mladen; Kuzmanović Elabjer, Biljana; Bosnar, Damir; Ramić, Senad; Miletić, Daliborka; Andrijašević, Lidija; Kondža Krstonijević, Edita; Jakovljević, Vid; Bišćan Tvrdi, Ana; Predović, Jurica; Kokot, Antonio; Bišćan, Filip; Kovačević Ljubić, Mirna; Motušić Aras, Ranka

    2016-02-01

    To present and evaluate a new screening protocol for amblyopia in preschool children. Zagreb Amblyopia Preschool Screening (ZAPS) study protocol performed screening for amblyopia by near and distance visual acuity (VA) testing of 15 648 children aged 48-54 months attending kindergartens in the City of Zagreb County between September 2011 and June 2014 using Lea Symbols in lines test. If VA in either eye was >0.1 logMAR, the child was re-tested, if failed at re-test, the child was referred to comprehensive eye examination at the Eye Clinic. 78.04% of children passed the screening test. Estimated prevalence of amblyopia was 8.08%. Testability, sensitivity, and specificity of the ZAPS study protocol were 99.19%, 100.00%, and 96.68% respectively. The ZAPS study used the most discriminative VA test with optotypes in line as they do not underestimate amblyopia. The estimated prevalence of amblyopia was considerably higher than reported elsewhere. To the best of our knowledge, the ZAPS study protocol reached the highest sensitivity and specificity when evaluating diagnostic accuracy of VA tests for screening. The pass level defined at ≤0.1 logMAR for 4-year-old children, using Lea Symbols in lines missed no amblyopia cases, advocating that both near and distance VA testing should be performed when screening for amblyopia.

  11. Study on genetic coadaptability of wild quail populations in China

    Institute of Scientific and Technical Information of China (English)

    CHANG; Guobin; CHANG; Hong; LIU; Xiangping; YANG; Zhangping; CHEN; Guohong; ZHAO; Wenming; JI; Dejun; XUE; Yan; HUANG; Feng; HASSAN; Hussein

    2006-01-01

    Genetic coadaptability of wild Japanese quail, wild Common quail and Domestic quail populations in China was studied using 7 microsatellite DNA markers and Monte Carlo method to test genetic disequilibrium. The molecular effects of genetic coadaptability were analyzed through a new statistical model of neutral site. The results showed that genetic coadaptability dominated the genetic disequilibrium of the three quail populations, and totally 16.67%, 9.66% and 10.05% of non-allelic combinations were in the genetic disequilibrium in wild Japanese quail, wild Common quail and Domestic quail populations, respectively. Genetic coadaptability existed at almost all the tested sites. In the molecular point of view, genetic coadaptability plays an important role of keeping lots of polymorphisms in natural populations. Therefore, it is another key factor to the genetic disequilibrium in the population except for linkage. The results enrich the conceptions and connotations of genetic disequilibrium, and help us know more about genetic coadaptability and its effects, and lay a foundation of evaluation and protection of wild quail genetic resources in China.

  12. Multicentre trial of preimplantation genetic screening reported in the New England Journal of Medicine: an in-depth look at the findings.

    Science.gov (United States)

    Cohen, Jacques; Grifo, James A

    2007-10-01

    A randomized clinical trial of 406 patients with advanced maternal age by Mastenbroek and co-workers recently published in the New England Journal of Medicine showed a significant decrease in pregnancy outcome after preimplantation genetic screening (PGS). It is our opinion that this study suffers from a number of insurmountable inaccuracies and that these are either a direct consequence of the inexperience of the team or of a general disregard of vital guidelines reported in the literature. Most importantly, the authors show that in their hands embryo biopsy may affect as many as half the embryos. The error rate was not presented, shedding doubt on the authors' abilities to reliably diagnose the biopsied cells. An evaluation of the study indicates that poor biopsy technique, sub standard fixation and FISH methods, poor IVF outcomes and inappropriate patient selection are the cause of the discouraging results obtained by these authors rather than problems inherent to PGS.

  13. Acceptability, benefit and costs of early screening for hearing disability: a study of potential screening tests and models.

    Science.gov (United States)

    Davis, A; Smith, P; Ferguson, M; Stephens, D; Gianopoulos, I

    2007-10-01

    To show that hearing loss has such a high prevalence in the older population to justify screening, if effective and acceptable methods are available; and that population take-up and benefit can make a measurable outcome difference in quality of life. A population study of people aged 55-74 years was undertaken. A clinical effectiveness study of differently organised screening programmes was carried out using a controlled trial to identify those who might benefit from intervention (and the extent of the benefit). A retrospective case-control study examined the very long-term (more than 10 years) compliance of patients in using their hearing aids after early identification and determined the extent to which early-identified hearing-impaired people have better outcomes than equivalent people identified later. An examination of the costs and cost-effectiveness of different potential screening programmes was also undertaken. A population study was designed in the UK, with specific stages being conducted in more depth on a sample of people from Nottingham and Southampton. The clinical effectiveness study was conducted in general practices in Nottingham and Bath using a systematic or opportunistic screen. The retrospective case-control study compared a group of early-identified hearing aid users, with control matched for age, gender and occupation, in Cardiff, Glasgow and Manchester. In Great Britain responses were obtained for 34,362 individuals from the postal questionnaire as part of a population study, 506 were interviewed, 351 were assessed for benefit from amplification and 87 were fitted with a hearing aid. The clinical effectiveness study received 1461 replies from the first-stage questionnaire screen, with 306 people assessed in the clinic, of whom 156 were fitted with hearing aids. The retrospective case-control study traced 116 previously fitted hearing aid users, who had been identified by a screen, and then conducted a case-control using 50 of these for whom

  14. Attitudes of young adults to prenatal screening and genetic correction for human attributes and psychiatric conditions.

    Science.gov (United States)

    Milner, K K; Collins, E E; Connors, G R; Petty, E M

    1998-03-05

    With recent advances in DNA technology, questions have arisen as to how this technology should be appropriately used. In this article, results obtained from a survey designed to elicit attitudes of college students to prenatal testing and gene therapy for human attributes and psychiatric conditions are reported. The eleven hypothetical disease phenotypes included schizophrenia, alcoholism, tendency toward violent behavior, attention deficit/hyperactivity disorder, depression requiring medical treatment, obesity, involvement in "dangerous" sports activities, homosexuality, borderline normal IQ (80-100), proportional short stature, and inability to detect perfect pitch. Most students supported prenatal genetic testing for psychiatric disorders and behavior that might result in harm to others (i.e., tendency towards violent behavior) and found prenatal genetic testing for human attributes less desirable. However, the lack of unilateral agreement or disagreement toward any one condition or attribute suggests the potential difficulties ahead in the quest for guidelines for the application of new technologies available to manipulate the human genome.

  15. Root Glucosinolate Profiles for Screening of Radish (Raphanus sativus L.) Genetic Resources.

    Science.gov (United States)

    Yi, Gibum; Lim, Sooyeon; Chae, Won Byoung; Park, Jeong Eun; Park, Hye Rang; Lee, Eun Jin; Huh, Jin Hoe

    2016-01-13

    Radish (Raphanus sativus L.), a root vegetable, is rich in glucosinolates (GLs), which are beneficial secondary metabolites for human health. To investigate the genetic variations in GL content in radish roots and the relationship with other root phenotypes, we analyzed 71 accessions from 23 different countries for GLs using HPLC. The most abundant GL in radish roots was glucoraphasatin, a GL with four-carbon aliphatic side chain. The content of glucoraphasatin represented at least 84.5% of the total GL content. Indolyl GL represented only 3.1% of the total GL at its maximum. The principal component analysis of GL profiles with various root phenotypes showed that four different genotypes exist in the 71 accessions. Although no strong correlation with GL content and root phenotype was observed, the varied GL content levels demonstrate the genetic diversity of GL content, and the amount that GLs could be potentially improved by breeding in radishes.

  16. Genetically designed biosensing systems for high-throughput screening of pharmaceuticals, clinical diagnostics, and environmental monitoring

    Science.gov (United States)

    Wenner, Brett R.; Douglass, Phillip; Shrestha, Suresh; Sharma, Bethel V.; Lai, Siyi; Madou, Marc J.; Daunert, Sylvia

    2001-05-01

    The genetically-modified binding proteins calmodulin, the phosphate binding protein, the sulfate binding protein, and the galactose/glucose binding protein have been successfully employed as biosensing elements for the detection of phenothiazines, phosphate, sulfate, and glucose, respectively. Mutant proteins containing unique cysteine residues were utilized in the site-specific labeling of environment-sensitive fluorescent probes. Changes in the environment of the probes upon ligand-induced conformational changes of the proteins result in changes in fluorescence intensity.

  17. Screening frequency and histologic type influence the efficacy of cervical cancer screening: A nationwide cohort study.

    Science.gov (United States)

    Chiang, Ying-Cheng; Chen, Yun-Yuan; Hsieh, Shu-Feng; Chiang, Chun-Ju; You, San-Lin; Cheng, Wen-Fang; Lai, Mei-Shu; Chen, Chi-An

    2017-08-01

    To evaluate the influence of age, screening interval, and histologic type on the effect of Pap smears in cervical cancer screening. Data were retrieved from the Taiwan National Cancer Registry and Cervical Cancer Screening Registration System for the period from 2002 to 2010. Age, Pap smear interval, FIGO stage, and histology were further analyzed. A total of 12,294 women with cervical cancer were enrolled, including 10,040 with squamous cell carcinoma (SCC), 1720 with adenocarcinoma (ADC), 401 with adenosquamous carcinoma (ASC), and 133 with small cell neuroendocrine carcinoma (SMC). Women who had a Pap smear at an interval of <3 years had a significantly higher proportion of stage I disease than women who had never undergone cervical cancer screening (p < 0.0001). Greater than 40% of women with SCCs in each age group had never had a Pap smear; however, women with ADCs were predominantly in the younger age and greater than 40% of women with ADCs had Pap smear at intervals < 3 years. Pap smear is more effective in screening for cervical SCCs compared to cervical ADCs. Improving adherence to screening recommendations is important for the prevention of cervical SCC, especially in elderly women. Copyright © 2017. Published by Elsevier B.V.

  18. A high throughput genetic screen identifies new early meiotic recombination functions in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Arnaud De Muyt

    2009-09-01

    Full Text Available Meiotic recombination is initiated by the formation of numerous DNA double-strand breaks (DSBs catalysed by the widely conserved Spo11 protein. In Saccharomyces cerevisiae, Spo11 requires nine other proteins for meiotic DSB formation; however, unlike Spo11, few of these are conserved across kingdoms. In order to investigate this recombination step in higher eukaryotes, we took advantage of a high-throughput meiotic mutant screen carried out in the model plant Arabidopsis thaliana. A collection of 55,000 mutant lines was screened, and spo11-like mutations, characterised by a drastic decrease in chiasma formation at metaphase I associated with an absence of synapsis at prophase, were selected. This screen led to the identification of two populations of mutants classified according to their recombination defects: mutants that repair meiotic DSBs using the sister chromatid such as Atdmc1 or mutants that are unable to make DSBs like Atspo11-1. We found that in Arabidopsis thaliana at least four proteins are necessary for driving meiotic DSB repair via the homologous chromosomes. These include the previously characterised DMC1 and the Hop1-related ASY1 proteins, but also the meiotic specific cyclin SDS as well as the Hop2 Arabidopsis homologue AHP2. Analysing the mutants defective in DSB formation, we identified the previously characterised AtSPO11-1, AtSPO11-2, and AtPRD1 as well as two new genes, AtPRD2 and AtPRD3. Our data thus increase the number of proteins necessary for DSB formation in Arabidopsis thaliana to five. Unlike SPO11 and (to a minor extent PRD1, these two new proteins are poorly conserved among species, suggesting that the DSB formation mechanism, but not its regulation, is conserved among eukaryotes.

  19. Genetic network models: a comparative study

    Science.gov (United States)

    van Someren, Eugene P.; Wessels, Lodewyk F. A.; Reinders, Marcel J. T.

    2001-06-01

    Currently, the need arises for tools capable of unraveling the functionality of genes based on the analysis of microarray measurements. Modeling genetic interactions by means of genetic network models provides a methodology to infer functional relationships between genes. Although a wide variety of different models have been introduced so far, it remains, in general, unclear what the strengths and weaknesses of each of these approaches are and where these models overlap and differ. This paper compares different genetic modeling approaches that attempt to extract the gene regulation matrix from expression data. A taxonomy of continuous genetic network models is proposed and the following important characteristics are suggested and employed to compare the models: inferential power; predictive power; robustness; consistency; stability and computational cost. Where possible, synthetic time series data are employed to investigate some of these properties. The comparison shows that although genetic network modeling might provide valuable information regarding genetic interactions, current models show disappointing results on simple artificial problems. For now, the simplest models are favored because they generalize better, but more complex models will probably prevail once their bias is more thoroughly understood and their variance is better controlled.

  20. Development and validation study of the Smartphone Overuse Screening Questionnaire.

    Science.gov (United States)

    Lee, Han-Kyeong; Kim, Ji-Hae; Fava, Maurizio; Mischoulon, David; Park, Jae-Hyun; Shim, Eun-Jung; Lee, Eun-Ho; Lee, Ji Hyeon; Jeon, Hong Jin

    2017-08-02

    The aim of this study was to develop a screening questionnaire that could distinguish individuals at high risk of smartphone overuse from casual users. The reliability, validity, and diagnostic ability of the Smartphone Overuse Screening Questionnaire (SOS-Q) were evaluated. Preliminary items were assessed by 50 addiction experts on-line, and 28 questions were selected. A total of 158 subjects recruited from six community centers for internet addiction participated in this study. The SOS-Q, Young's internet addiction scale, Korean scale for internet addiction, and Smartphone Scale for Smartphone Addiction (S-Scale) were used to assess the concurrent validity. Construct validity was supported by a six-factor model using an exploratory factor analysis. The internal consistency and the item-total correlations were favorable (α = 0.95, r = 0.35-0.81). The test-retest reliability was moderate (r = 0.70). The SOS-Q showed superior concurrent validity with the highest correlation between the S-Scale (r = 0.76). Receiver operating characteristic curve analysis revealed an area under the curve of 0.877. A cut-off point of 49 effectively categorized addiction high-risk group with a sensitivity of 0.81 and specificity of 0.86. Overall, the current study supports the use of SOS-Q as both a primary and supplementary measurement tool in a variety of settings. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  1. Genetics

    Science.gov (United States)

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  2. A Tri-Part Model for Genetics Literacy: Exploring Undergraduate Student Reasoning about Authentic Genetics Dilemmas

    Science.gov (United States)

    Shea, Nicole A.; Duncan, Ravit Golan; Stephenson, Celeste

    2015-01-01

    Genetics literacy is becoming increasingly important as advancements in our application of genetic technologies such as stem cell research, cloning, and genetic screening become more prevalent. Very few studies examine how genetics literacy is applied when reasoning about authentic genetic dilemmas. However, there is evidence that situational…

  3. A Tri-Part Model for Genetics Literacy: Exploring Undergraduate Student Reasoning about Authentic Genetics Dilemmas

    Science.gov (United States)

    Shea, Nicole A.; Duncan, Ravit Golan; Stephenson, Celeste

    2015-01-01

    Genetics literacy is becoming increasingly important as advancements in our application of genetic technologies such as stem cell research, cloning, and genetic screening become more prevalent. Very few studies examine how genetics literacy is applied when reasoning about authentic genetic dilemmas. However, there is evidence that situational…

  4. Controversies about cervical cancer screening: A qualitative study of Roma women's (non)participation in cervical cancer screening in Romania.

    Science.gov (United States)

    Andreassen, Trude; Weiderpass, Elisabete; Nicula, Florian; Suteu, Ofelia; Itu, Andreea; Bumbu, Minodora; Tincu, Aida; Ursin, Giske; Moen, Kåre

    2017-06-01

    Romania has Europe's highest incidence and mortality of cervical cancer. While a free national cervical cancer-screening programme has been in operation since 2012, participation in the programme is low, particularly in minority populations. The aim of this study was to explore Roma women's (non)participation in the programme from women's own perspectives and those of healthcare providers and policy makers. We carried out fieldwork for a period of 125 days in 2015/16 involving 144 study participants in Cluj and Bucharest counties. Fieldwork entailed participant observation, qualitative interviewing and focus group discussions. A striking finding was that screening providers and Roma women had highly different takes on the national screening programme. We identified four fundamental questions about which there was considerable disagreement between them: whether a free national screening programme existed in the first place, whether Roma women were meant to be included in the programme if it did, whether Roma women wanted to take part in screening, and to what degree screening participation would really benefit women's health. On the background of insights from actor-network theory, the article discusses to what degree the programme could be said to speak to the interest of its intended Roma public, and considers the controversies in light of the literature on patient centred care and user involvement in health care. The paper contributes to the understanding of the health and health-related circumstances of the largest minority in Europe. It also problematizes the use of the concept of "barriers" in research into participation in cancer screening, and exemplifies how user involvement can potentially help transform and improve screening programmes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Overdiagnosis in organised mammography screening in Denmark. A comparative study

    DEFF Research Database (Denmark)

    Jørgensen, Karsten J; Zahl, Per-Henrik; Gøtzsche, Peter C

    2009-01-01

    BACKGROUND: Overdiagnosis in cancer screening is the detection of cancer lesions that would otherwise not have been detected. It is arguably the most important harm. We quantified overdiagnosis in the Danish mammography screening programme, which is uniquely suited for this purpose, as only 20......% of the Danish population has been offered organised mammography screening over a long time-period. METHODS: We collected incidence rates of carcinoma in situ and invasive breast cancer in areas with and without screening over 13 years with screening (1991-2003), and 20 years before its introduction (1971...

  6. Evolution of cyclizing 5-aminolevulinate synthases in the biosynthesis of actinomycete secondary metabolites: outcomes for genetic screening techniques.

    Science.gov (United States)

    Petříčková, Kateřina; Chroňáková, Alica; Zelenka, Tomáš; Chrudimský, Tomáš; Pospíšil, Stanislav; Petříček, Miroslav; Krištůfek, Václav

    2015-01-01

    A combined approach, comprising PCR screening and genome mining, was used to unravel the diversity and phylogeny of genes encoding 5-aminolevulinic acid synthases (ALASs, hemA gene products) in streptomycetes-related strains. In actinomycetes, these genes were believed to be directly connected with the production of secondary metabolites carrying the C5N unit, 2-amino-3-hydroxycyclopent-2-enone, with biological activities making them attractive for future use in medicine and agriculture. Unlike "classical" primary metabolism ALAS, the C5N unit-forming cyclizing ALAS (cALAS) catalyses intramolecular cyclization of nascent 5-aminolevulinate. Specific amino acid sequence changes can be traced by comparison of "classical" ALASs against cALASs. PCR screening revealed 226 hemA gene-carrying strains from 1,500 tested, with 87% putatively encoding cALAS. Phylogenetic analysis of the hemA homologs revealed strain clustering according to putative type of metabolic product, which could be used to select producers of specific C5N compound classes. Supporting information was acquired through analysis of actinomycete genomic sequence data available in GenBank and further genetic or metabolic characterization of selected strains. Comparison of 16S rRNA taxonomic identification and BOX-PCR profiles provided evidence for numerous horizontal gene transfers of biosynthetic genes or gene clusters within actinomycete populations and even from non-actinomycete organisms. Our results underline the importance of environmental and evolutionary data in the design of efficient techniques for identification of novel producers.

  7. Identification of small molecule and genetic modulators of AON-induced dystrophin exon skipping by high-throughput screening.

    Directory of Open Access Journals (Sweden)

    Debra A O'Leary

    Full Text Available One therapeutic approach to Duchenne Muscular Dystrophy (DMD recently entering clinical trials aims to convert DMD phenotypes to that of a milder disease variant, Becker Muscular Dystrophy (BMD, by employing antisense oligonucleotides (AONs targeting splice sites, to induce exon skipping and restore partial dystrophin function. In order to search for small molecule and genetic modulators of AON-dependent and independent exon skipping, we screened approximately 10,000 known small molecule drugs, >17,000 cDNA clones, and >2,000 kinase- targeted siRNAs against a 5.6 kb luciferase minigene construct, encompassing exon 71 to exon 73 of human dystrophin. As a result, we identified several enhancers of exon skipping, acting on both the reporter construct as well as endogenous dystrophin in mdx cells. Multiple mechanisms of action were identified, including histone deacetylase inhibition, tubulin modulation and pre-mRNA processing. Among others, the nucleolar protein NOL8 and staufen RNA binding protein homolog 2 (Stau2 were found to induce endogenous exon skipping in mdx cells in an AON-dependent fashion. An unexpected but recurrent theme observed in our screening efforts was the apparent link between the inhibition of cell cycle progression and the induction of exon skipping.

  8. Genetic screen in Drosophila muscle identifies autophagy-mediated T-tubule remodeling and a Rab2 role in autophagy

    Science.gov (United States)

    Fujita, Naonobu; Huang, Wilson; Lin, Tzu-han; Groulx, Jean-Francois; Jean, Steve; Nguyen, Jen; Kuchitsu, Yoshihiko; Koyama-Honda, Ikuko; Mizushima, Noboru; Fukuda, Mitsunori; Kiger, Amy A

    2017-01-01

    Transverse (T)-tubules make-up a specialized network of tubulated muscle cell membranes involved in excitation-contraction coupling for power of contraction. Little is known about how T-tubules maintain highly organized structures and contacts throughout the contractile system despite the ongoing muscle remodeling that occurs with muscle atrophy, damage and aging. We uncovered an essential role for autophagy in T-tubule remodeling with genetic screens of a developmentally regulated remodeling program in Drosophila abdominal muscles. Here, we show that autophagy is both upregulated with and required for progression through T-tubule disassembly stages. Along with known mediators of autophagosome-lysosome fusion, our screens uncovered an unexpected shared role for Rab2 with a broadly conserved function in autophagic clearance. Rab2 localizes to autophagosomes and binds to HOPS complex members, suggesting a direct role in autophagosome tethering/fusion. Together, the high membrane flux with muscle remodeling permits unprecedented analysis both of T-tubule dynamics and fundamental trafficking mechanisms. DOI: http://dx.doi.org/10.7554/eLife.23367.001 PMID:28063257

  9. Skin Cancer Screening

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  10. NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae.

    Science.gov (United States)

    Hu, Chunxiao; Dillon, James; Kearn, James; Murray, Caitriona; O'Connor, Vincent; Holden-Dye, Lindy; Morgan, Hywel

    2013-01-01

    Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.

  11. A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Senthilkumar Deivasigamani

    2014-10-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5–10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci – TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2 that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt and VAP(P58S, but in a contrasting manner. Reversal of VAP(P58S bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease.

  12. NeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvae.

    Directory of Open Access Journals (Sweden)

    Chunxiao Hu

    Full Text Available Genetic and chemical biology screens of C. elegans have been of enormous benefit in providing fundamental insight into neural function and neuroactive drugs. Recently the exploitation of microfluidic devices has added greater power to this experimental approach providing more discrete and higher throughput phenotypic analysis of neural systems. Here we make a significant addition to this repertoire through the design of a semi-automated microfluidic device, NeuroChip, which has been optimised for selecting worms based on the electrophysiological features of the pharyngeal neural network. We demonstrate this device has the capability to sort mutant from wild-type worms based on high definition extracellular electrophysiological recordings. NeuroChip resolves discrete differences in excitatory, inhibitory and neuromodulatory components of the neural network from individual animals. Worms may be fed into the device consecutively from a reservoir and recovered unharmed. It combines microfluidics with integrated electrode recording for sequential trapping, restraining, recording, releasing and recovering of C. elegans. Thus mutant worms may be selected, recovered and propagated enabling mutagenesis screens based on an electrophysiological phenotype. Drugs may be rapidly applied during the recording thus permitting compound screening. For toxicology, this analysis can provide a precise description of sub-lethal effects on neural function. The chamber has been modified to accommodate L2 larval stages showing applicability for small size nematodes including parasitic species which otherwise are not tractable to this experimental approach. We also combine NeuroChip with optogenetics for targeted interrogation of the function of the neural circuit. NeuroChip thus adds a new tool for exploitation of C. elegans and has applications in neurogenetics, drug discovery and neurotoxicology.

  13. A genetic screen identifies Tor as an interactor of VAPB in a Drosophila model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Deivasigamani, Senthilkumar; Verma, Hemant Kumar; Ueda, Ryu; Ratnaparkhi, Anuradha; Ratnaparkhi, Girish S

    2014-10-31

    Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by selective death of motor neurons. In 5-10% of the familial cases, the disease is inherited because of mutations. One such mutation, P56S, was identified in human VAPB that behaves in a dominant negative manner, sequestering wild type protein into cytoplasmic inclusions. We have conducted a reverse genetic screen to identify interactors of Drosophila VAPB. We screened 2635 genes and identified 103 interactors, of which 45 were enhancers and 58 were suppressors of VAPB function. Interestingly, the screen identified known ALS loci - TBPH, alsin2 and SOD1. Also identified were genes involved in cellular energetics and homeostasis which were used to build a gene regulatory network of VAPB modifiers. One key modifier identified was Tor, whose knockdown reversed the large bouton phenotype associated with VAP(P58S) expression in neurons. A similar reversal was seen by over-expressing Tuberous Sclerosis Complex (Tsc1,2) that negatively regulates TOR signaling as also by reduction of S6K activity. In comparison, the small bouton phenotype associated with VAP(wt) expression was reversed with Tsc1 knock down as well as S6K-CA expression. Tor therefore interacts with both VAP(wt) and VAP(P58S), but in a contrasting manner. Reversal of VAP(P58S) bouton phenotypes in larvae fed with the TOR inhibitor Rapamycin suggests upregulation of TOR signaling in response to VAP(P58S) expression. The VAPB network and further mechanistic understanding of interactions with key pathways, such as the TOR cassette, will pave the way for a better understanding of the mechanisms of onset and progression of motor neuron disease.

  14. DFNB59 Gene Mutation Screening Using PCR-SSCP/HA Technique in Non-syndromic Genetic Hearing Loss in Bushehr Province

    Directory of Open Access Journals (Sweden)

    Fatemeh Azadegan Dehkordi

    2010-09-01

    Full Text Available Background: Hearing impairment (HI is the most prevalent Neurosensory disorder which is heterogenous and can also occur due to environmental causes. The majority of hearing deficiencies are of genetic origin affecting about 60% of the HI cases. A novel gene DFNB59 encodes pejvakin has been recently shown to cause deafness. This study aims to determine the frequency of DFNB59 gene mutations in coding region the gene in Bushehr province. Methods: In this descriptive experimental study, we investigated the presence of DFNB59 gene mutations in Exons (2-7 of the gene in 80 deaf subjects. DNA was extracted using standard phenol –chloroform method. The screening of gene mutations was performed by PCR-SSCP/HA procedure. Finally, the possible mutations were confirmed by direct sequencing. Results: In all, 9 polymorphisms 793C>G were found in 80 non-syndromic, genetic hearing loss subjects studied. However no DFNB59 gene mutation was identified. Conclusion: We conclude that the association of DFNB59 gene mutations with hearing loss is very low in samples studies

  15. Moving mammogram-reluctant women to screening: a pilot study.

    Science.gov (United States)

    Costanza, Mary E; Luckmann, Roger; White, Mary Jo; Rosal, Milagros C; LaPelle, Nancy; Cranos, Caroline

    2009-06-01

    Effective interventions are needed for women long overdue for screening mammography. The purpose of this study is to pilot test an intervention for motivating overdue women to receive a mammogram. Subjects aged 45-79 without a mammogram in > or =27 months and enrolled in study practices were identified from claims data. The intervention included a mailed, educational booklet, computer-assisted barrier-specific tailored counseling and motivational interviewing, and facilitated, short-interval mammography scheduling. Of 127 eligible women, 45 (35.4%) agreed to counseling and data collection. Most were > or =3 years overdue. Twenty-six (57.8%) of the counseled women got a mammogram within 12 months. Thirty-one (72.1%) of 43 counseled women moved > or =1 stage closer to screening, based on a modified Precaution Adoption Process Model. It is feasible to reach and counsel women who are long overdue for a mammogram and to advance their stage of adoption. The intervention should be formally evaluated in a prospective trial comparing it to control or to proven interventions.

  16. Chemical Genetic Screens for TDP-43 Modifiers and ALS Drug Discovery

    Science.gov (United States)

    2013-10-01

    Jean-Pierre Julien Betty Diamond 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: p.drapeau@umontreal.ca 5f. WORK UNIT NUMBER 7... Ash PE, Zhang YJ, Roberts CM, Saldi T, Hutter H, et al. (2010) Neurotoxic effects of TDP-43 overexpression in C. elegans. Hum Mol Genet. 30. Zhang T...elegans. PloS One 7, e31321. Vaccaro, A., Tauffenberger, A., Ash , P.E., Carlomagno, Y., Petrucelli, L., Parker, J.A., 2012b. TDP-1/TDP-43 regulates

  17. Implications of population structure and ancestry on asthma genetic studies.

    Science.gov (United States)

    Ortega, Victor E; Meyers, Deborah A

    2014-10-01

    The frequency and severity of asthma differ between different racial and ethnic groups. An understanding of the genetic basis for these differences could constitute future genetic biomarker panels for predicting asthma risk and progression in individuals from different ethnic groups. The recent mixing of different ancestries during the European colonization of the Americas and the African slave trade has resulted in the complex population structures identified in different ethnic groups. These population structures represent varying degrees of genetic diversity which impacts the allele frequency of individual variants and, thus, how the gene variation is utilized in genetic association studies. In this review, we will discuss the basis for the complex population structures of modern human genomes and the impact of genetic diversity on genetic studies in different ethnic groups. We will also highlight the potential for admixture and rare variant-based genetic studies to identify novel genetic loci for asthma susceptibility and severity. The ability to account for the consequences of genetic diversity in different racial and ethnic groups will be critical in developing genetic profiles for personalized or precision medicine approaches tailored to asthmatic patients from different ethnic groups.

  18. Mycobacterium avium restriction fragment lenght polymorphism-IS IS1245 and the simple double repetitive element polymerase chain reaction typing method to screen genetic diversity in Brazilian strains

    Directory of Open Access Journals (Sweden)

    Patrícia Carvalho de Sequeira

    2005-11-01

    Full Text Available Simple double repetitive element polymerase chain reaction (MaDRE-PCR and Pvu II-IS1245 restriction fragment length polymorphism (RFLP typing methods were used to type 41 Mycobacterium avium isolates obtained from 14 Aids inpatients and 10 environment and animals specimens identified among 53 mycobacteria isolated from 237 food, chicken, and pig. All environmental and animals strains showed orphan patterns by both methods. By MaDRE-PCR four patients, with multiple isolates, showed different patterns, suggesting polyclonal infection that was confirmed by RFLP in two of them. This first evaluation of MaDRE-PCR on Brazilian M. avium strains demonstrated that the method seems to be useful as simple and less expensive typing method for screening genetic diversity in M. avium strains on selected epidemiological studies, although with limitation on analysis identical patterns except for one band.

  19. Screening and genetic diagnosis of Hemoglobinopathies in Southern and Northern Europe: Two examples

    Directory of Open Access Journals (Sweden)

    Antonio Amato

    2009-08-01

    Full Text Available Prevention of Hemoglobinopathies has developed around the world based upon the experience done in pioneering endemic countries and is now facing a new phase in non-endemic areas with a recent immigration history. We describe two situations, taking Latium (central Italy and The Netherlands as two models for endemic and non-endemic countries both confronted with a large multi-ethnic immigrant society. We present prevention results and discuss aspects such as local knowledge and organization. We illustrate the importance of issues like information, carrier diagnostics, screening, counseling and prenatal diagnosis in particular situation of contrasting interest an different ethical opinions. We conclude by underlining the importance of implementing primary prevention at the European level, based upon better information, diagnostics and counseling.

  20. Does population screening for Chlamydia trachomatis raise anxiety among those tested? Findings from a population based chlamydia screening study

    Directory of Open Access Journals (Sweden)

    Low Nicola

    2006-04-01

    Full Text Available Abstract Background The advent of urine testing for Chlamydia trachomatis has raised the possibility of large-scale screening for this sexually transmitted infection, which is now the most common in the United Kingdom. The purpose of this study was to investigate the effect of an invitation to be screened for chlamydia and of receiving a negative result on levels of anxiety, depression and self-esteem. Methods 19,773 men and women aged 16 to 39 years, selected at random from 27 general practices in two large city areas (Bristol and Birmingham were invited by post to send home-collected urine samples or vulvo-vaginal swabs for chlamydia testing. Questionnaires enquiring about anxiety, depression and self-esteem were sent to random samples of those offered screening: one month before the dispatch of invitations; when participants returned samples; and after receiving a negative result. Results Home screening was associated with an overall reduction in anxiety scores. An invitation to participate did not increase anxiety levels. Anxiety scores in men were lower after receiving the invitation than at baseline. Amongst women anxiety was reduced after receipt of negative test results. Neither depression nor self-esteem scores were affected by screening. Conclusion Postal screening for chlamydia does not appear to have a negative impact on overall psychological well-being and can lead to a decrease in anxiety levels among respondents. There is, however, a clear difference between men and women in when this reduction occurs.

  1. Medical Genetics and the First Studies of the Genetics of Populations in Mexico.

    Science.gov (United States)

    Barahona, Ana

    2016-09-01

    Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén's studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl's studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker's studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts. Copyright © 2016 by

  2. Screening and genetic improvement of pectinolytic fungi for degumming of textile fibers

    Directory of Open Access Journals (Sweden)

    Molina Silvia M.G.

    2001-01-01

    Full Text Available Aiming at contributing to technological improvements in plant fiber processing methods, this paper reports research work on the obtainment of more efficient pectinase-producing fungi strains. More specifically, this work reports the analysis of 18 strains of filamentous fungi, with the purpose of obtaining enzymes for textile fibers degumming. The strains were evaluated for production of pectinolytic enzymes under several growth conditions (culture medium and growth temperature. Production of pectinases was measured by an enzymatic index (EI in solid pectin medium. Among the tested strains, Penicillium chrysogenum IFO 4626 (Q 176 showed the best performance. Genetic improvement of this strain was carried out to increase its pectinase production, while keeping cellulase activity down to a negligible level, since cellulases are known to decrease the resistance of the fiber. Variability was induced through several cycles of mutation and selection by exposing conidea to ultra-violet light (UV. We selected 39 out of 390 isolated colonies. Resulting mutants produced nine times more pectin lyase (PL than the original strain in terms of PL specific activity, and five times more in terms of PL activity (i.e. mmoles liberated per minute of reaction per mL of medium. Periodically, mutant performance was evaluated in solid pectin medium. Genetic stability was maintained for four years after isolation.

  3. Functional-mixed effects models for candidate genetic mapping in imaging genetic studies.

    Science.gov (United States)

    Lin, Ja-An; Zhu, Hongtu; Mihye, Ahn; Sun, Wei; Ibrahim, Joseph G

    2014-12-01

    The aim of this paper is to develop a functional-mixed effects modeling (FMEM) framework for the joint analysis of high-dimensional imaging data in a large number of locations (called voxels) of a three-dimensional volume with a set of genetic markers and clinical covariates. Our FMEM is extremely useful for efficiently carrying out the candidate gene approaches in imaging genetic studies. FMEM consists of two novel components including a mixed effects model for modeling nonlinear genetic effects on imaging phenotypes by introducing the genetic random effects at each voxel and a jumping surface model for modeling the variance components of the genetic random effects and fixed effects as piecewise smooth functions of the voxels. Moreover, FMEM naturally accommodates the correlation structure of the genetic markers at each voxel, while the jumping surface model explicitly incorporates the intrinsically spatial smoothness of the imaging data. We propose a novel two-stage adaptive smoothing procedure to spatially estimate the piecewise smooth functions, particularly the irregular functional genetic variance components, while preserving their edges among different piecewise-smooth regions. We develop weighted likelihood ratio tests and derive their exact approximations to test the effect of the genetic markers across voxels. Simulation studies show that FMEM significantly outperforms voxel-wise approaches in terms of higher sensitivity and specificity to identify regions of interest for carrying out candidate genetic mapping in imaging genetic studies. Finally, FMEM is used to identify brain regions affected by three candidate genes including CR1, CD2AP, and PICALM, thereby hoping to shed light on the pathological interactions between these candidate genes and brain structure and function.

  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. Comprehensive genetic screening of KCNQ4 in a large autosomal dominant nonsyndromic hearing loss cohort: genotype-phenotype correlations and a founder mutation.

    Directory of Open Access Journals (Sweden)

    Takehiko Naito

    Full Text Available The present study of KCNQ4 mutations was carried out to 1 determine the prevalence by unbiased population-based genetic screening, 2 clarify the mutation spectrum and genotype/phenotype correlations, and 3 summarize clinical characteristics. In addition, a review of the reported mutations was performed for better understanding of this deafness gene. The screening using 287 probands from unbiased Japanese autosomal dominant nonsyndromic hearing loss (ADNSHL families identified 19 families with 7 different disease causing mutations, indicating that the frequency is 6.62% (19/287. While the majority were private mutations, one particular recurrent mutation, c.211delC, was observed in 13 unrelated families. Haplotype analysis in the vicinity of c.211delC suggests existence of a common ancestor. The majority of the patients showed all frequency, but high-frequency predominant, sensorineural hearing loss. The present study adds a new typical audiogram configuration characterized by mid-frequency predominant hearing loss caused by the p.V230E mutation. A variant at the N-terminal site (c. 211delC showed typical ski-slope type audiogram configuration. Concerning clinical features, onset age was from 3 to 40 years old, and mostly in the teens, and hearing loss was gradually progressive. Progressive nature is a common feature of patients with KCNQ4 mutations regardless of the mutation type. In conclusion, KCNQ4 mutations are frequent among ADNSHL patients, and therefore screening of the gene and molecular confirmation of these mutations have become important in the diagnosis of these conditions.

  6. Study books on ADHD genetics: balanced or biased?

    Science.gov (United States)

    Te Meerman, Sanne; Batstra, Laura; Hoekstra, Rink; Grietens, Hans

    2017-06-01

    Academic study books are essential assets for disseminating knowledge about ADHD to future healthcare professionals. This study examined if they are balanced with regard to genetics. We selected and analyzed study books (N=43) used in (pre) master's programmes at 10 universities in the Netherlands. Because the mere behaviourally informed quantitative genetics give a much higher effect size of the genetic involvement in ADHD, it is important that study books contrast these findings with molecular genetics' outcomes. The latter studies use real genetic data, and their low effect sizes expose the potential weaknesses of quantitative genetics, like underestimating the involvement of the environment. Only a quarter of books mention both effect sizes and contrast these findings, while another quarter does not discuss any effect size. Most importantly, however, roughly half of the books in our sample mention only the effect sizes from quantitative genetic studies without addressing the low explained variance of molecular genetic studies. This may confuse readers by suggesting that the weakly associated genes support the quite spectacular, but potentially flawed estimates of twin, family and adoption studies, while they actually contradict them.

  7. Preimplantation genetic screening as an alternative to prenatal testing for Down syndrome : preferences of women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment

    NARCIS (Netherlands)

    Twisk, Moniek; Haadsma, Maaike L.; van der Veen, Fulco; Repping, Sjoerd; Mastenbroek, Sebastiaan; Heineman, Maas-Jan; Bossuyt, Patrick M. M.; Korevaar, Johanna C.

    2007-01-01

    Objective: Although the primary goal of preimplantation genetic screening (PGS) is to increase pregnancy rates in women undergoing IVF/intracytoplasmic sperm injection treatment, it has been suggested that it may also be used as an alternative to prenatal testing for Down syndrome. Design: Trade-off

  8. A "Genetic Study" of the Galaxy

    Science.gov (United States)

    2006-09-01

    Looking in detail at the composition of stars with ESO's VLT, astronomers are providing a fresh look at the history of our home galaxy, the Milky Way. They reveal that the central part of our Galaxy formed not only very quickly but also independently of the rest. "For the first time, we have clearly established a 'genetic difference' between stars in the disc and the bulge of our Galaxy," said Manuela Zoccali, lead author of the paper presenting the results in the journal Astronomy and Astrophysics [1]. "We infer from this that the bulge must have formed more rapidly than the disc, probably in less than a billion years and when the Universe was still very young." ESO PR Photo 34a/06 ESO PR Photo 34a/06 The Field around Baade's Window The Milky Way is a spiral galaxy, having pinwheel-shaped arms of gas, dust, and stars lying in a flattened disc, and extending directly out from a spherical nucleus of stars in the central region. The spherical nucleus is called a bulge, because it bulges out from the disc. While the disc of our Galaxy is made up of stars of all ages, the bulge contains old stars dating from the time the galaxy formed, more than 10 billion years ago. Thus, studying the bulge allows astronomers to know more about how our Galaxy formed. To do this, an international team of astronomers [2] analysed in detail the chemical composition of 50 giant stars in four different areas of the sky towards the Galactic bulge. They made use of the FLAMES/UVES spectrograph on ESO's Very Large Telescope to obtain high-resolution spectra. The chemical composition of stars carries the signature of the enrichment processes undergone by the interstellar matter up to the moment of their formation. It depends on the previous history of star formation and can thus be used to infer whether there is a 'genetic link' between different stellar groups. In particular, comparison between the abundance of oxygen and iron in stars is very illustrative. Oxygen is predominantly produced in

  9. HPV DNA testing in population-based cervical screening (VUSA-Screen study) : results and implications

    NARCIS (Netherlands)

    Rijkaart, D. C.; Berkhof, J.; van Kemenade, F. J.; Coupe, V. M. H.; Rozendaal, L.; Heideman, D. A. M.; Verheijen, R. H. M.; Bulk, S.; Verweij, W.; Snijders, P. J. F.; Meijer, C. J. L. M.

    2012-01-01

    BACKGROUND: Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening. METHODS: In all, 25 871 women (29-61) enrolled in our population-based

  10. HPV DNA testing in population-based cervical screening (VUSA-Screen study) : results and implications

    NARCIS (Netherlands)

    Rijkaart, D. C.; Berkhof, J.; van Kemenade, F. J.; Coupe, V. M. H.; Rozendaal, L.; Heideman, D. A. M.; Verheijen, R. H. M.; Bulk, S.; Verweij, W.; Snijders, P. J. F.; Meijer, C. J. L. M.

    2012-01-01

    BACKGROUND: Human papillomavirus (HPV) testing is more sensitive than cytology for detecting high-grade cervical intraepithelial neoplasia (CIN). We evaluated the performance of high-risk HPV (hrHPV) testing in routine screening. METHODS: In all, 25 871 women (29-61) enrolled in our population-based

  11. The Substance Abuse Subtle Screening Inventory-3 and Stages of Change: A Screening Validity Study

    Science.gov (United States)

    Laux, John M.; Piazza, Nick J.; Salyers, Kathleen; Roseman, Christopher P.

    2012-01-01

    The sensitivity of the Substance Abuse Subtle Screening Inventory-3 (SASSI-3) was examined among substance-dependent adults enrolled in a family drug court. The SASSI-3 had a high sensitivity rate with this population, even across varying levels of motivation to change. (Contains 2 tables.)

  12. Molecular Genetic Study of Human Esophageal Carcinoma

    Science.gov (United States)

    1991-07-16

    carcinogenic processes ( Doerfler , 1983). Direct evidence has shown that the DNA alkylation product, o’-methyl deoxyguanosine was higher in the DNA...of north China and the genetic approach to its control. Genes and Disease, (Science Press, Beijing, China) 1985. Doerfler , W. DNA methylation and

  13. Forward genetics studies of seed phytic acid

    Science.gov (United States)

    Both the chemical composition and total amount of seed phosphorus (P) are important to the end-use quality of cereal and legume seed crops. The chemistry of seed total P largely revolves around the synthesis and storage of phytic acid (myo-inositol hexaphosphate). Forward genetics research, beginnin...

  14. Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort.

    Science.gov (United States)

    Chang, Ruey-Kang R; Lan, Yueh-Tze; Silka, Michael J; Morrow, Hallie; Kwong, Alan; Smith-Lang, Janna; Wallerstein, Robert; Lin, Henry J

    2014-03-01

    Autosomal recessive long QT syndrome (LQTS), or Jervell and Lange-Nielsen syndrome (JLNS), can be associated with sensorineural hearing loss. We aimed to explore newborn hearing screening combined with electrocardiograms (ECGs) for early JLNS detection. In California, we conducted statewide, prospective ECG screening of children ≤ 6 years of age with unilateral or bilateral, severe or profound, sensorineural or mixed hearing loss. Families were identified through newborn hearing screening and interviewed about medical and family histories. Twelve-lead ECGs were obtained. Those with positive histories or heart rate corrected QT (QTc) intervals ≥ 450 ms had repeat ECGs. DNA sequencing of 12 LQTS genes was performed for repeat QTc intervals ≥ 450 ms. We screened 707 subjects by ECGs (number screened/number of responses = 91%; number of responses/number of families who were mailed invitations = 54%). Of these, 73 had repeat ECGs, and 19 underwent gene testing. No subject had homozygous or compound heterozygous LQTS mutations, as in JLNS. However, 3 individuals (with QTc intervals of 472, 457, and 456 ms, respectively) were heterozygous for variants that cause truncation or missplicing: 2 in KCNQ1 (c.1343dupC or p.Glu449Argfs*14; c.1590+1G>A or p.Glu530sp) and 1 in SCN5A (c.5872C>T or p.Arg1958*). In contrast to reports of JLNS in up to 4% of children with sensorineural hearing loss, we found no examples of JLNS. Because the 3 variants identified were unrelated to hearing, they likely represent the prevalence of potential LQTS mutations in the general population. Further studies are needed to define consequences of such mutations and assess the overall prevalence. Published by Mosby, Inc.

  15. Incorporating Genetics into Your Studies: A Guide for Social Scientists

    Directory of Open Access Journals (Sweden)

    Danielle eDick

    2011-05-01

    Full Text Available AbstractThere has been a surge of interest in recent years in incorporating genetic components into on-going longitudinal, developmental studies and related psychological studies. While this represents an exciting new direction in developmental science, much of the research on genetic topics in developmental science does not reflect the most current practice in genetics. This is likely due, in part, to the rapidly changing landscape of the field of genetics, and the difficulty this presents for developmental scientists who are trying to learn this new area. In this review, we present an overview of the paradigm shifts that have occurred in genetics and we introduce the reader to basic genetic methodologies. We present our view of the current stage of research ongoing at the intersection of genetics and social science, and we provide recommendations for how we could do better. We also address a number of issues that social scientists face as they integrate genetics into their projects, including choice of a study design (candidate gene versus genome-wide association versus sequencing, different methods of DNA collection, and special considerations involved in the analysis of genotypic data. Through this review, we hope to equip social scientists with a deeper understanding of the many considerations that go into genetics research, in an effort to foster more meaningful cross-disciplinary initiatives.

  16. A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability

    Science.gov (United States)

    Cantisani, Maria Carmela; Parascandolo, Alessia; Perälä, Merja; Allocca, Chiara; Fey, Vidal; Sahlberg, Niko; Merolla, Francesco; Basolo, Fulvio; Laukkanen, Mikko O.; Kallioniemi, Olli Pekka; Santoro, Massimo; Castellone, Maria Domenica

    2016-01-01

    RET, BRAF and other protein kinases have been identified as major molecular players in thyroid cancer. To identify novel kinases required for the viability of thyroid carcinoma cells, we performed a RNA interference screening in the RET/PTC1(CCDC6-RET)-positive papillary thyroid cancer cell line TPC1 using a library of synthetic small interfering RNAs (siRNAs) targeting the human kinome and related proteins. We identified 14 hits whose silencing was able to significantly reduce the viability and the proliferation of TPC1 cells; most of them were active also in BRAF-mutant BCPAP (papillary thyroid cancer) and 8505C (anaplastic thyroid cancer) and in RAS-mutant CAL62 (anaplastic thyroid cancer) cells. These included members of EPH receptor tyrosine kinase family as well as SRC and MAPK (mitogen activated protein kinases) families. Importantly, silencing of the identified hits did not affect significantly the viability of Nthy-ori 3-1 (hereafter referred to as NTHY) cells derived from normal thyroid tissue, suggesting cancer cell specificity. The identified proteins are worth exploring as potential novel druggable thyroid cancer targets. PMID:27058903

  17. A Model Inquiry-Based Genetics Experiment for Introductory Biology Students: Screening for Enhancers & Suppressors of Ptpmeg

    Science.gov (United States)

    Setty, Sumana; Kosinski-Collins, Melissa S.

    2015-01-01

    It has been noted that undergraduate project-based laboratories lead to increased interest in scientific research and student understanding of biological concepts. We created a novel, inquiry-based, multiweek genetics research project studying Ptpmeg, for the Introductory Biology Laboratory course at Brandeis University. Ptpmeg is a protein…

  18. Genetic Breeding and Diversity of the Genus Passiflora: Progress and Perspectives in Molecular and Genetic Studies

    Directory of Open Access Journals (Sweden)

    Carlos Bernard M. Cerqueira-Silva

    2014-08-01

    Full Text Available Despite the ecological and economic importance of passion fruit (Passiflora spp., molecular markers have only recently been utilized in genetic studies of this genus. In addition, both basic genetic researches related to population studies and pre-breeding programs of passion fruit remain scarce for most Passiflora species. Considering the number of Passiflora species and the increasing use of these species as a resource for ornamental, medicinal, and food purposes, the aims of this review are the following: (i to present the current condition of the passion fruit crop; (ii to quantify the applications and effects of using molecular markers in studies of Passiflora; (iii to present the contributions of genetic engineering for passion fruit culture; and (iv to discuss the progress and perspectives of this research. Thus, the present review aims to summarize and discuss the relationship between historical and current progress on the culture, breeding, and molecular genetics of passion fruit.

  19. Performance of systematic and non-systematic ('opportunistic') screening mammography: a comparative study from Denmark

    DEFF Research Database (Denmark)

    Bihrmann, Kristine; Jensen, Allan; Olsen, Anne Helene;

    2008-01-01

    OBJECTIVES: Evaluation and comparison of the performance of organized and opportunistic screening mammography. METHODS: Women attending screening mammography in Denmark in 2000. The study included 37,072 women attending organized screening. Among these, 320 women were diagnosed with breast cancer...

  20. Cancer screening behaviours among South Asian immigrants in the UK, US and Canada: a scoping study.

    Science.gov (United States)

    Crawford, Joanne; Ahmad, Farah; Beaton, Dorcas; Bierman, Arlene S

    2016-03-01

    South Asian (SA) immigrants settled in the United Kingdom (UK) and North America [United States (US) and Canada] have low screening rates for breast, cervical and colorectal cancers. Incidence rates of these cancers increase among SA immigrants after migration, becoming similar to rates in non-Asian native populations. However, there are disparities in cancer screening, with low cancer screening uptake in this population. We conducted a scoping study using Arksey & O'Malley's framework to examine cancer screening literature on SA immigrants residing in the UK, US and Canada. Eight electronic databases, key journals and reference lists were searched for English language studies and reports. Of 1465 identified references, 70 studies from 1994 to November 2014 were included: 63% on breast or cervical cancer screening or both; 10% examined colorectal cancer screening only; 16% explored health promotion/service provision; 8% studied breast, cervical and colorectal cancer screening; and 3% examined breast and colorectal cancer screening. A thematic analysis uncovered four dominant themes: (i) beliefs and attitudes towards cancer and screening included centrality of family, holistic healthcare, fatalism, screening as unnecessary and emotion-laden perceptions; (ii) lack of knowledge of cancer and screening related to not having heard about cancer and its causes, or lack of awareness of screening, its rationale and/or how to access services; (iii) barriers to access including individual and structural barriers; and (iv) gender differences in screening uptake and their associated factors. Findings offer insights that can be used to develop culturally sensitive interventions to minimise barriers and increase cancer screening uptake in these communities, while recognising the diversity within the SA culture. Further research is required to address the gap in colorectal cancer screening literature to more fully understand SA immigrants' perspectives, as well as research to

  1. A designed screening study with prespecified combinations of factor settings

    Energy Technology Data Exchange (ETDEWEB)

    Anderson-cook, Christine M [Los Alamos National Laboratory; Robinson, Timothy J [U. WYOMING

    2009-01-01

    In many applications, the experimenter has limited options about what factor combinations can be chosen for a designed study. Consider a screening study for a production process involving five input factors whose levels have been previously established. The goal of the study is to understand the effect of each factor on the response, a variable that is expensive to measure and results in destruction of the part. From an inventory of available parts with known factor values, we wish to identify a best collection of factor combinations with which to estimate the factor effects. Though the observational nature of the study cannot establish a causal relationship involving the response and the factors, the study can increase understanding of the underlying process. The study can also help determine where investment should be made to control input factors during production that will maximally influence the response. Because the factor combinations are observational, the chosen model matrix will be nonorthogonal and will not allow independent estimation of factor effects. In this manuscript we borrow principles from design of experiments to suggest an 'optimal' selection of factor combinations. Specifically, we consider precision of model parameter estimates, the issue of replication, and abilities to detect lack of fit and to estimate two-factor interactions. Through an example, we present strategies for selecting a subset of factor combinations that simultaneously balance multiple objectives, conduct a limited sensitivity analysis, and provide practical guidance for implementing our techniques across a variety of quality engineering disciplines.

  2. Predictive Modeling of Tacrolimus Dose Requirement Based on High-Throughput Genetic Screening.

    Science.gov (United States)

    Damon, C; Luck, M; Toullec, L; Etienne, I; Buchler, M; Hurault de Ligny, B; Choukroun, G; Thierry, A; Vigneau, C; Moulin, B; Heng, A-E; Subra, J-F; Legendre, C; Monnot, A; Yartseva, A; Bateson, M; Laurent-Puig, P; Anglicheau, D; Beaune, P; Loriot, M A; Thervet, E; Pallet, N

    2017-04-01

    Any biochemical reaction underlying drug metabolism depends on individual gene-drug interactions and on groups of genes interacting together. Based on a high-throughput genetic approach, we sought to identify a set of covariant single-nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C0 ) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable-selection strategy to reinforce the stability of the variable-selection process and multivariate modeling. Our predictive models explained up to 70% of total variability in Tac C0 per dose with a maximum of 44 gene variants (p-value <0.001 with a permutation test). These models included molecular networks of drug metabolism with oxidoreductase activities and the multidrug-resistant ABCC8 transporter, which was found in the most stringent model. Finally, we identified an intronic variant of the gene encoding SLC28A3, a drug transporter, as a key gene involved in Tac metabolism, and we confirmed it in an independent validation cohort. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Cancer genetic association studies in the genome-wide age

    OpenAIRE

    Savage, Sharon A

    2008-01-01

    Genome-wide association studies of hundreds of thousands of SNPs have led to a deluge of studies of genetic variation in cancer and other common diseases. Large case–control and cohort studies have identified novel SNPs as markers of cancer risk. Genome-wide association study SNP data have also advanced understanding of population-specific genetic variation. While studies of risk profiles, combinations of SNPs that may increase cancer risk, are not yet clinically applicable, future, large-sca...

  4. Cryptogenic Polyneuropathy : Clinical, Environmental, And Genetic Studies

    OpenAIRE

    Lindh, Jonas

    2011-01-01

    Objectives: The purpose of this medical thesis was to describe the clinical and neurophysiological features and to evaluate the health related quality of life (HR-QoL) in patients with cryptogenic polyneuropathy. We also wanted to investigate different occupational, and leisure time exposures as determinants for cryptogenic polyneuropathy, and to analyze whether polymorphisms for the null alleles of Glutathione S-Transferase Mu-1 (GSTM1), and Theta-1 (GSTT1), and a low activity genetic variat...

  5. Evaluation of cancer service screening: case referent studies recommended.

    NARCIS (Netherlands)

    Verbeek, A.L.M.; Broeders, M.J.M.

    2010-01-01

    Various cancer screening trials, randomised or otherwise controlled, have demonstrated reductions in cancer mortality. As a consequence, population screening programmes have been implemented. In the mean time, major advances are being made in early detection and treatment modalities of specific canc

  6. Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study

    DEFF Research Database (Denmark)

    Mitra, Anita V; Bancroft, Elizabeth K; Barbachano, Yolanda;

    2011-01-01

    Study Type - Diagnostic (validating cohort)
Level of Evidence 1b OBJECTIVES: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening...... in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported. MATERIALS AND METHODS: Men aged 40-69 years from families with BRCA1 or BRCA2...... mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA >3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (± 5 years) who were negative for the familial mutation. RESULTS: In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2...

  7. A chemical genetic screen uncovers a small molecule enhancer of the N-acylethanolamine degrading enzyme, fatty acid amide hydrolase, in Arabidopsis

    Science.gov (United States)

    Khan, Bibi Rafeiza; Faure, Lionel; Chapman, Kent D.; Blancaflor, Elison B.

    2017-01-01

    N-Acylethanolamines (NAEs) are a group of fatty acid amides that play signaling roles in diverse physiological processes in eukaryotes. Fatty acid amide hydrolase (FAAH) degrades NAE into ethanolamine and free fatty acid to terminate its signaling function. In animals, chemical inhibitors of FAAH have been used for therapeutic treatment of pain and as tools to probe deeper into biochemical properties of FAAH. In a chemical genetic screen for small molecules that dampened the inhibitory effect of N-lauroylethanolamine (NAE 12:0) on Arabidopsis thaliana seedling growth, we identified 6-(2-methoxyphenyl)-1,3-dimethyl-5-phenyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3 H,6 H)-dione (or MDPD). MDPD alleviated the growth inhibitory effects of NAE 12:0, in part by enhancing the enzymatic activity of Arabidopsis FAAH (AtFAAH). In vitro, biochemical assays showed that MDPD enhanced the apparent Vmax of AtFAAH but did not alter the affinity of AtFAAH for its NAE substrates. Structural analogs of MDPD did not affect AtFAAH activity or dampen the inhibitory effect of NAE 12:0 on seedling growth indicating that MDPD is a specific synthetic chemical activator of AtFAAH. Collectively, our study demonstrates the feasibility of using an unbiased chemical genetic approach to identify new pharmacological tools for manipulating FAAH- and NAE-mediated physiological processes in plants. PMID:28112243

  8. Evolution of cyclizing 5-aminolevulinate synthases in the biosynthesis of actinomycete secondary metabolites: Outcomes for genetic screening techniques

    Directory of Open Access Journals (Sweden)

    Katerina ePetrickova

    2015-08-01

    Full Text Available A combined approach, comprising PCR screening and genome mining, was used to unravel the diversity and phylogeny of genes encoding 5-aminolevulinic acid synthases (ALASs, hemA gene products in streptomycetes-related strains. In actinomycetes, these genes were believed to be directly connected with the production of secondary metabolites carrying the C5N unit, 2-amino-3-hydroxycyclopent-2-enone, with biological activities making them attractive for future use in medicine and agriculture. Unlike classical primary metabolism ALAS, the C5N unit-forming cALAS (cyclizing ALAS catalyses intramolecular cyclization of nascent 5-aminolevulinate. Specific amino acid sequence changes can be traced by comparison of classical ALASs against cALASs. PCR screening revealed 226 hemA gene-carrying strains from 1,500 tested, with 87 % putatively encoding cALAS. Phylogenetic analysis of the hemA homologues revealed strain clustering according to putative type of metabolic product, which could be used to select producers of specific C5N compound classes. Supporting information was acquired through analysis of actinomycete genomic sequence data available in GeneBank and further genetic or metabolic characterization of selected strains. Comparison of 16S rRNA taxonomic identification and BOX-PCR profiles provided evidence for numerous horizontal gene transfers of biosynthetic genes or gene clusters within actinomycete populations and even from non-actinomycete organisms. Our results underline the importance of environmental and evolutionary data in the design of efficient techniques for identification of novel producers.

  9. Genetic screening of new genes responsible for cellular adaptation to hypoxia using a genome-wide shRNA library.

    Science.gov (United States)

    Yoshino, Seiko; Hara, Toshiro; Weng, Jane S; Takahashi, Yuka; Seiki, Motoharu; Sakamoto, Takeharu

    2012-01-01

    Oxygen is a vital requirement for multi-cellular organisms to generate energy and cells have developed multiple compensatory mechanisms to adapt to stressful hypoxic conditions. Such adaptive mechanisms are intricately interconnected with other signaling pathways that regulate cellular functions such as cell growth. However, our understanding of the overall system governing the cellular response to the availability of oxygen remains limited. To identify new genes involved in the response to hypoxic stress, we have performed a genome-wide gene knockdown analysis in human lung carcinoma PC8 cells using an shRNA library carried by a lentiviral vector. The knockdown analysis was performed under both normoxic and hypoxic conditions to identify shRNA sequences enriched or lost in the resulting selected cell populations. Consequently, we identified 56 candidate genes that might contribute to the cellular response to hypoxia. Subsequent individual knockdown of each gene demonstrated that 13 of these have a significant effect upon oxygen-sensitive cell growth. The identification of BCL2L1, which encodes a Bcl-2 family protein that plays a role in cell survival by preventing apoptosis, validates the successful design of our screen. The other selected genes have not previously been directly implicated in the cellular response to hypoxia. Interestingly, hypoxia did not directly enhance the expression of any of the identified genes, suggesting that we have identified a new class of genes that have been missed by conventional gene expression analyses to identify hypoxia response genes. Thus, our genetic screening method using a genome-wide shRNA library and the newly-identified genes represent useful tools to analyze the cellular systems that respond to hypoxic stress.

  10. Genetic studies in congenital anterior midline cervical cleft

    DEFF Research Database (Denmark)

    Jakobsen, L P; Pfeiffer, P; Andersen, M

    2012-01-01

    Congenital anterior midline cervical cleft (CAMCC) is a rare anomaly, with less than 100 cases reported. The cause of CAMCC is unknown, but genetic factors must be considered as part of the etiology. Three cases of CAMCC are presented. This is the first genetic study of isolated CAMCC. Conventional...

  11. A high-throughput strategy for screening of bacterial artificial chromosome libraries and anchoring of clones on a genetic map constructed with single nucleotide polymorphisms

    Directory of Open Access Journals (Sweden)

    Deal Karin R

    2009-01-01

    Full Text Available Abstract Background Current techniques of screening bacterial artificial chromosome (BAC libraries for molecular markers during the construction of physical maps are slow, laborious and often assign multiple BAC contigs to a single locus on a genetic map. These limitations are the principal impediment in the construction of physical maps of large eukaryotic genomes. It is hypothesized that this impediment can be overcome by screening multidimensional pools of BAC clones using the highly parallel Illumina GoldenGate™ assay. Results To test the efficacy of the Golden Gate assay in BAC library screening, multidimensional pools involving 302976 Aegilops tauschii BAC clones were genotyped for the presence/absence of specific gene sequences with multiplexed Illumina GoldenGate oligonucleotide assays previously used to place single nucleotide polymorphisms on an Ae. tauschii genetic map. Of 1384 allele-informative oligonucleotide assays, 87.6% successfully clustered BAC pools into those positive for a BAC clone harboring a specific gene locus and those negative for it. The location of the positive BAC clones within contigs assembled from 199190 fingerprinted Ae. tauschii BAC clones was used to evaluate the precision of anchoring of BAC clones and contigs on the Ae. tauschii genetic map. For 41 (95% assays, positive BAC clones were neighbors in single contigs. Those contigs could be unequivocally assigned to loci on the genetic map. For two (5% assays, positive clones were in two different contigs and the relationships of these contigs to loci on the Ae. tauschii genetic map were equivocal. Screening of BAC libraries with a simple five-dimensional BAC pooling strategy was evaluated and shown to allow direct detection of positive BAC clones without the need for manual deconvolution of BAC clone pools. Conclusion The highly parallel Illumina oligonucleotide assay is shown here to be an efficient tool for screening BAC libraries and a strategy for high

  12. Quantitative Assessment of Eye Phenotypes for Functional Genetic Studies Using Drosophila melanogaster

    Science.gov (United States)

    Iyer, Janani; Wang, Qingyu; Le, Thanh; Pizzo, Lucilla; Grönke, Sebastian; Ambegaokar, Surendra S.; Imai, Yuzuru; Srivastava, Ashutosh; Troisí, Beatriz Llamusí; Mardon, Graeme; Artero, Ruben; Jackson, George R.; Isaacs, Adrian M.; Partridge, Linda; Lu, Bingwei; Kumar, Justin P.; Girirajan, Santhosh

    2016-01-01

    About two-thirds of the vital genes in the Drosophila genome are involved in eye development, making the fly eye an excellent genetic system to study cellular function and development, neurodevelopment/degeneration, and complex diseases such as cancer and diabetes. We developed a novel computational method, implemented as Flynotyper software (http://flynotyper.sourceforge.net), to quantitatively assess the morphological defects in the Drosophila eye resulting from genetic alterations affecting basic cellular and developmental processes. Flynotyper utilizes a series of image processing operations to automatically detect the fly eye and the individual ommatidium, and calculates a phenotypic score as a measure of the disorderliness of ommatidial arrangement in the fly eye. As a proof of principle, we tested our method by analyzing the defects due to eye-specific knockdown of Drosophila orthologs of 12 neurodevelopmental genes to accurately document differential sensitivities of these genes to dosage alteration. We also evaluated eye images from six independent studies assessing the effect of overexpression of repeats, candidates from peptide library screens, and modifiers of neurotoxicity and developmental processes on eye morphology, and show strong concordance with the original assessment. We further demonstrate the utility of this method by analyzing 16 modifiers of sine oculis obtained from two genome-wide deficiency screens of Drosophila and accurately quantifying the effect of its enhancers and suppressors during eye development. Our method will complement existing assays for eye phenotypes, and increase the accuracy of studies that use fly eyes for functional evaluation of genes and genetic interactions. PMID:26994292

  13. In Vivo RNAi-Based Screens: Studies in Model Organisms

    Directory of Open Access Journals (Sweden)

    Miki Yamamoto-Hino

    2013-11-01

    Full Text Available RNA interference (RNAi is a technique widely used for gene silencing in organisms and cultured cells, and depends on sequence homology between double-stranded RNA (dsRNA and target mRNA molecules. Numerous cell-based genome-wide screens have successfully identified novel genes involved in various biological processes, including signal transduction, cell viability/death, and cell morphology. However, cell-based screens cannot address cellular processes such as development, behavior, and immunity. Drosophila and Caenorhabditis elegans are two model organisms whose whole bodies and individual body parts have been subjected to RNAi-based genome-wide screening. Moreover, Drosophila RNAi allows the manipulation of gene function in a spatiotemporal manner when it is implemented using the Gal4/UAS system. Using this inducible RNAi technique, various large-scale screens have been performed in Drosophila, demonstrating that the method is straightforward and valuable. However, accumulated results reveal that the results of RNAi-based screens have relatively high levels of error, such as false positives and negatives. Here, we review in vivo RNAi screens in Drosophila and the methods that could be used to remove ambiguity from screening results.

  14. Offering fragile X syndrome carrier screening: a prospective mixed-methods observational study comparing carrier screening of pregnant and non-pregnant women in the general population

    Science.gov (United States)

    Martyn, M; Anderson, V; Archibald, A; Carter, R; Cohen, J; Delatycki, M; Donath, S; Emery, J; Halliday, J; Hill, M; Sheffield, L; Slater, H; Tassone, F; Younie, S; Metcalfe, S

    2013-01-01

    Introduction Fragile X syndrome (FXS) is the leading cause of inherited intellectual and developmental disability. Policy development relating to carrier screening programmes for FXS requires input from large studies examining not only test uptake but also psychosocial aspects. This study will compare carrier screening in pregnant and non-pregnant populations, examining informed decision-making, psychosocial issues and health economics. Methods and Analysis Pregnant and non-pregnant women are being recruited from general practices and obstetric services. Women receive study information either in person or through clinic mail outs. Women are provided pretest counselling by a genetic counsellor and make a decision about testing in their own time. Data are being collected from two questionnaires: one completed at the time of making the decision about testing and the second 1 month later. Additional data are gathered through qualitative interviews conducted at several time points with a subset of participating women, including all women with a positive test result, and with staff from recruiting clinics. A minimum sample size of 500 women/group has been calculated to give us 88% power to detect a 10% difference in test uptake and 87% power to detect a 10% difference in informed choice between the pregnant and non-pregnant groups. Questionnaire data will be analysed using descriptive statistics and multivariate logistic regression models. Interview data will be thematically analysed. Willingness-to-pay and cost effectiveness analyses will also be performed. Recruitment started in July 2009 and data collection will be completed by December 2013. Ethics and Dissemination Ethics approval has been granted by the Universities of Melbourne and Western Australia and by recruiting clinics, where required. Results will be reported in peer-reviewed publications, conference presentations and through a website http://www.fragilexscreening.net.au. The results of this study will

  15. Cost-effectiveness of genetic studies in inherited heart diseases

    Directory of Open Access Journals (Sweden)

    María Sabater-Molina

    2013-05-01

    Full Text Available There is a need to evidence the cost of genetic testing and know their profitability in order to establish criteria for priorizing access to genetic testing for these diseases. We determinated the cost per positive genotyping in 234 index cases with diagnosis of hypertrophic cardiomyopathy (HCM, arrhythmogenic right ventricular cardiomyopathy (ARVC, long-QT syndrome (LQTS, or Brugada syndrome (BS. The genetic tests of the most prevalent genes and the estimation of the costs of periodical screening in wildtype relatives (WT were calculated. A total of 738 individuals (517 HCM, 76 ARVC, 71 LQTS and 74 BS from 234 probands were genotyped. The savings made by not having to perform the clinical testing of WT relatives exceeded the cost of genotyping for HCM families € +220,710, ARVC families € +9405 and LQTS families € +8362. The balance in BS was negative (€ –25,112. Our data suggests that individuals with conclusive clinical diagnostic of HCM should have a priority to access genetic testing. A positive overall benefit was also demonstrated in ARVC and LQTS.

  16. Development and validation of duplex, triplex, and pentaplex real-time PCR screening assays for the detection of genetically modified organisms in food and feed.

    Science.gov (United States)

    Huber, Ingrid; Block, Annette; Sebah, Daniela; Debode, Frédéric; Morisset, Dany; Grohmann, Lutz; Berben, Gilbert; Stebih, Dejan; Milavec, Mojca; Zel, Jana; Busch, Ulrich

    2013-10-30

    Worldwide, qualitative methods based on PCR are most commonly used as screening tools for genetically modified material in food and feed. However, the increasing number and diversity of genetically modified organisms (GMO) require effective methods for simultaneously detecting several genetic elements marking the presence of transgenic events. Herein we describe the development and validation of a pentaplex, as well as complementary triplex and duplex real-time PCR assays, for the detection of the most common screening elements found in commercialized GMOs: P-35S, T-nos, ctp2-cp4-epsps, bar, and pat. The use of these screening assays allows the coverage of many GMO events globally approved for commercialization. Each multiplex real-time PCR assay shows high specificity and sensitivity with an absolute limit of detection below 20 copies for the targeted sequences. We demonstrate by intra- and interlaboratory tests that the assays are robust as well as cost- and time-effective for GMO screening if applied in routine GMO analysis.

  17. Development of 10 microsatellite markers from Pantala flavescens and their applicability in studying genetics diversity.

    Science.gov (United States)

    Cao, Lingzhen; Fu, Xiaowei; Wu, Kongming

    2015-08-01

    Pantala flavescens (Fabricius 1798) is one of the most common species among migration dragonflies. It is often encountered in large swarms during migration or directed dispersal flights. For a better understanding of its gene flow, genetic structure and migration patterns throughout the world, 10 polymorphic microsatellite markers were isolated in this study. We respectively collected 32 P. flavescens from three places (Hunan, Liaoning and Heilongjiang) and 20 P. flavescens from Beijing. Partial genomic libraries containing microsatellite sequences were constructed with magnetic-bead enrichment method. By screening, sequence analysis, PCR amplification and so on, ten 10 polymorphic microsatellite markers were isolated. In order to assess their applicability, genetic diversity of these novel markers was tested in 96 individuals from three populations in China (Hunan, Liaoning and Heilongjiang). These markers were highly polymorphic, with 3-12 alleles per markers. The observed (Ho) and expected (He) heterozygosities ranged 0.321-0.667 and from 0.531 to 0.948 respectively. The genetic difference between Hunan and Liaoning is 0.429, while the genetic difference between Liaoning and Heilongjiang is 0.0508. These microsatellite markers for P. flavescens were developed for the first time, and will be a powerful tool for studying population genetic diversity and dispersal behavior of P. flavescens in China and worldwide.

  18. The Tourette International Collaborative Genetics (TIC Genetics) study, finding the genes causing Tourette syndrome

    DEFF Research Database (Denmark)

    Dietrich, Andrea; Fernandez, Thomas V; King, Robert A

    2015-01-01

    Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarif......Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet......, it is clear that large patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene...... discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent-child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA...

  19. Genetic epidemiology of tuberculosis susceptibility: impact of study design.

    Science.gov (United States)

    Stein, Catherine M

    2011-01-20

    Several candidate gene studies have provided evidence for a role of host genetics in susceptibility to tuberculosis (TB). However, the results of these studies have been very inconsistent, even within a study population. Here, we review the design of these studies from a genetic epidemiological perspective, illustrating important differences in phenotype definition in both cases and controls, consideration of latent M. tuberculosis infection versus active TB disease, population genetic factors such as population substructure and linkage disequilibrium, polymorphism selection, and potential global differences in M. tuberculosis strain. These considerable differences between studies should be accounted for when examining the current literature. Recommendations are made for future studies to further clarify the host genetics of TB.

  20. Factors influencing young men's decision to undergo health screening in Malaysia: a qualitative study

    Science.gov (United States)

    Teo, Chin Hai; Ng, Chirk Jenn; White, Alan

    2017-01-01

    Objectives Uptake of health screening is low in men, particularly among those aged purposively sampled according to their ethnicity, job position, age and screening status in order to achieve maximal variation. Results Eight IDIs and five FGDs were conducted (n=31) and six themes emerged from the analysis. (1) Young men did not consider screening as part of prevention and had low risk perception. (2) The younger generation was more receptive to health screening due to their exposure to health information through the internet. (3) Health screening was not a priority in young men except for those who were married. (4) Young men had limited income and would rather invest in health insurance than screening. (5) Young men tended to follow doctors' advice when it comes to screening and preferred doctors of the same gender and ethnicity. (6) Medical overuse was also raised where young men wanted more screening tests while doctors tended to promote unnecessary screening tests to them. Conclusions This study identified important factors that influenced young men's screening behaviour. Health authorities should address young men's misperceptions, promote the importance of early detection and develop a reasonable health screening strategy for them. Appropriate measures must be put in place to reduce low value screening practices. PMID:28283491

  1. Exploring general practitioners' experience of informing women about prenatal screening tests for foetal abnormalities: A qualitative focus group study

    Directory of Open Access Journals (Sweden)

    Meiser Bettina

    2008-05-01

    Full Text Available Abstract Background Recent developments have made screening tests for foetal abnormalities available earlier in pregnancy and women have a range of testing options accessible to them. It is now recommended that all women, regardless of their age, are provided with information on prenatal screening tests. General Practitioners (GPs are often the first health professionals a woman consults in pregnancy. As such, GPs are well positioned to inform women of the increasing range of prenatal screening tests available. The aim of this study was to explore GPs experience of informing women of prenatal genetic screening tests for foetal abnormality. Methods A qualitative study consisting of four focus groups was conducted in metropolitan and rural Victoria, Australia. A discussion guide was used and the audio-taped transcripts were independently coded by two researchers using thematic analysis. Multiple coders and analysts and informant feedback were employed to reduce the potential for researcher bias and increase the validity of the findings. Results Six themes were identified and classified as 'intrinsic' if they occurred within the context of the consultation or 'extrinsic' if they consisted of elements that impacted on the GP beyond the scope of the consultation. The three intrinsic themes were the way GPs explained the limitations of screening, the extent to which GPs provided information selectively and the time pressures at play. The three extrinsic factors were GPs' attitudes and values towards screening, the conflict they experienced in offering screening information and the sense of powerlessness within the screening test process and the health care system generally. Extrinsic themes reveal GPs' attitudes and values to screening and to disability, as well as raising questions about the fundamental premise of testing. Conclusion The increasing availability and utilisation of screening tests, in particular first trimester tests, has expanded GPs

  2. A genetic study of male sexual orientation.

    Science.gov (United States)

    Bailey, J M; Pillard, R C

    1991-12-01

    Homosexual male probands with monozygotic cotwins, dizygotic cotwins, or adoptive brothers were recruited using homophile publications. Sexual orientation of relatives was assessed either by asking relatives directly, or when this was impossible, asking the probands. Of the relatives whose sexual orientation could be rated, 52% (29/56) of monozygotic cotwins, 22% (12/54) of dizygotic cotwins, and 11% (6/57) of adoptive brothers were homosexual. Heritabilities were substantial under a wide range of assumptions about the population base rate of homosexuality and ascertainment bias. However, the rate of homosexuality among nontwin biological siblings, as reported by probands, 9.2% (13/142), was significantly lower than would be predicted by a simple genetic hypothesis and other published reports. A proband's self-reported history of childhood gender non-conformity did not predict homosexuality in relatives in any of the three subsamples. Thus, childhood gender nonconformity does not appear to be an indicator of genetic loading for homosexuality. Cotwins from concordant monozygotic pairs were very similar for childhood gender nonconformity.

  3. Six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and β-thalassemia in Saudi Arabia.

    Science.gov (United States)

    Memish, Ziad Ahmed; Saeedi, Mohammad Y

    2011-01-01

    Saudi Arabia has a high prevalence of hereditary hemoglobin disorders. Data has been collected by the Saudi Premarital Screening and Genetic Counseling Program on the prevalence of sickle cell disease and β-thalassemia but the outcomes were not quantified. We used six years of premarital screening data to estimate the burden of sickle disease and β-thalassemia over the program period and to assess the frequency of at-risk marriage detection and prevention. Retrospective review, premarital couples attending premarital and genetic counseling clinics with marriage proposals between 2004 and 2009. Blood samples obtained from all couples with marriage proposals between 2004 and 2009 were tested for sickle cell disease and β-thalassemia. Test results were shared with all examinees and genetic counseling was offered for all at-risk couples. Marriage certificates were issued irrespective of the results and compliance with medical advice was voluntary. Out of all men and women examined, 70,962 (4.5%) and 29,006 (1.8%) were carriers or cases of sickle cell disease and β-thalassemia, respectively. While the prevalence of sickle cell disease was constant between 2004 and 2009 (average 45.1 per 1000 examined persons, P=.803), the prevalence of β-thalassemia steadily decreased from 32.9 to 9.0 per 1000 examined persons (Ppremarital screening in Saudi Arabia markedly reduced the number of at-risk marriages, which may considerably reduce the genetic disease burden in Saudi Arabia in the next decades.

  4. Genetic screening of functional properties of lactic acid bacteria in a fermented pearl millet slurry and in the metagenome of fermented starchy foods.

    Science.gov (United States)

    Turpin, Williams; Humblot, Christèle; Guyot, Jean-Pierre

    2011-12-01

    Lactic acid bacteria (LAB) (n = 152) in African pearl millet slurries and in the metagenomes of amylaceous fermented foods were investigated by screening 33 genes involved in probiotic and nutritional functions. All isolates belonged to six species of the genera Pediococcus and Lactobacillus, and Lactobacillus fermentum was the dominant species. We screened the isolates for the abilities to survive passage through the gastrointestinal tract and to synthesize folate and riboflavin. The isolates were also tested in vitro for their abilities to survive exposure to bile salts and to survive at pH 2. Because the ability to hydrolyze starch confers an ecological advantage on LAB that grow in starchy matrixes as well as improving the nutritional properties of the gruels, we screened for genes involved in starch metabolism. The results showed that genes with the potential ability to survive passage through the gastrointestinal tract were widely distributed among isolates and metagenomes, whereas in vitro tests showed that only a limited set of isolates, mainly those belonging to L. fermentum, could tolerate a low pH. In contrast, the wide distribution of genes associated with bile salt tolerance, in particular bsh, is consistent with the high frequency of tolerance to bile salts observed. Genetic screening revealed a potential for folate and riboflavin synthesis in both isolates and metagenomes, as well as high variability among genes related to starch metabolism. Genetic screening of isolates and metagenomes from fermented foods is thus a promising approach for assessing the functional potential of food microbiotas.

  5. Genetic Screening of Functional Properties of Lactic Acid Bacteria in a Fermented Pearl Millet Slurry and in the Metagenome of Fermented Starchy Foods▿

    Science.gov (United States)

    Turpin, Williams; Humblot, Christèle; Guyot, Jean-Pierre

    2011-01-01

    Lactic acid bacteria (LAB) (n = 152) in African pearl millet slurries and in the metagenomes of amylaceous fermented foods were investigated by screening 33 genes involved in probiotic and nutritional functions. All isolates belonged to six species of the genera Pediococcus and Lactobacillus, and Lactobacillus fermentum was the dominant species. We screened the isolates for the abilities to survive passage through the gastrointestinal tract and to synthesize folate and riboflavin. The isolates were also tested in vitro for their abilities to survive exposure to bile salts and to survive at pH 2. Because the ability to hydrolyze starch confers an ecological advantage on LAB that grow in starchy matrixes as well as improving the nutritional properties of the gruels, we screened for genes involved in starch metabolism. The results showed that genes with the potential ability to survive passage through the gastrointestinal tract were widely distributed among isolates and metagenomes, whereas in vitro tests showed that only a limited set of isolates, mainly those belonging to L. fermentum, could tolerate a low pH. In contrast, the wide distribution of genes associated with bile salt tolerance, in particular bsh, is consistent with the high frequency of tolerance to bile salts observed. Genetic screening revealed a potential for folate and riboflavin synthesis in both isolates and metagenomes, as well as high variability among genes related to starch metabolism. Genetic screening of isolates and metagenomes from fermented foods is thus a promising approach for assessing the functional potential of food microbiotas. PMID:22003019

  6. A PCR-based forward genetics screening, using expression domain-specific markers, identifies mutants in endosperm transfer cell development

    Directory of Open Access Journals (Sweden)

    Luis Miguel Muñiz

    2014-04-01

    Full Text Available Mutant collections are an invaluable source of material on which forward genetic approaches allow the identification of genes affecting a wide variety of biological processes. However, some particular developmental stages and morphological structures may resist analysis due to their physical inaccessibility or to deleterious effects associated to their modification. Furthermore, lethal mutations acting early in development may escape detection. We have approached the characterisation of 101 maize seed mutants, selected from a collection of 27500 visually screened Mu-insertion lines, using a molecular marker approach based on a set of genes previously ascribed to different tissue compartments within the early developing kernel. A streamlined combination of qRT-PCR assays has allowed us to preliminary pinpoint the affected compartment, establish developmental comparisons to WT siblings and select mutant lines with alterations in the different compartments. Furthermore, clusters of markers co-affected by the underlying mutation were identified. We have analysed more extensively a set of lines presenting significant variation in transfer cell-associated expression markers, and have performed morphological observations, and immunolocalization experiments to confirm the results, validating this approach as an efficient mutant description tool.

  7. An unbiased genetic screen reveals the polygenic nature of the influenza virus anti-interferon response.

    Science.gov (United States)

    Pérez-Cidoncha, Maite; Killip, Marian J; Oliveros, Juan C; Asensio, Víctor J; Fernández, Yolanda; Bengoechea, José A; Randall, Richard E; Ortín, Juan

    2014-05-01

    Influenza A viruses counteract the cellular innate immune response at several steps, including blocking RIG I-dependent activation of interferon (IFN) transcription, interferon (IFN)-dependent upregulation of IFN-stimulated genes (ISGs), and the activity of various ISG products; the multifunctional NS1 protein is responsible for most of these activities. To determine the importance of other viral genes in the interplay between the virus and the host IFN response, we characterized populations and selected mutants of wild-type viruses selected by passage through non-IFN-responsive cells. We reasoned that, by allowing replication to occur in the absence of the selection pressure exerted by IFN, the virus could mutate at positions that would normally be restricted and could thus find new optimal sequence solutions. Deep sequencing of selected virus populations and individual virus mutants indicated that nonsynonymous mutations occurred at many phylogenetically conserved positions in nearly all virus genes. Most individual mutants selected for further characterization induced IFN and ISGs and were unable to counteract the effects of exogenous IFN, yet only one contained a mutation in NS1. The relevance of these mutations for the virus phenotype was verified by reverse genetics. Of note, several virus mutants expressing intact NS1 proteins exhibited alterations in the M1/M2 proteins and accumulated large amounts of deleted genomic RNAs but nonetheless replicated to high titers. This suggests that the overproduction of IFN inducers by these viruses can override NS1-mediated IFN modulation. Altogether, the results suggest that influenza viruses replicating in IFN-competent cells have tuned their complete genomes to evade the cellular innate immune system and that serial replication in non-IFN-responsive cells allows the virus to relax from these constraints and find a new genome consensus within its sequence space. In natural virus infections, the production of interferons

  8. A Study on Knowledge and Screening for Cervical Cancer among ...

    African Journals Online (AJOL)

    More than three-fourth of these patients are diagnosed in advanced ... Knowledge about cervical cancer, its screening among women. • Role of ... doctors earlier, they were neither educated about cervical cancer nor were they told about.

  9. Studies on antibacterial screening of corm of Amorphophallus campanulatus (Roxb.

    Directory of Open Access Journals (Sweden)

    Bhagwan Mariba Waghmare

    2017-05-01

    Full Text Available Objective: To study the antibacterial screening of corm of Amorphophallus campanulatus (Roxb. (A. campanulatus. Methods: Antibacterial activities of methanolic, petroleum ether and ethyl acetate extracts of corm of A. campanulatus were studied by agar diffusion technique to determine in vitro antibacterial activities. The antibacterial activity was measured with respect to the standard antibacterial drug. In addition, minimum inhibitory concentration was also determined by using serial dilution method to determine and evaluate antibacterial potency of test corm extracts of A. campanulatus. Results: The results showed significant antibacterial activities against four pathogenic bacteria. The minimum inhibitory concentration values against test bacteria were found to be remarkable range in bacteria like methicillin-resistant Staphylococcus aureus at concentration 0.25 mg/ well, in Pseudomonas aeruginosa at 0.5 mg/well concentration, in Vibrio cholerae was 2 mg/ well, Streptococcus pyogenes at concentration of 0.5 mg/well and Proteus mirabilis was at concentration of 2 mg/well. Conclusions: The methanolic and petroleum ether extracts are capable to maximum inhibition of the tested pathogenic bacteria.

  10. Enhanced genetic maps from family-based disease studies: population-specific comparisons

    Directory of Open Access Journals (Sweden)

    Buyske Steven

    2011-01-01

    Full Text Available Abstract Background Accurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS provide appropriate data for generating more accurate maps. Results We collected a large sample of uncleaned genotype data for 461 markers generated by the MGS using the Weber screening sets 9 and 10. This collection includes genotypes for over 4,400 pedigrees containing over 17,000 genotyped individuals from different populations. We identified and cleaned numerous relationship and genotyping errors, as well as verified the marker orders. We used this dataset to test for population-specific genetic maps, and to re-estimate the genetic map distances with greater precision; standard errors for all intervals are provided. The map-interval sizes from the European (or European descent, Chinese, and Hispanic samples are in quite good agreement with each other. We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples. When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p. Several significant differences were also identified between populations in chromosomal and genome lengths. Conclusions Our new population-specific screening set maps can be used to improve the accuracy of disease-mapping studies. As a result of the large sample size, the average length of the 95% confidence interval (CI for a 10 cM map interval is only 2.4 cM, which is considerably smaller than on previously published maps.

  11. Class - III malocclusion: Genetics or environment? A twins study

    Directory of Open Access Journals (Sweden)

    Jena A

    2005-03-01

    Full Text Available Etiology of class-III malocclusion is generally believed to be genetic. A wide range of environmental factors have been suggested as contributing factors for the development of class-III malocclusion. Twin study is one of the most effective methods available for investigating genetically determined variables of malocclusion. Discordancy for class-III malocclusion is a frequent finding in dizygotic twins. However, class-III malocclusion discordancy in monozygotic twins is a rare finding. The purpose of this study of monozygotic twins is to assess the genetic and environmental components of variation within the cranio-dento-facial complex.

  12. A qualitative study exploring why individuals opt out of lung cancer screening.

    Science.gov (United States)

    Carter-Harris, Lisa; Brandzel, Susan; Wernli, Karen J; Roth, Joshua A; Buist, Diana S M

    2017-04-01

    Lung cancer screening with annual low-dose computed tomography is relatively new for long-term smokers in the USA supported by a US Preventive Services Task Force Grade B recommendation. As screening programs are more widely implemented nationally and providers engage patients about lung cancer screening, it is critical to understand behaviour among high-risk smokers who opt out to improve shared decision-making processes for lung cancer screening. The purpose of this study was to explore the reasons for screening-eligible patients' decisions to opt out of screening after receiving a provider recommendation. Semi-structured qualitative telephone interviews were performed with 18 participants who met lung cancer screening criteria for age, smoking and pack-year history in Washington State from November 2015 to January 2016. Two researchers with cancer screening and qualitative methodology expertise conducted data analysis using thematic content analytic procedures from audio-recorded interviews. Five primary themes emerged for reasons of opting out of lung cancer screening: (i) Knowledge Avoidance; (ii) Perceived Low Value; (iii) False-Positive Worry; (iv) Practical Barriers; and (v) Patient Misunderstanding. The participants in our study provided insight into why some patients make the decision to opt out of low-dose computed tomography screening, which provides knowledge that can inform intervention development to enhance shared decision-making processes between long-term smokers and their providers and decrease decisional conflict about screening.

  13. [A study on origin of genetic ethics problem and countermeasure].

    Science.gov (United States)

    Cheng, Yan-Ping

    2008-03-01

    The genetic ethical problem is one of problems which are the most disputable or difficult to resolve perfectly in the fields of life science. In these years the research for the problems is being concentrated on the types of genetic ethical problem and the ways to resolve them. But the systematic research for origin of genetic ethical problem is rare to be known. Thus it seems to be short of theoretical support to bring forward corresponding countermeasure. In this paper we focus on the evolving germ of genetic ethical problem and its evolving rule from the twofold views of human biological evolution and cultural evolution. A human being is a double offspring with biological evolution and cultural evolution . And he is a species which has both biological and cultural attribute on the earth. Through comparing and studying human biological evolution , cultural evolution, and characteristics of both biological attribute and cultural attribute, we bring forward a viewpoint that all ethical problems originate from a conflict originating from interplay of human biological evolution and cultural evolution. We intend to seek for the gist of theory and practice in order to research for genetic ethical problem and put forward some corresponding countermeasures. At the same time we'll advance a series of corresponding countermeasures of genetic ethical problem. The final aim in the paper is that not only some of our opinions will be admitted, but also through learning and understanding genetic ethical problem and its origin, the decision-makers and investigators in genetics field will be promoted to have more sense of fate and responsibility , so that the average public are able to misunderstand less and understand more for studying and genetics applying. We all work hard for genetics career to make it in healthy and continuing development and give a lot of happiness to human beings.

  14. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  15. Study Points to Genetic Subtypes of Esophageal Cancer

    Science.gov (United States)

    A Cancer Currents blog post about a study by The Cancer Genome Atlas Research Network that identified distinct genetic and molecular changes in esophageal cancers that could improve their classification and identify potential new treatments.

  16. Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers : Results from the Initial Screening Round of the IMPACT Study

    NARCIS (Netherlands)

    Bancroft, Elizabeth K.; Page, Elizabeth C.; Castro, Elena; Lilja, Hans; Vickers, Andrew; Sjoberg, Daniel; Assel, Melissa; Foster, Christopher S.; Mitchell, Gillian; Drew, Kate; Maehle, Lovise; Axcrona, Karol; Evans, D. Gareth; Bulman, Barbara; Eccles, Diana; McBride, Donna; van Asperen, Christi; Vasen, Hans; Kiemeney, Lambertus A.; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Selkirk, Christina; Hulick, Peter J.; Bojesen, Anders; Skytte, Anne-Bine; Lam, Jimmy; Taylor, Louise; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A.; Oosterwijk, Jan C.; Blanco, Ignacio; Salinas, Monica; Cook, Jackie; Rosario, Derek J.; Buys, Saundra; Conner, Tom; Ausems, Margreet G.; Ong, Kai-ren; Hoffman, Jonathan; Domchek, Susan; Powers, Jacquelyn; Teixeira, Manuel R.; Maia, Sofia; Foulkes, William D.; Taherian, Nassim; Ruijs, Marielle; Helderman-van den Enden, Apollonia T.; Izatt, Louise; Davidson, Rosemarie; Adank, Muriel A.; Walker, Lisa; Schmutzler, Rita; Tucker, Kathy; Kirk, Judy; Hodgson, Shirley; Harris, Marion; Douglas, Fiona; Lindeman, Geoffrey J.; Zgajnar, Janez; Tischkowitz, Marc; Clowes, Virginia E.; Susman, Rachel; Ramon y Cajal, Teresa; Patcher, Nicholas; Gadea, Neus; Spigelman, Allan; van Os, Theo; Liljegren, Annelie; Side, Lucy; Brewer, Carole; Brady, Angela F.; Donaldson, Alan; Stefansdottir, Vigdis; Friedman, Eitan; Chen-Shtoyerman, Rakefet; Amor, David J.; Copakova, Lucia; Barwell, Julian; Giri, Veda N.; Murthy, Vedang; Nicolai, Nicola; Teo, Soo-Hwang; Greenhalgh, Lynn; Strom, Sara; Henderson, Alex; McGrath, John; Gallagher, David; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Dearnaley, David; Costello, Philandra; Eyfjord, Jorunn; Rothwell, Jeanette; Falconer, Alison; Gronberg, Henrik; Hamdy, Freddie C.; Johannsson, Oskar; Khoo, Vincent; Kote-Jarai, Zsofia; Lubinski, Jan; Axcrona, Ulrika; Melia, Jane; McKinley, Joanne; Mitra, Anita V.; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Wilson, Penny; Killick, Emma; Moss, Sue; Eeles, Rosalind A.

    Background: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in

  17. Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

    NARCIS (Netherlands)

    Bancroft, E.K.; Page, E.C.; Castro, E.; Lilja, H.; Vickers, A.; Sjoberg, D.; Assel, M.; Foster, C.S.; Mitchell, G.; Drew, K.; Maehle, L.; Axcrona, K.; Evans, D.G.; Bulman, B.; Eccles, D.; McBride, D.; Asperen, C. van; Vasen, H.; Kiemeney, B.; Ringelberg, J.; Cybulski, C.; Wokolorczyk, D.; Selkirk, C.; Hulick, P.J.; Bojesen, A.; Skytte, A.B.; Lam, J.; Taylor, L.; Oldenburg, R.; Cremers, R.; Verhaegh, G.; Zelst-Stams, W.A.G. van; Oosterwijk, J.C.; Blanco, I.; Salinas, M.; Cook, J.; Rosario, D.J.; Buys, S.; Conner, T.; Ausems, M.G.; Ong, K.R.; Hoffman, J.; Domchek, S.; Powers, J.; Teixeira, M.R.; Maia, S.; Foulkes, W.D.; Taherian, N.; Ruijs, M.; Enden, A.T. den; Izatt, L.; Davidson, R.; Adank, M.A.; Walker, L.; Schmutzler, R.; Tucker, K.; Kirk, J.; Hodgson, S.; Harris, M.; Douglas, F.; Lindeman, G.J.; Zgajnar, J.; Tischkowitz, M.; Clowes, V.E.; Susman, R.; Ramon, Y.C.T.; Patcher, N.; Gadea, N.; Spigelman, A.; Os, T. van; Liljegren, A.; Side, L.; Brewer, C.; Brady, A.F.; Donaldson, A.; Stefansdottir, V.; Friedman, E.; Chen-Shtoyerman, R.; Amor, D.J.; Copakova, L.; Barwell, J.; Giri, V.N.; Murthy, V.; Nicolai, N.; Teo, S.H.; Greenhalgh, L.; Strom, S.; Henderson, A.; McGrath, J.; Gallagher, D.; Aaronson, N.; Ardern-Jones, A.; Bangma, C.; Dearnaley, D.; Costello, P.; Eyfjord, J.; Rothwell, J.; Falconer, A.; Gronberg, H.; Hamdy, F.C.

    2014-01-01

    BACKGROUND: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in

  18. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: Results from the initial screening round of the IMPACT study

    NARCIS (Netherlands)

    Bancroft, E.K.; Page, E.C.; Castro, E.; Lilja, H.; Vickers, A.; Sjoberg, D.; Assel, M.; Foster, C.S.; Mitchell, G.; Drew, K.; Maehle, L.; Axcrona, K.; Evans, D.G.; Bulman, B.; Eccles, D.; McBride, D.; van Asperen, C.; Vasen, H.; Kiemeney, L.A.; Ringelberg, J.; Cybulski, C.; Wokolorczyk, D.; Selkirk, C.; Hulick, P.J.; Bojesen, A.; Skytte, A.B.; Lam, J.; Taylor, L.; Oldenburg, R.; Cremers, R.; Verhaegh, G.; van Zelst-Stams, W.A.; Oosterwijk, J.C.; Blanco, I.; Salinas, M.; Cook, J.; Rosario, D.J.; Buys, S.; Conner, T.; Ausems, M.G.; Ong, K.R.; Hoffman, J.; Domchek, S.; Powers, J.; Teixeira, M.R.; Maia, S.; Foulkes, W.D.; Taherian, N.; Ruijs, M.; den Enden, A.T.; Izatt, L.; Davidson, R.; Adank, M.A.; Walker, L.; Schmutzler, R.; Tucker, K.; Kirk, J.; Hodgson, S.; Harris, M.; Douglas, F.; Lindeman, G.J.; Zgajnar, J.; Tischkowitz, M.; Clowes, V.E.; Susman, R.; Ramón Y Cajal, T.; Patcher, N.; Gadea, N.; Spigelman, A.; van Os, T.; Liljegren, A.; Side, L.; Brewer, C.; Brady, A.F.; Donaldson, A.; Stefansdottir, V.; Friedman, E.; Chen-Shtoyerman, R.; Amor, D.J.; Copakova, L.; Barwell, J.; Giri, V.N.; Murthy, V.; Nicolai, N.; Teo, S.H.; Greenhalgh, L.; Strom, S.; Henderson, A.; McGrath, J.; Gallagher, D.; Aaronson, N.K.; Ardern-Jones, A.; Bangma, C.; Dearnaley, D.; Costello, P.; Eyfjord, J.; Rothwell, J.; Falconer, A.; Gronberg, H.; Hamdy, F.C.; Johannsson, O.; Khoo, V.; Kote-Jarai, Z.; Lubinski, J.; Axcrona, U.; Melia, J.; McKinley, J.; Mitra, A.V.; Moynihan, C.; Rennert, G.; Suri, M.; Wilson, P.; Killick, E.; Moss, S.; Eeles, R.A.

    2014-01-01

    Background: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in

  19. Molecular dynamics study of phonon screening in graphene

    Science.gov (United States)

    Javvaji, Brahmanandam; Roy Mahapatra, D.; Raha, S.

    2014-04-01

    Phonon interaction with electrons or phonons or with structural defects result in a phonon mode conversion. The mode conversion is governed by the frequency wave-vector dispersion relation. The control over phonon mode or the screening of phonon in graphene is studied using the propagation of amplitude modulated phonon wave-packet. Control over phonon properties like frequency and velocity opens up several wave guiding, energy transport and thermo-electric applications of graphene. One way to achieve this control is with the introduction of nano-structured scattering in the phonon path. Atomistic model of thermal energy transport is developed which is applicable to devices consisting of source, channel and drain parts. Longitudinal acoustic phononmode is excited fromone end of the device. Molecular dynamics based time integration is adopted for the propagation of excited phonon to the other end of the device. The amount of energy transfer is estimated from the relative change of kinetic energy. Increase in the phonon frequency decreases the kinetic energy transmission linearly in the frequency band of interest. Further reduction in transmission is observed with the tuning of channel height of the device by increasing the boundary scattering. Phonon mode selective transmission control have potential application in thermal insulation or thermo-electric application or photo-thermal amplification.

  20. Screening studies of yeasts capable of utilizing petroleum fractions

    Energy Technology Data Exchange (ETDEWEB)

    El-Masry, H.G.; Foda, M.S.

    1979-01-01

    In these studies 23 yeasts cultures belonging to 10 genera of ascosporogenous, ballistosporogenous, and asporogenous yeasts, were screened with respect to their abilities of hydrocarbon utilization in synthetic media. Thus, kerosene, n-hexadecane, and wax distillate were compared as sole carbon sources in 2% final concentration. Kerosene exhibited marked inhibition on the growth of the majority of the strains, whereas active growth was observed with Debaryomyces vanrijii and many species of the genus Candida in media with n-hexadecane or wax distillate as sole source of carbon. In addition, some cultures belonging to the genera Sporobolomyces, Hansenula, Cryptococcus, and Trigonopsis could utilize some of these substrates, but to a lesser extent. Highest yield of cells and protein was obtained with Candida lipolytica NRRL 1094 in n-hexadecane medium, supplied with 0.03% yeast extract and trace element solutions. The results are discussed with respect to the possibilities of using new yeast genera, with special reference to the genus Debaryomyces, in microbial protein production.

  1. [The application of genetic risk score in genetic studies of complex human diseases].

    Science.gov (United States)

    Dayan, Niu; Weili, Yan

    2015-12-01

    Complex diseases such as cardiovascular disease, type 2 diabetes, essential hypertension, asthma, obesity and cancer have spread across the globe and become the predominant cause of death. There are growing concerns over the role of genetic susceptibility in pathogenesis of complex diseases. However, the related susceptibility genes and sequence variations are still unknown. To elucidate the genetic basis of complex diseases, researchers have identified a large number of genetic variants associated with complex diseases through genome-wide association studies (GWAS) and candidate gene studies recently. The identification of these causal and/or associated variants promotes the development of approaches for complex diseases prediction and prevention. Genetic risk score (GRS), an emerging method for exploring correlation between single nucleotide polymorphisms (SNPs) and clinical phenotypes of complex diseases, integrates weak effects of multiple SNPs and dramatically enhances predictability of complex diseases by gene polymorphisms. This method has been applied successfully in genetic studies of many complex diseases. Here we focus on the introduction of the computational methods and evaluation criteria of GRS, enumerate a series of achievements through GRS application, discuss some limitations during application, and finally prospect the future of GRS.

  2. Genetic screening of the FLCN gene identify six novel variants and a Danish founder mutation

    DEFF Research Database (Denmark)

    Rossing, Maria; Albrechtsen, Anders; Skytte, Anne-Bine

    2016-01-01

    Pathogenic germline mutations in the folliculin (FLCN) tumor suppressor gene predispose to Birt-Hogg-Dubé (BHD) syndrome, a rare disease characterized by the development of cutaneous hamartomas (fibrofolliculomas), multiple lung cysts, spontaneous pneumothoraces and renal cell cancer. In this study...

  3. Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia

    NARCIS (Netherlands)

    Allali, Slimane; Le Goff, Carine; Pressac-Diebold, Isabelle; Pfennig, Gwendoline; Mahaut, Clementine; Dagoneau, Nathalie; Alanay, Yasemin; Brady, Angela F.; Crow, Yanick J.; Devriendt, Koen; Drouin-Garraud, Valerie; Flori, Elisabeth; Genevieve, David; Hennekam, Raoul C.; Hurst, Jane; Krakow, Deborah; Le Merrer, Martine; Lichtenbelt, Klaske D.; Lynch, Sally A.; Lyonnet, Stanislas; MacDermot, Kay; Mansour, Sahar; Megarbane, Andre; Santos, Heloisa G.; Splitt, Miranda; Superti-Furga, Andrea; Unger, Sheila; Williams, Denise; Munnich, Arnold; Cormier-Daire, Valerie

    2011-01-01

    Background Geleophysic dysplasia (GD, OMIM 231050) is an autosomal recessive disorder characterised by short stature, small hands and feet, stiff joints, and thick skin. Patients often present with a progressive cardiac valvular disease which can lead to an early death. In a previous study including

  4. Data on screening and identification of genetically modified papaya in food supplements

    NARCIS (Netherlands)

    Prins, Theo W.; Scholtens-Toma, Ingrid; Bak, Arno W.; Dijk, Van Jeroen P.; Voorhuijzen, Marleen M.; Laurensse, Emile J.; Kok, Esther J.

    2016-01-01

    This article contains data related to the research article entitled “A case study to determine the geographical origin of unknown GM papaya in routine food sample analysis, followed by identification of papaya events 16-0-1 and 18-2-4” (Prins et al., 2016) [1]. Quantitative real-time PCR (qPCR) with

  5. Application of AFLP markers for population genetic study on half-smooth tongue sole Cynoglossus semilaevis

    Institute of Scientific and Technical Information of China (English)

    LIU Yunguo; LI Junfeng; YE Naihao

    2011-01-01

    The genetic diversity of wild and hatchery populations of half-smooth tongue sole Cynoglossus semilaevis, based on observation of amplified fragment length polymorphism (AFLP) was described. Two hundred individuals from four wild populations, Laizhou (LZ), Weihai (WH), Qingdao (QD), Rizhao (RZ), and one hatchery population, Mingbo (MB), were screened using eight different AFLP primer combinations. A total of 384 loci were screened in the five studied populations. 48.4%, 51.3%,50.7%, 49.3% and 45.8% of these loci were polymorphic among the individuals tested in the LZ, WH,QD, RZ and MB populations, respectively. The number of polymorphic loci detected by single primer combinations ranged from 17 to 35. The average heterozygosity of the LZ, WH, QD, RZ and MB populations was 0.072, 0.093, 0.092, 0.090 and 0.063, respectively. The WH population showed the highest genetic diversity in terms of total number of AFLP bands, total number of polymorphic bands,average heterozygosity and percentage of low frequency (0-0.2) polymorphic loci among all the populations,while the LZ population was the lowest among the wild populations. Compared with the wild populations,the hatchery population showed a low genetic viability.

  6. Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

    Science.gov (United States)

    Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

    2016-10-01

    Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

  7. A Genetic Screen for Functional Partners of Condensin in Fission Yeast

    OpenAIRE

    Robellet, Xavier; Fauque, Lydia; Legros, Pénélope; Mollereau, Esther; Janczarski, Stéphane; Parrinello, Hugues; Desvignes, Jean-Pierre; Thevenin, Morgane; Bernard, Pascal

    2013-01-01

    Mitotic chromosome condensation is a prerequisite for the accurate segregation of chromosomes during cell division, and the conserved condensin complex a central player of this process. However, how condensin binds chromatin and shapes mitotic chromosomes remain poorly understood. Recent genome-wide binding studies showing that in most species condensin is enriched near highly expressed genes suggest a conserved link between condensin occupancy and high transcription rates. To gain insight in...

  8. Screening Preschool Children for Visual Disorders: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Suman Adhikari, BOptom

    2013-12-01

    Full Text Available Purpose: Ocular and/or vision defects are one of the most common reasons for the referral of young children to the hospital. Vision disorders are the fourth most common disability of children and the leading cause of handicapping conditions in childhood. In preschool-age children, amblyopia and amblyogenic risk factors, such as strabismus and significant refractive errors, are the most prevalent and important visual disorders. The purpose of this pilot study was to determine the prevalence of visual disorders in preschool children in Kathmandu Valley, Nepal.Methods: Four hundred and eighty-four children attending eight preschools in Kathmandu Valley underwent detailed optometric examination. Visual acuity was assessed with either Sheridan Gardiner or Kay Picture chart monocularly. Binocularity was assessed with cover test and prism bar neutralisation. Refraction was carried out in all children. In most instances this was done without the use of a cycloplegic agent. Stereopsis was assessed with the Lang stereo test. Anterior and posterior segment abnormalities were assessed by using a pen light, hand-held slit lamp, and direct ophthalmoscope.Results: Refractive error was the most common visual disorder. Considering our criteria of refractive error for myopia ≥ 0.50 D, hyperopia ≥ 1.50 D, astigmatism ≥ 1.00 D, and anisometropia ≥ 1.00 D, the overall prevalence of refractive error in our study was 31.82%. The overall prevalence of myopia, hyperopia, and astigmatism was 24.17%, 2.48%, and 5.17%, respectively. Anisometropia was present in 1.65% of the participants, and 2%, 1.4%, and 0.2% had strabismus, amblyopia, and nystagmus, respectively.Conclusion: The relatively high prevalence of refractive error in our studied population needs more attention. The results suggest that there is a need for a large-scale community-based preschool screening program in Nepal so that affected children can be identified early and appropriate treatment can be

  9. Genetic association studies in lumbar disc degeneration: a systematic review.

    Directory of Open Access Journals (Sweden)

    Pasi J Eskola

    Full Text Available OBJECTIVE: Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI in humans. METHODS: A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. RESULTS: Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat, COL11A1 (rs1676486, GDF5 (rs143383, SKT (rs16924573, THBS2 (rs9406328 and MMP9 (rs17576. CONCLUSIONS: Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

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

    CERN Document Server

    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 the size of the contribution by such factors is significant. In this respect, some recent simulation-based studies have shed more light to the prospect of genetic tests. In this report, we discuss several aspects of simulation-based studies: their parameters, their assumptions, and the information they provide.

  11. Multiple comparisons in genetic association studies: a hierarchical modeling approach.

    Science.gov (United States)

    Yi, Nengjun; Xu, Shizhong; Lou, Xiang-Yang; Mallick, Himel

    2014-02-01

    Multiple comparisons or multiple testing has been viewed as a thorny issue in genetic association studies aiming to detect disease-associated genetic variants from a large number of genotyped variants. We alleviate the problem of multiple comparisons by proposing a hierarchical modeling approach that is fundamentally different from the existing methods. The proposed hierarchical models simultaneously fit as many variables as possible and shrink unimportant effects towards zero. Thus, the hierarchical models yield more efficient estimates of parameters than the traditional methods that analyze genetic variants separately, and also coherently address the multiple comparisons problem due to largely reducing the effective number of genetic effects and the number of statistically "significant" effects. We develop a method for computing the effective number of genetic effects in hierarchical generalized linear models, and propose a new adjustment for multiple comparisons, the hierarchical Bonferroni correction, based on the effective number of genetic effects. Our approach not only increases the power to detect disease-associated variants but also controls the Type I error. We illustrate and evaluate our method with real and simulated data sets from genetic association studies. The method has been implemented in our freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/).

  12. Genetic screening of Scandinavian families with febrile seizures and epilepsy or GEFS+

    DEFF Research Database (Denmark)

    Selmer, K K; Egeland, T; Solaas, M H

    2008-01-01

    Background - Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. Objective - To study the occurrence of mutations in these genes in families...... with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. Material and methods - We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. Results - We...

  13. Adolescent Scoliosis Screening in Nara City Schools: A 23-Year Retrospective Cross-Sectional Study

    OpenAIRE

    Yamamoto, Satoshi; Shigematsu, Hideki; Kadono, Fumihiko; Tanaka, Yukihiro; Tatematsu, Masataka; Okuda, Akinori; Iwata, Eiichiro; Koizumi, Munehisa; Tanaka, Yasuhito

    2015-01-01

    Study Design Retrospective cross-sectional study. Purpose To determine the prevalence of idiopathic scoliosis, define the distribution of the curve magnitude, evaluate the accuracy of Moiré topography as a screening tool, and investigate the cost-effectiveness of our screening system. Overview of Literature Early detection of idiopathic scoliosis provides the opportunity for conservative treatment before the deformity is noticeable. We believe that scoliosis screening in schools is useful for...

  14. Digital mammography in a screening programme and its implications for pathology: a comparative study.

    LENUS (Irish Health Repository)

    Feeley, Linda

    2011-03-01

    Most studies comparing full-field digital mammography (FFDM) with conventional screen-film mammography (SFM) have been radiology-based. The pathological implications of FFDM have received little attention in the literature, especially in the context of screening programmes. The primary objective of this retrospective study is to compare FFDM with SFM in a population-based screening programme with regard to a number of pathological parameters.

  15. Adolescent Scoliosis Screening in Nara City Schools: A 23-Year Retrospective Cross-Sectional Study.

    OpenAIRE

    YAMAMOTO, Satoshi; Shigematsu, Hideki; Kadono, Fumihiko; Tanaka, Yukihiro; Tatematsu, Masataka; Okuda, Akinori; Iwata, Eiichiro; Koizumi, Munehisa; Tanaka, Yasuhito

    2015-01-01

    STUDY DESIGN: Retrospective cross-sectional study. PURPOSE: To determine the prevalence of idiopathic scoliosis, define the distribution of the curve magnitude, evaluate the accuracy of Moiré topography as a screening tool, and investigate the cost-effectiveness of our screening system. OVERVIEW OF LITERATURE: Early detection of idiopathic scoliosis provides the opportunity for conservative treatment before the deformity is noticeable. We believe that scoliosis screening in schools is useful ...

  16. Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish.

    Science.gov (United States)

    Kok, Fatma O; Shin, Masahiro; Ni, Chih-Wen; Gupta, Ankit; Grosse, Ann S; van Impel, Andreas; Kirchmaier, Bettina C; Peterson-Maduro, Josi; Kourkoulis, George; Male, Ira; DeSantis, Dana F; Sheppard-Tindell, Sarah; Ebarasi, Lwaki; Betsholtz, Christer; Schulte-Merker, Stefan; Wolfe, Scot A; Lawson, Nathan D

    2015-01-12

    The widespread availability of programmable site-specific nucleases now enables targeted gene disruption in the zebrafish. In this study, we applied site-specific nucleases to generate zebrafish lines bearing individual mutations in more than 20 genes. We found that mutations in only a small proportion of genes caused defects in embryogenesis. Moreover, mutants for ten different genes failed to recapitulate published Morpholino-induced phenotypes (morphants). The absence of phenotypes in mutant embryos was not likely due to maternal effects or failure to eliminate gene function. Consistently, a comparison of published morphant defects with the Sanger Zebrafish Mutation Project revealed that approximately 80% of morphant phenotypes were not observed in mutant embryos, similar to our mutant collection. Based on these results, we suggest that mutant phenotypes become the standard metric to define gene function in zebrafish, after which Morpholinos that recapitulate respective phenotypes could be reliably applied for ancillary analyses.

  17. GENETIC STUDY OF HUMAN CELLS IN VITRO

    Science.gov (United States)

    Chang, R. Shihman

    1960-01-01

    The isolation of carbohydrate variants from cultures of HeLa and conjunctival cells was described. Factors inherent in the cell culture system, such as parent populations and dialyzed serums, have been shown to influence the outcome of variant isolations. Established stable variants incorporated significantly more pentoses or lactate into various cell fractions than the parent cultures. Besides their abilities to propagate continuously in the selecting environments, the variants multiplied slower, were more susceptible to sub-zero preservation and the cytotoxic effect of D-2-deoxyglucose, showed lower cloning efficiencies and were less susceptible to the deleterious effect of glucose oxidase. The ribose variants also differed from the parent cultures in morphological appearance such as formation of multinucleated cells and ring-shaped colonies. They converted more ribose into other component sugars of mucopolysaccharides than the parent cultures. Preliminary analyses of the mucopolysaccharides extracted from the ribose variants and parent cultures showed large difference in their carbohydrate (Molisch-positive materials) and DNA ratios. Evidence suggests that a sequence of interrelated events from genetic selection to primitive morphogenesis has been established. PMID:13692337

  18. Study on conglutination model for fine moist material during screening

    Institute of Scientific and Technical Information of China (English)

    陈惜明; 邓凡政; 赵跃民; 朱红; 高庆宇

    2002-01-01

    All coal preparation in which fine coal is handled depends to some extent on the wettability of coal surface by water. The content of external water in fine moist material plays significant role on screening. This article probed into the causations why fine moist materials adhere to the screen deck on common vibrator in the process of screening. Although the wetting that results from interactions between the coal surface and water molecules that are determined by the composition of coal matrix (interrelated with coal rank) and heterogeneous constituents such as oxygen function groups, mineral impurities and pores have something to do with adhering, we found that the effect of wettability is not the key causation to agglomeration, in other words, water bridges among particles are the key causation to the fine moist materials adhesion. This paper also shows how the capillary adhesive forces forms and how to calculate and measure these forces.

  19. Multi-Touch Screen Interfaces And Gesture Analysis: A Study

    Directory of Open Access Journals (Sweden)

    Mrudula Nimbarte

    2011-12-01

    Full Text Available The way how we handle computers today will soon change. The future technology will allow us tointeract with the computer on different level from the current technology what we are used to. The toolssuch as the mouse and the keyboard need to communicate with the computer will slowly disappearand be replaced with more comfortable and more natural tools for the human being to use. That future isalready here. The rate of how touch screen hardware and applications are used is growing rapidlyand will break new r e c o r ds in n e a r f ut u r e . This new technology requires different ways ofdetecting inputs from the user - inputs which will be made out of on- screen gestures rather than byclicking of buttons or scrolling mouse wheels. In this paper we s tudied the gestures defined formulti-touch screen interfaces, the methods used to detect them and how they are passed on to otherapplications.

  20. Mass Spectrometry-Based Diagnosis of Hemoglobinopathies: A Potential Tool for the Screening of Genetic Disorder.

    Science.gov (United States)

    Das, Rajdeep; Mitra, Gopa; Mathew, Boby; Bhat, Vijay; Ross, Cecil; Pal, Debnath; Mandal, Amit Kumar

    2016-12-01

    Hemoglobinopathies are caused by point mutation in globin gene that results in structural variant of hemoglobin. While 7 % of world populations are carrier of hemoglobinopathies, the prevalence of the disease varies between 3 to 17 % across different population groups in India. In a diagnostic laboratory, alkaline gel electrophoresis and cation exchange-based HPLC (CE-HPLC) are most widely used techniques for characterization of hemoglobin variants. In the above methods, the differential surface charge of hemoglobin molecule in variants is exploited for their characterization. Sometime, co-migration of variants in gel electrophoresis and co-elution or elution with unknown retention time in automated CE-HPLC might lead to ambiguity in the analysis of hemoglobinopathies. Under such circumstances, it is necessary to use other analytical methods that provide unambiguous results. Mass spectrometry-based proteomics approach and DNA sequence analysis are examples of such alternative methods. In the present study, liquid chromatography coupled to mass spectrometry has been used for three commonly observed variants in India, e.g., HbE, HbQ India and HbD Punjab that appeared with inappropriate results in the conventional analysis. A customized hemoglobin variant database has been used in the mass spectrometry-based analysis of those three variants. Mass spectrometry-based proteomics approach was used to analyze above variant sample accurately.

  1. Genetics of dietary habits and obesity - a twin study

    DEFF Research Database (Denmark)

    Hasselbalch, Ann Louise

    2010-01-01

    exposures as well as genetic differences between individuals, resulting in differentiated susceptibility to environmental exposures. The evidence for genetic influence on anthropometry has previously been established and has been estimated to be 60-70% based on twin studies. These inter...... mass, but only limited evidence for associations between habitual dietary intake and anthropometry exists. Differences in habitual dietary intake are also partly determined by differences in genes influencing smell and taste preferences. But, so far, only few studies have investigated genetic...... influences on dietary intake in adults and the interplay between diet, genes and obesity. The focus of the thesis was to investigate the genetic and environmental influence on habitual diet and obesity as well as the association between habitual diet and anthropometry. The thesis is based on structural...

  2. Cannabis controversies: how genetics can inform the study of comorbidity.

    Science.gov (United States)

    Agrawal, Arpana; Lynskey, Michael T

    2014-03-01

    To review three key and controversial comorbidities of cannabis use-other illicit drug use, psychosis and depression, as well as suicide, from a genetically informed perspective. Selective review. Genetic factors play a critical role in the association between cannabis use, particularly early-onset use and use of other illicit drugs, psychosis and depression, as well as suicide, albeit via differing mechanisms. For other illicit drugs, while there is strong evidence for shared genetic influences, residual association that is attributable to causal or person-specific environmental factors cannot be ruled out. For depression, common genetic influences are solely responsible for the association with cannabis use but for suicidal attempt, evidence for person-specific factors persists. Finally, even though rates of cannabis use are inordinately high in those with psychotic disorders, there is no evidence of shared genetic etiologies underlying this comorbidity. Instead, there is limited evidence that adolescent cannabis use might moderate the extent to which diathesis influences psychosis. Overlapping genetic influences underlie the association between early-onset cannabis use and other illicit drug use as well as depression and suicide. For psychosis, mechanisms other than shared genetic influences might be at play. © 2014 Society for the Study of Addiction.

  3. Class - III malocclusion: Genetics or environment? A twins study

    OpenAIRE

    Jena A; Duggal R; Mathur V; Parkash H

    2005-01-01

    Etiology of class-III malocclusion is generally believed to be genetic. A wide range of environmental factors have been suggested as contributing factors for the development of class-III malocclusion. Twin study is one of the most effective methods available for investigating genetically determined variables of malocclusion. Discordancy for class-III malocclusion is a frequent finding in dizygotic twins. However, class-III malocclusion discordancy in monozygotic twins is a rare finding. The p...

  4. Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.

    Directory of Open Access Journals (Sweden)

    Richard T Timms

    Full Text Available The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral ubiquitin E3 ligases which downregulate MHC-I and additional cell surface immunoreceptors. To identify novel cellular genes required for K5 function we performed a forward genetic screen in near-haploid human KBM7 cells. The screen identified proteolipid protein 2 (PLP2, a MARVEL domain protein of unknown function, as essential for K5 activity. Genetic loss of PLP2 traps the viral ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5-expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range of novel K5 targets, all of which required PLP2 for their K5-mediated downregulation. This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system.

  5. Haploid genetic screens identify an essential role for PLP2 in the downregulation of novel plasma membrane targets by viral E3 ubiquitin ligases.

    Directory of Open Access Journals (Sweden)

    Richard T Timms

    Full Text Available The Kaposi's sarcoma-associated herpesvirus gene products K3 and K5 are viral ubiquitin E3 ligases which downregulate MHC-I and additional cell surface immunoreceptors. To identify novel cellular genes required for K5 function we performed a forward genetic screen in near-haploid human KBM7 cells. The screen identified proteolipid protein 2 (PLP2, a MARVEL domain protein of unknown function, as essential for K5 activity. Genetic loss of PLP2 traps the viral ligase in the endoplasmic reticulum, where it is unable to ubiquitinate and degrade its substrates. Subsequent analysis of the plasma membrane proteome of K5-expressing KBM7 cells in the presence and absence of PLP2 revealed a wide range of novel K5 targets, all of which required PLP2 for their K5-mediated downregulation. This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system.

  6. SCREENING FOR GLAUCOMA IN RURAL POPULATION: A HOSPITAL BASED STUDY

    Directory of Open Access Journals (Sweden)

    Rhutuja A

    2015-12-01

    Full Text Available AIM To estimate the prevalence of blindness due to glaucoma in patients aged 40 years and above attending Tertiary Care Hospital. MATERIAL AND METHODS The study was conducted in the Department of Ophthalmology, Mahatma Gandhi Institute of Medical Sciences, Sevagram. Visual acuity, anterior segment examination and anterior chamber depth assessment by slit lamp, digital tension, non-contact tonometry, confrontation field test, fundus examination, direct ophthalmoscopy and fundus imaging was done. Gonioscopy and automated perimetry was done in glaucoma suspects. RESULTS 7600 eyes of 3800 patients were examined, 108 eyes were diagnosed to have glaucoma. Based on the best corrected visual acuity, 15(13.8% eyes and 8(0.22% persons had visual impairment and 33(30.5% eyes and 20(31.7% persons were blind. The prevalence of glaucoma in eyes was 1.42%. The prevalence of blindness due to glaucoma in eyes was 0.43% and person was 0.52%. The prevalence of Primary Open Angle Glaucoma in eyes was 1%, Primary Angle Closure Glaucoma in eyes was 0.15%, Neovascular glaucoma in eyes was 0.07%, Lens Induced Glaucoma in eyes was 0.17% and Pseudoexfoliative Glaucoma in eyes was 0.03%. IOP>20mmHg was present in 50(36.1% glaucomatous eyes, majority of the eyes being in Open Angle Glaucoma 24(31.5% eyes; 58(53.7% glaucomatous eyes had IOP in the range 11-20mmHg, among them 38 eyes were on treatment and 20 eyes were operated. CONCLUSION Being an irreversible disease if diagnosed early, blindness can be avoided. So screening is very important for early diagnosis and their proper management thereon.

  7. Genetic variations of human neuropsin gene and psychiatric disorders: polymorphism screening and possible association with bipolar disorder and cognitive functions.

    Science.gov (United States)

    Izumi, Aiko; Iijima, Yoshimi; Noguchi, Hiroko; Numakawa, Tadahiro; Okada, Takeya; Hori, Hiroaki; Kato, Tadafumi; Tatsumi, Masahiko; Kosuga, Asako; Kamijima, Kunitoshi; Asada, Takashi; Arima, Kunimasa; Saitoh, Osamu; Shiosaka, Sadao; Kunugi, Hiroshi

    2008-12-01

    Human neuropsin (NP) (hNP) has been implicated in the progressive change of cognitive abilities during primate evolution. The hNP gene maps to chromosome 19q13, a region reportedly linked to schizophrenia and bipolar disorder. Therefore, hNP is a functional and positional candidate gene for association with schizophrenia, mood disorders, and cognitive ability. Polymorphism screening was performed for the entire hNP gene. The core promoter region was determined and whether or not transcriptional activity alters in an allele-dependent manner was examined by using the dual-luciferase system. Allelic and genotypic distributions of five single-nucleotide polymorphisms (SNPs) were compared between patients with schizophrenia (n=439), major depression (n=409), bipolar disorder (n=207), and controls (n=727). A possible association of the hNP genotype with memory index (assessed with Wechsler Memory Scale, revised, WMS-R) and intelligence quotient (IQ assessed with Wechsler Adult Intelligence Scale, revised; WAIS-R) was examined in healthy controls (n=166). A total of 28 SNPs, including nine novel SNPs, were identified. No significant effects on transcriptional activity were observed for SNPs in the promoter region. A significant allelic association was found between several SNPs and bipolar disorder (for SNP23 at the 3' regulatory region; odds ratio 1.48, 95% confidential interval 1.16-1.88, P=0.0015). However, such an association was not detected for schizophrenia or depression. Significant differences were observed between SNP23 and attention/concentration sub-scale score of WMS-R (P=0.016) and verbal IQ (P<0.001). Genetic variation of the hNP gene may contribute to molecular mechanisms of bipolar disorder and some aspects of memory and intelligence.

  8. Universal Developmental Screening: Preliminary Studies in Galicia, Spain

    Science.gov (United States)

    Sarmiento Campos, Jose A.; Squires, Jane; Ponte, Jaime

    2011-01-01

    "A_Tempo" is a research project that is currently under development in Galicia, an autonomous community of Spain. Its main aim is to propose an effective universal screening procedure for early identification of developmental disorders in children from zero to three years of age who attend Galician pre-primary schools.…

  9. Multicenter study of the COPD-6 screening device

    DEFF Research Database (Denmark)

    Kjeldgaard, Peter; Lykkegaard Karlsen, Jesper; Spillemose, Heidi

    2017-01-01

    BACKGROUND AND AIM: Early detection of COPD may reduce the future burden of the disease. We aimed to investigate whether prescreening with a COPD-6 screening device (measuring FEV1 and FEV6) facilitates early detection of COPD in primary care. METHODS: In primary care, individuals at high risk of...

  10. Premarital genetic screening for beta thalassemia carrier status of indexed families using HbA2 electrophoresis.

    Science.gov (United States)

    Nosheen, Aneeqa; Ahmad, Habib; Qayum, Iftikhar; Siddiqui, Noaman; Abbasi, Fida Muhammad; Iqbal, Muhammad Sajjad

    2015-10-01

    To devise a strategy for prevention of beta thalassemia in newborns through reliable screening of indexed families. The cross-sectional study was conducted over six months in 2011 and comprised blood samples collected from subjects belonging to different ethnic groups from families of beta thalassemia major children registered with the Abbottonian Medical Association Blood Care Centre, Abbottabad, in Pakistan's Khyber Pakhtunkhwa province. Electrophoretic separation of human haemoglobin like A, F, S and C was done and then haemoglobin in the gel was immobilised in a fixative solution and the gel was dried to a film. Haemoglobin pattern was visualised by staining the film with a protein-specific stain. The pattern was quantified by densitometry. Of the 98 samples, 57(58.2%) had b-thalassemia trait with elevated haemoglobin alpha 2 level, and 41(41.8%) had normal level. Out of the 57 carriers, 33(57.89%) were males and 24(42.10%) were females. Mean age of carriers was 11.65±6.25 years compared to 10.93±7.75 in normal patients. Mean haemoglobin alpha 2 level of carriers was 5.2±0.56% compared to 2.34±0.57% in normal subjects. Carrying out mass screening programmes throughout Pakistan for the detection of thalassemia carriers and providing them the benefit of marriage counselling may decrease the incidence of thalassemia Major.

  11. Bowel cancer screening in England: a qualitative study of GPs' attitudes and information needs

    OpenAIRE

    Woodrow Chris; Rozmovits Linda; Hewitson Paul; Rose Peter; Austoker Joan; Watson Eila

    2006-01-01

    Abstract Background The National Health Service Bowel Cancer Screening Programme is to be introduced in England during 2006. General Practitioners are a potentially important point of contact for participants throughout the screening process. The aims of the study were to examine GPs' attitudes and information needs with regard to bowel cancer screening, with a view to developing an information pack for primary care teams that will be circulated prior to the introduction of the programme. Met...

  12. Methods for Analyzing Multivariate Phenotypes in Genetic Association Studies

    Directory of Open Access Journals (Sweden)

    Qiong Yang

    2012-01-01

    Full Text Available Multivariate phenotypes are frequently encountered in genetic association studies. The purpose of analyzing multivariate phenotypes usually includes discovery of novel genetic variants of pleiotropy effects, that is, affecting multiple phenotypes, and the ultimate goal of uncovering the underlying genetic mechanism. In recent years, there have been new method development and application of existing statistical methods to such phenotypes. In this paper, we provide a review of the available methods for analyzing association between a single marker and a multivariate phenotype consisting of the same type of components (e.g., all continuous or all categorical or different types of components (e.g., some are continuous and others are categorical. We also reviewed causal inference methods designed to test whether the detected association with the multivariate phenotype is truly pleiotropy or the genetic marker exerts its effects on some phenotypes through affecting the others.

  13. Genetic diversity studies of Kherigarh cattle based on microsatellite markers

    Indian Academy of Sciences (India)

    A. K. Pandey; Rekha Sharma; Yatender Singh; B. B. Prakash; S. P. S. Ahlawat

    2006-08-01

    We report a genetic diversity study of Kherigarh cattle, a utility draught-purpose breed of India, currently declining at a startling rate, by use of microsatellite markers recommended by the Food and Agriculture Organization. Microsatellite genotypes were derived, and allelic and genotypic frequencies, heterozygosities and gene diversity were estimated. A total of 131 alleles were distinguished by the 21 microsatellite markers used. All the microsatellites were highly polymorphic, with mean (± s.e.) allelic number of 6.24 ± 1.7, ranging 4–10 per locus. The observed heterozygosity in the population ranged between 0.261 and 0.809, with mean (± s.e.) of 0.574 ± 0.131, indicating considerable genetic variation in this population. Genetic bottleneck hypotheses were also explored. Our data suggest that the Kherigarh breed has not experienced a genetic bottleneck in the recent past.

  14. Screening for gestational diabetes mellitus by a model based on risk indicators: a prospective study

    DEFF Research Database (Denmark)

    Jensen, Dorte; Mølsted-Pedersen, Lars; Beck-Nielsen, Henning;

    2003-01-01

    This study was performed to prospectively evaluate a screening model for gestational diabetes mellitus on the basis of clinical risk indicators.......This study was performed to prospectively evaluate a screening model for gestational diabetes mellitus on the basis of clinical risk indicators....

  15. A genetic Study of Mortality in Danish Jersey Heifer Calves

    DEFF Research Database (Denmark)

    Norberg, Elise; Pryce, Jennie; Pedersen, Jørn

    2013-01-01

    . The mortality traits included in the analysis were defined as mortality in 8 different periods from 24h after birth to age 180d (d 1–14, d 15–30, d 31–60, d 61–90, d 91–120, d 121–150, and d 151–180) and mortality over the entire period. A linear model was used for estimation of genetic parameters, breeding......The aim of this study was to estimate genetic parameters for mortality of Jersey heifer calves during the first 6mo after birth, calculate the genetic trend of the trait, and estimate breeding values of widely used Jersey sires. More than 260,000 heifer calves were included in the study...... values of sires, and genetic trend. Fixed effects included in the model were herd-year class, month of birth, parity of mother, and whether the calf was sold to another farm in the first 6mo. Both direct and maternal genetic effects were included in the model; however, the maternal genetic effect...

  16. Deaf Adults' Reasons for Genetic Testing Depend on Cultural Affiliation: Results from a Prospective, Longitudinal Genetic Counseling and Testing Study

    Science.gov (United States)

    Boudreault, Patrick; Baldwin, Erin E.; Fox, Michelle; Dutton, Loriel; Tullis, LeeElle; Linden, Joyce; Kobayashi, Yoko; Zhou, Jin; Sinsheimer, Janet S.; Sininger, Yvonne; Grody, Wayne W.; Palmer, Christina G. S.

    2010-01-01

    This article examines the relationship between cultural affiliation and deaf adults' motivations for genetic testing for deafness in the first prospective, longitudinal study to examine the impact of genetic counseling and genetic testing on deaf adults and the deaf community. Participants (n = 256), classified as affiliating with hearing, Deaf,…

  17. Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: Efficient identification of known microduplications and identification of a novel microduplication in ASMT

    Directory of Open Access Journals (Sweden)

    Reichert Jennifer G

    2008-10-01

    Full Text Available Abstract Background It has previously been shown that specific microdeletions and microduplications, many of which also associated with cognitive impairment (CI, can present with autism spectrum disorders (ASDs. Multiplex ligation-dependent probe amplification (MLPA represents an efficient method to screen for such recurrent microdeletions and microduplications. Methods In the current study, a total of 279 unrelated subjects ascertained for ASDs were screened for genomic disorders associated with CI using MLPA. Fluorescence in situ hybridization (FISH, quantitative polymerase chain reaction (Q-PCR and/or direct DNA sequencing were used to validate potential microdeletions and microduplications. Methylation-sensitive MLPA was used to characterize individuals with duplications in the Prader-Willi/Angelman (PWA region. Results MLPA showed two subjects with typical ASD-associated interstitial duplications of the 15q11-q13 PWA region of maternal origin. Two additional subjects showed smaller, de novo duplications of the PWA region that had not been previously characterized. Genes in these two novel duplications include GABRB3 and ATP10A in one case, and MKRN3, MAGEL2 and NDN in the other. In addition, two subjects showed duplications of the 22q11/DiGeorge syndrome region. One individual was found to carry a 12 kb deletion in one copy of the ASPA gene on 17p13, which when mutated in both alleles leads to Canavan disease. Two subjects showed partial duplication of the TM4SF2 gene on Xp11.4, previously implicated in X-linked non-specific mental retardation, but in our subsequent analyses such variants were also found in controls. A partial duplication in the ASMT gene, located in the pseudoautosomal region 1 (PAR1 of the sex chromosomes and previously suggested to be involved in ASD susceptibility, was observed in 6–7% of the cases but in only 2% of controls (P = 0.003. Conclusion MLPA proves to be an efficient method to screen for chromosomal

  18. Consent for Genetic Research in the Framingham Heart Study

    Science.gov (United States)

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

    2010-01-01

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

  19. Genetic Geostatistical Framework for Spatial Analysis of Fine-Scale Genetic Heterogeneity in Modern Populations: Results from the KORA Study

    OpenAIRE

    Diaz-Lacava, A. N.; Walier, M; D. Holler; Steffens, M; Gieger, C; C. Furlanello; Lamina, C; Wichmann, H E; Becker, T

    2015-01-01

    Aiming to investigate fine-scale patterns of genetic heterogeneity in modern humans from a geographic perspective, a genetic geostatistical approach framed within a geographic information system is presented. A sample collected for prospective studies in a small area of southern Germany was analyzed. None indication of genetic heterogeneity was detected in previous analysis. Socio-demographic and genotypic data of German citizens were analyzed (212 SNPs; n = 728). Genetic heterogeneity was ev...

  20. WONOEP appraisal: new genetic approaches to study epilepsy

    Science.gov (United States)

    Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

    2014-01-01

    Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non

  1. Carrier screening for spinal muscular atrophy (SMA in 107,611 pregnant women during the period 2005-2009: a prospective population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Yi-Ning Su

    Full Text Available BACKGROUND: Spinal muscular atrophy (SMA is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50 as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program. METHODS AND FINDINGS: This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1 pregnant women were tested for SMA heterozygosity; (2 if the mother was determined to be heterozygous for SMA (carrier status, the paternal partner was then tested; (3 if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%. The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49% and SMA was diagnosed in 12 (27.91% fetuses. The prevalence of SMA in our population was 1 in 8,968. CONCLUSION: The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling.

  2. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report

    DEFF Research Database (Denmark)

    Field, John K; Smith, Robert A; Aberle, Denise R

    2011-01-01

    The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer......, which are summarized in this report. The recommendation from the workshop, and supported by the IASLC Board of Directors, was to set up the Strategic CT Screening Advisory Committee (IASLC-SSAC). The Strategic CT Screening Advisory Committee is currently engaging professional societies and organizations...

  3. Genetics of dietary habits and obesity - a twin study.

    Science.gov (United States)

    Hasselbalch, Ann Louise

    2010-09-01

    Obesity has become a major health concern due to the increased risk of co-morbidities, resulting in decreased quality of life, stigmatization, reduced working ability and early death. This causes a great challenge for the health care systems and results in increased direct costs related to treatment of obesity and co-morbidities, as well as increased indirect costs related to reduced function and withdrawal from the labour market. Both between and within societies, large variation in the prevalence of overweight and obesity exists. This variation is caused by differences in environmental exposures as well as genetic differences between individuals, resulting in differentiated susceptibility to environmental exposures. The evidence for genetic influence on anthropometry has previously been established and has been estimated to be 60-70% based on twin studies. These inter-individual differences can, however, not explain the increase in obesity prevalence during the past 70 years. Environmental factors must therefore play an important role in the obesity epidemic. Habitual diet is one of many environmental factors that potentially contribute to the inter-individual differences in body fat mass, but only limited evidence for associations between habitual dietary intake and anthropometry exists. Differences in habitual dietary intake are also partly determined by differences in genes influencing smell and taste preferences. But, so far, only few studies have investigated genetic influences on dietary intake in adults and the interplay between diet, genes and obesity. The focus of the thesis was to investigate the genetic and environmental influence on habitual diet and obesity as well as the association between habitual diet and anthropometry. The thesis is based on structural equation modelling of twin data from the Danish Twin Registry with special focus on the GEMINAKAR twin study that was performed in 1997-2000. In this study, anthropometric traits of the twin pairs

  4. Genetic and biomarker studies of human longevity

    NARCIS (Netherlands)

    Deelen, Joris

    2014-01-01

    The aim of this thesis was to identify novel lifespan regulating loci that influence human longevity and population mortality. To this end, we performed two genome-wide association studies, one of long-lived individuals from the family-based Leiden Longevity Study (LLS) and an extended one of long-l

  5. Disease-Concordant Twins Empower Genetic Association Studies.

    Science.gov (United States)

    Tan, Qihua; Li, Weilong; Vandin, Fabio

    2017-01-01

    Genome-wide association studies with moderate sample sizes are underpowered, especially when testing SNP alleles with low allele counts, a situation that may lead to high frequency of false-positive results and lack of replication in independent studies. Related individuals, such as twin pairs 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 and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size 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. © 2016 John Wiley & Sons Ltd/University College London.

  6. Chip-based mtDNA mutation screening enables fast and reliable genetic diagnosis of OXPHOS patients

    NARCIS (Netherlands)

    R.G.E. van Eijsden (Rudy); E. Briem (Egill); V. Tiranti (Valeria); H.J.M. Smeets (Hubert); M. Gerards (Mike); L.M.T. Eijssen (Lars); A. Hendrickx (Alexandra); R.J.E. Jongbloed (Roselie); J.H.J. Wokke (John); R.Q. Hintzen (Rogier); M.E. Rubio-Gozalbo (Estela); I.F.M. de Coo (René)

    2006-01-01

    textabstractPURPOSE: Oxidative phosphorylation is under dual genetic control of the nuclear and the mitochondrial DNA (mtDNA). Oxidative phosphorylation disorders are clinically and genetically heterogeneous, which makes it difficult to determine the genetic defect, and symptom-based protocols which

  7. Statistical Analysis of Genetic Data in Twin Studies and Association Studies

    NARCIS (Netherlands)

    Setiawan, A.

    2007-01-01

    In studies in human genetics we want to answer questions such as: how important are genetic effects on a phenotype; what kind of action and interaction exists between gene products in the pathways between genotypes and phenotype; are the genetic effects on a phenotype consistent across sexes; do

  8. Statistical Analysis of Genetic Data in Twin Studies and Association Studies

    NARCIS (Netherlands)

    Setiawan, A.

    2007-01-01

    In studies in human genetics we want to answer questions such as: how important are genetic effects on a phenotype; what kind of action and interaction exists between gene products in the pathways between genotypes and phenotype; are the genetic effects on a phenotype consistent across sexes; do

  9. Preconceptions influence women's perceptions of information on breast cancer screening: a qualitative study.

    Science.gov (United States)

    Henriksen, Mikael Johannes Vuokko; Guassora, Ann Dorrit; Brodersen, John

    2015-09-03

    Screening for breast cancer has been subject to intense debate in recent decades regarding benefits and risks. Participation in breast cancer screening should be based on informed choice, and most countries approach this by sending information leaflets with invitations to attend screening. However, very little attention has been paid to the decision-making process and how the information leaflets are used and understood by women. The aim of this study is twofold. First, we use a theoretical framework to explore how the framing of information influences the intention to participate in breast cancer screening. Second, we discuss how information and attitudes held prior to receiving the invitation influence the perception of the balance between the benefits and risks harms of screening. We used a qualitative design and interviewed six women who were soon to receive their first invitation to participate in the breast screening programme in Denmark. The selected women received a copy of the official information leaflet 1 week before we interviewed them. The six women were interviewed individually using an interview guide based on the theory of planned behaviour. We used meaning condensation for our initial analysis, and further analysis was guided by the theory of cognitive dissonance. For our participants, the decision-making process was dominated by the attitudes of the women's circle of acquaintances and, to a lesser extent, by the information that accompanied the screening invitation. Information that conflicted with attitudes the women already held was actively disregarded. The risk of overdiagnosis as a potentially harmful effect of participation in mammography screening was unknown to the women in our study. An isolated framing effect was not found. Women have expectations about breast cancer screening that are formed before they receive information from the screening programme. These expectations compromise the perception of balance between screening benefits

  10. Psychological barriers and facilitators of colorectal cancer screening: a French qualitative study

    Directory of Open Access Journals (Sweden)

    Morgiane Bridou

    2013-06-01

    Full Text Available The aim of this qualitative study was to explore the psychological barriers to and facilitators of undergoing the Hemoccult-II® colorectal cancer screening test in France. Sixty-nine French people aged 50 to 74 years were divided into seven qualitative focus groups. Three issues were discussed with participants: knowledge and beliefs about colorectal cancer screening; facilitators of colorectal cancer screening by Hemoccult-II®; barriers to colorectal cancer screening by Hemoccult-II®. All the discussions were led by two psychologists and were recorded, transcribed verbatim and analyzed using qualitative data analysis software. Correspondence factor analyses identified three dimensions for each topic. The main psychological facilitators of colorectal cancer screening were: information about colorectal cancer screening, perceived simplicity of using Hemoccult-II®, and perception of risk. Uncertainty about the reliability of Hemoccult-II®, health anxiety, and embarrassment emerged as the main barriers to colorectal cancer screening. Cross-sectional analyses identified the differences between the views expressed by women and men. Women appeared more embarrassed about Hemoccult-II® and men seemed to be more worried about colorectal cancer. This preliminary study suggests that psychological factors play an important role in colorectal cancer screening by Hemoccult-II®. This finding may help health organizations to conceive better awareness campaigns to promote colorectal cancer screening in order to reduce the related mortality rate by taking into account psychological determinants.

  11. A Study on contact drying with flexible screen

    Institute of Scientific and Technical Information of China (English)

    陆仁书; 王伟宏; 花军

    2000-01-01

    Three types of material as platen in contact drying process were tested in Composition Board Laboratory of Northeast Forestry University in 1998. Poplar veneers were dried under 0.3 MPa at 160℃ or 180℃. Through comparison a non-metal flexible material was chosen as screen for designing contact dryer and replacing curved metal plate. The new type contact dryer solved the problem of long auxiliary time by loading wet veneers into press and unloading dried veneers out of press at the same time. This increased productivity. Veneer’s moisture content (MC) varied with drying time in index law. The process of contact drying with non-metal flexible screen was analyzed by stages of preheating, high-speed drying, retarded drying and extremely slow drying.

  12. The study of genetic diversity of Daemonorops draco (Palmae using ISSR markers

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    REVIS ASRA

    2014-10-01

    Full Text Available Asra R, Syamsuardi, Mansyurdin, Witono JR. 2014. The study of genetic diversity of Daemonorops draco (Palmae using ISSR markers. Biodiversitas 15: 109-114. The genetic diversity in five populations of Daemonorops draco(Willd. Blume (Jernang: in Bahasa Indonesia was analyzed using Inter Simple Sequence Repeat (ISSR markers. The screening results from using 15 ISSR primers showed that only 5 of ISSR primers had clear and reproducible bands. Based on the data from the matrix binary analyzed using POPGENE version 3.2, the highest genetic diversity was found in the Sepintun population at 0.0969 average heterozygosis (H and 0.146 average Shannon Index (I. The heterozygosis calculation of the total population (HT was 0.2571. The heterozygosis value within a population (HS=0.0704 was smaller than that between populations (DST=0.1867. Using the clustering analysis program Past version 32 on 43 individuals of D. draco, we found that there were three groups of D. draco. Group A consisted of 8 individuals in the Bengayoan population, group B consisted of 9 units in the Nunusan population and group C consisted of three populations; Tebo, Sepintun and Mandiangin consisted of 10, 8 and 8 individuals. The genetic similarity varied among all populations withthe values between 0.07-0.93.

  13. Advances in genetic studies of substance abuse in China

    Institute of Scientific and Technical Information of China (English)

    Yan SUN; Shiqiu MENG; Jiali LI; Jie SHI; Lin LU

    2013-01-01

    Summary:The importance of genetic factors in substance addiction has long been established. The rationale for this work is that understanding of the function of addiction genes and delineation of the key molecular pathways of these genes would enhance the development of novel therapeutic targets and biomarkers that could be used in the prevention and management of substance abuse. Over the past few years, there has been a substantial increase in the number of genetic studies conducted on addiction in China;these studies have primarily focused on heroin, alcohol, and nicotine dependence. Most studies of candidate genes have concentrated on the dopamine, opioid, and serotonin systems. A number of genes associated with substance abuse in Caucasians are also risk factors in Chinese, but several novel genes and genetic risk factors associated with substance abuse in Chinese subjects have also been identified. This paper reviews the genetic studies of substance abuse performed by Chinese researchers. Genotypes and alleles related to addictive behavior in Chinese individuals are discussed and the contributions of Chinese researchers to the international corpus of knowledge about the genetic understanding of substance abuse are described.

  14. Genetic Screen Reveals Link between the Maternal Effect Sterile Gene mes-1 and Pseudomonas aeruginosa-induced Neurodegeneration in Caenorhabditis elegans.

    Science.gov (United States)

    Wu, Qiuli; Cao, Xiou; Yan, Dong; Wang, Dayong; Aballay, Alejandro

    2015-12-01

    Increasing evidence indicates that immune responses to microbial infections may contribute to neurodegenerative diseases. Here, we show that Pseudomonas aeruginosa infection of Caenorhabditis elegans causes a number of neural changes that are hallmarks of neurodegeneration. Using an unbiased genetic screen to identify genes involved in the control of P. aeruginosa-induced neurodegeneration, we identified mes-1, which encodes a receptor tyrosine kinase-like protein that is required for unequal cell divisions in the early embryonic germ line. We showed that sterile but not fertile mes-1 animals were resistant to neurodegeneration induced by P. aeruginosa infection. Similar results were observed using animals carrying a mutation in the maternal effect gene pgl-1, which is required for postembryonic germ line development, and the germ line-deficient strains glp-1 and glp-4. Additional studies indicated that the FOXO transcription factor DAF-16 is required for resistance to P. aeruginosa-induced neurodegeneration in germ line-deficient strains. Thus, our results demonstrate that P. aeruginosa infection results in neurodegeneration phenotypes in C. elegans that are controlled by the germ line in a cell-nonautonomous manner.

  15. A healthy delivery of twins by assisted reproduction followed by preimplantation genetic screening in a woman with X-linked dominant incontinentia pigmenti.

    Science.gov (United States)

    Kim, Myung Joo; Lyu, Sang Woo; Seok, Hyun Ha; Park, Ji Eun; Shim, Sung Han; Yoon, Tae Ki

    2014-12-01

    The purpose of this study is to report a successful twin pregnancy and delivery in a female patient with X-linked dominant incontinentia pigmenti (IP) who underwent assisted reproductive technology followed by preimplantation genetic screening (PGS). A 29-year-old female with IP had a previous history of recurrent spontaneous abortion. A molecular analysis revealed the patient had a de novo mutation, 1308_1309insCCCCTTG(p.Ala438ProfsTer26), in the inhibitor of the kappa B kinase gamma gene located in the Xq28 region. IVF/ICSI and PGS was performed, in which male embryos were sexed using array-based comparative genomic hybridization (aCGH). After IVF/ICSI and PGS using aCGH on seven embryos, two euploid male blastocysts were transferred with a 50% probability of a viable male pregnancy. The dizygotic twin pregnancy was confirmed and the amniocentesis results of each twin were normal with regard to the mutation found in the mother. The patient delivered healthy twin babies during the 37th week of gestation. This case shows the beneficial role of PGS in achieving a successful pregnancy through euploid male embryo gender selection in a woman with X-linked dominant IP with a history of multiple male miscarriages.

  16. Genetic screening in infertile Mexican men: chromosomal abnormalities, Y chromosome deletions, and androgen receptor CAG repeat length.

    Science.gov (United States)

    Martínez-Garza, Sandra Guadalupe; Gallegos-Rivas, Mayra Celina; Vargas-Maciel, Marcos; Rubio-Rubio, Juan Manuel; de Los Monteros-Rodríguez, Mario Espinosa; González-Ortega, Claudia; Cancino-Villarreal, Patricia; de Lara, Luis G Vazquez; Gutiérrez-Gutiérrez, Antonio Martín

    2008-01-01

    In our study, we analyzed chromosomal abnormalities, Y chromosome deletions, androgen receptor CAG repeat length and their association with defective spermatogenesis in infertile Mexican men. Eighty-two infertile patients and 40 controls were screened for karyotypic abnormalities, Y chromosome microdeletions, and CAG repeats. Nine infertile males (11%) carried chromosomal abnormalities and 10 (12.2%) presented Y chromosome microdeletions. The mean CAG repeat length was 21.6 and 20.88 base pairs in idiopathic infertile males and controls, respectively. Our results suggest that chromosomal aberrations and Y-chromosomal microdeletions are related to male infertility in Mexican men. In addition, expansion of the CAG repeat segments of the androgen receptor is not correlated with male idiopathic infertility.

  17. Psychosocial impact of genetic testing for hemochromatosis in the HEIRS Study: a comparison of participants recruited in Canada and in the United States.

    Science.gov (United States)

    Power, Tara E; Adams, Paul C; Barton, James C; Acton, Ronald T; Howe, Edmund; Palla, Shana; Walker, Ann P; Anderson, Roger; Harrison, Barbara

    2007-01-01

    The Hemochromatosis and Iron Overload Screening (HEIRS) Study screened 101,168 participants recruited from primary-care clinics in Canada and the United States. The present study investigated differences in the psychological effects of genetic screening for hemochromatosis (HFE mutation analysis) in participants from each country. Study participants comprised a subset of 2,654 individuals who donated blood for HFE mutation analysis. The initial screening and 1-month post-result questionnaires included measures of General Health, Mental Health (SF-36), and a measure of the percentage of individuals who experienced at least one example of worry in response to the genetic testing. Participants reported similar changes in general health and mental health, regardless of mutation result, or country. Although a significantly lower percentage of Canadian participants than U.S. participants indicated at least one negative emotional response to the genetic testing, greater than 50% of C282Y homozygote participants (the gene mutation most strongly associated with hemochromatosis) from both countries experienced such in response to testing. Thus, although not serious enough to affect individuals' mental or physical health, there was evidence of at least one element of negative emotional response to the genetic testing. These findings suggest that population screening for common HFE mutations associated with hemochromatosis risk has similar psychological effects on Canadian and U.S. individuals, although fewer Canadians may experience a negative response to such testing.

  18. Developmental genetics in emerging rodent models: case studies and perspectives.

    Science.gov (United States)

    Mallarino, Ricardo; Hoekstra, Hopi E; Manceau, Marie

    2016-08-01

    For decades, mammalian developmental genetic studies have focused almost entirely on two laboratory models: Mus and Rattus, species that breed readily in the laboratory and for which a wealth of molecular and genetic resources exist. These species alone, however, do not capture the remarkable diversity of morphological, behavioural and physiological traits seen across rodents, a group that represents >40% of all mammal species. Due to new advances in molecular tools and genomic technologies, studying the developmental events underlying natural variation in a wide range of species for a wide range of traits has become increasingly feasible. Here we review several recent studies and discuss how they not only provided technical resources for newly emerging rodent models in developmental genetics but also are instrumental in further encouraging scientists, from a wide range of research fields, to capitalize on the great diversity in development that has evolved among rodents.

  19. The Etruscans: a population-genetic study

    DEFF Research Database (Denmark)

    Vernesi, Cristiano; Caramelli, David; Dupanloup, Isabelle;

    2004-01-01

    The origins of the Etruscans, a non-Indo-European population of preclassical Italy, are unclear. There is broad agreement that their culture developed locally, but the Etruscans' evolutionary and migrational relationships are largely unknown. In this study, we determined mitochondrial DNA sequences...

  20. Indian studies on genetic polymorphisms and cancer risk

    Directory of Open Access Journals (Sweden)

    A Bag

    2012-01-01

    Full Text Available Genetic influences on cancer development have been extensively investigated during the last decade following publication of human genome sequence. The present review summarizes case-control studies on genetic polymorphisms and cancer risk in Indians. It is observed that the most commonly studied genes in the Indian population included members of phase I and phase II metabolic enzymes. Other than these genes, genetic polymorphisms for cell cycle and apoptosis-related factors, DNA repair enzymes, immune response elements, growth factors, folate metabolizing enzymes, vitamin/hormone receptors, etc., were investigated. Several studies also evidenced a stronger risk for combined genotypes rather than a single polymorphism. Gene-environment interaction was also found to be a determining factor for cancer development in some experiments. Data for single polymorphism and single cancer type, however, was insufficient to validate an association. It appears that much more experiments involving larger sample size, cross-tabulating genetic polymorphisms and environmental factors are required in order to identify genetic markers for different cancers in Indian populations.

  1. Rotterdam AMBlyopia screening effectiveness study: Detection and causes of amblyopia in a large birth cohort

    NARCIS (Netherlands)

    J.H. Groenewoud (Hanny); A.M. Tjiam (Angela); V.K. Lantau (Kathleen); W.C. Hoogeveen; J.T.H.N. de Faber; R.E. Juttmann (Rikard); H.J. de Koning (Harry); H.J. Simonsz (Huib)

    2010-01-01

    textabstractPurpose. The Dutch population-based child health monitoring program includes regular preverbal (age range, 1-24 months) and preschool (age range, 36-72 months) vision screening. This study is on the contribution of an organized vision screening program to the detection of amblyopia.

  2. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report

    DEFF Research Database (Denmark)

    Field, John K; Smith, Robert A; Aberle, Denise R;

    2011-01-01

    The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer...

  3. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 Report

    NARCIS (Netherlands)

    Field, John K.; Smith, Robert A.; Aberle, Denise R.; Oudkerk, Matthijs; Baldwin, David R.; Yankelevitz, David; Pedersen, Jesper Holst; Swanson, Scott James; Travis, William D.; Wisbuba, Ignacio I.; Noguchi, Masayuki; Mulshine, Jim L.

    2012-01-01

    The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer de

  4. Should we screen BRCA1 mutation carriers only with MRI? A multicenter study

    NARCIS (Netherlands)

    Obdeijn, I.-M.; Winter-Warnars, G.A.O.; Mann, R.M.; Hooning, M.J.; Hunink, M.G.M.; Tilanus-Linthorst, M.M.

    2014-01-01

    BRCA1 mutation carriers are offered screening with MRI and mammography. Aim of the study was to investigate the additional value of digital mammography over MRI screening. BRCA1 mutation carriers, who developed breast cancer since the introduction of digital mammography between January 2003 and Marc

  5. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 Report

    NARCIS (Netherlands)

    Field, John K.; Smith, Robert A.; Aberle, Denise R.; Oudkerk, Matthijs; Baldwin, David R.; Yankelevitz, David; Pedersen, Jesper Holst; Swanson, Scott James; Travis, William D.; Wisbuba, Ignacio I.; Noguchi, Masayuki; Mulshine, Jim L.

    The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer

  6. MULTISCAN--a Scandinavian multicenter second trimester obstetric ultrasound and serum screening study

    DEFF Research Database (Denmark)

    Jørgensen, F S; Valentin, L; Salvesen, K A

    1999-01-01

    AIM: To study the detection rates of second trimester ultrasound screening for neural tube defects (NTD), abdominal wall defects (AWD) and Down's syndrome (DS) in low risk populations at tertiary centers, and to compare the ultrasound screening detection rates with those that were obtainable by b...

  7. Impact of human genome initiative-derived technology on genetic testing, screening and counseling: Cultural, ethical and legal issues. Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Trottier, R.W.; Hodgin, F.C.; Imara, M.; Phoenix, D.; Lybrook, S. [Morehouse Coll., Atlanta, GA (United States). School of Medicine; Crandall, L.A.; Moseley, R.E.; Armotrading, D. [Florida Univ., Gainesville, FL (United States). Coll. of Medicine

    1993-03-01

    Genetic medical services provided by the Georgia Division of Public Health in two northern and two central districts are compared to services provided in a district in which a tertiary care facility is located. Genetics outreach public health nurses play key roles in Georgia`s system of Children`s Health Services Genetics Program, including significant roles as counselors and information sources on special needs social services and support organizations. Unique features of individual health districts, (e.g., the changing face of some rural communities in ethnocultural diversity and socioeconomic character), present new challenges to current and future genetics services delivery. Preparedness as to educational needs of both health professionals and the lay population is of foremost concern in light of the ever expanding knowledge and technology in medical genetics. Perspectives on genetics and an overview of services offered by a local private sector counselor are included for comparison to state supported services. The nature of the interactions which transpire between private and public genetic services resources in Georgia will be described. A special focus of this research includes issues associated with sickle cell disease newborn screening service delivery process in Georgia, with particular attention paid to patient follow-up and transition to primary care. Of particular interest to this focus is the problem of loss to follow-up in the current system. Critical factors in education and counseling of sickle cell patients and the expectations of expanding roles of primary care physicians are discussed. The Florida approach to the delivery of genetic services contrasts to the Georgia model by placing more emphasis on a consultant-specialist team approach.

  8. Barriers to colorectal cancer screening in community health centers: A qualitative study

    Directory of Open Access Journals (Sweden)

    Fletcher Robert H

    2008-02-01

    Full Text Available Abstract Background Colorectal cancer screening rates are low among disadvantaged patients; few studies have explored barriers to screening in community health centers. The purpose of this study was to describe barriers to/facilitators of colorectal cancer screening among diverse patients served by community health centers. Methods We identified twenty-three outpatients who were eligible for colorectal cancer screening and their 10 primary care physicians. Using in-depth semi-structured interviews, we asked patients to describe factors influencing their screening decisions. For each unscreened patient, we asked his or her physician to describe barriers to screening. We conducted patient interviews in English (n = 8, Spanish (n = 2, Portuguese (n = 5, Portuguese Creole (n = 1, and Haitian Creole (n = 7. We audiotaped and transcribed the interviews, and then identified major themes in the interviews. Results Four themes emerged: 1 Unscreened patients cited lack of trust in doctors as a barrier to screening whereas few physicians identified this barrier; 2 Unscreened patients identified lack of symptoms as the reason they had not been screened; 3 A doctor's recommendation, or lack thereof, significantly influenced patients' decisions to be screened; 4 Patients, but not their physicians, cited fatalistic views about cancer as a barrier. Conversely, physicians identified competing priorities, such as psychosocial stressors or comorbid medical illness, as barriers to screening. In this culturally diverse group of patients seen at community health centers, similar barriers to screening were reported by patients of different backgrounds, but physicians perceived other factors as more important. Conclusion Further study of these barriers is warranted.

  9. Genetic epidemiological study of schizophrenia: reproduction behaviour.

    Science.gov (United States)

    Ritsner, M; Sherina, O; Ginath, Y

    1992-06-01

    Data from the Tomsk Epidemiological Register and epidemiological family sample were used to study the relationship between schizophrenics' reproductive behaviour (marital status and fertility rate), severity of ICD-9 schizophrenia and risk of illness among relatives of probands. The results are interpreted in terms of multifactorial threshold and single monolocus models. Their importance for the interpretation of epidemiological data (a change of prevalence rate, cohort effect and clinical polymorphism) is discussed.

  10. Laterally orienting C. elegans using geometry at microscale for high-throughput visual screens in neurodegeneration and neuronal development studies.

    Directory of Open Access Journals (Sweden)

    Ivan de Carlos Cáceres

    Full Text Available C. elegans is an excellent model system for studying neuroscience using genetics because of its relatively simple nervous system, sequenced genome, and the availability of a large number of transgenic and mutant strains. Recently, microfluidic devices have been used for high-throughput genetic screens, replacing traditional methods of manually handling C. elegans. However, the orientation of nematodes within microfluidic devices is random and often not conducive to inspection, hindering visual analysis and overall throughput. In addition, while previous studies have utilized methods to bias head and tail orientation, none of the existing techniques allow for orientation along the dorso-ventral body axis. Here, we present the design of a simple and robust method for passively orienting worms into lateral body positions in microfluidic devices to facilitate inspection of morphological features with specific dorso-ventral alignments. Using this technique, we can position animals into lateral orientations with up to 84% efficiency, compared to 21% using existing methods. We isolated six mutants with neuronal development or neurodegenerative defects, showing that our technology can be used for on-chip analysis and high-throughput visual screens.

  11. Combinations of genetic data in a study of oral cancer

    DEFF Research Database (Denmark)

    Mellerup, Erling Thyge; Møller, Gert Lykke; Mondal, Pinaki

    2015-01-01

    for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented...... with an analysis of combinations of two SNP genotypes from among the 325 SNPs. Two clusters of combinations containing 95 patient specific combinations were significantly associated with oral cancer or leukoplakia. Of 373 patients with oral cancer 205 patients had a number of these 95 combinations in their genome...

  12. Advances in molecular genetic studies of primary dystonia

    Directory of Open Access Journals (Sweden)

    MA Ling-yan

    2013-07-01

    Full Text Available Dystonias are heterogeneous hyperkinetic movement disorders characterized by involuntary muscle contractions which result in twisting, repetitive movements and abnormal postures. In recent years, there was a great advance in molecular genetic studies of primary dystonia. This paper will review the clinical characteristics and molecular genetic studies of primary dystonia, including early-onset generalized torsion dystonia (DYT1, whispering dysphonia (DYT4, dopa-responsive dystonia (DYT5, mixed-type dystonia (DYT6, paroxysmal kinesigenic dyskinesia (DYT10, myoclonus-dystonia syndrome (DYT11, rapid-onset dystonia parkinsonism (DYT12, adult-onset cervical dystonia (DYT23, craniocervical dystonia (DYT24 and primary torsion dystonia (DYT25.

  13. Why Is Studying the Genetics of Intelligence So Controversial?

    Science.gov (United States)

    Tabery, James

    2015-01-01

    From the very beginning, studies of the nature and nurture of intelligence have been closely associated with an interest in intervening, and those interventions have been surrounded by controversy. The nature of those controversies has not always been the same, however. Since the mid-nineteenth century, when Francis Galton imagined a science that would assess the extent to which a trait like "genius" was due to nature or due to nurture, science and technology have changed dramatically, and so have the interventions that have been envisioned in light of those developments. A scientist today can search for particular stretches of DNA and assess whether differences in those stretches are associated with differences in a human trait of interest; a genetic counselor today can genetically test an individual (be it an embryo, fetus, newborn, child, or adult) and provide information about what that genetic result means, allowing for interventions that can range from terminating a pregnancy to prescribing chemotherapy. So when one asks a question like, "Why is studying the genetics of intelligence controversial?," it is important to realize up front that the answer will be, "It can be controversial for a variety of different reasons, and those reasons have evolved over time." The purpose of this essay is to provide a survey of the controversies that surround genetic studies of intelligence. With the survey in place, I will then draw out several lessons both for scientists who study the genetics of intelligence as well as for science studies scholars (bioethicists, philosophers, historians, sociologists) who reflect and comment on the controversies surrounding that research.

  14. Alcohol, Genetics and Risk of Breast Cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

    Science.gov (United States)

    McCarty, Catherine A.; Reding, Douglas J.; Commins, John; Williams, Craig; Yeager, Meredith; Burmester, James K.; Schairer, Catherine; Ziegler, Regina G.

    2012-01-01

    Background We tested the hypothesis that genes involved in the alcohol oxidation pathway modify the association between alcohol intake and breast cancer. Methods Subjects were women aged 55–74 at baseline from the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Incident breast cancers were identified through annual health surveys. Controls were frequency matched to cases by age and year of entry into the trial. A self-administered food frequency questionnaire queried frequency and usual serving size of beer, wine or wine coolers and liquor. Three SNPs in genes in the alcohol metabolism pathway were genotyped: alcohol dehydrogenase 2, alcohol dehydrogenase 3 and CYP2E1. Results The study included 1041 incident breast cancer cases and 1070 controls. In comparison to non-drinkers, the intake of any alcohol significantly increased the risk of breast cancer, and this risk increased with each category of daily alcohol intake, (OR=2.01, 95% CL=1.14, 3.53) for women who drank three or more standard drinks per day. Stratification by genotype revealed significant gene/environment interactions. For the ADH1B gene, there were statistically significant associations between all levels of alcohol intake and risk of breast cancer (all OR>1.34 and all lower CL >1.01), while for women with the GA or AA genotype, there were no significant associations between alcohol intake and risk of breast cancer. Conclusion Alcohol intake, genes involved in alcohol metabolism and their interaction increase the risk of breast cancer in post-menopausal women. Impact This information could be useful for primary care providers to personalize information about breast cancer risk reduction. PMID:22331481

  15. Alcohol, genetics and risk of breast cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

    Science.gov (United States)

    McCarty, Catherine A; Reding, Douglas J; Commins, John; Williams, Craig; Yeager, Meredith; Burmester, James K; Schairer, Catherine; Ziegler, Regina G

    2012-06-01

    We tested the hypothesis that genes involved in the alcohol oxidation pathway modify the association between alcohol intake and breast cancer. Subjects were women aged 55-74 at baseline from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Incident breast cancers were identified through annual health surveys. Controls were frequency matched to cases by age and year of entry into the trial. A self-administered food frequency questionnaire queried frequency and usual serving size of beer, wine or wine coolers, and liquor. Three SNPs in genes in the alcohol metabolism pathway were genotyped: alcohol dehydrogenase 2, alcohol dehydrogenase 3, and CYP2E1. The study included 1,041 incident breast cancer cases and 1,070 controls. In comparison to non-drinkers, the intake of any alcohol significantly increased the risk of breast cancer, and this risk increased with each category of daily alcohol intake (OR 2.01, 95% CI 1.14, 3.53) for women who drank three or more standard drinks per day. Stratification by genotype revealed significant gene/environment interactions. For the ADH1B gene, there were statistically significant associations between all levels of alcohol intake and risk of breast cancer (all OR > 1.34 and all lower CI > 1.01), while for women with the GA or AA genotype, there were no significant associations between alcohol intake and risk of breast cancer. Alcohol intake, genes involved in alcohol metabolism and their interaction increase the risk of breast cancer in post-menopausal women. This information could be useful for primary care providers to personalize information about breast cancer risk reduction.

  16. Genetics of dietary habits and obesity - a twin study

    DEFF Research Database (Denmark)

    Hasselbalch, Ann Louise

    2010-01-01

    exposures as well as genetic differences between individuals, resulting in differentiated susceptibility to environmental exposures. The evidence for genetic influence on anthropometry has previously been established and has been estimated to be 60-70% based on twin studies. These inter......Obesity has become a major health concern due to the increased risk of co-morbidities, resulting in decreased quality of life, stigmatization, reduced working ability and early death. This causes a great challenge for the health care systems and results in increased direct costs related...... mass, but only limited evidence for associations between habitual dietary intake and anthropometry exists. Differences in habitual dietary intake are also partly determined by differences in genes influencing smell and taste preferences. But, so far, only few studies have investigated genetic...

  17. Genetic and ecological studies of animals in Chernobyl and Fukushima.

    Science.gov (United States)

    Mousseau, Timothy A; Møller, Anders P

    2014-01-01

    Recent advances in genetic and ecological studies of wild animal populations in Chernobyl and Fukushima have demonstrated significant genetic, physiological, developmental, and fitness effects stemming from exposure to radioactive contaminants. The few genetic studies that have been conducted in Chernobyl generally show elevated rates of genetic damage and mutation rates. All major taxonomic groups investigated (i.e., birds, bees, butterflies, grasshoppers, dragonflies, spiders, mammals) displayed reduced population sizes in highly radioactive parts of the Chernobyl Exclusion Zone. In Fukushima, population censuses of birds, butterflies, and cicadas suggested that abundances were negatively impacted by exposure to radioactive contaminants, while other groups (e.g., dragonflies, grasshoppers, bees, spiders) showed no significant declines, at least during the first summer following the disaster. Insufficient information exists for groups other than insects and birds to assess effects on life history at this time. The differences observed between Fukushima and Chernobyl may reflect the different times of exposure and the significance of multigenerational mutation accumulation in Chernobyl compared to Fukushima. There was considerable variation among taxa in their apparent sensitivity to radiation and this reflects in part life history, physiology, behavior, and evolutionary history. Interestingly, for birds, population declines in Chernobyl can be predicted by historical mitochondrial DNA base-pair substitution rates that may reflect intrinsic DNA repair ability. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. A comparative phylogenetic study of genetics and folk music.

    Science.gov (United States)

    Pamjav, Horolma; Juhász, Zoltán; Zalán, Andrea; Németh, Endre; Damdin, Bayarlkhagva

    2012-04-01

    Computer-aided comparison of folk music from different nations is one of the newest research areas. We were intrigued to have identified some important similarities between phylogenetic studies and modern folk music. First of all, both of them use similar concepts and representation tools such as multidimensional scaling for modelling relationship between populations. This gave us the idea to investigate whether these connections are merely accidental or if they mirror population migrations from the past. We raised the question; does the complex structure of musical connections display a clear picture and can this system be interpreted by the genetic analysis? This study is the first to systematically investigate the incidental genetic background of the folk music context between different populations. Paternal (42 populations) and maternal lineages (56 populations) were compared based on Fst genetic distances of the Y chromosomal and mtDNA haplogroup frequencies. To test this hypothesis, the corresponding musical cultures were also compared using an automatic overlap analysis of parallel melody styles for 31 Eurasian nations. We found that close musical relations of populations indicate close genetic distances (folk music; maternal lineages have a more important role in folk music traditions than paternal lineages. Furthermore, the combination of these disciplines establishing a new interdisciplinary research field of "music-genetics" can be an efficient tool to get a more comprehensive picture on the complex behaviour of populations in prehistoric time.

  19. [Felines: an alternative in genetic toxicology studies?].

    Science.gov (United States)

    Zamora-Perez, Ana; Gómez-Meda, Belinda C; Ramos-Ibarra, Maria L; Batista-González, Cecilia M; Luna-Aguirre, Jaime; González-Rodríguez, Andrés; Rodríguez-Avila, José L; Zúñiga-González, Guillermo M

    2008-06-01

    The micronuclei (MN) test carry out in peripheral blood is fast, simple, economic and it is used to detect genotoxic environmental agents. MN are fragments of chromosomes or complete chromosomes remaining in the cytoplasm after cell division, which increase when organisms are exposed to genotoxic agents. Therefore, species with the highest values of spontaneous micronucleated erythrocytes (MNE) are the most suitable to be potentials biomonitor of micronucleogenic agents, using a drop of blood. Nine species of Felines that present spontaneous MNE in peripheral blood are shown. From these species, the cat has been previously proven, with positive results and also lion (Panthera leo), yaguaroundi (Felis yagoaroundi), lynx (Lynx ruffus), jaguar (Panthera onca), puma (Puma concolor), tiger (Panthera tigris), ocelote (Felis padalis) and leopard (Panthera pardus) display spontaneous MNE, and with this characteristic this Family can be propose like a potential group to be used in toxicogenetic studies.

  20. Genetic studies of Crohn's disease: past, present and future.

    Science.gov (United States)

    Liu, Jimmy Z; Anderson, Carl A

    2014-06-01

    The exact aetiology of Crohn's disease is unknown, though it is clear from early epidemiological studies that a combination of genetic and environmental risk factors contributes to an individual's disease susceptibility. Here, we review the history of gene-mapping studies of Crohn's disease, from the linkage-based studies that first implicated the NOD2 locus, through to modern-day genome-wide association studies that have discovered over 140 loci associated with Crohn's disease and yielded novel insights into the biological pathways underlying pathogenesis. We describe on-going and future gene-mapping studies that utilise next generation sequencing technology to pinpoint causal variants and identify rare genetic variation underlying Crohn's disease risk. We comment on the utility of genetic markers for predicting an individual's disease risk and discuss their potential for identifying novel drug targets and influencing disease management. Finally, we describe how these studies have shaped and continue to shape our understanding of the genetic architecture of Crohn's disease.

  1. The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening

    Directory of Open Access Journals (Sweden)

    Bellon Gabriel

    2006-10-01

    subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling.

  2. 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...

  3. Genetic-linked Inattentiveness Protects Individuals from Internet Overuse: A Genetic Study of Internet Overuse Evaluating Hypotheses Based on Addiction, Inattention, Novelty-seeking and Harm-avoidance

    Directory of Open Access Journals (Sweden)

    Cheng Sun

    2016-06-01

    Full Text Available The all-pervasive Internet has created serious problems, such as Internet overuse, which has triggered considerable debate over its relationship with addiction. To further explore its genetic susceptibilities and alternative explanations for Internet overuse, we proposed and evaluated four hypotheses, each based on existing knowledge of the biological bases of addiction, inattention, novelty-seeking, and harm-avoidance. Four genetic loci including DRD4 VNTR, DRD2 Taq1A, COMT Val158Met and 5-HTTLPR length polymorphisms were screened from seventy-three individuals. Our results showed that the DRD4 4R/4R individuals scored significantly higher than the 2R or 7R carriers in Internet Addiction Test (IAT. The 5-HTTLPR short/short males scored significantly higher in IAT than the long variant carriers. Bayesian analysis showed the most compatible hypothesis with the observed genetic results was based on attention (69.8%, whereas hypotheses based harm-avoidance (21.6%, novelty-seeking (7.8% and addiction (0.9% received little support. Our study suggests that carriers of alleles (DRD4 2R and 7R, 5-HTTLPR long associated with inattentiveness are more likely to experience disrupted patterns and reduced durations of Internet use, protecting them from Internet overuse. Furthermore, our study suggests that Internet overuse should be categorized differently from addiction due to the lack of shared genetic contributions.

  4. Primary care physician characteristics associated with cancer screening: a retrospective cohort study in Ontario, Canada.

    Science.gov (United States)

    Lofters, Aisha K; Ng, Ryan; Lobb, Rebecca

    2015-02-01

    Primary care physicians can serve as both facilitators and barriers to cancer screening, particularly for under-screened groups such as immigrant patients. The objective of this study was to inform physician-targeted interventions by identifying primary care physician characteristics associated with cancer screening for their eligible patients, for their eligible immigrant patients, and for foreign-trained physicians, for their eligible immigrant patients from the same world region. A population-based retrospective cohort study was performed, looking back 3 years from 31 December 2010. The study was performed in urban primary care practices in Ontario, Canada's largest province. A total of 6303 physicians serving 1,156,627 women eligible for breast cancer screening, 2,730,380 women eligible for cervical screening, and 2,260,569 patients eligible for colorectal screening participated. Appropriate breast screening was defined as at least one mammogram in the previous 2 years, appropriate cervical screening was defined as at least one Pap test in the previous 3 years, and appropriate colorectal screening as at least one fecal occult blood test in the previous 2 years or at least one colonoscopy or barium enema in the previous 10 years. Just fewer than 40% of physicians were female, and 26.1% were foreign trained. In multivariable analyses, physicians who attended medical schools in the Caribbean/Latin America, the Middle East/North Africa, South Asia, and Western Europe were less likely to screen their patients than Canadian graduates. South Asian-trained physicians were significantly less likely to screen South Asian women for cervical cancer than other foreign-trained physicians who were seeing region-congruent patients (adjusted odds ratio: 0.56 [95% confidence interval 0.32-0.98] versus physicians from the USA, Australia and New Zealand). South Asian patients were the most vulnerable to under-screening, and decreasing patient income quintile was consistently

  5. Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome.

    Science.gov (United States)

    Petek, Erwin; Schwarzbraun, Thomas; Noor, Abdul; Patel, Megha; Nakabayashi, Kazuhiko; Choufani, Sanaa; Windpassinger, Christian; Stamenkovic, Mara; Robertson, Mary M; Aschauer, Harald N; Gurling, Hugh M D; Kroisel, Peter M; Wagner, Klaus; Scherer, Stephen W; Vincent, John B

    2007-01-01

    We recently reported the disruption of the inner mitochondrial membrane peptidase 2-like (IMMP2L) gene by a chromosomal breakpoint in a patient with Gilles de la Tourette syndrome (GTS). In the present study we sought to identify genetic variation in IMMP2L, which, through alteration of protein function or level of expression might contribute to the manifestation of GTS. We screened 39 GTS patients, and, due to the localization of IMMP2L in the critical region for the autistic disorder (AD) locus on chromosome 7q (AUTS1), 95 multiplex AD families; however, no coding mutations were found in either GTS or AD patients. In addition, no parental-specific expression of IMMP2L was detected in somatic cell hybrids containing human chromosome 7 and human cell lines carrying a maternal uniparental disomy for chromosome 7 (mUPD7). Despite the fact that no deleterious mutations in IMMPL2 (other than the inverted duplication identified previously) were identified in either GTS or AD, this gene cannot be excluded as a possible rare cause of either disorder.

  6. Automated Screening for Three Inborn Metabolic Disorders: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Kavitha S

    2006-12-01

    Full Text Available Background: Inborn metabolic disorders (IMDs form a large group of rare, but often serious, metabolic disorders. Aims: Our objective was to construct a decision tree, based on classification algorithm for the data on three metabolic disorders, enabling us to take decisions on the screening and clinical diagnosis of a patient. Settings and Design: A non-incremental concept learning classification algorithm was applied to a set of patient data and the procedure followed to obtain a decision on a patient’s disorder. Materials and Methods: Initially a training set containing 13 cases was investigated for three inborn errors of metabolism. Results: A total of thirty test cases were investigated for the three inborn errors of metabolism. The program identified 10 cases with galactosemia, another 10 cases with fructosemia and the remaining 10 with propionic acidemia. The program successfully identified all the 30 cases. Conclusions: This kind of decision support systems can help the healthcare delivery personnel immensely for early screening of IMDs.

  7. Molecular mechanisms underlying noncoding risk variations in psychiatric genetic studies.

    Science.gov (United States)

    Xiao, X; Chang, H; Li, M

    2017-01-03

    Recent large-scale genetic approaches such as genome-wide association studies have allowed the identification of common genetic variations that contribute to risk architectures of psychiatric disorders. However, most of these susceptibility variants are located in noncoding genomic regions that usually span multiple genes. As a result, pinpointing the precise variant(s) and biological mechanisms accounting for the risk remains challenging. By reviewing recent progresses in genetics, functional genomics and neurobiology of psychiatric disorders, as well as gene expression analyses of brain tissues, here we propose a roadmap to characterize the roles of noncoding risk loci in the pathogenesis of psychiatric illnesses (that is, identifying the underlying molecular mechanisms explaining the genetic risk conferred by those genomic loci, and recognizing putative functional causative variants). This roadmap involves integration of transcriptomic data, epidemiological and bioinformatic methods, as well as in vitro and in vivo experimental approaches. These tools will promote the translation of genetic discoveries to physiological mechanisms, and ultimately guide the development of preventive, therapeutic and prognostic measures for psychiatric disorders.Molecular Psychiatry advance online publication, 3 January 2017; doi:10.1038/mp.2016.241.

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

    DEFF Research Database (Denmark)

    Zeggini, Eleftheria; Gloyn, Anna L; Hansen, Torben

    2016-01-01

    for diabetes and metabolic disease, drawing on specific examples from populations in Greece and Greenland. This review summarises a presentation given at the 'Exciting news in genetics of diabetes' symposium at the 2015 annual meeting of the EASD, with topics presented by Eleftheria Zeggini and Torben Hansen...... 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...

  9. A modified Delphi study of screening for fetal alcohol spectrum disorders in Australia

    Directory of Open Access Journals (Sweden)

    Watkins Rochelle E

    2013-01-01

    Full Text Available Abstract Background There is little reliable information on the prevalence of fetal alcohol spectrum disorders (FASD in Australia and no coordinated national approach to facilitate case detection. The aim of this study was to identify health professionals’ perceptions about screening for FASD in Australia. Method A modified Delphi process was used to assess perceptions of the need for, and the process of, screening for FASD in Australia. We recruited a panel of 130 Australian health professionals with experience or expertise in FASD screening or diagnosis. A systematic review of the literature was used to develop Likert statements on screening coverage, components and assessment methods which were administered using an online survey over two survey rounds. Results Of the panel members surveyed, 95 (73% responded to the questions on screening in the first survey round and, of these, 81 (85% responded to the second round. Following two rounds there was consensus agreement on the need for targeted screening at birth (76% and in childhood (84%. Participants did not reach consensus agreement on the need for universal screening at birth (55% or in childhood (40%. Support for targeted screening was linked to perceived constraints on service provision and the need to examine the performance, costs and benefits of screening. For targeted screening of high risk groups, we found highest agreement for siblings of known cases of FASD (96% and children of mothers attending alcohol treatment services (93%. Participants agreed that screening for FASD primarily requires assessment of prenatal alcohol exposure at birth (86% and in childhood (88%, and that a checklist is needed to identify the components of screening and criteria for referral at birth (84% and in childhood (90%. Conclusions There is an agreed need for targeted but not universal screening for FASD in Australia, and sufficient consensus among health professionals to warrant development and

  10. GESDB: a platform of simulation resources for genetic epidemiology studies.

    Science.gov (United States)

    Yao, Po-Ju; Chung, Ren-Hua

    2016-01-01

    Computer simulations are routinely conducted to evaluate new statistical methods, to compare the properties among different methods, and to mimic the observed data in genetic epidemiology studies. Conducting simulation studies can become a complicated task as several challenges can occur, such as the selection of an appropriate simulation tool and the specification of parameters in the simulation model. Although abundant simulated data have been generated for human genetic research, currently there is no public database designed specifically as a repository for these simulated data. With the lack of such a database, for similar studies, similar simulations may have been repeated, which resulted in redundant work. Thus, we created an online platform, the Genetic Epidemiology Simulation Database (GESDB), for simulation data sharing and discussion of simulation techniques for genetic epidemiology studies. GESDB consists of a database for storing simulation scripts, simulated data and documentation from published articles as well as a discussion forum, which provides a platform for discussion of the simulated data and exchanging simulation ideas. Moreover, summary statistics such as the simulation tools that are most commonly used and datasets that are most frequently downloaded are provided. The statistics will be informative for researchers to choose an appropriate simulation tool or select a common dataset for method comparisons. GESDB can be accessed at http://gesdb.nhri.org.twDatabase URL: http://gesdb.nhri.org.tw.

  11. A genetic study of loser cows in Danish dairy herds

    DEFF Research Database (Denmark)

    Pedersen, Louise Dybdahl; Jørgensen, Hanne Birgitte Hede; Kargo, Morten

    2013-01-01

    Following the recent years' increase in herd size, the awareness of a group of cows with a generally lowered health and production level, the “loser cows,” has arisen in Denmark. The aim of this study was to estimate genetic correlations between the loser cow score, 305d protein yield and realize...

  12. Studies on the Pathophysiology and Genetic Basis of Migraine

    Science.gov (United States)

    Gasparini, Claudia F; Sutherland, Heidi G.; Griffiths, Lyn R

    2013-01-01

    Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies. PMID:24403849

  13. Studies of twins indicate that genetics influence dietary intake

    DEFF Research Database (Denmark)

    Hasselbalch, Ann Louise; Heitmann, Berit L; Kyvik, Kirsten O

    2008-01-01

    Habitual dietary intake is a complex behavior that may have both biological and nonbiological bases. We estimated the contribution of genetic and environmental influences on dietary intake in a large population-based sample of healthy twins. Data originated from a cross-sectional study of 600 mal...

  14. Genetic studies in chronic kidney disease: interpretation and clinical applicability.

    Science.gov (United States)

    Witasp, Anna; Nordfors, Louise; Carrero, Juan Jesus; Luttropp, Karin; Lindholm, Bengt; Schalling, Martin; Stenvinkel, Peter

    2012-01-01

    The tools of modern molecular biology are evolving rapidly, resulting in vastly more efficient approaches to illuminating human genetic variations and their effects on common multifactorial disorders such as chronic kidney disease (CKD). Indeed, candidate gene association studies and genome-wide association studies (GWASs) have generated novel genetic variants in previously unrecognized biological pathways, highlighting disease mechanisms with a potential role in CKD etiology, morbidity and mortality. Nephrologists now need to find ways to make use of these advancements and meet the increasingly stringent requirements for valid study design, data handling and interpretation of genetic studies. Adding to our prior article in this journal, which introduced the basics of genotype-phenotype association studies in CKD, this second article focuses on how to ascertain robust and reproducible findings by applying adequate methodological and statistical approaches to genotype-phenotype studies in CKD populations. Moreover, this review will briefly discuss genotype-based risk prediction, pharmacotherapy, drug target identification and individualized treatment solutions, specifically highlighting potentially important findings in CKD patients. This increased knowledge will hopefully facilitate the exciting transition from conventional clinical medicine to gene-based medicine. However, before this can be accomplished, unsolved issues regarding the complex human genetic architecture as well technical and clinically oriented obstacles will have to be overcome. Additionally, new policies and standardized risk evaluations for genetic testing in the clinical setting will have to be established to guarantee that CKD patients are provided with high-quality genotype-guided counseling that will help to improve their poor outcomes.

  15. Evaluation and Genetic Polymorphism studies of Jatropha (Jatropha curcus for Water Stress Tolerance

    Directory of Open Access Journals (Sweden)

    Borse Tushar

    2010-05-01

    Full Text Available Jatropha (Jatropha curcus is an alternative resource for biodiesel. To boost the rural economy in sustainable manner it is estimated that 30 Million hector plantation may replace current use of fossil fuel. Although Jatropha has an inbuilt ability to grow under water limited conditions, scanty information is available about natural genetic variation for water stress tolerance. Three local genotypes from Pune district were collected and initially screened by imparting artificial stress using PEG – 6000. Seedlings were subjected to increasing concentration of PEG – 6000 (30, 60, 90, 120 and 150 gm/l to study effect on growth parameters.The root growth, number of secondary roots, true leaf expansion at morphological level and palisade mesophyll height, xylem vessel expansion at anatomical level showed drastic negative impact as compared to control. It is worth to note that local germplasm performance was categorized into susceptible group as compared to tolerant genotype [Chattisgadh Selection] indicating need for genetic improvement. These genotypes were further studied at molecular level with RAPD and ISSR markers to amplify genetic variation. Polymorphic bands from Chattisgadh selection genotype are being evaluated for their usefulness as markers for water stress tolerance.

  16. Blood cholesterol screening in several environments using a portable, dry-chemistry analyzer and fingerstick blood samples. Lipid Research Clinics Cholesterol Screening Study Group.

    Science.gov (United States)

    Bradford, R H; Bachorik, P S; Roberts, K; Williams, O D; Gotto, A M

    1990-01-01

    A multicenter study of blood cholesterol screening was performed in several typical environments, such as community sites (shopping malls and a supermarket), health care sites, work sites, a blood bank and a school. Cholesterol was measured with a portable, dry-chemistry analyzer using capillary blood obtained by fingerstick. Data are reported from a total of 13,824 participants, spanning the entire age spectrum. Overall, 25% of screened subjects had blood cholesterol levels above the age-specific cutpoints used in the current study. Although in the aggregate this screening experience very closely approximates the expected level of referrals, the proportion of referred screened subjects differed significantly among the 5 types of screening environments and by gender. Follow-up telephone interviews indicated that 53% of referrals had initiated a physician contact. More than 75% of those who had seen a physician reported that the diagnosis of hypercholesterolemia had been confirmed, and almost 72% had been prescribed a diet. A large proportion of referred screened subjects reported having modified their diet, particularly when recommended to do so by a physician. This study has yielded encouraging evidence that physicians gave referred screened subjects appropriate initial advice for managing hypercholesterolemia. The new technology for blood cholesterol measurement evaluated in the current study has proven to be a feasible and reliable means for measuring blood cholesterol in typical screening settings.

  17. Comparison of digital screening mammography and screen-film mammography in the early detection of clinically relevant cancers: a multicenter study

    NARCIS (Netherlands)

    Bluekens, A.M.; Holland, R.; Karssemeijer, N.; Broeders, M.J.M.; Heeten, G.J. den

    2012-01-01

    Purpose: To compare screen-film mammography with digital mammography in a breast cancer screening program, with a focus on the clinical relevance of detected cancers. Materials and Methods: The study was approved by the regional medical ethics review board. Informed consent was not required. Before

  18. Study on drying rate in contact drying with flexible screen

    Institute of Scientific and Technical Information of China (English)

    王伟宏; 陆仁书; 张显权

    2000-01-01

    The moisture contents (MC) of popular veneers were tested in Composition Board Laboratory of Northeast Forestry University by contact drying with flexible screen. The influence factors considered included temperature, initial moisture contents (IMC), and veneer thickness. Veneer-drying laws under different hot press conditions were analyzed. The results showed that the drying rate increased with temperature rising. 160℃ was considered to be more efficient than 140℃ and 180℃ because excessive high temperature has no significant contribution to drying rate. IMC had significant effect on drying rate. The veneer with high IMC had a higher drying rate at above fiber saturation point (FSP) and a lower drying rate at below FSP, compared to the veneer with low IMC. Average drying rate also varied with thickness in power law.

  19. Screening uptake rates and the clinical and cost effectiveness of screening for gestational diabetes mellitus in primary versus secondary care: study protocol for a randomised controlled trial.

    LENUS (Irish Health Repository)

    O Dea, Angela

    2014-01-17

    The risks associated with gestational diabetes mellitus (GDM) are well recognized, and there is increasing evidence to support treatment of the condition. However, clear guidance on the ideal approach to screening for GDM is lacking. Professional groups continue to debate whether selective screening (based on risk factors) or universal screening is the most appropriate approach. Additionally, there is ongoing debate about what levels of glucose abnormalities during pregnancy respond best to treatment and which maternal and neonatal outcomes benefit most from treatment. Furthermore, the implications of possible screening options on health care costs are not well established. In response to this uncertainty there have been repeated calls for well-designed, randomised trials to determine the efficacy of screening, diagnosis, and management plans for GDM. We describe a randomised controlled trial to investigate screening uptake rates and the clinical and cost effectiveness of screening in primary versus secondary care settings. The objective of this study is to assess screening uptake rates, and the clinical and cost effectiveness of screening for GDM in primary versus secondary care.

  20. A large-scale complex haploinsufficiency-based genetic interaction screen in Candida albicans: analysis of the RAM network during morphogenesis.

    Directory of Open Access Journals (Sweden)

    Nike Bharucha

    2011-04-01

    Full Text Available The morphogenetic transition between yeast and filamentous forms of the human fungal pathogen Candida albicans is regulated by a variety of signaling pathways. How these pathways interact to orchestrate morphogenesis, however, has not been as well characterized. To address this question and to identify genes that interact with the Regulation of Ace2 and Morphogenesis (RAM pathway during filamentation, we report the first large-scale genetic interaction screen in C. albicans.Our strategy for this screen was based on the concept of complex haploinsufficiency (CHI. A heterozygous mutant of CBK1(cbk1Δ/CBK1, a key RAM pathway protein kinase, was subjected to transposon-mediated, insertional mutagenesis. The resulting double heterozygous mutants (6,528 independent strains were screened for decreased filamentation on SpiderMedium (SM. From the 441 mutants showing altered filamentation, 139 transposon insertion sites were sequenced,yielding 41 unique CBK1-interacting genes. This gene set was enriched in transcriptional targets of Ace2 and, strikingly, the cAMP-dependent protein kinase A (PKA pathway, suggesting an interaction between these two pathways. Further analysis indicates that the RAM and PKA pathways co-regulate a common set of genes during morphogenesis and that hyperactivation of the PKA pathway may compensate for loss of RAM pathway function. Our data also indicate that the PKA–regulated transcription factor Efg1 primarily localizes to yeast phase cells while the RAM–pathway regulated transcription factor Ace2 localizes to daughter nuclei of filamentous cells, suggesting that Efg1 and Ace2 regulate a common set of genes at separate stages of morphogenesis. Taken together, our observations indicate that CHI–based screening is a useful approach to genetic interaction analysis in C. albicans and support a model in which these two pathways regulate a common set of genes at different stages of filamentation.

  1. Exploring the Effectiveness of Mandatory Premarital Screening and Genetic Counselling Programmes for β-Thalassaemia in the Middle East: A Scoping Review.

    Science.gov (United States)

    Saffi, Marwa; Howard, Natasha

    2015-01-01

    β-Thalassaemia is a common genetic blood disorder in the Middle Eastern region. Mandatory premarital screening and genetic counselling (PMSGC) programmes are implemented in 8 Middle East countries to reduce at-risk marriages and thus disease prevalence. A scoping review was conducted to explore the effectiveness of these programmes. The 6-stage scoping framework of Arksey and O'Malley [Int J Soc Res Methodol 2005;8:19-32] was used. Reported outcomes were analysed per country, with success defined as achieving a 65% reduction in at-risk marriages and/or thalassaemia-affected births. Emergent enablers and barriers were analysed thematically. Twenty-one sources were included from the 1,348 identified, discussing 7 country programmes, with 95% (20/21) published during 2003-2013. Five publications each were included for Iran and Saudi Arabia, 3 for Turkey, 2 each for Bahrain and Iraq (Kurdistan), and 1 for the United Arab Emirates, plus 2 multi-country evaluations. No programme achieved a 65% at-risk marriage cancellation rate. Though data on thalassaemia-affected birth reductions were minimal, programmes in Iran, Turkey and Iraq reported at least 65% reductions. A thematic analysis found that screening timing, access to prenatal detection and abortion, socio-religious issues, awareness and counselling affected decisions. This review found that PMSGC programmes were unsuccessful in discouraging at-risk marriages but successful in reducing the prevalence of affected births in countries providing prenatal detection and therapeutic abortion. A life cycle approach to prevention, incorporation of school screening, awareness campaigns, reconsideration of therapeutic abortion, and screening and counselling of couples married prior to programme inception are likely to improve the effectiveness of such programmes in the Middle Eastern region. © 2015 S. Karger AG, Basel.

  2. Study of hearing screening for rural school children

    Institute of Scientific and Technical Information of China (English)

    Xiaolu Li; Xingkuan Bu; Carlie Driscoll

    2006-01-01

    Objective: To develop an appropriate mass screening system to evaluate hearing loss for primary school children, especially in rural areas. Methods: In Jiangsu Province, at a rural primary school-Longdu Primary School, 317 of 479 rural students (from Grade 1 to Grade 6, over 50 students for each grade) were screened by, using the Chinese Hearing Questionnaire for School Children (CHQS). Two weeks later, they accepted transiently evoked otoacoustic emissions (TEOAEs) test. At the same time, all participants were given a 'gold standard' audiological assessment that comprised of otoscopy, pure tone, and tympanometry. After eight weeks, 103 out of the 317 students accepted the second TEOAEs and 'gold standard' test to confirm the results. Results: There was no statistical difference in the results of two 'gold standard' test (χ2 = 0.14, 0.5 < P < 0.75). Compared with the 'gold standard' results, the hit rate, sensitivity, specificity of the CHQS was 57% ± 2.78%, 61% ± 10.18%, 57%± 2.89% respectively(α = 0.43, β = 0.39). Youden Index J, LR+, LR-, PV+ and PV- was 0.18 ± 0.11, 1.42, 0.68, 0.10, 0.95(Az < 0.54, EF = 0.75-0.95). While a higher system accuracy was obtained by TEOAEs [HR = 97 ± 0.71%, Sen = 69 ± 7.8%,Spe = 98 ± 0.52%(α = 0.02, β = 0.31), Youden Index J = 0.67 ± 0.08, LR+ = 34.5, LR- = 0.32, PV+ = 0.71, PV- = 0.99(Az = 0.85, EF = 0.97)]. Conclusion: TEOAEs got a high efficiency and specificity values with reasonable sensitivity. However,CHQS needs substantial modifications to improve its sensitivity in evaluating hearing loss.

  3. ESHRE PGD Consortium/Embryology Special Interest Group--best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS)

    DEFF Research Database (Denmark)

    Harton, G L; Magli, M C; Lundin, K

    2011-01-01

    have seen the introduction of a number of new technologies as well as the evolution of current techniques. Additionally, in light of ESHRE's recent advice on how practice guidelines should be written and formulated, the Consortium believed it was timely to revise and update the PGD guidelines. Rather...... and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS). Here we have updated the sections that pertain to embryology (including cryopreservation) and biopsy of embryos prior to PGD or PGS. Topics covered in this guideline include uses of embryo biopsy, laboratory issues relating...... to biopsy, timing of biopsy, biopsy procedure and cryopreserving biopsied embryos....

  4. Lab-on-a-disc platform for screening of genetically modified E. coli cells via cell-free electrochemical detection of p-Coumaric acid

    DEFF Research Database (Denmark)

    Sanger, Kuldeep; Zor, Kinga; Jendresen, Christian Bille

    2017-01-01

    obtained from the electrochemical measurements showed good correlation with high performance liquid chromatographic analysis. The developed LoD system offers fast and easy detection of pHCA, enabling screening of genetically modified organisms based on the quantity of produced secondary metabolites....... filtration and electrochemical detection units, the sample filtration was performed by rotating the disc using a programmable closed-loop stepper motor. The electrodes, patterned on plastic substrate, were connected through a printed circuit board to the slip ring using a robust magnetic clamping system...

  5. The genetic study of three population microisolates in South Tyrol (MICROS: study design and epidemiological perspectives

    Directory of Open Access Journals (Sweden)

    Pinggera Gerd K

    2007-06-01

    Full Text Available Abstract Background There is increasing evidence of the important role that small, isolated populations could play in finding genes involved in the etiology of diseases. For historical and political reasons, South Tyrol, the northern most Italian region, includes several villages of small dimensions which remained isolated over the centuries. Methods The MICROS study is a population-based survey on three small, isolated villages, characterized by: old settlement; small number of founders; high endogamy rates; slow/null population expansion. During the stage-1 (2002/03 genealogical data, screening questionnaires, clinical measurements, blood and urine samples, and DNA were collected for 1175 adult volunteers. Stage-2, concerning trait diagnoses, linkage analysis and association studies, is ongoing. The selection of the traits is being driven by expert clinicians. Preliminary, descriptive statistics were obtained. Power simulations for finding linkage on a quantitative trait locus (QTL were undertaken. Results Starting from participants, genealogies were reconstructed for 50,037 subjects, going back to the early 1600s. Within the last five generations, subjects were clustered in one pedigree of 7049 subjects plus 178 smaller pedigrees (3 to 85 subjects each. A significant probability of familial clustering was assessed for many traits, especially among the cardiovascular, neurological and respiratory traits. Simulations showed that the MICROS pedigree has a substantial power to detect a LOD score ≥ 3 when the QTL specific heritability is ≥ 20%. Conclusion The MICROS study is an extensive, ongoing, two-stage survey aimed at characterizing the genetic epidemiology of Mendelian and complex diseases. Our approach, involving different scientific disciplines, is an advantageous strategy to define and to study population isolates. The isolation of the Alpine populations, together with the extensive data collected so far, make the MICROS study a

  6. Rationale and Design of the Lung Cancer Screening Implementation. Evaluation of Patient-Centered Care Study.

    Science.gov (United States)

    Miranda, Leah S; Datta, Santanu; Melzer, Anne C; Wiener, Renda Soylemez; Davis, James M; Tong, Betty C; Golden, Sara E; Slatore, Christopher G

    2017-10-01

    Screening for lung cancer using low-dose computed tomography has been demonstrated to reduce lung cancer-related mortality and is being widely implemented. Further research in this area is needed to assess the impact of screening on patient-centered outcomes. Here, we describe the design and rationale for a new study entitled Lung Cancer Screening Implementation: Evaluation of Patient-Centered Care. The protocol is composed of an interconnected series of studies evaluating patients and clinicians who are engaged in lung cancer screening in real-world settings. The primary goal of this study is to evaluate communication processes that are being used in routine care and to identify best practices that can be readily scaled up for implementation in multiple settings. We hypothesize that higher overall quality of patient-clinician communication processes will be associated with lower levels of distress and decisional conflict as patients decide whether or not to participate in lung cancer screening. This work is a critical step toward identifying modifiable mechanisms that are associated with high quality of care for the millions of patients who will consider lung cancer screening. Given the enormous potential benefits and burdens of lung cancer screening on patients, clinicians, and the healthcare system, it is important to identify and then scale up quality communication practices that positively influence patient-centered care.

  7. CANCER SCREENING AWARENESS AMONG NURSING STAFF IN GOVERNMENT MEDICAL COLLEGE: A PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Mukesh Shanthilal

    2016-07-01

    Full Text Available BACKGROUND Cervical and breast cancers are the common malignancies among female population in India. Though there are approved screening methods available to prevent and detect these cancers at an early stage, there is a lack of awareness about cancer screening among general public as well as the health care professionals. This study is aimed to identify the knowledge, attitude and practice (KAP among the nursing staff regarding cancer screening in these two diseases. METHOD A cross-sectional interview based survey was conducted among 303 female nursing staff working in a government medical college hospital from November 2015 to December 2015. Ethical committee approval was taken. Verbal informed consent was sought from the study subjects. Nursing staff who gave consent to participate in the study were enrolled. There were no specific inclusion or exclusion criteria for the study subjects. A structured pretested questionnaire regarding knowledge, attitude and practice (KAP was used to collect the data. The questions were open-ended. Recall and recognition type of questions were used. The data was entered into MS Excel worksheet and analysed using descriptive statistics. RESULTS Total of 303 nurses included in the study. The age ranged from 21 to 64 years. Median age is 38 years. Only 24.4% (74/303 of Nurses were aware of cancer screening and many of them were aware of Pap smear (55.1%, 167/303 and mammogram (66.3%, 201/303 as investigational tools in diagnosing cancer. Only 17 out of 303 (5.6% nurses had Pap smear test done with an average of 1.23% Pap smear per individual. Mammogram screening was done in 13% (15/115 of the eligible nurses with an average of 1.2% mammogram per individual. The most common reason for not undergoing screening as expressed was they did not feel the need to be screened unless they were symptomatic (55%, they are too young for screening (14.8%, shyness (11.1%, fear (11.1% and lack of time (7.4%. However, 90% of them

  8. Promoting chlamydia screening with posters and leaflets in general practice - a qualitative study

    Directory of Open Access Journals (Sweden)

    Ford-Young William

    2009-10-01

    Full Text Available Abstract Background General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP, have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Methods Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Results Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. Conclusion The NCSP

  9. Initial maternal serum human chorionic gonadotropin levels in pregnancies achieved after assisted reproductive technology are higher after preimplantation genetic screening and after frozen embryo transfer: a retrospective cohort.

    Science.gov (United States)

    Hobeika, Elie; Singh, Sonali; Malik, Shaveta; Knochenhauer, Eric S; Traub, Michael L

    2017-06-21

    Few published articles have compared initial hCG values across all different types of ART cycles, including cycles with fresh or frozen embryo transfer. No articles have compared initial hCG values in cycles utilizing preimplantation genetic screening (PGS). The purpose of this study is to compare initial hCG values after fresh embryo transfer, frozen embryo transfer, and after PGS. This was a single-center retrospective cohort study at an academically affiliated private IVF center. All fresh and frozen embryo transfers between January 2013 and December 31, 2015 were included. We compared mean initial serum hCG values 14 days after oocyte retrieval for fresh cycles and 9 days after frozen embryo transfer. We examined cycles of single embryo transfer (SET) and double embryo transfer (DET). Two hundred elven IVF (fresh embryo transfer), 128 FET (frozen embryo transfer cycles, no PGS), and 111 PGS cycles (ovarian stimulation with embryo cryopreservation, PGS, and frozen transfer in a subsequent estrogen-primed cycle) with initial positive hCG values were analyzed. In patients achieving a positive hCG after SET, initial hCG values were higher after PGS compared to FET (182.4 versus 124.0 mIU/mL, p = 0.02) and IVF (182.4 versus 87.1 mIU/mL, p transfer of a frozen embryo compared to a fresh embryo. This suggests that initial hCG values relate to the chromosomal status of embryos. Initial hCG values may help determine intervention and monitoring later in pregnancy.

  10. [A community-based genetic screening of large-scale population and prenatal diagnosis for alpha and beta thalassemia in Zhuhai city of Guangdong province].

    Science.gov (United States)

    Zhou, Yu-qiu; Mo, Qiu-hua; Lu, Jin-han; Li, Li-yan; Liang, Xiong; Jia, Shi-qi; Xiao, Ge-fei; Zhou, Wan-jun; Xiao, Qi-zhi; Xu, Xiang-min

    2008-06-01

    To describe a community-based model for prevention and control of severe alpha and beta thalassemias in Zhuhai city of Guangdong province. Couples for premarital medical examination or regular healthcare examination in pregnancy were enrolled in this prospective screening program, which was supported by the two-level network composed of 6 local hospitals for testing thalassemias and follow-up for genetic counseling. A conventional heterozygote screening strategy was used to determine alpha and beta thalassemia traits in women and their partners according to the standard procedures of hematological phenotype analysis. Then confirmative diagnosis of alpha and beta thalassemia was performed on those couples suspected at-risk for severe thalassemia by using the PCR-based molecular diagnostic assays. The couples at-risk for severe thalassemia were counseled and offered prenatal diagnosis and termination of pregnancy in case of an affected fetus. During the period between January 1998 and December 2005, the screened records included 85522 young females and their partners for premarital screening and 10439 pregnant women for prenatal screening, with 71.38% coverage of total population recorded in this city for premarital screening. Six thousands five hundreds and sixty-three individuals in total were found to be the carriers of thalassemias, with 4312 for alpha thalassemia (4.5%) and 2251 for beta thalassemia (2.3%), respectively. One hundred and forty-eight couples were diagnosed to be at-risk for thalassemias, including 103 for alpha thalassemia and 45 for beta thalassemia, respectively. Successful prenatal diagnosis was made for 142 (98 for alpha thalassemia and 44 for beta thalassemia) out of 148 (95.9%) pregnancies at-risk for severe thalassemias. Twenty-three cases of hydrops fetalis, 4 of Hb H diseases and 14 of beta thalassemia were identified. All 41 pregnancies with affected fetuses were voluntarily terminated. Thus, this has led to a marked decrease of severe

  11. A bow-tie genetic architecture for morphogenesis suggested by a genome-wide RNAi screen in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Matthew D Nelson

    2011-03-01

    Full Text Available During animal development, cellular morphogenesis plays a fundamental role in determining the shape and function of tissues and organs. Identifying the components that regulate and drive morphogenesis is thus a major goal of developmental biology. The four-celled tip of the Caenorhabditis elegans male tail is a simple but powerful model for studying the mechanism of morphogenesis and its spatiotemporal regulation. Here, through a genome-wide post-embryonic RNAi-feeding screen, we identified 212 components that regulate or participate in male tail tip morphogenesis. We constructed a working hypothesis for a gene regulatory network of tail tip morphogenesis. We found regulatory roles for the posterior Hox genes nob-1 and php-3, the TGF-β pathway, nuclear hormone receptors (e.g. nhr-25, the heterochronic gene blmp-1, and the GATA transcription factors egl-18 and elt-6. The majority of the pathways converge at dmd-3 and mab-3. In addition, nhr-25 and dmd-3/mab-3 regulate each others' expression, thus placing these three genes at the center of a complex regulatory network. We also show that dmd-3 and mab-3 negatively regulate other signaling pathways and affect downstream cellular processes such as vesicular trafficking (e.g. arl-1, rme-8 and rearrangement of the cytoskeleton (e.g. cdc-42, nmy-1, and nmy-2. Based on these data, we suggest that male tail tip morphogenesis is governed by a gene regulatory network with a bow-tie architecture.

  12. Effect of adding screening ultrasonography to screening mammography on patient recall and cancer detection rates: A retrospective study in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Tohno, Eriko, E-mail: tohno@tmch.or.jp [Total Health Evaluation Center Tsukuba, 1-2, Amakubo, Tsukuba, Ibaraki 305-0005 (Japan); Umemoto, Takeshi, E-mail: umemoto@tmch.or.jp [Tsukuba Medical Center Hospital, 1-3-1, Amakubo, Tsukuba, Ibaraki 305-0005 (Japan); Sasaki, Kyoko, E-mail: kdon@za.cyberhome.ne.jp [Tsukuba Medical Center Hospital, 1-3-1, Amakubo, Tsukuba, Ibaraki 305-0005 (Japan); Morishima, Isamu, E-mail: morishima@tmch.or.jp [Tsukuba Medical Center Hospital, 1-3-1, Amakubo, Tsukuba, Ibaraki 305-0005 (Japan); Ueno, Ei, E-mail: e-ueno@tmch.or.jp [Tsukuba Medical Center Hospital, 1-3-1, Amakubo, Tsukuba, Ibaraki 305-0005 (Japan)

    2013-08-15

    Purpose: To determine whether adding screening ultrasonography to screening mammography can reduce patient recall rates and increase cancer detection rates. Materials and methods: We analyzed the results of mammography and ultrasonography breast screenings performed at the Total Health Evaluation Center Tsukuba, Japan, between April 2011 and March 2012. We also reviewed the modalities and results of diagnostic examinations from women w