WorldWideScience

Sample records for hapmap ceph founders

  1. Geographical affinities of the HapMap samples.

    Directory of Open Access Journals (Sweden)

    Miao He

    Full Text Available The HapMap samples were collected for medical-genetic studies, but are also widely used in population-genetic and evolutionary investigations. Yet the ascertainment of the samples differs from most population-genetic studies which collect individuals who live in the same local region as their ancestors. What effects could this non-standard ascertainment have on the interpretation of HapMap results?We compared the HapMap samples with more conventionally-ascertained samples used in population- and forensic-genetic studies, including the HGDP-CEPH panel, making use of published genome-wide autosomal SNP data and Y-STR haplotypes, as well as producing new Y-STR data. We found that the HapMap samples were representative of their broad geographical regions of ancestry according to all tests applied. The YRI and JPT were indistinguishable from independent samples of Yoruba and Japanese in all ways investigated. However, both the CHB and the CEU were distinguishable from all other HGDP-CEPH populations with autosomal markers, and both showed Y-STR similarities to unusually large numbers of populations, perhaps reflecting their admixed origins.The CHB and JPT are readily distinguished from one another with both autosomal and Y-chromosomal markers, and results obtained after combining them into a single sample should be interpreted with caution. The CEU are better described as being of Western European ancestry than of Northern European ancestry as often reported. Both the CHB and CEU show subtle but detectable signs of admixture. Thus the YRI and JPT samples are well-suited to standard population-genetic studies, but the CHB and CEU less so.

  2. Ceph, a distributed storage system for scientific computing

    CERN Multimedia

    CERN. Geneva

    2013-01-01

    Ceph is a distributed storage system designed to providing high performance and reliability at scales of up to thousands of storage nodes. The system is based on a distributed object storage layer call RADOS that provides durability, availability, efficient data distribution, and rich object semantics. This storage can be consumed directly via an object-based interface, or via file, block, or REST-based object services that are built on top of it. Clusters are composed of commodity components to provide a reliable storage service serving multiple use-cases. This seminar will cover the basic architecture of Ceph, with a focus on how each service can be consumed in a research and infrastructure environment. About the speaker Sage Weil, Founder and current CTO of Inktank Inc, is the creator of the Ceph project. He originally designed it as part of his PhD research in Storage Systems at the University of California, Santa Cruz. Since graduating, he has continued to refine the system with the goal of providi...

  3. Manila on CephFS at CERN

    CERN Document Server

    Wiebalck, Arne

    2017-01-01

    In response to the user demand for a light-weight provisioning of distributed file system shares, the OpenStack and Ceph teams at CERN have recently added Manila/CephFS to their service catalogues. While leveraging the operational experience with a 190'000 core OpenStack deployment and a 12 PB Ceph cluster for such a self-service kiosque suggested itself, the service design and setup phases were followed by a number of functionality and stress tests to ensure the individual components are ready for production use. The final service design and the results obtained during the pre-production phase, for instance when scaling to a large number of Manila and CephFS clients or the integration with Magnum/Kubernetes, will be presented alongside the initial use cases and our first experiences running these new services in production.

  4. Overview and Status of the Ceph File System

    CERN Multimedia

    CERN. Geneva

    2017-01-01

    The Ceph file system (CephFS) is the POSIX-compatible distributed file system running on top of Ceph's powerful and stable object store. This presentation will give a general introduction of CephFS and detail the recent work the Ceph team has done to improve its stability and usability. In particular, we will cover directory fragmentation, multiple active metadata servers, and directory subtree pinning to metadata servers, features slated for stability in the imminent Luminous release. This talk will also give an overview of how we are measuring performance of multiple active metadata servers using large on-demand cloud deployments. The results will highlight how CephFS distributes metadata load across metadata servers to achieve scaling. About the speaker Patrick Donnelly is a software engineer at Red Hat, Inc. currently working on the Ceph distributed file system. In 2016 he completed his Ph.D. in computer science at the University of Notre Dame with a dissertation on the topic of file transfer management...

  5. An evaluation of the performance of tag SNPs derived from HapMap in a Caucasian population.

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    Alexandre Montpetit

    2006-03-01

    Full Text Available The Haplotype Map (HapMap project recently generated genotype data for more than 1 million single-nucleotide polymorphisms (SNPs in four population samples. The main application of the data is in the selection of tag single-nucleotide polymorphisms (tSNPs to use in association studies. The usefulness of this selection process needs to be verified in populations outside those used for the HapMap project. In addition, it is not known how well the data represent the general population, as only 90-120 chromosomes were used for each population and since the genotyped SNPs were selected so as to have high frequencies. In this study, we analyzed more than 1,000 individuals from Estonia. The population of this northern European country has been influenced by many different waves of migrations from Europe and Russia. We genotyped 1,536 randomly selected SNPs from two 500-kbp ENCODE regions on Chromosome 2. We observed that the tSNPs selected from the CEPH (Centre d'Etude du Polymorphisme Humain from Utah (CEU HapMap samples (derived from US residents with northern and western European ancestry captured most of the variation in the Estonia sample. (Between 90% and 95% of the SNPs with a minor allele frequency of more than 5% have an r2 of at least 0.8 with one of the CEU tSNPs. Using the reverse approach, tags selected from the Estonia sample could almost equally well describe the CEU sample. Finally, we observed that the sample size, the allelic frequency, and the SNP density in the dataset used to select the tags each have important effects on the tagging performance. Overall, our study supports the use of HapMap data in other Caucasian populations, but the SNP density and the bias towards high-frequency SNPs have to be taken into account when designing association studies.

  6. Ceph-based storage services for Run2 and beyond

    CERN Document Server

    van der Ster, Daniel C; Mascetti, Luca; Peters, Andreas J; Rousseau, Herv

    2015-01-01

    In 2013, CERN IT evaluated then deployed a petabyte-scale Ceph cluster to support OpenStack use-cases in production. With now more than a year of smooth operations, we will present our experience and tuning best-practices. Beyond the cloud storage use-cases, we have been exploring Ceph-based services to satisfy the growing storage requirements during and after Run2. First, we have developed a Ceph back-end for CASTOR, allowing this service to deploy thin disk server nodes which act as gateways to Ceph, this feature marries the strong data archival and cataloging features of CASTOR with the resilient and high performance Ceph subsystem for disk. Second, we have developed RADOSFS, a lightweight storage API which builds a POSIX-like filesystem on top of the Ceph object layer. When combined with Xrootd, RADOSFS can offer a scalable object interface compatible with our HEP data processing applications. Lastly the same object layer is being used to build a scalable and inexpensive NFS service for several user commu...

  7. Ceph-based storage services for Run2 and beyond

    Science.gov (United States)

    van der Ster, Daniel C.; Lamanna, Massimo; Mascetti, Luca; Peters, Andreas J.; Rousseau, Hervé

    2015-12-01

    In 2013, CERN IT evaluated then deployed a petabyte-scale Ceph cluster to support OpenStack use-cases in production. With now more than a year of smooth operations, we will present our experience and tuning best-practices. Beyond the cloud storage use-cases, we have been exploring Ceph-based services to satisfy the growing storage requirements during and after Run2. First, we have developed a Ceph back-end for CASTOR, allowing this service to deploy thin disk server nodes which act as gateways to Ceph; this feature marries the strong data archival and cataloging features of CASTOR with the resilient and high performance Ceph subsystem for disk. Second, we have developed RADOSFS, a lightweight storage API which builds a POSIX-like filesystem on top of the Ceph object layer. When combined with Xrootd, RADOSFS can offer a scalable object interface compatible with our HEP data processing applications. Lastly the same object layer is being used to build a scalable and inexpensive NFS service for several user communities.

  8. Building an organic block storage service at CERN with Ceph

    International Nuclear Information System (INIS)

    Ster, Daniel van der; Wiebalck, Arne

    2014-01-01

    Emerging storage requirements, such as the need for block storage for both OpenStack VMs and file services like AFS and NFS, have motivated the development of a generic backend storage service for CERN IT. The goals for such a service include (a) vendor neutrality, (b) horizontal scalability with commodity hardware, (c) fault tolerance at the disk, host, and network levels, and (d) support for geo-replication. Ceph is an attractive option due to its native block device layer RBD which is built upon its scalable, reliable, and performant object storage system, RADOS. It can be considered an 'organic' storage solution because of its ability to balance and heal itself while living on an ever-changing set of heterogeneous disk servers. This work will present the outcome of a petabyte-scale test deployment of Ceph by CERN IT. We will first present the architecture and configuration of our cluster, including a summary of best practices learned from the community and discovered internally. Next the results of various functionality and performance tests will be shown: the cluster has been used as a backend block storage system for AFS and NFS servers as well as a large OpenStack cluster at CERN. Finally, we will discuss the next steps and future possibilities for Ceph at CERN.

  9. Building an organic block storage service at CERN with Ceph

    Science.gov (United States)

    van der Ster, Daniel; Wiebalck, Arne

    2014-06-01

    Emerging storage requirements, such as the need for block storage for both OpenStack VMs and file services like AFS and NFS, have motivated the development of a generic backend storage service for CERN IT. The goals for such a service include (a) vendor neutrality, (b) horizontal scalability with commodity hardware, (c) fault tolerance at the disk, host, and network levels, and (d) support for geo-replication. Ceph is an attractive option due to its native block device layer RBD which is built upon its scalable, reliable, and performant object storage system, RADOS. It can be considered an "organic" storage solution because of its ability to balance and heal itself while living on an ever-changing set of heterogeneous disk servers. This work will present the outcome of a petabyte-scale test deployment of Ceph by CERN IT. We will first present the architecture and configuration of our cluster, including a summary of best practices learned from the community and discovered internally. Next the results of various functionality and performance tests will be shown: the cluster has been used as a backend block storage system for AFS and NFS servers as well as a large OpenStack cluster at CERN. Finally, we will discuss the next steps and future possibilities for Ceph at CERN.

  10. CephFS: a new generation storage platform for Australian high energy physics

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    Borges, G.; Crosby, S.; Boland, L.

    2017-10-01

    This paper presents an implementation of a Ceph file system (CephFS) use case at the ARC Center of Excellence for Particle Physics at the Terascale (CoEPP). CoEPP’s CephFS provides a posix-like file system on top of a Ceph RADOS object store, deployed on commodity hardware and without single points of failure. By delivering a unique file system namespace at different CoEPP centres spread across Australia, local HEP researchers can store, process and share data independently of their geographical locations. CephFS is also used as the back-end file system for a WLCG ATLAS user area at the Australian Tier-2. Dedicated SRM and XROOTD services, deployed on top of CoEPP’s CephFS, integrates it in ATLAS data distributed operations. This setup, while allowing Australian HEP researchers to trigger data movement via ATLAS grid tools, also enables local posix-like read access providing greater control to scientists of their data flows. In this article we will present details on CoEPP’s Ceph/CephFS implementation and report performance I/O metrics collected during the testing/tuning phase of the system.

  11. Cephalopod Experimental Projected Habitat (CEPH: Virtual Reality for Underwater Organisms

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    Noam Josef

    2018-03-01

    Full Text Available Cephalopods' visually driven, dynamic, and diverse skin display makes them a key animal model in sensory ethology and camouflage research. Development of novel methods is critically important in order to monitor and objectively quantify cephalopod behavior. In this work, the development of Cephalopod Experimental Projected Habitat (CEPH is described. This newly developed experimental design bridges computational and ethological sciences, providing a visually controlled arena which requires limited physical space and minimal previous technical background. Created from relatively inexpensive and readily available materials, the experimental apparatus utilizes reflected light which closely resembles natural settings. Preliminary results suggest the experimental design reproducibly challenges marine organisms with visually dynamic surroundings, including videos of prey and predator. This new approach should offer new avenues for marine organism sensory research and may serve researchers from various fields.

  12. Do (Female) Founders Influence (Female) Joiners to Become Founders too?

    DEFF Research Database (Denmark)

    Rocha, Vera; Van Praag, Mirjam

    -founder (gender) homophily affects the likelihood of female and male joiners to become founders themselves. We find a relatively large and robust positive effect among female joiners that can be attributed to the role modeling function of female founders. Female entrepreneurs hiring personnel may thus have...

  13. European gene mapping project (EUROGEM) : Breakpoint panels for human chromosomes based on the CEPH reference families

    NARCIS (Netherlands)

    Attwood, J; Bryant, SP; Bains, R; Povey, R; Povey, S; Rebello, M; Kapsetaki, M; Moschonas, NK; Grzeschik, KH; Otto, M; Dixon, M; Sudworth, HE; Kooy, RF; Wright, A; Teague, P; Terrenato, L; Vergnaud, G; Monfouilloux, S; Weissenbach, J; Alibert, O; Dib, C; Faure, S; Bakker, E; Pearson, NM; Vossen, RHAM; Gal, A; MuellerMyhsok, B; Cann, HM; Spurr, NK

    Meiotic breakpoint panels for human chromosomes 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 14, 15, 17; 18, 20 and X were constructed from genotypes from the CEPH reference families. Each recombinant chromosome included has a breakpoint well-supported with reference to defined quantitative criteria. The panels

  14. Founder Mutations in Xeroderma Pigmentosum

    Science.gov (United States)

    Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth H.

    2012-01-01

    In this issue, Soufir et al. report a founder mutation in the XPC DNA repair gene in 74% of families with xeroderma pigmentosum (XP) in the Maghreb region (Algeria, Morocco, and Tunisia) of northern Africa. These patients have a high frequency of skin cancer. The presence of this founder mutation provides an opportunity for genetic counseling and early diagnosis of XP. PMID:20463673

  15. Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA.

    Science.gov (United States)

    Royle, N J; Armour, J A; Crosier, M; Jeffreys, A J

    1993-01-01

    Somatic events that result in the reduction to hemi- or homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis.

  16. Identification and replication of loci involved in camptothecin-induced cytotoxicity using CEPH pedigrees.

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    Venita Gresham Watson

    2011-05-01

    Full Text Available To date, the Centre d'Etude Polymorphism Humain (CEPH cell line model has only been used as a pharmacogenomic tool to evaluate which genes are responsible for the disparity in response to a single drug. The purpose of this study was demonstrate the model's ability to establish a specific pattern of quantitative trait loci (QTL related to a shared mechanism for multiple structurally related drugs, the camptothecins, which are Topoisomerase 1 inhibitors. A simultaneous screen of six camptothecin analogues for in vitro sensitivity in the CEPH cell lines resulted in cytotoxicity profiles and orders of potency which were in agreement with the literature. For all camptothecins studied, heritability estimates for cytotoxic response averaged 23.1 ± 2.6%. Nonparametric linkage analysis was used to identify a relationship between genetic markers and response to the camptothecins. Ten QTLs on chromosomes 1, 3, 5, 6, 11, 12, 16 and 20 were identified as shared by all six camptothecin analogues. In a separate validation experiment, nine of the ten QTLs were replicated at the significant and suggestive levels using three additional camptothecin analogues. To further refine this list of QTLs, another validation study was undertaken and seven of the nine QTLs were independently replicated for all nine camptothecin analogues. This is the first study using the CEPH cell lines that demonstrates that a specific pattern of QTLs could be established for a class of drugs which share a mechanism of action. Moreover, it is the first study to report replication of linkage results for drug-induced cytotoxicity using this model. The QTLs, which have been identified as shared by all camptothecins and replicated across multiple datasets, are of considerable interest; they harbor genes related to the shared mechanism of action for the camptothecins, which are responsible for variation in response.

  17. Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study.

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    Paul S de Vries

    Full Text Available An increasing number of genome-wide association (GWA studies are now using the higher resolution 1000 Genomes Project reference panel (1000G for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10-8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10-8, the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.

  18. OSiRIS: a distributed Ceph deployment using software defined networking for multi-institutional research

    Science.gov (United States)

    McKee, Shawn; Kissel, Ezra; Meekhof, Benjeman; Swany, Martin; Miller, Charles; Gregorowicz, Michael

    2017-10-01

    We report on the first year of the OSiRIS project (NSF Award #1541335, UM, IU, MSU and WSU) which is targeting the creation of a distributed Ceph storage infrastructure coupled together with software-defined networking to provide high-performance access for well-connected locations on any participating campus. The projects goal is to provide a single scalable, distributed storage infrastructure that allows researchers at each campus to read, write, manage and share data directly from their own computing locations. The NSF CC*DNI DIBBS program which funded OSiRIS is seeking solutions to the challenges of multi-institutional collaborations involving large amounts of data and we are exploring the creative use of Ceph and networking to address those challenges. While OSiRIS will eventually be serving a broad range of science domains, its first adopter will be the LHC ATLAS detector project via the ATLAS Great Lakes Tier-2 (AGLT2) jointly located at the University of Michigan and Michigan State University. Part of our presentation will cover how ATLAS is using the OSiRIS infrastructure and our experiences integrating our first user community. The presentation will also review the motivations for and goals of the project, the technical details of the OSiRIS infrastructure, the challenges in providing such an infrastructure, and the technical choices made to address those challenges. We will conclude with our plans for the remaining 4 years of the project and our vision for what we hope to deliver by the projects end.

  19. Achieving cost/performance balance ratio using tiered storage caching techniques: A case study with CephFS

    Science.gov (United States)

    Poat, M. D.; Lauret, J.

    2017-10-01

    As demand for widely accessible storage capacity increases and usage is on the rise, steady IO performance is desired but tends to suffer within multi-user environments. Typical deployments use standard hard drives as the cost per/GB is quite low. On the other hand, HDD based solutions for storage is not known to scale well with process concurrency and soon enough, high rate of IOPs create a “random access” pattern killing performance. Though not all SSDs are alike, SSDs are an established technology often used to address this exact “random access” problem. In this contribution, we will first discuss the IO performance of many different SSD drives (tested in a comparable and standalone manner). We will then be discussing the performance and integrity of at least three low-level disk caching techniques (Flashcache, dm-cache, and bcache) including individual policies, procedures, and IO performance. Furthermore, the STAR online computing infrastructure currently hosts a POSIX-compliant Ceph distributed storage cluster - while caching is not a native feature of CephFS (only exists in the Ceph Object store), we will show how one can implement a caching mechanism profiting from an implementation at a lower level. As our illustration, we will present our CephFS setup, IO performance tests, and overall experience from such configuration. We hope this work will service the community’s interest for using disk-caching mechanisms with applicable uses such as distributed storage systems and seeking an overall IO performance gain.

  20. Genotype Imputation for Latinos Using the HapMap and 1000 Genomes Project Reference Panels

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    Xiaoyi eGao

    2012-06-01

    Full Text Available Genotype imputation is a vital tool in genome-wide association studies (GWAS and meta-analyses of multiple GWAS results. Imputation enables researchers to increase genomic coverage and to pool data generated using different genotyping platforms. HapMap samples are often employed as the reference panel. More recently, the 1000 Genomes Project resource is becoming the primary source for reference panels. Multiple GWAS and meta-analyses are targeting Latinos, the most populous and fastest growing minority group in the US. However, genotype imputation resources for Latinos are rather limited compared to individuals of European ancestry at present, largely because of the lack of good reference data. One choice of reference panel for Latinos is one derived from the population of Mexican individuals in Los Angeles contained in the HapMap Phase 3 project and the 1000 Genomes Project. However, a detailed evaluation of the quality of the imputed genotypes derived from the public reference panels has not yet been reported. Using simulation studies, the Illumina OmniExpress GWAS data from the Los Angles Latino Eye Study and the MACH software package, we evaluated the accuracy of genotype imputation in Latinos. Our results show that the 1000 Genomes Project AMR+CEU+YRI reference panel provides the highest imputation accuracy for Latinos, and that also including Asian samples in the panel can reduce imputation accuracy. We also provide the imputation accuracy for each autosomal chromosome using the 1000 Genomes Project panel for Latinos. Our results serve as a guide to future imputation-based analysis in Latinos.

  1. Unexpected Relationships and Inbreeding in HapMap Phase III Populations

    Science.gov (United States)

    Stevens, Eric L.; Baugher, Joseph D.; Shirley, Matthew D.; Frelin, Laurence P.; Pevsner, Jonathan

    2012-01-01

    Correct annotation of the genetic relationships between samples is essential for population genomic studies, which could be biased by errors or omissions. To this end, we used identity-by-state (IBS) and identity-by-descent (IBD) methods to assess genetic relatedness of individuals within HapMap phase III data. We analyzed data from 1,397 individuals across 11 ethnic populations. Our results support previous studies (Pemberton et al., 2010; Kyriazopoulou-Panagiotopoulou et al., 2011) assessing unknown relatedness present within this population. Additionally, we present evidence for 1,657 novel pairwise relationships across 9 populations. Surprisingly, significant Cotterman's coefficients of relatedness K1 (IBD1) values were detected between pairs of known parents. Furthermore, significant K2 (IBD2) values were detected in 32 previously annotated parent-child relationships. Consistent with a hypothesis of inbreeding, regions of homozygosity (ROH) were identified in the offspring of related parents, of which a subset overlapped those reported in previous studies (Gibson et al. 2010; Johnson et al. 2011). In total, we inferred 28 inbred individuals with ROH that overlapped areas of relatedness between the parents and/or IBD2 sharing at a different genomic locus between a child and a parent. Finally, 8 previously annotated parent-child relationships had unexpected K0 (IBD0) values (resulting from a chromosomal abnormality or genotype error), and 10 previously annotated second-degree relationships along with 38 other novel pairwise relationships had unexpected IBD2 (indicating two separate paths of recent ancestry). These newly described types of relatedness may impact the outcome of previous studies and should inform the design of future studies relying on the HapMap Phase III resource. PMID:23185369

  2. Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study

    DEFF Research Database (Denmark)

    de Vries, Paul S; Sabater-Lleal, Maria; Chasman, Daniel I

    2017-01-01

    An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In...

  3. Generating samples for association studies based on HapMap data

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    Chen Yixuan

    2008-01-01

    Full Text Available Abstract Background With the completion of the HapMap project, a variety of computational algorithms and tools have been proposed for haplotype inference, tag SNP selection and genome-wide association studies. Simulated data are commonly used in evaluating these new developed approaches. In addition to simulations based on population models, empirical data generated by perturbing real data, has also been used because it may inherit specific properties from real data. However, there is no tool that is publicly available to generate large scale simulated variation data by taking into account knowledge from the HapMap project. Results A computer program (gs was developed to quickly generate a large number of samples based on real data that are useful for a variety of purposes, including evaluating methods for haplotype inference, tag SNP selection and association studies. Two approaches have been implemented to generate dense SNP haplotype/genotype data that share similar local linkage disequilibrium (LD patterns as those in human populations. The first approach takes haplotype pairs from samples as inputs, and the second approach takes patterns of haplotype block structures as inputs. Both quantitative and qualitative traits have been incorporated in the program. Phenotypes are generated based on a disease model, or based on the effect of a quantitative trait nucleotide, both of which can be specified by users. In addition to single-locus disease models, two-locus disease models have also been implemented that can incorporate any degree of epistasis. Users are allowed to specify all nine parameters in a 3 × 3 penetrance table. For several commonly used two-locus disease models, the program can automatically calculate penetrances based on the population prevalence and marginal effects of a disease that users can conveniently specify. Conclusion The program gs can effectively generate large scale genetic and phenotypic variation data that can be

  4. Semantic Modeling for SNPs Associated with Ethnic Disparities in HapMap Samples

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    HyoYoung Kim

    2014-03-01

    Full Text Available Single-nucleotide polymorphisms (SNPs have been emerging out of the efforts to research human diseases and ethnic disparities. A semantic network is needed for in-depth understanding of the impacts of SNPs, because phenotypes are modulated by complex networks, including biochemical and physiological pathways. We identified ethnicity-specific SNPs by eliminating overlapped SNPs from HapMap samples, and the ethnicity-specific SNPs were mapped to the UCSC RefGene lists. Ethnicity-specific genes were identified as follows: 22 genes in the USA (CEU individuals, 25 genes in the Japanese (JPT individuals, and 332 genes in the African (YRI individuals. To analyze the biologically functional implications for ethnicity-specific SNPs, we focused on constructing a semantic network model. Entities for the network represented by "Gene," "Pathway," "Disease," "Chemical," "Drug," "ClinicalTrials," "SNP," and relationships between entity-entity were obtained through curation. Our semantic modeling for ethnicity-specific SNPs showed interesting results in the three categories, including three diseases ("AIDS-associated nephropathy," "Hypertension," and "Pelvic infection", one drug ("Methylphenidate", and five pathways ("Hemostasis," "Systemic lupus erythematosus," "Prostate cancer," "Hepatitis C virus," and "Rheumatoid arthritis". We found ethnicity-specific genes using the semantic modeling, and the majority of our findings was consistent with the previous studies - that an understanding of genetic variability explained ethnicity-specific disparities.

  5. SNPexp - A web tool for calculating and visualizing correlation between HapMap genotypes and gene expression levels

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    Franke Andre

    2010-12-01

    Full Text Available Abstract Background Expression levels for 47294 transcripts in lymphoblastoid cell lines from all 270 HapMap phase II individuals, and genotypes (both HapMap phase II and III of 3.96 million single nucleotide polymorphisms (SNPs in the same individuals are publicly available. We aimed to generate a user-friendly web based tool for visualization of the correlation between SNP genotypes within a specified genomic region and a gene of interest, which is also well-known as an expression quantitative trait locus (eQTL analysis. Results SNPexp is implemented as a server-side script, and publicly available on this website: http://tinyurl.com/snpexp. Correlation between genotype and transcript expression levels are calculated by performing linear regression and the Wald test as implemented in PLINK and visualized using the UCSC Genome Browser. Validation of SNPexp using previously published eQTLs yielded comparable results. Conclusions SNPexp provides a convenient and platform-independent way to calculate and visualize the correlation between HapMap genotypes within a specified genetic region anywhere in the genome and gene expression levels. This allows for investigation of both cis and trans effects. The web interface and utilization of publicly available and widely used software resources makes it an attractive supplement to more advanced bioinformatic tools. For the advanced user the program can be used on a local computer on custom datasets.

  6. Effective selection of informative SNPs and classification on the HapMap genotype data

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    Wang Lipo

    2007-12-01

    Full Text Available Abstract Background Since the single nucleotide polymorphisms (SNPs are genetic variations which determine the difference between any two unrelated individuals, the SNPs can be used to identify the correct source population of an individual. For efficient population identification with the HapMap genotype data, as few informative SNPs as possible are required from the original 4 million SNPs. Recently, Park et al. (2006 adopted the nearest shrunken centroid method to classify the three populations, i.e., Utah residents with ancestry from Northern and Western Europe (CEU, Yoruba in Ibadan, Nigeria in West Africa (YRI, and Han Chinese in Beijing together with Japanese in Tokyo (CHB+JPT, from which 100,736 SNPs were obtained and the top 82 SNPs could completely classify the three populations. Results In this paper, we propose to first rank each feature (SNP using a ranking measure, i.e., a modified t-test or F-statistics. Then from the ranking list, we form different feature subsets by sequentially choosing different numbers of features (e.g., 1, 2, 3, ..., 100. with top ranking values, train and test them by a classifier, e.g., the support vector machine (SVM, thereby finding one subset which has the highest classification accuracy. Compared to the classification method of Park et al., we obtain a better result, i.e., good classification of the 3 populations using on average 64 SNPs. Conclusion Experimental results show that the both of the modified t-test and F-statistics method are very effective in ranking SNPs about their classification capabilities. Combined with the SVM classifier, a desirable feature subset (with the minimum size and most informativeness can be quickly found in the greedy manner after ranking all SNPs. Our method is able to identify a very small number of important SNPs that can determine the populations of individuals.

  7. POSIX and Object Distributed Storage Systems Performance Comparison Studies With Real-Life Scenarios in an Experimental Data Taking Context Leveraging OpenStack Swift & Ceph

    Science.gov (United States)

    Poat, M. D.; Lauret, J.; Betts, W.

    2015-12-01

    The STAR online computing infrastructure has become an intensive dynamic system used for first-hand data collection and analysis resulting in a dense collection of data output. As we have transitioned to our current state, inefficient, limited storage systems have become an impediment to fast feedback to online shift crews. Motivation for a centrally accessible, scalable and redundant distributed storage system had become a necessity in this environment. OpenStack Swift Object Storage and Ceph Object Storage are two eye-opening technologies as community use and development have led to success elsewhere. In this contribution, OpenStack Swift and Ceph have been put to the test with single and parallel I/O tests, emulating real world scenarios for data processing and workflows. The Ceph file system storage, offering a POSIX compliant file system mounted similarly to an NFS share was of particular interest as it aligned with our requirements and was retained as our solution. I/O performance tests were run against the Ceph POSIX file system and have presented surprising results indicating true potential for fast I/O and reliability. STAR'S online compute farm historical use has been for job submission and first hand data analysis. The goal of reusing the online compute farm to maintain a storage cluster and job submission will be an efficient use of the current infrastructure.

  8. TH-C-17A-05: Cherenkov Excited Phosphorescence Oxygen (CEPhOx) Imaging During Multi-Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, R; Pogue, B [Dartmouth College, Hanover, NH (United States); Holt, R [Dartmouth College, Hanover, NH - New Hampshire (United States); Esipova, T; Vinogradov, S [University of Pennsylvania, Philadelphia, PA (United States); Gladstone, D [Dartmouth-Hitchcock Medical Center, Hanover, City of Lebanon (Lebanon)

    2014-06-15

    Purpose: Cherenkov radiation is created during external beam radiation therapy that can excite phosphorescence in tissue from oxygen-sensitive, bio-compatible probes. Utilizing the known spatial information of the treatment plan with directed multiple beam angles, Cherenkov Excited Phosphorescence Oxygen (CEPhOx) imaging was realized from the reconstructions of Cherenkov excited phosphorescence lifetime. Methods: Platinum(II)-G4 (PtG4) was used as the oxygen-sensitive phosphorescent probe and added to a oxygenated cylindrical liquid phantom with a oxygenated/deoxygenated cylindrical anomaly. Cherenkov excited phosphorescence was imaged using a time-gated ICCD camera temporallysynchronized to the LINAC pulse output. Lifetime reconstruction was carried out in NIRFAST software. Multiple angles of the incident radiation beam was combined with the location of the prescribed treatment volume (PTV) to improve the tomographic recovery as a function of location. The tissue partial pressure of oxygen (pO2) in the background and PTV was calculated based on the recovered lifetime distribution and Stern-Volmer equation. Additionally a simulation study was performed to examine the accuracy of this technique in the setting of a human brain tumor. Results: Region-based pO2 values in the oxygenated background and oxygenated/deoxygenated PTV were correctly recovered, with the deoxygenated anomaly (15.4 mmHg) easily distinguished from the oxygenated background (143 mmHg). The data acquisition time could be achieved within the normal irradiation time for a human fractionated plan. The simulations indicated that CEPhOx would be a sufficient to sample tumor pO2 sensing from tumors which are larger than 2cm in diameter or within 23mm depth from the surface. Conclusion: CEPhOx could be a novel imaging tool for pO2 assessment during external radiation beam therapy. It is minimally invasive and should work within the established treatment plan of radiation therapy with multiple beams in

  9. GLIDERS - A web-based search engine for genome-wide linkage disequilibrium between HapMap SNPs

    Directory of Open Access Journals (Sweden)

    Broxholme John

    2009-10-01

    Full Text Available Abstract Background A number of tools for the examination of linkage disequilibrium (LD patterns between nearby alleles exist, but none are available for quickly and easily investigating LD at longer ranges (>500 kb. We have developed a web-based query tool (GLIDERS: Genome-wide LInkage DisEquilibrium Repository and Search engine that enables the retrieval of pairwise associations with r2 ≥ 0.3 across the human genome for any SNP genotyped within HapMap phase 2 and 3, regardless of distance between the markers. Description GLIDERS is an easy to use web tool that only requires the user to enter rs numbers of SNPs they want to retrieve genome-wide LD for (both nearby and long-range. The intuitive web interface handles both manual entry of SNP IDs as well as allowing users to upload files of SNP IDs. The user can limit the resulting inter SNP associations with easy to use menu options. These include MAF limit (5-45%, distance limits between SNPs (minimum and maximum, r2 (0.3 to 1, HapMap population sample (CEU, YRI and JPT+CHB combined and HapMap build/release. All resulting genome-wide inter-SNP associations are displayed on a single output page, which has a link to a downloadable tab delimited text file. Conclusion GLIDERS is a quick and easy way to retrieve genome-wide inter-SNP associations and to explore LD patterns for any number of SNPs of interest. GLIDERS can be useful in identifying SNPs with long-range LD. This can highlight mis-mapping or other potential association signal localisation problems.

  10. Founder of a scientific school on plasma

    International Nuclear Information System (INIS)

    Anon

    2003-01-01

    The academician Mikhail Aleksandrovitch Leontovitch is a physicist-theorist of a wide profile (physical optics, oscillation theory, acoustics, statistical physics, thermodynamics), who became the founder of the largest scientific schools on the radiophysics and plasma physics. Namely due to his effective leadership in developing the theory our theoretical studies on the controlled thermonuclear synthesis reached high level and facilitated the success of the experiment [ru

  11. New Firm Performance and the Replacement of Founder-CEOs

    DEFF Research Database (Denmark)

    Chen, Jing; Thompson, Peter

    2015-01-01

    We study the causes and consequences of the replacement of founder-CEOs in a sample of 4,172 Danish start-ups. We propose that founder-CEO replacement is driven in part by mismatches between business quality and founder ability. Our framework suggests that replacements are more likely among...... the worst- and best-performing firms, with low (high)-ability founders replaced by manager with higher (lower) ability. Replacement is not unambiguously associated with better subsequent performance. Firms that replaced the founder were much more likely to fail, but the surviving firms among them grew...

  12. New Firm Performance and the Replacement of Founders

    DEFF Research Database (Denmark)

    Chen, Jing; Thompson, Peter

    We construct a simple model of founder turnover in which there may be mismatches between the quality of a startup and the ability of the founder. When high-ability founders establish poor-quality businesses, they either choose to close the business or hire a less able CEO. In contrast, low......-ability founders with highquality businesses hire a more able CEO. We derive implications of the model for the relationship between firm performance and founder turnover. These predictions are tested using a large sample of Danish startups....

  13. Single-molecule optical genome mapping of a human HapMap and a colorectal cancer cell line.

    Science.gov (United States)

    Teo, Audrey S M; Verzotto, Davide; Yao, Fei; Nagarajan, Niranjan; Hillmer, Axel M

    2015-01-01

    Next-generation sequencing (NGS) technologies have changed our understanding of the variability of the human genome. However, the identification of genome structural variations based on NGS approaches with read lengths of 35-300 bases remains a challenge. Single-molecule optical mapping technologies allow the analysis of DNA molecules of up to 2 Mb and as such are suitable for the identification of large-scale genome structural variations, and for de novo genome assemblies when combined with short-read NGS data. Here we present optical mapping data for two human genomes: the HapMap cell line GM12878 and the colorectal cancer cell line HCT116. High molecular weight DNA was obtained by embedding GM12878 and HCT116 cells, respectively, in agarose plugs, followed by DNA extraction under mild conditions. Genomic DNA was digested with KpnI and 310,000 and 296,000 DNA molecules (≥ 150 kb and 10 restriction fragments), respectively, were analyzed per cell line using the Argus optical mapping system. Maps were aligned to the human reference by OPTIMA, a new glocal alignment method. Genome coverage of 6.8× and 5.7× was obtained, respectively; 2.9× and 1.7× more than the coverage obtained with previously available software. Optical mapping allows the resolution of large-scale structural variations of the genome, and the scaffold extension of NGS-based de novo assemblies. OPTIMA is an efficient new alignment method; our optical mapping data provide a resource for genome structure analyses of the human HapMap reference cell line GM12878, and the colorectal cancer cell line HCT116.

  14. The reality and importance of founder speciation in evolution.

    Science.gov (United States)

    Templeton, Alan R

    2008-05-01

    A founder event occurs when a new population is established from a small number of individuals drawn from a large ancestral population. Mayr proposed that genetic drift in an isolated founder population could alter the selective forces in an epistatic system, an observation supported by recent studies. Carson argued that a period of relaxed selection could occur when a founder population is in an open ecological niche, allowing rapid population growth after the founder event. Selectable genetic variation can actually increase during this founder-flush phase due to recombination, enhanced survival of advantageous mutations, and the conversion of non-additive genetic variance into additive variance in an epistatic system, another empirically confirmed prediction. Templeton combined the theories of Mayr and Carson with population genetic models to predict the conditions under which founder events can contribute to speciation, and these predictions are strongly confirmed by the empirical literature. Much of the criticism of founder speciation is based upon equating founder speciation to an adaptive peak shift opposed by selection. However, Mayr, Carson and Templeton all modeled a positive interaction of selection and drift, and Templeton showed that founder speciation is incompatible with peak-shift conditions. Although rare, founder speciation can have a disproportionate importance in adaptive innovation and radiation, and examples are given to show that "rare" does not mean "unimportant" in evolution. Founder speciation also interacts with other speciation mechanisms such that a speciation event is not a one-dimensional process due to either selection alone or drift alone. (c) 2008 Wiley Periodicals, Inc.

  15. Corporate Social Responsibility in Large Family and Founder Firms

    NARCIS (Netherlands)

    J.H. Block (Jörn); M. Wagner (Marcus)

    2010-01-01

    textabstractBased on arguments about long-term orientation and corporate reputation, we argue that family and founder firms differ from other firms with regard to corporate social responsibility. Using Bayesian analysis, we then show that family and founder ownership are associated with a lower

  16. Analysis of global variability in 15 established and 5 new European Standard Set (ESS) STRs using the CEPH human genome diversity panel

    DEFF Research Database (Denmark)

    Philips, C.; Fernandez-Formoso, L.; Garcia-Magarinos, M.

    2011-01-01

    in detail the extent of substructure shown by the 20 STRs amongst populations and between their parent population groups. An assessment was made of the forensic informativeness of the new ESS STRs compared to the loci they will replace: CSF1PO, D5S818, D7S820, D13S317 and TPOX, with results showing a clear...... enhancement of discrimination power using multiplexes that genotype the new ESS loci. We also measured the ability of Identifiler and ESS STRs to infer the ancestry of the CEPH-HGDP samples and demonstrate that forensic STRs in large multiplexes have the potential to differentiate the major population groups...

  17. Comparison of Antidepressant Efficacy-related SNPs Among Taiwanese and Four Populations in the HapMap Database

    Directory of Open Access Journals (Sweden)

    Mei-Hung Chi

    2011-07-01

    Full Text Available The genetic influence of single nucleotide polymorphisms (SNPs on antidepressant efficacy has been previously demonstrated. To evaluate whether there are ethnic differences, we compared the allele frequencies of antidepressant efficacy-related SNPs between the Taiwanese population and four other populations in the HapMap database. We recruited 198 Taiwanese major depression patients and 106 Taiwanese controls. A panel of possible relevant SNPs (in brain-derived neurotrophic factor, 5-hydroxytryptamine receptor 2A, interleukin 1 beta, and G-protein beta 3 subunit genes was selected for comparisons of allele frequencies using the χ2 test. Our results suggested no difference between Taiwanese patients and controls, but there were significant differences among Taiwanese controls and the other four ethnic groups in brain-derived neurotrophic factor, 5-hydroxytryptamine receptor 2A, interleukin 1 beta and G-protein beta 3 subunit genes. We conclude that there are ethnic differences in the allele frequencies of antidepressant efficacy-related SNPs, and that the degree of variations is consistent with geographic distances. Further investigation is required to verify the attribution of genetic differences to ethnic-specific antidepressant responses.

  18. Genome-wide screen for universal individual identification SNPs based on the HapMap and 1000 Genomes databases.

    Science.gov (United States)

    Huang, Erwen; Liu, Changhui; Zheng, Jingjing; Han, Xiaolong; Du, Weian; Huang, Yuanjian; Li, Chengshi; Wang, Xiaoguang; Tong, Dayue; Ou, Xueling; Sun, Hongyu; Zeng, Zhaoshu; Liu, Chao

    2018-04-03

    Differences among SNP panels for individual identification in SNP-selecting and populations led to few common SNPs, compromising their universal applicability. To screen all universal SNPs, we performed a genome-wide SNP mining in multiple populations based on HapMap and 1000Genomes databases. SNPs with high minor allele frequencies (MAF) in 37 populations were selected. With MAF from ≥0.35 to ≥0.43, the number of selected SNPs decreased from 2769 to 0. A total of 117 SNPs with MAF ≥0.39 have no linkage disequilibrium with each other in every population. For 116 of the 117 SNPs, cumulative match probability (CMP) ranged from 2.01 × 10-48 to 1.93 × 10-50 and cumulative exclusion probability (CEP) ranged from 0.9999999996653 to 0.9999999999945. In 134 tested Han samples, 110 of the 117 SNPs remained within high MAF and conformed to Hardy-Weinberg equilibrium, with CMP = 4.70 × 10-47 and CEP = 0.999999999862. By analyzing the same number of autosomal SNPs as in the HID-Ion AmpliSeq Identity Panel, i.e. 90 randomized out of the 110 SNPs, our panel yielded preferable CMP and CEP. Taken together, the 110-SNPs panel is advantageous for forensic test, and this study provided plenty of highly informative SNPs for compiling final universal panels.

  19. The Lublin Philosophical School: Founders, Motives, Characteristics

    Directory of Open Access Journals (Sweden)

    Mieczysław A. Krąpiec

    2015-12-01

    Full Text Available The article is focused on the Lublin Philosophical School; it explains its name, presents its founders, reveals the causes of its rise, and introduce the specific character of the School’s philosophy.It starts with stating the fact that in the proper sense, the term “Lublin Philosophical School” describes a way of cultivating realistic (classical philosophy developed in the 1950s by a group of philosophers at the Catholic University of Lublin, Poland. The Lublin Philosophical School is characterized by cognitive realism (the object of cognition is really existing being, maximalism (taking up all existentially important questions, methodological autonomy (in relation to the natural-mathematical sciences and theology, transcendentalism in its assertions (its assertions refer to all reality, methodological-epistemological unity (the same method applied in objectively cultivated philosophical disciplines, coherence (which guarantees the objective unity of the object, and objectivity (achieved by the verifiability of assertions on their own terms, which is achieved by relating them in each instance to objective evidence. The term is the name of the Polish school of realistic (classical philosophy that arose as a response to the Marxism that was imposed administratively on Polish institutions of learning, and also as a response to other philosophical currents dominant at the time such as phenomenology, existentialism, and logical positivism.

  20. Fanconi anemia founder mutation in Macedonian patients.

    Science.gov (United States)

    Madjunkova, Svetlana; Kocheva, Svetlana A; Plaseska-Karanfilska, Dijana

    2014-01-01

    Fanconi anemia (FA) is a rare autosomal recessive disorder clinically characterized by developmental abnormalities, progressive bone marrow failure (BMF) and profound cancer predisposition. Approximately 65% of all affected individuals have mutation in the FANCA (Fanconi anemia complementation group A) gene. The mutation spectrum of the FANCA gene is highly heterogeneous. FA-A is usually associated with private FANCA mutations in individual families. We describe 3 unrelated patients with FA with a similar clinical presentation: BMF, renal anomalies and café-au-lait pigmentation without major skeletal abnormality. The molecular analysis of the FANCA gene using the FA MLPA kit P031-A2/P032 FANCA, showed homozygous deletion of exon 3 in all 3 patients. Molecular analysis of the flanking regions of exon 3 precisely defined unique deletion of 2,040 bp and duplication of C (1788_3828dupC). These are the first 3 patients homozygous for deletion of FANCA exon 3 described to date. Although not related, the patients originated from the same Gypsy-like ethnic population. We conclude that c.190-256_283 + 1680del2040 dupC mutation in the FANCA gene is a founder mutation in Macedonian FA patients of Gypsy-like ethnic origin. Our finding has very strong implications for these patients in formulating diagnostic and carrier-screening strategy for BMF and FA and to enable comprehensive genetic counseling. © 2013 S. Karger AG, Basel.

  1. The Effect of Founder Family Influence on Hedging and Speculation

    DEFF Research Database (Denmark)

    Aabo, Tom; Kuhn, Jochen; Zanotti, Giovanna

    We investigate the effect of founder family influence in the form of managers, board of directors, and/or ownership on hedging and speculation in medium-sized, manufacturing firms in Denmark. On a crude measure of use / non-use of derivatives we find only a weak indication of differences between...... founder family firms and other firms in relation to their management of foreign exchange rate, interest rate, and commodity price exposures. Digging deeper into a subsample of users of foreign exchange derivatives and debt denominated in foreign currency, we find that founder family firms not only tend...

  2. Founders at work stories of startups'' early days

    CERN Document Server

    Livingston, Jessica

    2008-01-01

    Livingston presents a collection of interviews with founders of famous technology companies about what happens in the very earliest days. Includes interviews with Steve Wozniak (Apple), Max Levchin (PayPal), and others.

  3. Recurrent and founder mutations in the PMS2 gene.

    Science.gov (United States)

    Tomsic, J; Senter, L; Liyanarachchi, S; Clendenning, M; Vaughn, C P; Jenkins, M A; Hopper, J L; Young, J; Samowitz, W; de la Chapelle, A

    2013-03-01

    Germline mutations in PMS2 are associated with Lynch syndrome (LS), the most common known cause of hereditary colorectal cancer. Mutation detection in PMS2 has been difficult due to the presence of several pseudogenes, but a custom-designed long-range PCR strategy now allows adequate mutation detection. Many mutations are unique. However, some mutations are observed repeatedly across individuals not known to be related due to the mutation being either recurrent, arising multiple times de novo at hot spots for mutations, or of founder origin, having occurred once in an ancestor. Previously, we observed 36 distinct mutations in a sample of 61 independently ascertained Caucasian probands of mixed European background with PMS2 mutations. Eleven of these mutations were detected in more than one individual not known to be related and of these, six were detected more than twice. These six mutations accounted for 31 (51%) ostensibly unrelated probands. Here, we performed genotyping and haplotype analysis in four mutations observed in multiple probands and found two (c.137G>T and exon 10 deletion) to be founder mutations and one (c.903G>T) a probable founder. One (c.1A>G) could not be evaluated for founder mutation status. We discuss possible explanations for the frequent occurrence of founder mutations in PMS2. © 2012 John Wiley & Sons A/S.

  4. Founder Family Influence and Foreign Exchange Risk Management

    DEFF Research Database (Denmark)

    Aabo, Tom; Kuhn, Jochen; Zanotti, Giovanni

    2011-01-01

    Purpose    The purpose of this study is to explore the influence of founder families in medium-sized, manufacturing firms and to investigate the impact of such influence on risk management - more specifically foreign exchange hedging and speculation. Design/methodology/approach This empirical study...... in the management team, are members of the board of directors, and/or are shareholders of the firm. We find no difference between such founder family firms and other firms in terms of the use / non-use decision related to foreign exchange derivatives but a marked difference in terms of the extent decision. Thus...... in medium-sized firms (as opposed to large, listed firms in most other studies) and adds to the sparse literature on the impact of founder family influence on risk management.  ...

  5. Utilization of founder lines for improved Citrus biotechnology via RMCE

    Science.gov (United States)

    On October 1st 2011 the CRB chose to fund a unique research project, the development of citrus cultivars specifically for genetic engineering (GE). The objective of this research was to develop GE citrus ‘Founder Lines’ containing DNA sequences that will allow the precise insertion of genes for de...

  6. Founders of share companies under the Ethiopian share company law

    African Journals Online (AJOL)

    This article explores the Commercial Code and other laws of Ethiopia regarding founders – who they are, liabilities and benefits - who are also called 'promoters' by many other company laws. To some extent, it also looks into the business practice based on documents like memorandum of associations, articles of ...

  7. What founders in developing countries learn about organizing microenterprise growth

    DEFF Research Database (Denmark)

    Pötz, Katharina Anna; Hjortsø, Carsten Nico Portefée

    organizational failure. In this regard, we find that only those founders that rapidly make sense of ineffective processes, gain management knowledge from different sources, and devote time and energy to managerial tasks, manage to sustain organizational growth by learning to make ‘fixes’ for internal problems...

  8. A common Greenlandic Inuit BRCA1 RING domain founder mutation

    DEFF Research Database (Denmark)

    Hansen, T.v.O.; Ejlertsen, B.; Albrechtsen, Anders

    2009-01-01

    of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit......, representing almost ~2% of the total Greenlandic Inuit population, showed that the frequency of the mutation was 1.0%. We conclude that the BRCA1 nucleotide 234 T > G is a common Greenlandic Inuit founder mutation. The relative high frequency in the general population, together with the ease of screening...... and possibility to reduce mortality in gene carriers, may warrant screening of the Greenlandic Inuit population. Provided screening is efficient, about 5% of breast- and 13% of ovarian cancers, respectively, may be prevented Udgivelsesdato: 2009/5...

  9. ABOUT THE FOUNDERS OF LEGAL SOCIOLOGY AND THEIR IDEAS

    Directory of Open Access Journals (Sweden)

    MIRELA CRISTIANA NILĂ STRATONE

    2013-05-01

    Full Text Available The main founders of the juridical sociology are considered to be Eugen Ehrlich, Max Weber, Theodor Geiger and Georges Gurvitch, The researches of juridical sociology from Romania are demonstrating the existence of a real tradition in this domain at a national standard. Some roumanian explores of formation jurists have practicated in the cognitive demarche a sociologycal abordation about the law, what have been fatal conduced to the fixing of the base of the juridical sociology in Romania.

  10. MSR Founders Narrative and Content Analysis of Scholarly Papers

    DEFF Research Database (Denmark)

    Tackney, Charles T.; Chappell, Stacie F.; Sato, Toyoko

    2017-01-01

    This is a founders’ narrative and research paper content analysis of the first 15 years of the Management Spirituality and Religion Interest Group (MSR) of the Academy of Management. Based on archival data and founder interviews, our inquiry recounts how the early collaborators established......: a corpus epitomizing MSR research and practice. The combined study is a benchmark of founding and institutionalization for current and potential MSR members. By tracing the research trends MSR has taken in light of the founding aspirations, we illuminate the distinctive values, tensions, and meanings...

  11. 50 years of Dutch immunology--founders, institutions, highlights.

    Science.gov (United States)

    Gmelig-Meyling, Frits H J; Meyaard, Linde; Mebius, Reina E

    2014-12-01

    At the occasion of the 50th anniversary of the Dutch Society for Immunology (DSI, de Nederlandse Vereniging voor Immunologie), this contribution deals with some highlights of 50 years of Immunology in the Netherlands. It narrates about the founders and first board members of the DSI, their institutes, progeny and patrimony, describes major centers of immunological activities, mentions key persons in the field, and touches upon some events dear to the Society and its members. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. The advantage of experienced start-up founders in venture capital acquisition: evidence from serial entrepreneurs

    OpenAIRE

    Zhang, Junfu

    2007-01-01

    Existing literature suggests that entrepreneurs with prior firm-founding experience have more skills and social connections than novice entrepreneurs. Such skills and social connections could give experienced founders some advantage in the process of raising venture capital. This paper uses a large database of venture-backed companies and their founders to examine experienced founders' access to venture capital. Compared to novice entrepreneurs, entrepreneurs with venture-backed founding expe...

  13. Founder takes all: density-dependent processes structure biodiversity.

    Science.gov (United States)

    Waters, Jonathan M; Fraser, Ceridwen I; Hewitt, Godfrey M

    2013-02-01

    Density-dependent processes play a key role in the spatial structuring of biodiversity. Specifically, interrelated demographic processes, such as gene surfing, high-density blocking, and competitive exclusion, can generate striking geographic contrasts in the distributions of genes and species. Here, we propose that well-studied evolutionary and ecological biogeographic patterns of postglacial recolonization, progressive island colonization, microbial sectoring, and even the 'Out of Africa' pattern of human expansion, are fundamentally similar, underpinned by a 'founder takes all' density-dependent principle. Additionally, we hypothesize that older historic constraints of density-dependent processes are seen today in the dramatic biogeographic shifts that occur in response to human-mediated extinction events, whereby surviving lineages rapidly expand their ranges to replace extinct sister taxa. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Imputation of variants from the 1000 Genomes Project modestly improves known associations and can identify low-frequency variant-phenotype associations undetected by HapMap based imputation.

    Science.gov (United States)

    Wood, Andrew R; Perry, John R B; Tanaka, Toshiko; Hernandez, Dena G; Zheng, Hou-Feng; Melzer, David; Gibbs, J Raphael; Nalls, Michael A; Weedon, Michael N; Spector, Tim D; Richards, J Brent; Bandinelli, Stefania; Ferrucci, Luigi; Singleton, Andrew B; Frayling, Timothy M

    2013-01-01

    Genome-wide association (GWA) studies have been limited by the reliance on common variants present on microarrays or imputable from the HapMap Project data. More recently, the completion of the 1000 Genomes Project has provided variant and haplotype information for several million variants derived from sequencing over 1,000 individuals. To help understand the extent to which more variants (including low frequency (1% ≤ MAF 1000 Genomes imputation, respectively, and 9 and 11 that reached a stricter, likely conservative, threshold of P1000 Genomes genotype data modestly improved the strength of known associations. Of 20 associations detected at P1000 Genomes imputed data and one was nominally more strongly associated in HapMap imputed data. We also detected an association between a low frequency variant and phenotype that was previously missed by HapMap based imputation approaches. An association between rs112635299 and alpha-1 globulin near the SERPINA gene represented the known association between rs28929474 (MAF = 0.007) and alpha1-antitrypsin that predisposes to emphysema (P = 2.5×10(-12)). Our data provide important proof of principle that 1000 Genomes imputation will detect novel, low frequency-large effect associations.

  15. Founder Control, Ownership Structure and Firm Value: Evidence from Entrepreneurial Listed Firms in China

    Directory of Open Access Journals (Sweden)

    Lijun Xia

    2008-06-01

    Full Text Available In emerging markets, the deviation between the ultimate controlling shareholders' voting rights and their cash flow rights (hereafter “DVC” in the listed firms is quite prevalent. DVC could be introduced due to the ultimate controlling shareholders' opportunistic incentives, as well as by their incentives to improve firm efficiency. This study uses 229 listed firms ultimately controlled by individuals or families (hereafter “entrepreneurial firms” for 2004 in China, to investigate the effect of DVC on firm value and to determine whether it is different between founder and non-founder controlled firms. We find that DVC has a positive effect on firm value for founder controlled firms. This result implies that investors believe that their interests are better protected by founder controlled firms than by non-founder controlled firms.

  16. Identification of kin structure among Guam rail founders: a comparison of pedigrees and DNA profiles

    Science.gov (United States)

    Haig, Susan M.; Ballou, J.D.; Casna, N.J.

    1994-01-01

    Kin structure among founders can have a significant effect on subsequent population structure. Here we use the correlation between DNA profile similarity and relatedness calculated from pedigrees to test hypotheses regarding kin structure among founders to the captive Guam rail (Rallus owstoni) population. Five different pedigrees were generated under the following hypotheses: (i) founders are unrelated; (ii) founders are unrelated except for same-nest chicks; (iii) founders from the same major site are siblings; (iv) founders from the same local site are siblings; and (v) founders are related as defined by a UPGMA cluster analysis of DNA similarity data. Relatedness values from pedigrees 1, 2 and 5 had the highest correlation with DNA similarity but the correlation between relatedness and similarity were not significantly different among pedigrees. Pedigree 5 resulted in the highest correlation overall when using only relatedness values that changed as a result of different founder hypotheses. Thus, founders were assigned relatedness based on pedigree 5 because it had the highest correlations with DNA similarity, was the most conservative approach, and incorporated all field data. The analyses indicated that estimating relatedness using DNA profiles remains problematic, therefore we compared mean kinship, a measure of genetic importance, with mean DNA profile similarity to determine if genetic importance among individuals could be determined via use of DNA profiles alone. The significant correlation suggests this method may provide more information about population structure than was previously thought. Thus, DNA profiles can provide a reasonable explanation for founder relatedness and mean DNA profile similarity may be helpful in determining relative genetic importance of individuals when detailed pedigrees are absent.

  17. Ludwig Edinger (1855-1918): founder of modern neuroanatomy.

    Science.gov (United States)

    Prithishkumar, Ivan James

    2012-03-01

    Ludwig Edinger, a German neurologist is considered as one of the founders of modern neuroanatomy. He was conferred the degree of Doctor of Medicine at the University of Strassburg. His observation of small living organisms under a microscope at an early age led him to study medicine. Edinger had many discoveries to his credit. He was the first to describe the ventral and dorsal spinocerebellar tracts, to distinguish between paleo-encephalon and neo-encephalon, and between paleo-cerebellum and neo-cerebellum. He coined the terms "gnosis" and "praxis," which were later adopted in psychological descriptions of agnosia and apraxia. He identified the Edinger-Westphal nucleus in 1885 and was the first to describe the syndrome of thalamic pain. Edinger worked with renowned clinicians and published a large number of papers. He founded the Neurological Institute at the Goethe University in Frankfurt, which is the oldest neurological Institute in Germany. Edinger was a rare combination of a profound scientist, a brilliant teacher, a fine artist, and a noted hypnotist. While at the height of his career, he underwent a surgery and died a few hours later. It was his last will that his brain should be dissected in his own institute. It showed extraordinarily well-developed occipital lobes as well as other unusual features. Copyright © 2011 Wiley-Liss, Inc.

  18. Cancer risks and immunohistochemical profiles linked to the Danish MLH1 Lynch syndrome founder mutation

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Isinger-Ekstrand, Anna; Ladelund, Steen

    2012-01-01

    Founder mutations with a large impact in distinct populations have been described in Lynch syndrome. In Denmark, the MLH1 c.1667+2_1667_+8TAAATCAdelinsATTT mutation accounts for 25 % of the MLH1 mutant families. We used the national Danish hereditary nonpolyposis colorectal cancer register...... to estimate the cumulative lifetime risks for Lynch syndrome-associated cancer in 16 founder mutation families with comparison to 47 other MLH1 mutant families. The founder mutation conferred comparable risks for colorectal cancer (relative risks, RR, of 0.99 for males and 0.79 for females) and lower risks...... in 68 % with extensive inter-tumor variability despite the same underlying germline mutation. In conclusion, the Danish MLH1 founder mutation that accounts for a significant proportion of Lynch syndrome and is associated with a lower risk for extracolonic cancers....

  19. Founder effects and genetic population structure of brown trout (Salmo trutta) in a Danish river system

    DEFF Research Database (Denmark)

    Hansen, Michael Møller; Mensberg, Karen-Lise Dons

    1996-01-01

    The influence of founder effects on the genetic population structure of brown trout (Salmo trutta) was studied in a small Danish river system. Samples of trout from seven locations were analysed by allozyme electrophoresis and mitochondrial DNA restriction fragment length polymorphism analysis....... For comparison, allozyme data from other Danish trout populations and mtDNA data from two hatchery strains were included. Genetic differentiation among populations was found to be small but significant. Pairwise tests for homogeneity of allele and haplotype frequencies between samples showed that significance...... simulations of the influence of founder effects on mitochondrial DNA differentiation and variability showed that the observed divergence could be due either to natural founder effects or to a genetic contribution by hatchery trout. However, the allozyme results pointed towards natural founder effects...

  20. The Slavic NBN Founder Mutation: A Role for Reproductive Fitness?

    Directory of Open Access Journals (Sweden)

    Eva Seemanova

    Full Text Available The vast majority of patients with Nijmegen Breakage Syndrome (NBS are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650 in the NBN gene on chromosome 8q21. This mutation is essentially confined to Slavic populations and may thus be considered a Slavic founder mutation. Notably, not a single parenthood of a homozygous c.657del5 carrier has been reported to date, while heterozygous carriers do reproduce but have an increased cancer risk. These observations seem to conflict with the considerable carrier frequency of c.657del5 of 0.5% to 1% as observed in different Slavic populations because deleterious mutations would be eliminated quite rapidly by purifying selection. Therefore, we propose that heterozygous c.657del5 carriers have increased reproductive success, i.e., that the mutation confers heterozygote advantage. In fact, in our cohort study of the reproductive history of 24 NBS pedigrees from the Czech Republic, we observed that female carriers gave birth to more children on average than female non-carriers, while no such reproductive differences were observed for males. We also estimate that c.657del5 likely occurred less than 300 generations ago, thus supporting the view that the original mutation predated the historic split and subsequent spread of the 'Slavic people'. We surmise that the higher fertility of female c.657del5 carriers reflects a lower miscarriage rate in these women, thereby reflecting the role of the NBN gene product, nibrin, in the repair of DNA double strand breaks and their processing in immune gene rearrangements, telomere maintenance, and meiotic recombination, akin to the previously described role of the DNA repair genes BRCA1 and BRCA2.

  1. N.A. Bernstein, the founder of modern biomechanics

    Directory of Open Access Journals (Sweden)

    Vazha M. Devishvili

    2015-12-01

    Full Text Available The paper deals with three major periods of scientific work of Nikolai Alexandrovich Bernstein, the outstanding Russian scientist, the founder the motor activity theory of human and animal. In 2016 is the 120th anniversary of Bernstein´s birth. The first period of his scientific activity, from 1922 when Bernstein started his research at the Central Institute of Labour Protection until the middle of the 30s of the 20th century. By this time, he formulated and published the basic principles and ideas of the annular motion control and sensor correction movements of varying complexity and various performance. The second period ends with the fundamental scientific work «On the Construction of Movements» awarded by the USSR State Prize in 1948. The book sums up Bernstein´s more than twenty years of research in the field of biomechanics and physiology of movement. The paper briefly describes the main assumptions of the three chapters of the book. The first chapter «Movements» reveals the evolutionary ideas about the origin of motor function and shaped the principle of the equation of building movements. The second chapter describes five levels with different functionality in varying degrees involved in the implementation of motor actions. The third chapter of the «Development and Decay» deals with the general laws of occurrence and levels of building movements being signs of confirming the level structure of motion in pathology and standards. In 1950-60-ies of the 20th century Bernstein greatly expanded representation of the functional content and neural substrate levels of building movements, detailed the stages and phases of shaping and improvement of motor skills. The author shows the importance of scientific achievements of N.A. Bernstein for modern research in the psychophysiology of movements.

  2. Business strategy versus human resources strategy: the influence of the founder in small business

    Directory of Open Access Journals (Sweden)

    Juliana Popp Barbosa Lima

    2016-12-01

    Full Text Available Small and medium-sized businesses with familiar characteristics have been object of study in recent years, especially about the succession process, considering it is extremely critical to the longevity and sustainability of the organization. However, the figure of the founder and its impact in these organizations is less explored in academia. Thus, this article seeks to fill this gap, addressing the influences of the founder in the dissemination of business and HR strategies in these companies. Through a qualitative and quantitative research, there was a case of a single organization study seeking further analysis of the subject. The collection of qualitative data was given through an interview with semi-structured interview with the founder of the organization and the qualitative by applying a questionnaire with closed questions with officials of various hierarchical levels. It was observed that the personal values and the founding principles are permeated the organization, reflected in the mission and values of the company, as well as how the founder treats topics such as business strategy and the role of people management are decisive for inclusion and driving these topics within family-based organizations. The purpose of analyzing the spread of business strategies and human resources of the Founder has been reached. It was found that, in general, strategies portray the way of the Founder, however, the spread of these to the various hierarchical levels, demonstrates a more complex, as in the HRM.

  3. The workforce composition of young firms and product innovation - complementarities in the skills of founders and their early employees

    OpenAIRE

    Müller, Bettina; Murmann, Martin

    2016-01-01

    We investigate the extent to which complementarities between technical and business skills of founders and employees matter for the generation of market novelties by new ventures. Using data about German start-ups, we find that there are no complementarities between technical and business skills within the group of founders, but that there are significant complementarities between technically trained founders and employees who have business skills. This suggests that the innovation potenti...

  4. Characterization of a mutation commonly associated with persistent stuttering: evidence for a founder mutation

    Science.gov (United States)

    Fedyna, Alison; Drayna, Dennis; Kang, Changsoo

    2010-01-01

    Stuttering is a disorder which affects the fluency of speech. It has been shown to have high heritability, and has recently been linked to mutations in the GNPTAB gene. One such mutation, Glu1200Lys, has been repeatedly observed in unrelated families and individual cases. Eight unrelated individuals carrying this mutation were analyzed in an effort to distinguish whether these arise from repeated mutation at the same site, or whether they represent a founder mutation with a single origin. Results show that all 12 chromosomes carrying this mutation share a common haplotype in this region, indicating it is a founder mutation. Further analysis estimated the age of this allele to be ~572 generations. Construction of a cladogram tracing the mutation through our study sample also supports the founder mutation hypothesis. PMID:20944643

  5. Do VCs use inside rounds to dilute founders? Some evidence from Silicon Valley

    OpenAIRE

    Fried, Jesse M.; Broughman, Brian J.

    2012-01-01

    In the bank-borrower setting, a firm’s existing lender may exploit its positional advantage to extract rents from the firm in subsequent financings. Analogously, a startup’s existing venture capital investors (VCs) may dilute the founder through a follow-on financing from these same VCs (an “inside” round) at an artificially low valuation. Using a hand-collected dataset of Silicon Valley startup firms, we find little evidence that VCs use inside rounds to dilute founders. Instead, our finding...

  6. A novel FKRP-related muscular dystrophy founder mutation in South ...

    African Journals Online (AJOL)

    porphyria variegata, familial hypercholesterolaemia, Gaucher's dis- ease and autosomal recessive polycystic kidney disease.[7-11]. FKRP founder mutations have been described in a number of populations around the world, for example the c.826C>A. (p.Leu276Ile) FKRP mutation in 20 LGMD German patients[12].

  7. Evaluating the importance of metamorphism in the foundering of continental crust.

    Science.gov (United States)

    Chapman, Timothy; Clarke, Geoffrey L; Piazolo, Sandra; Daczko, Nathan R

    2017-10-12

    The metamorphic conditions and mechanisms required to induce foundering in deep arc crust are assessed using an example of representative lower crust in SW New Zealand. Composite plutons of Cretaceous monzodiorite and gabbro were emplaced at ~1.2 and 1.8 GPa are parts of the Western Fiordland Orthogneiss (WFO); examples of the plutons are tectonically juxtaposed along a structure that excised ~25 km of crust. The 1.8 GPa Breaksea Orthogneiss includes suitably dense minor components (e.g. eclogite) capable of foundering at peak conditions. As the eclogite facies boundary has a positive dP/dT, cooling from supra-solidus conditions (T > 950 ºC) at high-P should be accompanied by omphacite and garnet growth. However, a high monzodioritic proportion and inefficient metamorphism in the Breaksea Orthogneiss resulted in its positive buoyancy and preservation. Metamorphic inefficiency and compositional relationships in the 1.2 GPa Malaspina Pluton meant it was never likely to have developed densities sufficiently high to founder. These relationships suggest that the deep arc crust must have primarily involved significant igneous accumulation of garnet-clinopyroxene (in proportions >75%). Crustal dismemberment with or without the development of extensional shear zones is proposed to have induced foundering of excised cumulate material at P > 1.2 GPa.

  8. The impact of founder events on chromosomal variability in multiply mating species

    DEFF Research Database (Denmark)

    Pool, John E; Nielsen, Rasmus

    2008-01-01

    size reductions and recent bottlenecks leading to decreased X/A diversity ratios. Here we use theory and simulation to investigate a separate demographic effect-that of founder events involving multiply mated females-and find that it leads to much stronger reductions in X/A diversity ratios than...

  9. How lead founder personality affects new venture performance : the mediating role of team conflict

    NARCIS (Netherlands)

    Jong, de A.; Song, M.; Song, L.Z.

    2013-01-01

    This empirical study of 323 new ventures examines how task and relationship conflict in the founding top management team mediates the effect of lead founder personality on new venture performance. The results reveal that (1) openness and agreeableness increase task conflict, whereas

  10. How Lead Founder Personality Affects New Venture Performance: The Mediating Role of Team Conflict

    NARCIS (Netherlands)

    de Jong, Ad; Song, Michael; Song, Lisa Z.

    2013-01-01

    This empirical study of 323 new ventures examines how task and relationship conflict in the founding top management team mediates the effect of lead founder personality on new venture performance. The results reveal that (1) openness and agreeableness increase task conflict, whereas

  11. Effects of founder population size on the performance of Orius laevigatus (Hemiptera: Anthocoridae) colonies

    NARCIS (Netherlands)

    Castañe, C.; Bueno, V.H.P.; Carvalho, L.M.; Lenteren, van J.C.

    2014-01-01

    Orius laevigatus (Hemiptera: Anthocoridae) is a key predator of thrips and is mass reared in large numbers for use in biological control. The aim of this study was to evaluate the effect of founder population size on the biological and behavioral performance of O. laevigatus over time. Laboratory

  12. A Dutch Fanconi Anemia FANCC Founder Mutation in Canadian Manitoba Mennonites

    Directory of Open Access Journals (Sweden)

    Yne de Vries

    2012-01-01

    Full Text Available Fanconi anemia (FA is a recessive DNA instability disorder associated with developmental abnormalities, bone marrow failure, and a predisposition to cancer. Based on their sensitivity to DNA cross-linking agents, FA cells have been assigned to 15 complementation groups, and the associated genes have been identified. Founder mutations have been found in different FA genes in several populations. The majority of Dutch FA patients belongs to complementation group FA-C. Here, we report 15 patients of Dutch ancestry and a large Canadian Manitoba Mennonite kindred carrying the FANCC c.67delG mutation. Genealogical investigation into the ancestors of the Dutch patients shows that these ancestors lived in four distinct areas in The Netherlands. We also show that the Dutch and Manitoba Mennonite FANCC c.67delG patients share the same haplotype surrounding this mutation, indicating a common founder.

  13. Pervasive Genotypic Mosaicism in Founder Mice Derived from Genome Editing through Pronuclear Injection.

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    Daniel Oliver

    Full Text Available Genome editing technologies, especially the Cas9/CRISPR system, have revolutionized biomedical research over the past several years. Generation of novel alleles has been simplified to unprecedented levels, allowing for rapid expansion of available genetic tool kits for researchers. However, the issue of genotypic mosaicism has become evident, making stringent analyses of the penetrance of genome-edited alleles essential. Here, we report that founder mice, derived from pronuclear injection of ZFNs or a mix of guidance RNAs and Cas9 mRNAs, display consistent genotypic mosaicism for both deletion and insertion alleles. To identify founders with greater possibility of transmitting the mutant allele through the germline, we developed an effective germline genotyping method. The awareness of the inherent genotypic mosaicism issue with genome editing will allow for a more efficient implementation of the technologies, and the germline genotyping method will save valuable time and resources.

  14. Subspecies composition and founder contribution of the captive U.S. chimpanzee (Pan troglodytes) population.

    Science.gov (United States)

    Ely, John J; Dye, Brent; Frels, William I; Fritz, Jo; Gagneux, Pascal; Khun, Henry H; Switzer, William M; Lee, D Rick

    2005-10-01

    Chimpanzees are presently classified into three subspecies: Pan troglodytes verus from west Africa, P.t. troglodytes from central Africa, and P.t. schweinfurthii from east Africa. A fourth subspecies (P.t. vellerosus), from Cameroon and northern Nigeria, has been proposed. These taxonomic designations are based on geographical origins and are reflected in sequence variation in the first hypervariable region (HVR-I) of the mtDNA D-loop. Although advances have been made in our understanding of chimpanzee phylogenetics, little has been known regarding the subspecies composition of captive chimpanzees. We sequenced part of the mtDNA HVR-I region in 218 African-born population founders and performed a phylogenetic analysis with previously characterized African sequences of known provenance to infer subspecies affiliations. Most founders were P.t. verus (95.0%), distantly followed by the troglodytes schweinfurthii clade (4.6%), and a single P.t. vellerosus (0.4%). Pedigree-based estimates of genomic representation in the descendant population revealed that troglodytes schweinfurthii founder representation was reduced in captivity, vellerosus representation increased due to prolific breeding by a single male, and reproductive variance resulted in uneven representation among male P.t.verus founders. No increase in mortality was evident from between-subspecies interbreeding, indicating a lack of outbreeding depression. Knowledge of subspecies and their genomic representation can form the basis for phylogenetically informed genetic management of extant chimpanzees to preserve rare genetic variation for research, conservation, or possible future breeding. Copyright 2005 Wiley-Liss, Inc.

  15. A serial founder effect model for human settlement out of Africa

    OpenAIRE

    Deshpande, Omkar; Batzoglou, Serafim; Feldman, Marcus W.; Luca Cavalli-Sforza, L.

    2008-01-01

    The increasing abundance of human genetic data has shown that the geographical patterns of worldwide genetic diversity are best explained by human expansion out of Africa. This expansion is modelled well by prolonged migration from a single origin in Africa with multiple subsequent serial founding events. We discuss a new simulation model for the serial founder effect out of Africa and compare it with results from previous studies. Unlike previous models, we distinguish colonization events fr...

  16. The scribe of the founder's inscription of Saint Sava in Studenica

    Directory of Open Access Journals (Sweden)

    Špadijer Irena

    2006-01-01

    Full Text Available The founder's inscription situated at the foot of the tambour in the Church of the Virgin in Studenica originating from 1208/9, is one of the oldest dated specimens of Serbian literacy. It was uncovered in 1951, during the conservation works in the monastery. Former research (conducted by Dj. Trifunović, has ascertained that inscriptions on the scrolls, books and frescoes in the monastery were written by the Greek artists who decorated the church. Scribal errors indicate beyond any doubt that Slavic was not the mother tongue of the scribes, and that they were not, or at least not sufficiently, familiar with the orthography of this language. In this paper the main focus has been directed at the founder's inscription, which has been put under detailed orthographic and palaeographic scrutiny. The morphology of some letters — the Greek "K", non-distinguishing between ižica (ippsilon and the Cyrillic "Č" — clearly indicates that in all probability the author of the inscription was a Greek, perhaps the very painter who signed his name in the Greek language on the Mandelion beneath the large founder's inscription.

  17. Clinical applications and implications of common and founder mutations in Indian subpopulations.

    Science.gov (United States)

    Ankala, Arunkanth; Tamhankar, Parag M; Valencia, C Alexander; Rayam, Krishna K; Kumar, Manisha M; Hegde, Madhuri R

    2015-01-01

    South Asian Indians represent a sixth of the world's population and are a racially, geographically, and genetically diverse people. Their unique anthropological structure, prevailing caste system, and ancient religious practices have all impacted the genetic composition of most of the current-day Indian population. With the evolving socio-religious and economic activities of the subsects and castes, endogamous and consanguineous marriages became a commonplace. Consequently, the frequency of founder mutations and the burden of heritable genetic disorders rose significantly. Specifically, the incidence of certain autosomal-recessive disorders is relatively high in select Indian subpopulations and communities that share common recent ancestry. Although today clinical genetics and molecular diagnostic services are making inroads in India, the high costs associated with the technology and the tests often keep patients from an exact molecular diagnosis, making more customized and tailored tests, such as those interrogating the most common and founder mutations or those that cater to select sects within the population, highly attractive. These tests offer a quick first-hand affordable diagnostic and carrier screening tool. Here, we provide a comprehensive catalog of known common mutations and founder mutations in the Indian population and discuss them from a molecular, clinical, and historical perspective. © 2014 WILEY PERIODICALS, INC.

  18. The founder-cell transcriptome in the Arabidopsis apetala1 cauliflower inflorescence meristem.

    Science.gov (United States)

    Frerichs, Anneke; Thoma, Rahere; Abdallah, Ali Taleb; Frommolt, Peter; Werr, Wolfgang; Chandler, John William

    2016-11-03

    Although the pattern of lateral organ formation from apical meristems establishes species-specific plant architecture, the positional information that confers cell fate to cells as they transit to the meristem flanks where they differentiate, remains largely unknown. We have combined fluorescence-activated cell sorting and RNA-seq to characterise the cell-type-specific transcriptome at the earliest developmental time-point of lateral organ formation using DORNRÖSCHEN-LIKE::GFP to mark founder-cell populations at the periphery of the inflorescence meristem (IM) in apetala1 cauliflower double mutants, which overproliferate IMs. Within the lateral organ founder-cell population at the inflorescence meristem, floral primordium identity genes are upregulated and stem-cell identity markers are downregulated. Additional differentially expressed transcripts are involved in polarity generation and boundary formation, and in epigenetic and post-translational changes. However, only subtle transcriptional reprogramming within the global auxin network was observed. The transcriptional network of differentially expressed genes supports the hypothesis that lateral organ founder-cell specification involves the creation of polarity from the centre to the periphery of the IM and the establishment of a boundary from surrounding cells, consistent with bract initiation. However, contrary to the established paradigm that sites of auxin response maxima pre-pattern lateral organ initiation in the IM, auxin response might play a minor role in the earliest stages of lateral floral initiation.

  19. A mitochondrial analysis reveals distinct founder effect signatures in Canarian and Balearic goats.

    Science.gov (United States)

    Ferrando, A; Manunza, A; Jordana, J; Capote, J; Pons, A; Pais, J; Delgado, T; Atoche, P; Cabrera, B; Martínez, A; Landi, V; Delgado, J V; Argüello, A; Vidal, O; Lalueza-Fox, C; Ramírez, O; Amills, M

    2015-08-01

    In the course of human migrations, domestic animals often have been translocated to islands with the aim of assuring food availability. These founder events are expected to leave a genetic footprint that may be recognised nowadays. Herewith, we have examined the mitochondrial diversity of goat populations living in the Canarian and Balearic archipelagos. Median-joining network analysis produced very distinct network topologies for these two populations. Indeed, a majority of Canarian goats shared a single ancestral haplotype that segregated in all sampled islands, suggesting a single founder effect followed by a stepping-stone pattern of diffusion. This haplotype also was present in samples collected from archaeological assemblies at Gran Canaria and Lanzarote, making evident its widespread distribution in ancient times. In stark contrast, goats from Majorca and Ibiza did not share any mitochondrial haplotypes, indicating the occurrence of two independent founder events. Furthermore, in Majorcan goats, we detected the segregation of the mitochondrial G haplogroup that has only been identified in goats from Egypt, Iran and Turkey. This finding suggests the translocation of Asian and/or African goats to Majorca, possibly as a consequence of the Phoenician and Carthaginian colonisations of this island. © 2015 Stichting International Foundation for Animal Genetics.

  20. THE INFLUENCE OF THE COMPETENCES OF THE MANAGER: FOUNDER ON THE SUCCESS OF THE ORGANIZATION

    Directory of Open Access Journals (Sweden)

    Ace Milenkovski

    2013-06-01

    Full Text Available The environment, where the changes are everyday occurrence and the competition continuous threat, forces the leading people in the organizations to look after everything that goes on inside the organizations, as well as everything that goes on outside of them. Thus, depending on the founder’s capability, respectively the manager of the organization, the success of the organization can go up or down. The individuals that have entrepreneurial spirit, that know how to combine their knowledge, education and work experience with the successful guiding of the employees toward the goal, strengthen their business and open possibilities for its expansion.If under competence we imply to the knowledge of business, working experience and skills necessary for effective performance at the workplace, then undoubtedly the entrepreneur–founder in order to obtain the optimum knowledge for the business that he starts, previously has to build his competences through appropriate education and work experience.Herein we present working research conducted in order to prove the connection of the organization’s success with the knowledge, skills and competences for the corresponding business of the organization’s founder, particularly if the founder is also general manager of the organization. This research is conducted within the frames of the scientific and research activity of the University of Tourism and Management in Skopje, FYRO Macedonia.As a research sample 271 respondents – employees and 10 leaders of the companies included in the research. The leaders are managers and founders of the private companies. As a research technique questionnaire is used. Practical aim of the research was to use the results in order to create a basis for improving the performance of companies by developing the competencies of the management teams in them. One of the main conclusions of the research is: The manager-founder who starts up a business, needs to have optimum

  1. Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

    Directory of Open Access Journals (Sweden)

    Damien C Tully

    2016-05-01

    Full Text Available Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU, we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.

  2. Constitutional Mismatch Repair Deficiency in Israel: High Proportion of Founder Mutations in MMR Genes and Consanguinity.

    Science.gov (United States)

    Baris, Hagit N; Barnes-Kedar, Inbal; Toledano, Helen; Halpern, Marisa; Hershkovitz, Dov; Lossos, Alexander; Lerer, Israela; Peretz, Tamar; Kariv, Revital; Cohen, Shlomi; Half, Elizabeth E; Magal, Nurit; Drasinover, Valerie; Wimmer, Katharina; Goldberg, Yael; Bercovich, Dani; Levi, Zohar

    2016-03-01

    Heterozygous germline mutations in any of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2, cause Lynch syndrome (LS), an autosomal dominant cancer predisposition syndrome conferring a high risk of colorectal, endometrial, and other cancers in adulthood. Offspring of couples where both spouses have LS have a 1:4 risk of inheriting biallelic MMR gene mutations. These cause constitutional MMR deficiency (CMMRD) syndrome, a severe recessively inherited cancer syndrome with a broad tumor spectrum including mainly hematological malignancies, brain tumors, and colon cancer in childhood and adolescence. Many CMMRD children also present with café au lait spots and axillary freckling mimicking neurofibromatosis type 1. We describe our experience in seven CMMRD families demonstrating the role and importance of founder mutations and consanguinity on its prevalence. Clinical presentations included brain tumors, colon cancer, lymphoma, and small bowel cancer. In children from two nonconsanguineous Ashkenazi Jewish (AJ) families, the common Ashkenazi founder mutations were detected; these were homozygous in one family and compound heterozygous in the other. In four consanguineous families of various ancestries, different homozygous mutations were identified. In a nonconsanguineous Caucasus/AJ family, lack of PMS2 was demonstrated in tumor and normal tissues; however, mutations were not identified. CMMRD is rare, but, especially in areas where founder mutations for LS and consanguinity are common, pediatricians should be aware of it since they are the first to encounter these children. Early diagnosis will enable tailored cancer surveillance in the entire family and a discussion regarding prenatal genetic diagnosis. © 2015 Wiley Periodicals, Inc.

  3. Rayleigh and S wave tomography constraints on subduction termination and lithospheric foundering in central California

    Science.gov (United States)

    Jiang, Chengxin; Schmandt, Brandon; Hansen, Steven M.; Dougherty, Sara L.; Clayton, Robert W.; Farrell, Jamie; Lin, Fan-Chi

    2018-01-01

    The crust and upper mantle structure of central California have been modified by subduction termination, growth of the San Andreas plate boundary fault system, and small-scale upper mantle convection since the early Miocene. Here we investigate the contributions of these processes to the creation of the Isabella Anomaly, which is a high seismic velocity volume in the upper mantle. There are two types of hypotheses for its origin. One is that it is the foundered mafic lower crust and mantle lithosphere of the southern Sierra Nevada batholith. The alternative suggests that it is a fossil slab connected to the Monterey microplate. A dense broadband seismic transect was deployed from the coast to the western Sierra Nevada to fill in the least sampled areas above the Isabella Anomaly, and regional-scale Rayleigh and S wave tomography are used to evaluate the two hypotheses. New shear velocity (Vs) tomography images a high-velocity anomaly beneath coastal California that is sub-horizontal at depths of ∼40–80 km. East of the San Andreas Fault a continuous extension of the high-velocity anomaly dips east and is located beneath the Sierra Nevada at ∼150–200 km depth. The western position of the Isabella Anomaly in the uppermost mantle is inconsistent with earlier interpretations that the Isabella Anomaly is connected to actively foundering foothills lower crust. Based on the new Vs images, we interpret that the Isabella Anomaly is not the dense destabilized root of the Sierra Nevada, but rather a remnant of Miocene subduction termination that is translating north beneath the central San Andreas Fault. Our results support the occurrence of localized lithospheric foundering beneath the high elevation eastern Sierra Nevada, where we find a lower crustal low Vs layer consistent with a small amount of partial melt. The high elevations relative to crust thickness and lower crustal low Vs zone are consistent with geological inferences that lithospheric foundering drove

  4. Rayleigh and S wave tomography constraints on subduction termination and lithospheric foundering in central California

    Science.gov (United States)

    Jiang, Chengxin; Schmandt, Brandon; Hansen, Steven M.; Dougherty, Sara L.; Clayton, Robert W.; Farrell, Jamie; Lin, Fan-Chi

    2018-04-01

    The crust and upper mantle structure of central California have been modified by subduction termination, growth of the San Andreas plate boundary fault system, and small-scale upper mantle convection since the early Miocene. Here we investigate the contributions of these processes to the creation of the Isabella Anomaly, which is a high seismic velocity volume in the upper mantle. There are two types of hypotheses for its origin. One is that it is the foundered mafic lower crust and mantle lithosphere of the southern Sierra Nevada batholith. The alternative suggests that it is a fossil slab connected to the Monterey microplate. A dense broadband seismic transect was deployed from the coast to the western Sierra Nevada to fill in the least sampled areas above the Isabella Anomaly, and regional-scale Rayleigh and S wave tomography are used to evaluate the two hypotheses. New shear velocity (Vs) tomography images a high-velocity anomaly beneath coastal California that is sub-horizontal at depths of ∼40-80 km. East of the San Andreas Fault a continuous extension of the high-velocity anomaly dips east and is located beneath the Sierra Nevada at ∼150-200 km depth. The western position of the Isabella Anomaly in the uppermost mantle is inconsistent with earlier interpretations that the Isabella Anomaly is connected to actively foundering foothills lower crust. Based on the new Vs images, we interpret that the Isabella Anomaly is not the dense destabilized root of the Sierra Nevada, but rather a remnant of Miocene subduction termination that is translating north beneath the central San Andreas Fault. Our results support the occurrence of localized lithospheric foundering beneath the high elevation eastern Sierra Nevada, where we find a lower crustal low Vs layer consistent with a small amount of partial melt. The high elevations relative to crust thickness and lower crustal low Vs zone are consistent with geological inferences that lithospheric foundering drove uplift

  5. Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation.

    Science.gov (United States)

    von Salomé, Jenny; Liu, Tao; Keihäs, Markku; Morak, Moni; Holinski-Feder, Elke; Berry, Ian R; Moilanen, Jukka S; Baert-Desurmont, Stéphanie; Lindblom, Annika; Lagerstedt-Robinson, Kristina

    2017-12-29

    Lynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genes MLH1, MSH2, MSH6 or PMS2, with the vast majority detected in MLH1 and MSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also acting as founders in other ethnic groups. Testing for founder mutations can facilitate molecular diagnosis of Lynch Syndrome more efficiently and more cost effective than screening for all possible mutations. Here we report a study of the missense mutation MLH1 c.2059C > T (p.Arg687Trp), a potential founder mutation identified in eight Swedish families and one Finnish family with Swedish ancestors. Haplotype analysis confirmed that the Finnish and Swedish families shared a haplotype of between 0.9 and 2.8 Mb. While MLH1 c.2059C > T exists worldwide, the Swedish haplotype was not found among mutation carriers from Germany or France, which indicates a common founder in the Swedish population. The geographic distribution of MLH1 c.2059C > T in Sweden suggests a single, ancient mutational event in the northern part of Sweden.

  6. Association of yield-related traits in founder genotypes and derivatives of common wheat (Triticum aestivum L.

    Directory of Open Access Journals (Sweden)

    Jie Guo

    2018-02-01

    Full Text Available Abstract Background Yield improvement is an ever-important objective of wheat breeding. Studying and understanding the phenotypes and genotypes of yield-related traits has potential for genetic improvement of crops. Results The genotypes of 215 wheat cultivars including 11 founder parents and 106 derivatives were analyzed by the 9 K wheat SNP iSelect assay. A total of 4138 polymorphic single nucleotide polymorphism (SNP loci were detected on 21 chromosomes, of which 3792 were mapped to single chromosome locations. All genotypes were phenotyped for six yield-related traits including plant height (PH, spike length (SL, spikelet number per spike (SNPS, kernel number per spike (KNPS, kernel weight per spike (KWPS, and thousand kernel weight (TKW in six irrigated environments. Genome-wide association analysis detected 117 significant associations of 76 SNPs on 15 chromosomes with phenotypic explanation rates (R 2 ranging from 2.03 to 12.76%. In comparing allelic variation between founder parents and their derivatives (106 and other cultivars (98 using the 76 associated SNPs, we found that the region 116.0–133.2 cM on chromosome 5A in founder parents and derivatives carried alleles positively influencing kernel weight per spike (KWPS, rarely found in other cultivars. Conclusion The identified favorable alleles could mark important chromosome regions in derivatives that were inherited from founder parents. Our results unravel the genetic of yield in founder genotypes, and provide tools for marker-assisted selection for yield improvement.

  7. High prevalence of BRCA1 founder mutations in Greek breast/ovarian families.

    Science.gov (United States)

    Konstantopoulou, I; Tsitlaidou, M; Fostira, F; Pertesi, M; Stavropoulou, A-V; Triantafyllidou, O; Tsotra, E; Tsiftsoglou, A P; Tsionou, C; Droufakou, S; Dimitrakakis, C; Fountzilas, G; Yannoukakos, D

    2014-01-01

    We have screened 473 breast/ovarian cancer patients with family history, aiming to define the prevalence and enrich the spectrum of BRCA1/2 pathogenic mutations occurring in the Greek population. An overall mutation prevalence of 32% was observed. Six BRCA1 recurrent/founder mutations dominate the observed spectrum (58.5% of all mutations found). These include three mutations in exon 20 and three large genomic deletions. Of the 44 different deleterious mutations found in both genes, 16 are novel and reported here for the first time. Correlation with available histopathology data showed that 80% of BRCA1 carriers presented a triple-negative breast cancer phenotype while 82% of BRCA2 carriers had oestrogen receptor positive tumours. This study provides a comprehensive view of the frequency, type and distribution of BRCA1/2 mutations in the Greek population as well as an insight of the screening strategy of choice for patients of Greek origin. We conclude that the Greek population has a diverse mutation spectrum influenced by strong founder effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. PRIMAL: Fast and accurate pedigree-based imputation from sequence data in a founder population.

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    Oren E Livne

    2015-03-01

    Full Text Available Founder populations and large pedigrees offer many well-known advantages for genetic mapping studies, including cost-efficient study designs. Here, we describe PRIMAL (PedigRee IMputation ALgorithm, a fast and accurate pedigree-based phasing and imputation algorithm for founder populations. PRIMAL incorporates both existing and original ideas, such as a novel indexing strategy of Identity-By-Descent (IBD segments based on clique graphs. We were able to impute the genomes of 1,317 South Dakota Hutterites, who had genome-wide genotypes for ~300,000 common single nucleotide variants (SNVs, from 98 whole genome sequences. Using a combination of pedigree-based and LD-based imputation, we were able to assign 87% of genotypes with >99% accuracy over the full range of allele frequencies. Using the IBD cliques we were also able to infer the parental origin of 83% of alleles, and genotypes of deceased recent ancestors for whom no genotype information was available. This imputed data set will enable us to better study the relative contribution of rare and common variants on human phenotypes, as well as parental origin effect of disease risk alleles in >1,000 individuals at minimal cost.

  9. Can a linguistic serial founder effect originating in Africa explain the worldwide phonemic cline?

    Science.gov (United States)

    Fort, Joaquim; Pérez-Losada, Joaquim

    2016-04-01

    It has been proposed that a serial founder effect could have caused the present observed pattern of global phonemic diversity. Here we present a model that simulates the human range expansion out of Africa and the subsequent spatial linguistic dynamics until today. It does not assume copying errors, Darwinian competition, reduced contrastive possibilities or any other specific linguistic mechanism. We show that the decrease of linguistic diversity with distance (from the presumed origin of the expansion) arises under three assumptions, previously introduced by other authors: (i) an accumulation rate for phonemes; (ii) small phonemic inventories for the languages spoken before the out-of-Africa dispersal; (iii) an increase in the phonemic accumulation rate with the number of speakers per unit area. Numerical simulations show that the predictions of the model agree with the observed decrease of linguistic diversity with increasing distance from the most likely origin of the out-of-Africa dispersal. Thus, the proposal that a serial founder effect could have caused the present observed pattern of global phonemic diversity is viable, if three strong assumptions are satisfied. © 2016 The Authors.

  10. A.T. STILL (1828–1917, THE FOUNDER OF OSTEOPATHY: THE COURSE OF LIFE

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    V. I. Karpova

    2016-01-01

    Full Text Available Osteopathy is a young medical specialty that has found official acceptance in Russia since 2013. The paper deals with the history of osteo pathy and its founder Andrew Taylor Still (1828–1917. He left a few printed scientific works, including his biography reporting much of his life and activities and the creation of osteopathy. The emergence date of osteopathy is considered to be 22 June 1874. Historically, modern osteopathy has come into existence not so long. We are almost contemporaries of it and its author, but despite this, the international osteopathy community is romanticizing and mythologizing the personality of A.T. Still. In our opinion, the reason is his magnetic personality and brilliant life. Thanks to A.T. Still’s personality, osteopathy may not have been lost among many medical areas and discoveries and continues to develop and attract new supporters. On the other hand, osteopathy is, in the opinion of its founder, a science; therefore a historical rather than mythological approach to A.T. Still’s bibliography, which takes into account all factors for personality formation, is considered correct. Modern science tells that these factors are inheritance, environment, and education. The authors have applied just this scientific approach and, without demolishing the myths, set forth an aim to study the factors forming the world outlook of A.T. Still in order to predict a further way to develope osteopathy in our country.

  11. Can a linguistic serial founder effect originating in Africa explain the worldwide phonemic cline?

    Science.gov (United States)

    2016-01-01

    It has been proposed that a serial founder effect could have caused the present observed pattern of global phonemic diversity. Here we present a model that simulates the human range expansion out of Africa and the subsequent spatial linguistic dynamics until today. It does not assume copying errors, Darwinian competition, reduced contrastive possibilities or any other specific linguistic mechanism. We show that the decrease of linguistic diversity with distance (from the presumed origin of the expansion) arises under three assumptions, previously introduced by other authors: (i) an accumulation rate for phonemes; (ii) small phonemic inventories for the languages spoken before the out-of-Africa dispersal; (iii) an increase in the phonemic accumulation rate with the number of speakers per unit area. Numerical simulations show that the predictions of the model agree with the observed decrease of linguistic diversity with increasing distance from the most likely origin of the out-of-Africa dispersal. Thus, the proposal that a serial founder effect could have caused the present observed pattern of global phonemic diversity is viable, if three strong assumptions are satisfied. PMID:27122180

  12. Haplotype variation in founders of the Mauremys annamensis population kept in European Zoos

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    Barbora Somerova

    2015-06-01

    Full Text Available The critically endangered Annam leaf turtle Mauremys annamensis faces extinction in nature. Because of that, the conservation value of the population kept in European zoos becomes substantial for reintroduction programmes. We sampled 39 specimens of M. annamensis from European zoos and other collections (mainly founders, imports and putatively unrelated individuals, and also four specimens of Mauremys mutica for comparison. In each animal, we sequenced 817 bp of the mitochondrial ND4 gene and 940 bp of the nuclear R35 intron that were used as phylogenetic markers for Mauremys mutica-annamensis group by previous authors. The sequences of the R35 intron, which are characteristic for M. annamensis and which clearly differ from those characteristic for M. mutica and/or other Mauremys species, were mutually shared by all of the examined M. annamensis. They also possessed mitochondrial haplotypes belonging to the annamensis subclades I and II, distinctness of which was clearly confirmed by phylogenetic analyses. Thus, both nuclear and mitochondrial markers agreed in the unequivocal assignment of the examined individuals to M. annamensis. Although no obvious hybrids were detected within the founders of the captive population, further careful genetic evaluation using genom-wide markers is required to unequivocally confirm this result.

  13. Signatures of seaway closures and founder dispersal in the phylogeny of a circumglobally distributed seahorse lineage.

    Science.gov (United States)

    Teske, Peter R; Hamilton, Healy; Matthee, Conrad A; Barker, Nigel P

    2007-08-15

    The importance of vicariance events on the establishment of phylogeographic patterns in the marine environment is well documented, and generally accepted as an important cause of cladogenesis. Founder dispersal (i.e. long-distance dispersal followed by founder effect speciation) is also frequently invoked as a cause of genetic divergence among lineages, but its role has long been challenged by vicariance biogeographers. Founder dispersal is likely to be common in species that colonize remote habitats by means of rafting (e.g. seahorses), as long-distance dispersal events are likely to be rare and subsequent additional recruitment from the source habitat is unlikely. In the present study, the relative importance of vicariance and founder dispersal as causes of cladogenesis in a circumglobally distributed seahorse lineage was investigated using molecular dating. A phylogeny was reconstructed using sequence data from mitochondrial and nuclear markers, and the well-documented closure of the Central American seaway was used as a primary calibration point to test whether other bifurcations in the phylogeny could also have been the result of vicariance events. The feasibility of three other vicariance events was explored: a) the closure of the Indonesian Seaway, resulting in sister lineages associated with the Indian Ocean and West Pacific, respectively; b) the closure of the Tethyan Seaway, resulting in sister lineages associated with the Indo-Pacific and Atlantic Ocean, respectively, and c) continental break-up during the Mesozoic followed by spreading of the Atlantic Ocean, resulting in pairs of lineages with amphi-Atlantic distribution patterns. Comparisons of pairwise genetic distances among the seahorse species hypothesized to have diverged as a result of the closure of the Central American Seaway with those of published teleost sequences having the same distribution patterns show that the seahorses were among the last to diverge. This suggests that their

  14. Signatures of seaway closures and founder dispersal in the phylogeny of a circumglobally distributed seahorse lineage

    Directory of Open Access Journals (Sweden)

    Matthee Conrad A

    2007-08-01

    Full Text Available Abstract Background The importance of vicariance events on the establishment of phylogeographic patterns in the marine environment is well documented, and generally accepted as an important cause of cladogenesis. Founder dispersal (i.e. long-distance dispersal followed by founder effect speciation is also frequently invoked as a cause of genetic divergence among lineages, but its role has long been challenged by vicariance biogeographers. Founder dispersal is likely to be common in species that colonize remote habitats by means of rafting (e.g. seahorses, as long-distance dispersal events are likely to be rare and subsequent additional recruitment from the source habitat is unlikely. In the present study, the relative importance of vicariance and founder dispersal as causes of cladogenesis in a circumglobally distributed seahorse lineage was investigated using molecular dating. A phylogeny was reconstructed using sequence data from mitochondrial and nuclear markers, and the well-documented closure of the Central American seaway was used as a primary calibration point to test whether other bifurcations in the phylogeny could also have been the result of vicariance events. The feasibility of three other vicariance events was explored: a the closure of the Indonesian Seaway, resulting in sister lineages associated with the Indian Ocean and West Pacific, respectively; b the closure of the Tethyan Seaway, resulting in sister lineages associated with the Indo-Pacific and Atlantic Ocean, respectively, and c continental break-up during the Mesozoic followed by spreading of the Atlantic Ocean, resulting in pairs of lineages with amphi-Atlantic distribution patterns. Results Comparisons of pairwise genetic distances among the seahorse species hypothesized to have diverged as a result of the closure of the Central American Seaway with those of published teleost sequences having the same distribution patterns show that the seahorses were among the last to

  15. Eduard Strasburger (1844-1912): founder of modern plant cell biology.

    Science.gov (United States)

    Volkmann, Dieter; Baluška, František; Menzel, Diedrik

    2012-10-01

    Eduard Strasburger, director of the Botany Institute and the Botanical Garden at the University of Bonn from 1881 to 1912, was one of the most admirable scientists in the field of plant biology, not just as the founder of modern plant cell biology but in addition as an excellent teacher who strongly believed in "education through science." He contributed to plant cell biology by discovering the discrete stages of karyokinesis and cytokinesis in algae and higher plants, describing cytoplasmic streaming in different systems, and reporting on the growth of the pollen tube into the embryo sac and guidance of the tube by synergides. Strasburger raised many problems which are hot spots in recent plant cell biology, e.g., structure and function of the plasmodesmata in relation to phloem loading (Strasburger cells) and signaling, mechanisms of cell plate formation, vesicle trafficking as a basis for most important developmental processes, and signaling related to fertilization.

  16. The founder of the church of Saint George at Pološko

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    Pavlović Dragana

    2015-01-01

    Full Text Available The paper seeks to establish who was the founder of the church of Saint George at Pološko and revise the conclusions of previous researchers regarding this issue. According to the opinion commonly adopted in the scholarly literature, Jovan Dragušin, a cousin of King Dušan, had merely undertaken the construction of church at Pološko, whereas his mother was responsible for the completion of construction and painting of frescoes in the church. Through an analysis of written and visual sources the conclusion is reached that the sole person responsible for the construction and painting of the church at Pološko was the nun Maria, the mother of Jovan Dragušin. [Projekat Ministarstva nauke Republike Srbije, br. 177036: Srpska srednjovekovna umetnost i njen evropski kontekst

  17. Preconception carrier screening for multiple disorders: evaluation of a screening offer in a Dutch founder population.

    Science.gov (United States)

    Mathijssen, Inge B; Holtkamp, Kim C A; Ottenheim, Cecile P E; van Eeten-Nijman, Janneke M C; Lakeman, Phillis; Meijers-Heijboer, Hanne; van Maarle, Merel C; Henneman, Lidewij

    2018-02-01

    Technological developments have enabled carrier screening for multiple disorders. This study evaluated experiences with a preconception carrier screening offer for four recessive disorders in a Dutch founder population. Questionnaires were completed by 182 attendees pretesting and posttesting and by 137 non-attendees. Semistructured interviews were conducted with seven of the eight carrier couples. Attendees were mainly informed about the existence of screening by friends/colleagues (49%) and family members (44%). Familiarity with the genetic disorders was high. Knowledge after counseling increased (p influencers (family/friends) can be used to raise awareness of a screening offer. Our findings provide lessons for the implementation of expanded carrier screening panels in other communities and other settings.

  18. XPC gene mutations in families with xeroderma pigmentosum from Pakistan; prevalent founder effect.

    Science.gov (United States)

    Ijaz, Ambreen; Basit, Sulman; Gul, Ajab; Batool, Lilas; Hussain, Abrar; Afzal, Sibtain; Ramzan, Khushnooda; Ahmad, Jamil; Wali, Abdul

    2018-03-23

    Xeroderma pigmentosum (XP) is a rare autosomal recessive skin disorder characterized by hyperpigmentation, premature skin aging, ocular and cutaneous photosensitivity, and increased risk of skin carcinoma. We investigated seven consanguineous XP families with nine patients from Pakistan. All the Patients exhibited typical clinical symptoms of XP since first year of life. Whole genome SNP genotyping identified a 14 Mb autozygous region segregating with the disease phenotype on chromosome 3p25.1. DNA sequencing of XPC gene revealed a founder homozygous splice site mutation (c.2251-1G>C) in patients from six families (A-F) and a homozygous nonsense mutation (c.1399C>T; p.Gln467*) in patients of family G. This is the first report of XPC mutations, underlying XP phenotype, in Pakistani population. © 2018 Japanese Teratology Society.

  19. Hematological consequences of a FANCG founder mutation in Black South African patients with Fanconi anemia.

    Science.gov (United States)

    Feben, Candice; Kromberg, Jennifer; Wainwright, Rosalind; Stones, David; Poole, Janet; Haw, Tabitha; Krause, Amanda

    2015-03-01

    Fanconi anemia (FA) is a rare disorder of DNA repair, associated with various somatic abnormalities but characterized by hematological disease that manifests as bone marrow aplasia and malignancy. The mainstay of treatment, in developed nations, is hematopoietic stem cell transplantation (HSCT) with subsequent surveillance for solid organ and non-hematological malignancies. In South Africa, FA in the Black population is caused by a homozygous deletion mutation in the FANCG gene in more than 80% of cases. Many affected patients are not diagnosed until late in the disease course when severe cytopenia and bone marrow aplasia are already present. Most patients are not eligible for HSCT at this late stage of the disease, even when it is available in the state health care system. In this study, the hematological presentation and disease progression in 30 Black South African patients with FA, confirmed to have the FANCG founder mutation, were evaluated and compared to those described in other FA cohorts. Our results showed that patients, homozygous for the FANCG founder mutation, present with severe cytopenia but progress to bone marrow failure at similar ages to other individuals affected with FA of heterogeneous genotype. Further, the incidence of myelodysplastic syndrome is similar to that which has been previously described in other FA cohorts. Although severe cytopenia at presentation may be predicted by a higher number of somatic anomalies, the recognition of the physical FA phenotype in Black South African patients is challenging and may not be useful in expediting referral of suspected FA patients for tertiary level investigations and care. Given the late but severe hematological presentation of FA in Black South African patients, an investigative strategy is needed for earlier recognition of affected individuals to allow for possible HSCT and management of bone marrow disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Brief communication: human cranial variation fits iterative founder effect model with African origin.

    Science.gov (United States)

    von Cramon-Taubadel, Noreen; Lycett, Stephen J

    2008-05-01

    Recent studies comparing craniometric and neutral genetic affinity matrices have concluded that, on average, human cranial variation fits a model of neutral expectation. While human craniometric and genetic data fit a model of isolation by geographic distance, it is not yet clear whether this is due to geographically mediated gene flow or human dispersal events. Recently, human genetic data have been shown to fit an iterative founder effect model of dispersal with an African origin, in line with the out-of-Africa replacement model for modern human origins, and Manica et al. (Nature 448 (2007) 346-349) have demonstrated that human craniometric data also fit this model. However, in contrast with the neutral model of cranial evolution suggested by previous studies, Manica et al. (2007) made the a priori assumption that cranial form has been subject to climatically driven natural selection and therefore correct for climate prior to conducting their analyses. Here we employ a modified theoretical and methodological approach to test whether human cranial variability fits the iterative founder effect model. In contrast with Manica et al. (2007) we employ size-adjusted craniometric variables, since climatic factors such as temperature have been shown to correlate with aspects of cranial size. Despite these differences, we obtain similar results to those of Manica et al. (2007), with up to 26% of global within-population craniometric variation being explained by geographic distance from sub-Saharan Africa. Comparative analyses using non-African origins do not yield significant results. The implications of these results are discussed in the light of the modern human origins debate. (c) 2007 Wiley-Liss, Inc.

  1. Distribution and medical impact of loss-of-function variants in the Finnish founder population.

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    Elaine T Lim

    2014-07-01

    Full Text Available Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5% variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10⁻⁸ including splice variants in LPA that lowered plasma lipoprotein(a levels (P = 1.5×10⁻¹¹⁷. Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10⁻⁴, demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health

  2. The first Dutch SDHB founder deletion in paraganglioma – pheochromocytoma patients

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    Devilee Peter

    2009-04-01

    Full Text Available Abstract Background Germline mutations of the tumor suppressor genes SDHB, SDHC and SDHD play a major role in hereditary paraganglioma and pheochromocytoma. These three genes encode subunits of succinate dehydrogenase (SDH, the mitochondrial tricarboxylic acid cycle enzyme and complex II component of the electron transport chain. The majority of variants of the SDH genes are missense and nonsense mutations. To date few large deletions of the SDH genes have been described. Methods We carried out gene deletion scanning using MLPA in 126 patients negative for point mutations in the SDH genes. We then proceeded to the molecular characterization of deletions, mapping breakpoints in each patient and used haplotype analysis to determine whether the deletions are due to a mutation hotspot or if a common haplotype indicated a single founder mutation. Results A novel deletion of exon 3 of the SDHB gene was identified in nine apparently unrelated Dutch patients. An identical 7905 bp deletion, c.201-4429_287-933del, was found in all patients, resulting in a frameshift and a predicted truncated protein, p.Cys68HisfsX21. Haplotype analysis demonstrated a common haplotype at the SDHB locus. Index patients presented with pheochromocytoma, extra-adrenal PGL and HN-PGL. A lack of family history was seen in seven of the nine cases. Conclusion The identical exon 3 deletions and common haplotype in nine patients indicates that this mutation is the first Dutch SDHB founder mutation. The predominantly non-familial presentation of these patients strongly suggests reduced penetrance. In this small series HN-PGL occurs as frequently as pheochromocytoma and extra-adrenal PGL.

  3. Genome-wide association studies in an isolated founder population from the Pacific Island of Kosrae.

    Directory of Open Access Journals (Sweden)

    Jennifer K Lowe

    2009-02-01

    Full Text Available It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and complex disease. A strong founder effect, severe isolation, and substantial inbreeding have dramatically reduced genetic diversity in natives from the island of Kosrae, Federated States of Micronesia, who exhibit a high prevalence of obesity and other metabolic disorders. We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects, making these alleles readily detectable in genome-wide association analysis. However, mapping in large, inbred cohorts introduces analytic challenges, as extensive relatedness between subjects violates the assumptions of independence upon which traditional association test statistics are based. We performed genome-wide association analysis for 15 quantitative traits in 2,906 members of the Kosrae population, using novel approaches to manage the extreme relatedness in the sample. As positive controls, we observe association to known loci for plasma cholesterol, triglycerides, and C-reactive protein and to a compelling candidate loci for thyroid stimulating hormone and fasting plasma glucose. We show that our study is well powered to detect common alleles explaining >/=5% phenotypic variance. However, no such large effects were observed with genome-wide significance, arguing that even in such a severely inbred population, common alleles typically have modest effects. Finally, we show that a majority of common variants discovered in Caucasians have indistinguishable effect sizes on Kosrae, despite the major differences in population genetics and environment.

  4. Mitochondrial Genome Diversity of Native Americans Supports a Single Early Entry of Founder Populations into America

    Science.gov (United States)

    Silva Jr., Wilson A.; Bonatto, Sandro L.; Holanda, Adriano J.; Ribeiro-dos-Santos, Andrea K.; Paixão, Beatriz M.; Goldman, Gustavo H.; Abe-Sandes, Kiyoko; Rodriguez-Delfin, Luis; Barbosa, Marcela; Paçó-Larson, Maria Luiza; Petzl-Erler, Maria Luiza; Valente, Valeria; Santos, Sidney E. B.; Zago, Marco A.

    2002-01-01

    There is general agreement that the Native American founder populations migrated from Asia into America through Beringia sometime during the Pleistocene, but the hypotheses concerning the ages and the number of these migrations and the size of the ancestral populations are surrounded by controversy. DNA sequence variations of several regions of the genome of Native Americans, especially in the mitochondrial DNA (mtDNA) control region, have been studied as a tool to help answer these questions. However, the small number of nucleotides studied and the nonclocklike rate of mtDNA control-region evolution impose several limitations to these results. Here we provide the sequence analysis of a continuous region of 8.8 kb of the mtDNA outside the D-loop for 40 individuals, 30 of whom are Native Americans whose mtDNA belongs to the four founder haplogroups. Haplogroups A, B, and C form monophyletic clades, but the five haplogroup D sequences have unstable positions and usually do not group together. The high degree of similarity in the nucleotide diversity and time of differentiation (i.e., ∼21,000 years before present) of these four haplogroups support a common origin for these sequences and suggest that the populations who harbor them may also have a common history. Additional evidence supports the idea that this age of differentiation coincides with the process of colonization of the New World and supports the hypothesis of a single and early entry of the ancestral Asian population into the Americas. PMID:12022039

  5. Congenital sucrase-isomaltase deficiency: identification of a common Inuit founder mutation.

    Science.gov (United States)

    Marcadier, Julien L; Boland, Margaret; Scott, C Ronald; Issa, Kheirie; Wu, Zaining; McIntyre, Adam D; Hegele, Robert A; Geraghty, Michael T; Lines, Matthew A

    2015-02-03

    Congenital sucrase-isomaltase deficiency is a rare hereditary cause of chronic diarrhea in children. People with this condition lack the intestinal brush-border enzyme required for digestion of di- and oligosaccharides, including sucrose and isomaltose, leading to malabsorption. Although the condition is known to be highly prevalent (about 5%-10%) in several Inuit populations, the genetic basis for this has not been described. We sought to identify a common mutation for congenital sucrase-isomaltase deficiency in the Inuit population. We sequenced the sucrase-isomaltase gene, SI, in a single Inuit proband with congenital sucrase-isomaltase deficiency who had severe fermentative diarrhea and failure to thrive. We then genotyped a further 128 anonymized Inuit controls from a variety of locales in the Canadian Arctic to assess for a possible founder effect. In the proband, we identified a novel, homozygous frameshift mutation, c.273_274delAG (p.Gly92Leufs*8), predicted to result in complete absence of a functional protein product. This change was very common among the Inuit controls, with an observed allele frequency of 17.2% (95% confidence interval [CI] 12.6%-21.8%). The predicted Hardy-Weinberg prevalence of congenital sucrase-isomaltase deficiency in Inuit people, based on this single founder allele, is 3.0% (95% CI 1.4%-4.5%), which is comparable with previous estimates. We found a common mutation, SI c.273_274delAG, to be responsible for the high prevalence of congenital sucrase-isomaltase deficiency among Inuit people. Targeted mutation testing for this allele should afford a simple and minimally invasive means of diagnosing this condition in Inuit patients with chronic diarrhea. © 2015 Canadian Medical Association or its licensors.

  6. A genetic cluster of patients with variant xeroderma pigmentosum with two different founder mutations.

    Science.gov (United States)

    Munford, V; Castro, L P; Souto, R; Lerner, L K; Vilar, J B; Quayle, C; Asif, H; Schuch, A P; de Souza, T A; Ienne, S; Alves, F I A; Moura, L M S; Galante, P A F; Camargo, A A; Liboredo, R; Pena, S D J; Sarasin, A; Chaibub, S C; Menck, C F M

    2017-05-01

    Xeroderma pigmentosum (XP) is a rare human syndrome associated with hypersensitivity to sunlight and a high frequency of skin tumours at an early age. We identified a community in the state of Goias (central Brazil), a sunny and tropical region, with a high incidence of XP (17 patients among approximately 1000 inhabitants). To identify gene mutations in the affected community and map the distribution of the affected alleles, correlating the mutations with clinical phenotypes. Functional analyses of DNA repair capacity and cell-cycle responses after ultraviolet exposure were investigated in cells from local patients with XP, allowing the identification of the mutated gene, which was then sequenced to locate the mutations. A specific assay was designed for mapping the distribution of these mutations in the community. Skin primary fibroblasts showed normal DNA damage removal but abnormal DNA synthesis after ultraviolet irradiation and deficient expression of the Polη protein, which is encoded by POLH. We detected two different POLH mutations: one at the splice donor site of intron 6 (c.764 +1 G>A), and the other in exon 8 (c.907 C>T, p.Arg303X). The mutation at intron 6 is novel, whereas the mutation at exon 8 has been previously described in Europe. Thus, these mutations were likely brought to the community long ago, suggesting two founder effects for this rare disease. This work describes a genetic cluster involving POLH, and, particularly unexpected, with two independent founder mutations, including one that likely originated in Europe. © 2016 British Association of Dermatologists.

  7. TGfU--Would You Know It if You Saw It? Benchmarks from the Tacit Knowledge of the Founders

    Science.gov (United States)

    Butler, Joy

    2014-01-01

    This paper explores the tacit expert knowledge and understanding about games curriculum and pedagogy of three men, Len Almond, David Bunker, and Rod Thorpe, credited as the founders of the Teaching Games for Understanding (TGfU) model. The model emerged from teacher practice in the late 1970s and was little theorized at the time, apart from a…

  8. Apple founder targets healthcare as NeXT market. Interview by Carolyn Dunbar and Michael L. Laughlin.

    Science.gov (United States)

    Jobs, S

    1992-12-01

    Cofounder and former chairman of the board of Apple Computer Steven Jobs looks beyond the 1980s image of a petulant, embittered young man, fighting with all who failed to share his vision, and many who did. Today, as a founder, president and chairman of NeXT, Inc., he looks to more high-minded applications of his computer genius.

  9. Elon Musk, founder of SpaceX and PayPal, to speak on campus Feb. 21

    OpenAIRE

    Crumbley, Liz

    2006-01-01

    Elon Musk, founder and chief executive officer of Space Exploration Technologies Co. (SpaceX), will speak on his company's Falcon rocket series and the future of university space research on Tuesday, Feb. 21 at 7:30 p.m. in Virginia Tech's Burruss Hall Auditorium. The event is free and open to the public.

  10. Org-1 is required for the diversification of circular visceral muscle founder cells and normal midgut morphogenesis.

    Science.gov (United States)

    Schaub, Christoph; Frasch, Manfred

    2013-04-15

    The T-Box family of transcription factors plays fundamental roles in the generation of appropriate spatial and temporal gene expression profiles during cellular differentiation and organogenesis in animals. In this study we report that the Drosophila Tbx1 orthologue optomotor-blind-related-gene-1 (org-1) exerts a pivotal function in the diversification of circular visceral muscle founder cell identities in Drosophila. In embryos mutant for org-1, the specification of the midgut musculature per se is not affected, but the differentiating midgut fails to form the anterior and central midgut constrictions and lacks the gastric caeca. We demonstrate that this phenotype results from the nearly complete loss of the founder cell specific expression domains of several genes known to regulate midgut morphogenesis, including odd-paired (opa), teashirt (tsh), Ultrabithorax (Ubx), decapentaplegic (dpp) and wingless (wg). To address the mechanisms that mediate the regulatory inputs from org-1 towards Ubx, dpp, and wg in these founder cells we genetically dissected known visceral mesoderm specific cis-regulatory-modules (CRMs) of these genes. The analyses revealed that the activities of the dpp and wg CRMs depend on org-1, the CRMs are bound by Org-1 in vivo and their T-Box binding sites are essential for their activation in the visceral muscle founder cells. We conclude that Org-1 acts within a well-defined signaling and transcriptional network of the trunk visceral mesoderm as a crucial founder cell-specific competence factor, in concert with the general visceral mesodermal factor Biniou. As such, it directly regulates several key genes involved in the establishment of morphogenetic centers along the anteroposterior axis of the visceral mesoderm, which subsequently organize the formation of midgut constrictions and gastric caeca and thereby determine the morphology of the midgut. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.

    Directory of Open Access Journals (Sweden)

    Kana Tanahashi

    Full Text Available Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH, and the 2 missense mutations c.736T>A (p.Cys246Ser and c.742C>A (p.His248Asn are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016, and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024. In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH.

  12. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

    Science.gov (United States)

    Liao, Hua-Xin; Lynch, Rebecca; Zhou, Tongqing; Gao, Feng; Alam, S. Munir; Boyd, Scott D.; Fire, Andrew Z.; Roskin, Krishna M.; Schramm, Chaim A.; Zhang, Zhenhai; Zhu, Jiang; Shapiro, Lawrence; Mullikin, James C.; Gnanakaran, S.; Hraber, Peter; Wiehe, Kevin; Kelsoe, Garnett; Yang, Guang; Xia, Shi-Mao; Montefiori, David C.; Parks, Robert; Lloyd, Krissey E.; Scearce, Richard M.; Soderberg, Kelly A.; Cohen, Myron; Kaminga, Gift; Louder, Mark K.; Tran, Lillan M.; Chen, Yue; Cai, Fangping; Chen, Sheri; Moquin, Stephanie; Du, Xiulian; Joyce, Gordon M.; Srivatsan, Sanjay; Zhang, Baoshan; Zheng, Anqi; Shaw, George M.; Hahn, Beatrice H.; Kepler, Thomas B.; Korber, Bette T.M.; Kwong, Peter D.; Mascola, John R.; Haynes, Barton F.

    2013-01-01

    Current HIV-1 vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in ~20% of HIV-1-infected individuals, and details of their generation could provide a roadmap for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from time of infection. The mature antibody, CH103, neutralized ~55% of HIV-1 isolates, and its co-crystal structure with gp120 revealed a novel loop-based mechanism of CD4-binding site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the CH103-lineage unmutated common ancestor avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data elucidate the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies and provide insights into strategies to elicit similar antibodies via vaccination. PMID:23552890

  13. Nukuleka as a founder colony for West Polynesian settlement : new insights from recent excavations

    International Nuclear Information System (INIS)

    Burley, D.V.; Barton, A.; Dickinson, W.R.; Connaughton, S.P.; Tache, K.

    2010-01-01

    Previous archaeological studies in the village of Nukuleka, Tongatapu, Kingdom of Tonga proposed it as a founder colony for Polynesia. Additional excavation and survey were undertaken in 2007 to evaluate this status further and to gain new insight into the nature of the occupation and its role in the subsequent peopling of west Polynesia. A review of this project and its findings are presented. Decorated ceramics of western Lapita style, the presence of tan paste ceramics foreign to Tonga, and new radiocarbon dates support Nukuleka as a site of first landfall in the interval 2850 to 2900 cal BP. The ceramic assemblage is distinct from west and central Fiji, and an independent origin for Fijian and Polynesian colonizers is argued. The settlement quickly expanded on the Nukuleka Peninsula to 20 ha or more in size, forming a central place for the eastern Lapita province in Tonga, Samoa and the Lau islands of Fiji. Nukuleka, we believe, provides insight into the cultural if not biological base from which ancestral Polynesian society emerged. (author). 35 refs., 11 figs., 3 tabs.

  14. Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families.

    Science.gov (United States)

    Chang, Wendy; Winder, Thomas L; LeDuc, Charles A; Simpson, Lynn L; Millar, William S; Dungan, Jeffrey; Ginsberg, Norman; Plaga, Stacey; Moore, Steven A; Chung, Wendy K

    2009-06-01

    Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of alpha-dystroglycan (alpha-DG) that is associated with brain malformations and eye anomalies. The Fukutin (FKTN) gene, which causes autosomal recessively inherited WWS is most often associated with Fukuyama congenital muscular dystrophy in Japan. We describe the clinical features of four nonconsanguinous Ashkenazi Jewish families with WWS and identify the underlying genetic basis for WWS. We screened for mutations in POMGnT1, POMT1, POMT2, and FKTN, genes causing WWS, by dideoxy sequence analysis. We identified an identical homozygous c.1167insA mutation in the FKTN gene on a common haplotype in all four families and identified 2/299 (0.7%) carriers for the c.1167insA mutation among normal American Ashkenazi Jewish adults. These data suggest that the c.1167insA FKTN mutation described by us is a founder mutation that can be used to target diagnostic testing and carrier screening in the Ashkenazi Jewish population. Copyright (c) 2009 John Wiley & Sons, Ltd.

  15. Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families†

    Science.gov (United States)

    Chang, Wendy; Winder, Thomas L.; LeDuc, Charles A.; Simpson, Lynn L.; Millar, William S.; Dungan, Jeffrey; Ginsberg, Norman; Plaga, Stacey; Moore, Steven A.; Chung, Wendy K.

    2009-01-01

    Objective Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (α-DG) that is associated with brain malformations and eye anomalies. The Fukutin (FKTN) gene, which causes autosomal recessively inherited WWS is most often associated with Fukuyama congenital muscular dystrophy in Japan. We describe the clinical features of four nonconsanguinous Ashkenazi Jewish families with WWS and identify the underlying genetic basis for WWS. Method We screened for mutations in POMGnT1, POMT1, POMT2, and FKTN, genes causing WWS, by dideoxy sequence analysis. Results We identified an identical homozygous c.1167insA mutation in the FKTN gene on a common haplotype in all four families and identified 2/299 (0.7%) carriers for the c.1167insA mutation among normal American Ashkenazi Jewish adults. Conclusion These data suggest that the c.1167insA FKTN mutation described by us is a founder mutation that can be used to target diagnostic testing and carrier screening in the Ashkenazi Jewish population. PMID:19266496

  16. Use of Dried Blood Spots to Elucidate Full-Length Transmitted/Founder HIV-1 Genomes

    Directory of Open Access Journals (Sweden)

    Jesus F. Salazar-Gonzalez

    2016-07-01

    Full Text Available Background: Identification of HIV-1 genomes responsible for establishing clinical infection in newly infected individuals is fundamental to prevention and pathogenesis research. Processing, storage, and transportation of the clinical samples required to perform these virologic assays in resource-limited settings requires challenging venipuncture and cold chain logistics. Here, we validate the use of dried-blood spots (DBS as a simple and convenient alternative to collecting and storing frozen plasma. Methods: We performed parallel nucleic acid extraction, single genome amplification (SGA, next generation sequencing (NGS, and phylogenetic analyses on plasma and DBS. Results: We demonstrated the capacity to extract viral RNA from DBS and perform SGA to infer the complete nucleotide sequence of the transmitted/founder (TF HIV-1 envelope gene and full-length genome in two acutely infected individuals. Using both SGA and NGS methodologies, we showed that sequences generated from DBS and plasma display comparable phylogenetic patterns in both acute and chronic infection. SGA was successful on samples with a range of plasma viremia, including samples as low as 1,700 copies/ml and an estimated ~50 viral copies per blood spot. Further, we demonstrated reproducible efficiency in gp160 env sequencing in DBS stored at ambient temperature for up to three weeks or at -20ºC for up to five months. Conclusions: These findings support the use of DBS as a practical and cost-effective alternative to frozen plasma for clinical trials and translational research conducted in resource-limited settings.

  17. Willet M. Hays, great benefactor to plant breeding and the founder of our association.

    Science.gov (United States)

    Troyer, A F; Stoehr, H

    2003-01-01

    Willet M. Hays was a great benefactor to plant breeding and the founder of the American Genetic Association (AGA). We commemorate the AGA's centennial. We mined university archives, U.S. Department of Agriculture (USDA) yearbooks, plant breeding textbooks, scientific periodicals, and descendants for information. Willet Hays first recognized the individual plant as the unit of selection and started systematic pure-line selection and progeny tests in 1888. He developed useful plant breeding methods. He selected superior flax (Linum usitatissimum L.), wheat (Triticum vulgare L.), corn (Zea mays L.), barley (Hordeum vulgare L.), and oat (Avena sativa L.) varieties, and discovered Grimm alfalfa (Medicago sativa L.); all became commercially important. He initiated branch stations for better performance testing. Willet Hays befriended colleagues in other universities, in federal stations, in a London conference, and in Europe. He gathered and spread the scientific plant breeding gospel. He also improved rural roads and initiated animal breeding records and agricultural economics records. He started the AGA in 1903, serving as secretary for 10 years. He became assistant secretary of agriculture in 1904. He introduced the project system for agricultural research. He authored or coauthored the Nelson Amendment, the Smith-Lever Act, the Smith-Hughes Act, and the protocol leading to the United Nations Food and Agriculture Organization-all involved teaching agricultural practices that improved the world.

  18. A serial founder effect model for human settlement out of Africa.

    Science.gov (United States)

    Deshpande, Omkar; Batzoglou, Serafim; Feldman, Marcus W; Cavalli-Sforza, L Luca

    2009-01-22

    The increasing abundance of human genetic data has shown that the geographical patterns of worldwide genetic diversity are best explained by human expansion out of Africa. This expansion is modelled well by prolonged migration from a single origin in Africa with multiple subsequent serial founding events. We discuss a new simulation model for the serial founder effect out of Africa and compare it with results from previous studies. Unlike previous models, we distinguish colonization events from the continued exchange of people between occupied territories as a result of mating. We conduct a search through parameter space to estimate the range of parameter values that best explain key statistics from published data on worldwide variation in microsatellites. The range of parameters we use is chosen to be compatible with an out-of-Africa migration at 50-60Kyr ago and archaeo-ethno-demographic information. In addition to a colonization rate of 0.09-0.18, for an acceptable fit to the published microsatellite data, incorporation into existing models of exchange between neighbouring populations is essential, but at a very low rate. A linear decay of genetic diversity with geographical distance from the origin of expansion could apply to any species, especially if it moved recently into new geographical niches.

  19. Founder effect of a prevalent phenylketonuria mutation in the Oriental population

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tao (Baylor College of Medicine, Houston, TX (United States) Chinese Academy of Medical Sciences, Beijing (China)); Okano, Yoshiyuki; Eisensmith, R.C.; Harvey, M.L.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States)); Lo, W.H.Y.; Yuan, Lifang (Chinese Academy of Medical Sciences, Beijing (China)); Huang, Shuzhen; Zeng, Yitao (Shanghai Children' s Hospital (China)); Furuyama, Junichi (Hyogo College of Medicine, Nishinomiya (Japan)); Oura, Toshiaki (Osaka Municipal Rehabilitation Center for the Disabled, Osaka (Japan)); Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    1991-03-15

    A missense mutation has been identified in the human phenylalanine hydroxylase Chinese patient with classic phenylketonuria (PKU). A G-to-C transition at the second base of codon 413 in exon 12 of the gene results in the substitution of Pro{sup 413} for Arg{sup 413} in the mutant protein. This mutation (R413P) results in negligible enzymatic activity when expressed in heterologous mammalian cells and is compatible with a classic PKU phenotype in the patient. Population genetic studies reveal that this mutation is tightly linked to restriction fragment length polymorphism haplotype 4, which is the predominant haplotype of the PAH locus in the Oriental population. It accounts for 13.8% of northern Chinese and 27% of Japanese PKU alleles, but it is rare in southern Chinese (2.2%) and is absent in the Caucasian population. The data demonstrate unambiguously that the mutation occurred after racial divergence of Orientals and Caucasians and suggest that the allele has spread throughout the Orient by a founder effect. Previous protein polymorphism studies in eastern Asia have led to the hypothesis that northern Mongoloids represented a founding population in Asia. The results are compatible with this hypothesis in that the PKU mutation might have occurred in northern Mongoloids and subsequently spread to the Chinese and Japanese populations.

  20. Founder effect of a prevalent phenylketonuria mutation in the Oriental population

    International Nuclear Information System (INIS)

    Wang, Tao; Okano, Yoshiyuki; Eisensmith, R.C.; Harvey, M.L.; Woo, S.L.C.; Lo, W.H.Y.; Yuan, Lifang; Huang, Shuzhen; Zeng, Yitao; Furuyama, Junichi; Oura, Toshiaki; Sommer, S.S.

    1991-01-01

    A missense mutation has been identified in the human phenylalanine hydroxylase Chinese patient with classic phenylketonuria (PKU). A G-to-C transition at the second base of codon 413 in exon 12 of the gene results in the substitution of Pro 413 for Arg 413 in the mutant protein. This mutation (R413P) results in negligible enzymatic activity when expressed in heterologous mammalian cells and is compatible with a classic PKU phenotype in the patient. Population genetic studies reveal that this mutation is tightly linked to restriction fragment length polymorphism haplotype 4, which is the predominant haplotype of the PAH locus in the Oriental population. It accounts for 13.8% of northern Chinese and 27% of Japanese PKU alleles, but it is rare in southern Chinese (2.2%) and is absent in the Caucasian population. The data demonstrate unambiguously that the mutation occurred after racial divergence of Orientals and Caucasians and suggest that the allele has spread throughout the Orient by a founder effect. Previous protein polymorphism studies in eastern Asia have led to the hypothesis that northern Mongoloids represented a founding population in Asia. The results are compatible with this hypothesis in that the PKU mutation might have occurred in northern Mongoloids and subsequently spread to the Chinese and Japanese populations

  1. Academician L. V. Pisarzhevsky is the founder of chemical science and education in Dnipropetrovsk university

    Directory of Open Access Journals (Sweden)

    Valerij S. Kovalenko

    2014-12-01

    Full Text Available The article is devoted to the 140 anniversary of birth of the academician Lev Vladimirovich Pisarzhevsky, who was a distinguished chemical scientist, founder of the important area of chemical science – electronic chemistry. The article dwells upon the basic stages of the scientist’s life and creative art. The major results of scientific and educational activity during Dnipropetrovsk period of his life are reported. His role in the foundation of dnipropetrovsk scientific school of physical chemistry, as well as in its establishment, is shown. The pioneering role of the academician L. V. Pisarzhevsky in the formation of the theory of redox reactions as processes of returning and joining of electrons, which is generally accepted nowadays, as well as in the creation of backgrounds of modern electronic theories of catalysis, has been shown. L. V. Pisarzhevsky is characterized as a wonderful lecturer and teacher who expounded chemical material from the point of view of electronic conception and laid the foundation for the reformation of chemistry. The role of the academician L. V. Pisarzhevsky in the foundation of Dnipropetrovsk University and its chemical department, as well as in the organization of educational process in this establishment, is exposed using archive materials, which are kept in the funds of the State Archive of the Dnipropetrovsk region and of the historical museum of Oles Honchar Dnipropetrovsk National University.

  2. A Mayan founder mutation is a common cause of deafness in Guatemala.

    Science.gov (United States)

    Carranza, C; Menendez, I; Herrera, M; Castellanos, P; Amado, C; Maldonado, F; Rosales, L; Escobar, N; Guerra, M; Alvarez, D; Foster, J; Guo, S; Blanton, S H; Bademci, G; Tekin, M

    2015-09-08

    Over 5% of the world's population has varying degrees of hearing loss. Mutations in GJB2 are the most common cause of autosomal recessive non-syndromic hearing loss (ARNHL) in many populations. The frequency and type of mutations are influenced by ethnicity. Guatemala is a multi-ethnic country with four major populations: Maya, Ladino, Xinca, and Garifuna. To determine the mutation profile of GJB2 in a ARNHL population from Guatemala, we sequenced both exons of GJB2 in 133 unrelated families. A total of six pathogenic variants were detected. The most frequent pathogenic variant is c.131G>A (p.Trp44*) detected in 21 of 266 alleles. We show that c.131G>A is associated with a conserved haplotype in Guatemala suggesting a single founder. The majority of Mayan population lives in the west region of the country from where all c.131G>A carriers originated. Further analysis of genome-wide variation of individuals carrying the c.131G>A mutation compared with those of Native American, European, and African populations shows a close match with the Mayan population. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. [HUGO STEINHAUS--CO-FOUNDER OF THE LWÓW SCHOOL OF MATHEMATICS].

    Science.gov (United States)

    Wócik, Wiesław

    2014-01-01

    The paper is dedicated to the presentation of professor Hugo Steinhaus--co-founder of the Lwów School of Mathematics. It is indicated that had it not been for the scholar, the founding and development of the Lwów School of Mathematics would have been almost impossible. The analyses focus on his undertakings during the Lvov period in the early 1920s and those events that preceded the founding of the school (namely Steinhaus's education at the Göttingen University, various meetings and gatherings, discussions, first fascinations and mathematical dissertations). This paper, however, does not look into the scientific output of Steinhaus, only presents his method of scientific work and highlights the strategy that he chose in order to create the scientific community. An attempt has been also made to justify the effectiveness of the adopted strategy by describing the scientific atmosphere of Lvov and intellectual potential of the students of the school. Steinhaus's activities in the 1930s will be only marginally presented with an impact on particularly interesting cooperation with the alumni of the Lwów School of Mathematics--Marek Kac, Stefan Kaczmarz, Paweł Nikliborec and scholars from other fields of science (as part of the process of the application of mathematics).

  4. Isolation mediates persistent founder effects on zooplankton colonisation in new temporary ponds

    Science.gov (United States)

    Badosa, Anna; Frisch, Dagmar; Green, Andy J.; Rico, Ciro; Gómez, Africa

    2017-03-01

    Understanding the colonisation process in zooplankton is crucial for successful restoration of aquatic ecosystems. Here, we analyzed the clonal and genetic structure of the cyclical parthenogenetic rotifer Brachionus plicatilis by following populations established in new temporary ponds during the first three hydroperiods. Rotifer populations established rapidly after first flooding, although colonisation was ongoing throughout the study. Multilocus genotypes from 7 microsatellite loci suggested that most populations (10 of 14) were founded by few clones. The exception was one of the four populations that persisted throughout the studied hydroperiods, where high genetic diversity in the first hydroperiod suggested colonisation from a historical egg bank, and no increase in allelic diversity was detected with time. In contrast, in another of these four populations, we observed a progressive increase of allelic diversity. This population became less differentiated from the other populations suggesting effective gene flow soon after its foundation. Allelic diversity and richness remained low in the remaining two, more isolated, populations, suggesting little gene flow. Our results highlight the complexity of colonisation dynamics, with evidence for persistent founder effects in some ponds, but not in others, and with early immigration both from external source populations, and from residual, historical diapausing egg banks.

  5. Genome-wide association study of pre-harvest sprouting resistance in Chinese wheat founder parents

    Directory of Open Access Journals (Sweden)

    Yu Lin

    2017-07-01

    Full Text Available Abstract Pre-harvest sprouting (PHS is a major abiotic factor affecting grain weight and quality, and is caused by an early break in seed dormancy. Association mapping (AM is used to detect correlations between phenotypes and genotypes based on linkage disequilibrium (LD in wheat breeding programs. We evaluated seed dormancy in 80 Chinese wheat founder parents in five environments and performed a genome-wide association study using 6,057 markers, including 93 simple sequence repeat (SSR, 1,472 diversity array technology (DArT, and 4,492 single nucleotide polymorphism (SNP markers. The general linear model (GLM and the mixed linear model (MLM were used in this study, and two significant markers (tPt-7980 and wPt-6457 were identified. Both markers were located on Chromosome 1B, with wPt-6457 having been identified in a previously reported chromosomal position. The significantly associated loci contain essential information for cloning genes related to resistance to PHS and can be used in wheat breeding programs.

  6. Founders Energy Ltd. 1998 annual report : fiscally prudent, value driven balanced growth strategy

    International Nuclear Information System (INIS)

    1999-01-01

    Founders Energy Ltd is a growth-oriented junior resource company engaged in the acquisition and development of oil and natural gas properties in Alberta, British Columbia and Saskatchewan. The annual review provides details of the company's operations and relevant financial performance during the 1998 fiscal year. In brief, the company realized significant increases in production and reserves, top quartile findings and development costs. It reported significant increases in leverage to natural gas through exploration success at Pouce Coupe and the acquisition of Opal Energy Inc.. It established new core areas in west-central Alberta, Peace River Arch and west-central Saskatchewan. It achieved a better balanced risk profile through geographical diversification and better balance to exploration and development. It increased undeveloped land area to 160,268 net acres and added 11.5 million barrels of established reserves at a finding cost of $ 6.28 per barrel. Financial highlights include increased gross revenue, increased net income per share, and increased shareholders' equity. tabs., figs

  7. Density of founder cells affects spatial pattern formation and cooperation in Bacillus subtilis biofilms.

    Science.gov (United States)

    van Gestel, Jordi; Weissing, Franz J; Kuipers, Oscar P; Kovács, Akos T

    2014-10-01

    In nature, most bacteria live in surface-attached sedentary communities known as biofilms. Biofilms are often studied with respect to bacterial interactions. Many cells inhabiting biofilms are assumed to express 'cooperative traits', like the secretion of extracellular polysaccharides (EPS). These traits can enhance biofilm-related properties, such as stress resilience or colony expansion, while being costly to the cells that express them. In well-mixed populations cooperation is difficult to achieve, because non-cooperative individuals can reap the benefits of cooperation without having to pay the costs. The physical process of biofilm growth can, however, result in the spatial segregation of cooperative from non-cooperative individuals. This segregation can prevent non-cooperative cells from exploiting cooperative neighbors. Here we examine the interaction between spatial pattern formation and cooperation in Bacillus subtilis biofilms. We show, experimentally and by mathematical modeling, that the density of cells at the onset of biofilm growth affects pattern formation during biofilm growth. At low initial cell densities, co-cultured strains strongly segregate in space, whereas spatial segregation does not occur at high initial cell densities. As a consequence, EPS-producing cells have a competitive advantage over non-cooperative mutants when biofilms are initiated at a low density of founder cells, whereas EPS-deficient cells have an advantage at high cell densities. These results underline the importance of spatial pattern formation for competition among bacterial strains and the evolution of microbial cooperation.

  8. [On the founders of the Institute of Mathematics and Physics, University of Bahia].

    Science.gov (United States)

    Dias, A L

    The reduced number of female students of mathematics at the University of Bahia School of Philosophy (Faculdade de Filosofia, Universidade da Bahia - FF/UBa) is quite surprising. To date, they are concentrated in areas traditionally viewed as feminine whereas men predominate in the mathematical fields. I have examined interview data from a few women who graduated in mathematics and went on to teach at the University of Bahia School of Mathematics (Faculdade de Filosofia - FF) and at the Institute of Mathematics and Physics (Instituto de Matemática e Física - IMF), where they were soon to outnumber men and constitute the majority of the mathematics teaching staff. In this study, I have investigated the course of their careers over time: from their early student days, through their time as teaching assistants and professors, and finally as founders of the Institute of Mathematics and Physics, in 1960. Special reference is made to Martha Maria de Souza Dantas, organizer of the I Brazilian Conference on Mathematics Teaching, an event which has provided the groundwork for what was to become the Institute (IMF); and to Arlete Cerqueira Lima, the mastermind behind its creation.

  9. Founder effect of the RET C611Y mutation in multiple endocrine neoplasia 2A in Denmark

    DEFF Research Database (Denmark)

    Mathiesen, Jes Sloth; Kroustrup, Jens Peter; Vestergaard, Peter

    2017-01-01

    BACKGROUND: Multiple endocrine neoplasia (MEN) 2A and 2B are caused by REarranged during Transfection (RET) germline mutations. In a recent nationwide study we reported of an unusually high prevalence (33%) of families with the C611Y mutation and hypothesized that this might be due to a founder...... effect. We conducted the first nationwide study of haplotypes in MEN2A families aiming to investigate the relatedness and occurrence of de novo mutations among Danish families carrying similar mutations. METHODS: The study included 21 apparently unrelated MEN2A families identified from a nationwide...... Danish RET cohort from 1994 to 2014. Twelve, two, two, three and two families carried the C611Y, C618F, C618Y, C620R and C634R mutation, respectively. Single nucleotide polymorphism chip data and identity by descent analysis were used to assess relatedness. RESULTS: A common founder mutation was found...

  10. Gerald J. Marks, M.D., FACS (1925-), founder of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES).

    Science.gov (United States)

    Yeo, Theresa P; Cowan, Scott W; Yeo, Charles J

    2018-03-01

    This historical vignette describes the professional career of Gerald J. Marks, the founder of the Society of American Gastrointestinal and Endoscopic Surgeons and the International Federation of Societies of Endoscopic Surgeons. Dr. Marks is also the founding Associate Editor of Surgical Endoscopy, which celebrated its 30th anniversary in 2017. Dr. Marks is a renowned colorectal surgeon, an accomplished watercolor artist, and a fascinating personality.

  11. KT seminar on entrepreneurship | "From CERN engineer to company founder: my journey" by Julio Lucas | 26 September

    CERN Multimedia

    2016-01-01

    Europe needs its economy to be boosted by the ideas of its most talented scientists and engineers. One of the best ways in which these ideas may contribute to society is by creating a new business. In this Knowledge Transfer seminar, Julio Lucas, Technical Director and co-founder of Elytt Energy and former CERN engineer gives a personal view on how to make your first steps in entrepreneurship.    

  12. 13 February 2012 - World Economic Forum Founder and Executive Chairman K. Schwab and Chairperson and Co-Founder Schwab Foundation for Social Entrepreneurship H. Schwab (Mrs)in the ATLAS experimental area at LHC Point 1 with Collaboration Former Spokesperson P. Jenni; signing the guest book with CERN Director-General R. Heuer and Head of International Relations F. Pauss.

    CERN Multimedia

    Jean-Claude Gadmer

    2012-01-01

    13 February 2012 - World Economic Forum Founder and Executive Chairman K. Schwab and Chairperson and Co-Founder Schwab Foundation for Social Entrepreneurship H. Schwab (Mrs)in the ATLAS experimental area at LHC Point 1 with Collaboration Former Spokesperson P. Jenni; signing the guest book with CERN Director-General R. Heuer and Head of International Relations F. Pauss.

  13. Identification of full-length transmitted/founder viruses and their progeny in primary HIV-1 infection

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette [Los Alamos National Laboratory; Hraber, Peter [Los Alamos National Laboratory; Giorgi, Elena [Los Alamos National Laboratory; Bhattacharya, T [Los Alamos National Laboratory

    2009-01-01

    Identification of transmitted/founder virus genomes and their progeny by is a novel strategy for probing the molecular basis of HIV-1 transmission and for evaluating the genetic imprint of viral and host factors that act to constrain or facilitate virus replication. Here, we show in a cohort of twelve acutely infected subjects (9 clade B; 3 clade C), that complete genomic sequences of transmitted/founder viruses could be inferred using single genome amplification of plasma viral RNA, direct amplicon sequencing, and a model of random virus evolution. This allowed for the precise identification, chemical synthesis, molecular cloning, and biological analysis of those viruses actually responsible for productive clinical infection and for a comprehensive mapping of sequential viral genomes and proteomes for mutations that are necessary or incidental to the establishment of HIV-1 persistence. Transmitted/founder viruses were CD4 and CCR5 tropic, replicated preferentially in activated primary T-Iymphocytes but not monocyte-derived macrophages, and were effectively shielded from most heterologous or broadly neutralizing antibodies. By 3 months of infection, the evolving viral quasispecies in three subjects showed mutational fixation at only 2-5 discreet genomic loci. By 6-12 months, mutational fixation was evident at 18-27 genomic loci. Some, but not all, of these mutations were attributable to virus escape from cytotoxic Tlymphocytes or neutralizing antibodies, suggesting that other viral or host factors may influence early HIV -1 fitness.

  14. Linkage disequilibrium analysis in young populations: Pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians

    Energy Technology Data Exchange (ETDEWEB)

    Labuda, M.; Glorieux, F.H. [McGill Univ., Montreal (Canada); Labuda, D.; Korab-Laskowska, M. [Universite de Montreal (Canada)] [and others

    1996-09-01

    Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be {approximately}12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbruck model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population. 48 refs., 5 figs., 2 tabs.

  15. Cost effectiveness of population based BRCA1 founder mutation testing in Sephardi Jewish women.

    Science.gov (United States)

    Patel, Shreeya; Legood, Rosa; Evans, D Gareth; Turnbull, Clare; Antoniou, Antonis C; Menon, Usha; Jacobs, Ian; Manchanda, Ranjit

    2018-04-01

    Population-based BRCA1/BRCA2 founder-mutation testing has been demonstrated as cost effective compared with family history based testing in Ashkenazi Jewish women. However, only 1 of the 3 Ashkenazi Jewish BRCA1/BRCA2 founder mutations (185delAG[c.68_69delAG]), 5382insC[c.5266dupC]), and 6174delT[c.5946delT]) is found in the Sephardi Jewish population (185delAG[c.68_69delAG]), and the overall prevalence of BRCA mutations in the Sephardi Jewish population is accordingly lower (0.7% compared with 2.5% in the Ashkenazi Jewish population). Cost-effectiveness analyses of BRCA testing have not previously been performed at these lower BRCA prevalence levels seen in the Sephardi Jewish population. Here we present a cost-effectiveness analysis for UK and US populations comparing population testing with clinical criteria/family history-based testing in Sephardi Jewish women. A Markov model was built comparing the lifetime costs and effects of population-based BRCA1 testing, with testing using family history-based clinical criteria in Sephardi Jewish women aged ≥30 years. BRCA1 carriers identified were offered magnetic resonance imaging/mammograms and risk-reducing surgery. Costs are reported at 2015 prices. Outcomes include breast cancer, ovarian cancer, and excess deaths from heart disease. All costs and outcomes are discounted at 3.5%. The time horizon is lifetime, and perspective is payer. The incremental cost-effectiveness ratio per quality-adjusted life-year was calculated. Parameter uncertainty was evaluated through 1-way and probabilistic sensitivity analysis. Population testing resulted in gain in life expectancy of 12 months (quality-adjusted life-year = 1.00). The baseline discounted incremental cost-effectiveness ratio for UK population-based testing was £67.04/quality-adjusted life-year and for US population was $308.42/quality-adjusted life-year. Results were robust in the 1-way sensitivity analysis. The probabilistic sensitivity analysis showed 100% of

  16. Master John of Arderne (1307-1380): a founder of modern surgery.

    Science.gov (United States)

    Pearn, John

    2012-01-01

    John of Arderne (1307-1380) was one founder of surgery as the profession is known today. He was the first English surgeon of whom biographic details survive. Born on the Arderne Estates at Newark, England, he served as a military surgeon in France in campaigns where gunpowder was used in combat for the first time. His best-known work, the Practica (De Arte Phisicali et de Cirurgia), formed the basis of practical surgical teaching in the medical schools of medieval Europe. Biographic research of primary and secondary archives and documents. John of Arderne's surgical practice was undertaken against a background of turbulent political, military and medical events. He survived the Black Death (1347) and its cyclical recurrences. He lived through the turbulent reigns of Edward II and Edward III and practised in London in the decades preceding the simmering unrest which preceded the Peasant's Revolt of 1381. Surgical and medical practice in the late Middle Ages was enmeshed in astrological beliefs. It was greatly influenced by church doctrine of disease causation. In this paper, the known details of John of Arderne's life are placed in the perspective of these societal and professional influences. He is one of several pre-Renaissance European doctors who were the first to challenge the received medical lore of Galen and later Arabic surgeons. Writing when he was 70 years of age, John of Arderne was the first to advocate that surgeons should trust their own clinical experience 'Wele ymagynyng subtile things' rather than following the directions of others, even including those advocated by himself. © 2011 The Author. ANZ Journal of Surgery © 2011 Royal Australasian College of Surgeons.

  17. Counting the founders: the matrilineal genetic ancestry of the Jewish Diaspora.

    Science.gov (United States)

    Behar, Doron M; Metspalu, Ene; Kivisild, Toomas; Rosset, Saharon; Tzur, Shay; Hadid, Yarin; Yudkovsky, Guennady; Rosengarten, Dror; Pereira, Luisa; Amorim, Antonio; Kutuev, Ildus; Gurwitz, David; Bonne-Tamir, Batsheva; Villems, Richard; Skorecki, Karl

    2008-04-30

    The history of the Jewish Diaspora dates back to the Assyrian and Babylonian conquests in the Levant, followed by complex demographic and migratory trajectories over the ensuing millennia which pose a serious challenge to unraveling population genetic patterns. Here we ask whether phylogenetic analysis, based on highly resolved mitochondrial DNA (mtDNA) phylogenies can discern among maternal ancestries of the Diaspora. Accordingly, 1,142 samples from 14 different non-Ashkenazi Jewish communities were analyzed. A list of complete mtDNA sequences was established for all variants present at high frequency in the communities studied, along with high-resolution genotyping of all samples. Unlike the previously reported pattern observed among Ashkenazi Jews, the numerically major portion of the non-Ashkenazi Jews, currently estimated at 5 million people and comprised of the Moroccan, Iraqi, Iranian and Iberian Exile Jewish communities showed no evidence for a narrow founder effect, which did however characterize the smaller and more remote Belmonte, Indian and the two Caucasus communities. The Indian and Ethiopian Jewish sample sets suggested local female introgression, while mtDNAs in all other communities studied belong to a well-characterized West Eurasian pool of maternal lineages. Absence of sub-Saharan African mtDNA lineages among the North African Jewish communities suggests negligible or low level of admixture with females of the host populations among whom the African haplogroup (Hg) L0-L3 sub-clades variants are common. In contrast, the North African and Iberian Exile Jewish communities show influence of putative Iberian admixture as documented by mtDNA Hg HV0 variants. These findings highlight striking differences in the demographic history of the widespread Jewish Diaspora.

  18. Founder effects and the evolution of asymmetrical sexual isolation in a rapidly-speciating clade

    Directory of Open Access Journals (Sweden)

    Kevin P. OH, Gina L. CONTE, Kerry L. SHAW

    2013-04-01

    Full Text Available Sexual isolation resulting from differences in mate choice behaviors is a hallmark of rapidly-speciating lineages. When present, asymmetrical sexual isolation may provide insights into the mechanisms responsible for the evolutionary change in mate signaling traits. In particular, Kaneshiro’s hypothesis suggests that divergence in sexual characters between populations may arise in allopatry when ‘derived’ founding populations are subject to severe population bottlenecks, accompanied by a relaxation of sexual selection relative to ‘ancestral’ source populations. In the present study, we tested predictions of asymmetrical sexual isolation between two allopatric species of Hawaiian Laupala crickets, representing ‘ancestral’ (L. makaio and ‘derived’ (L. nigra taxa. While crickets in this genus are notable for rapid divergence of male courtship songs, these species share similar song types, thus suggesting that patterns of sexual isolation are likely due to other mating cues. Analysis of behavioral responses in conspecific and heterospecific ‘no-choice’ mating trials revealed pronounced asymmetrical isolation in the direction predicted by Kaneshiro’s hypothesis, wherein we observed a significant reduction in mating success for crosses involving ‘derived’ males paired with ‘ancestral’ females, compared to the reciprocal heterospecific and both conspecific pairings. Further dissection of courtship behaviors suggested this difference did not reflect male mate choice, but rather, marked reduced spermatophore acceptance rates by ‘ancestral’ females paired with ‘derived’ males. The results are discussed with respect to founder effect models of speciation and the potential role of chemosensory signals in mate choice in these species [Current Zoology 59 (2: 230-238, 2013].

  19. Nature of the basement of the East Anatolian plateau: Implications for the lithospheric foundering processes

    Science.gov (United States)

    Topuz, G.; Candan, O.; Zack, T.; Yılmaz, A.

    2017-12-01

    Anatolian plateau have resulted from other processes of lithospheric foundering, rather than just slab steepening and break-off. This research is funded by a research grant (#114Y228) from TÜBİTAK.

  20. [Professor Adam Nowosławski (1925-2012)--founder of the Polish School of Immunopathology].

    Science.gov (United States)

    Madaliński, Kazimierz

    2012-01-01

    Professor dr med. Adam Nowosławski, has died at age of 87, on February 3, 2012, the founder of the Polish school of immunopathology, member of Polish Academy of Sciences and of Polish Academy of Art and Sciences. Professor was born on April 30, 1925 in Rzeszów (SE Poland). During the Second World War he took part in the anti-nazi resistance movement; he was the soldier of the 'Baszta' regiment of the Home Army. Subsequently, he was imprisoned in the Pawiak and concentration camps: Majdanek and Buchenwald. The medical studies he has completed at Warsaw Medical Academy between 1946-1951. The degree of doctor of medicine Prof. Adam Nowosławski has obtained in 1963, habilitation degree in the field of immunopathology--in 1966; the title of Professor he has obtained in 1980. His scientific achievements consist of 170 publications, including 101 original papers. His publications were quoted in several American books for students and physicians. Topics of his early papers concerned the immunopatogenesis ofPneumocystis carinii--induced pneumonia in premature babies, immunopatogenesis of rheumatoid arthritis, and the origin of rheumatoid factor. The enormous role in the field of hepatology played research on the virus of hepatitis B. These studies dealt with the discovery of HB core antigen which had the cellular localization different from HB surface antigen and with the parameters of the immune response to infection. Papers published on this topic were the mostly quoted in the literature and earned him national awards. The activity of Prof. Adam Nowosławski in the field of HIV/AIDS prevention was honored by the special prize of the Minister of Health. Professor was the honorary member of the two Societies: Polish Society of Pathologists and Polish Society of Hepatology. He was also the member of International Association for the Study of the Liver and International Academy of Pathology. Prof. Adam Nowosławski received the national medals: Polonia Restituta Crosses

  1. Identification of novel BRCA founder mutations in Middle Eastern breast cancer patients using capture and Sanger sequencing analysis.

    Science.gov (United States)

    Bu, Rong; Siraj, Abdul K; Al-Obaisi, Khadija A S; Beg, Shaham; Al Hazmi, Mohsen; Ajarim, Dahish; Tulbah, Asma; Al-Dayel, Fouad; Al-Kuraya, Khawla S

    2016-09-01

    Ethnic differences of breast cancer genomics have prompted us to investigate the spectra of BRCA1 and BRCA2 mutations in different populations. The prevalence and effect of BRCA 1 and BRCA 2 mutations in Middle Eastern population is not fully explored. To characterize the prevalence of BRCA mutations in Middle Eastern breast cancer patients, BRCA mutation screening was performed in 818 unselected breast cancer patients using Capture and/or Sanger sequencing. 19 short tandem repeat (STR) markers were used for founder mutation analysis. In our study, nine different types of deleterious mutation were identified in 28 (3.4%) cases, 25 (89.3%) cases in BRCA 1 and 3 (10.7%) cases in BRCA 2. Seven recurrent mutations identified accounted for 92.9% (26/28) of all the mutant cases. Haplotype analysis was performed to confirm c.1140 dupG and c.4136_4137delCT mutations as novel putative founder mutation, accounting for 46.4% (13/28) of all BRCA mutant cases and 1.6% (13/818) of all the breast cancer cases, respectively. Moreover, BRCA 1 mutation was significantly associated with BRCA 1 protein expression loss (p = 0.0005). Our finding revealed that a substantial number of BRCA mutations were identified in clinically high risk breast cancer from Middle East region. Identification of the mutation spectrum, prevalence and founder effect in Middle Eastern population facilitates genetic counseling, risk assessment and development of cost-effective screening strategy. © 2016 UICC.

  2. "Founder crops" v. wild plants: Assessing the plant-based diet of the last hunter-gatherers in southwest Asia

    Science.gov (United States)

    Arranz-Otaegui, Amaia; González Carretero, Lara; Roe, Joe; Richter, Tobias

    2018-04-01

    The Natufian culture (c. 14.6-11.5 ka cal. BP) represents the last hunter-gatherer society that inhabited southwest Asia before the development of plant food production. It has long been suggested that Natufians based their economy on the exploitation of the wild ancestors of the Neolithic "founder crops", and that these hunter-gatherers were therefore on the "threshold to agriculture". In this work we review the available data on Natufian plant exploitation and we report new archaeobotanical evidence from Shubayqa 1, a Natufian site located in northeastern Jordan (14.6-11.5 ka cal. BP). Shubayqa 1 has produced an exceptionally large plant assemblage, including direct evidence for the continuous exploitation of club-rush tubers (often regarded as "missing foods") and other wild plants, which were probably used as food, fuel and building materials. Taking together this data we evaluate the composition of archaeobotanical assemblages (plant macroremains) from the Natufian to the Early Pre-Pottery Neolithic B (EPPNB). Natufian assemblages comprise large proportions of non-founder plant species (>90% on average), amongst which sedges, small-seeded grasses and legumes, and fruits and nuts predominate. During the Pre-Pottery Neolithic, in particular the EPPNB, the presence of "founder crops" increases dramatically and constitute up to c. 42% of the archaeobotanical assemblages on average. Our results suggest that plant exploitation strategies during the Natufian were very different from those attested during subsequent Neolithic periods. We argue that historically driven interpretations of the archaeological record have over-emphasized the role of the wild ancestors of domesticated crops previous to the emergence of agriculture.

  3. The Expression of TALEN before Fertilization Provides a Rapid Knock-Out Phenotype in Xenopus laevis Founder Embryos.

    Science.gov (United States)

    Miyamoto, Kei; Suzuki, Ken-Ichi T; Suzuki, Miyuki; Sakane, Yuto; Sakuma, Tetsushi; Herberg, Sarah; Simeone, Angela; Simpson, David; Jullien, Jerome; Yamamoto, Takashi; Gurdon, J B

    2015-01-01

    Recent advances in genome editing using programmable nucleases have revolutionized gene targeting in various organisms. Successful gene knock-out has been shown in Xenopus, a widely used model organism, although a system enabling less mosaic knock-out in founder embryos (F0) needs to be explored in order to judge phenotypes in the F0 generation. Here, we injected modified highly active transcription activator-like effector nuclease (TALEN) mRNA to oocytes at the germinal vesicle (GV) stage, followed by in vitro maturation and intracytoplasmic sperm injection, to achieve a full knock-out in F0 embryos. Unlike conventional injection methods to fertilized embryos, the injection of TALEN mRNA into GV oocytes allows expression of nucleases before fertilization, enabling them to work from an earlier stage. Using this procedure, most of developed embryos showed full knock-out phenotypes of the pigmentation gene tyrosinase and/or embryonic lethal gene pax6 in the founder generation. In addition, our method permitted a large 1 kb deletion. Thus, we describe nearly complete gene knock-out phenotypes in Xenopus laevis F0 embryos. The presented method will help to accelerate the production of knock-out frogs since we can bypass an extra generation of about 1 year in Xenopus laevis. Meantime, our method provides a unique opportunity to rapidly test the developmental effects of disrupting those genes that do not permit growth to an adult able to reproduce. In addition, the protocol shown here is considerably less invasive than the previously used host transfer since our protocol does not require surgery. The experimental scheme presented is potentially applicable to other organisms such as mammals and fish to resolve common issues of mosaicism in founders.

  4. International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation

    DEFF Research Database (Denmark)

    Peixoto, Ana; Santos, Catarina; Pinheiro, Manuela

    2011-01-01

    The c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement...... individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences...... HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement....

  5. International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation

    DEFF Research Database (Denmark)

    Peixoto, Ana; Santos, Catarina; Pinheiro, Manuela

    2011-01-01

    The c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement...... individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 +/- 215 years ago. We further demonstrate significant quantitative differences...... HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement....

  6. Novel Founder Mutation in FANCA Gene (c.3446_3449dupCCCT) Among Romani Patients from the Balkan Region

    OpenAIRE

    Marija Dimishkovska; Vjosa Mulliqi Kotori; Zoran Gucev; Svetlana Kocheva; Momir Polenakovic; Dijana Plaseska-Karanfilska

    2018-01-01

    Background: Fanconi anemia is a rare autosomal recessive or X-linked disorder characterised by clinical and genetic heterogeneity. Most fanconi anemia patients harbour homozygous or double heterozygous mutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~10%) or FANCD2 (3-6%) genes. We have already reported the FANCA variant c.190–256_283+1680del2040dupC as a founder mutation among Macedonian fanconi anemia patients of Gypsy-like ethnic origin. Here, we present a novel FANCA mutation in t...

  7. Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa

    Science.gov (United States)

    Tipping, A. J.; Pearson, T.; Morgan, N. V.; Gibson, R. A.; Kuyt, L. P.; Havenga, C.; Gluckman, E.; Joenje, H.; de Ravel, T.; Jansen, S.; Mathew, C. G.

    2001-01-01

    Fanconi anemia (FA) is a rare, genetically heterogeneous autosomal recessive disorder associated with progressive aplastic anemia, congenital abnormalities, and cancer. FA has a very high incidence in the Afrikaner population of South Africa, possibly due to a founder effect. Previously we observed allelic association between polymorphic markers flanking the FA group A gene (FANCA) and disease chromosomes in Afrikaners. We genotyped 26 FA families with microsatellite and single nucleotide polymorphic markers and detected five FANCA haplotypes. Mutation scanning of the FANCA gene revealed association of these haplotypes with four different mutations. The most common was an intragenic deletion of exons 12–31, accounting for 60% of FA chromosomes in 46 unrelated Afrikaner FA patients, while two other mutations accounted for an additional 20%. Screening for these mutations in the European populations ancestral to the Afrikaners detected one patient from the Western Ruhr region of Germany who was heterozygous for the major deletion. The mutation was associated with the same unique FANCA haplotype as in Afrikaner patients. Genealogical investigation of 12 Afrikaner families with FA revealed that all were descended from a French Huguenot couple who arrived at the Cape on June 5, 1688, whereas mutation analysis showed that the carriers of the major mutation were descendants of this same couple. The molecular and genealogical evidence is consistent with transmission of the major mutation to Western Germany and the Cape near the end of the 17th century, confirming the existence of a founder effect for FA in South Africa. PMID:11344308

  8. A Founder Large Deletion Mutation in Xeroderma Pigmentosum-Variant Form in Tunisia: Implication for Molecular Diagnosis and Therapy

    Directory of Open Access Journals (Sweden)

    Mariem Ben Rekaya

    2014-01-01

    Full Text Available Xeroderma pigmentosum Variant (XP-V form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of the POLH gene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to the POLH gene with a founder haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a 3926 bp deletion compared to control individuals. Sequence analysis demonstrates that this deletion has occurred between two Alu-Sq2 repetitive sequences in the same orientation, respectively, in introns 9 and 10. We suggest that this mutation POLH NG_009252.1: g.36847_40771del3925 is caused by an equal crossover event that occurred between two homologous chromosomes at meiosis. These results allowed us to develop a simple test based on a simple PCR in order to screen suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be underestimated and clinical diagnosis is usually later. Cascade screening of this founder mutation by PCR in regions with high frequency of XP provides a rapid and cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa.

  9. Novel Founder Mutation in FANCA Gene (c.3446_3449dupCCCT) Among Romani Patients from the Balkan Region.

    Science.gov (United States)

    Dimishkovska, Marija; Kotori, Vjosa Mulliqi; Gucev, Zoran; Kocheva, Svetlana; Polenakovic, Momir; Plaseska-Karanfilska, Dijana

    2018-01-20

    Fanconi anemia is a rare autosomal recessive or X-linked disorder characterised by clinical and genetic heterogeneity. Most fanconi anemia patients harbour homozygous or double heterozygous mutations in the FANCA (60-65%), FANCC (10-15%), FANCG (~10%) or FANCD2 (3-6%) genes. We have already reported the FANCA variant c.190-256_283+1680del2040dupC as a founder mutation among Macedonian fanconi anemia patients of Gypsy-like ethnic origin. Here, we present a novel FANCA mutation in two patients from Macedonia and Kosovo. The novel FANCA mutation c.3446_3449dupCCCT was identified in two fanconi anemia patients with Romany ethnicity; a 2-year-old girl from Macedonia who is a compound heterozygote for a previously reported FANCA c.190-256_283+1680del2040dupC and the novel mutation and a 10-year-old girl from Kosovo who is a homozygote for the novel FANCA c.3446_3449dupCCCT mutation. The novel mutation is located in exon 35 in the FAAP20-binding domain which plays a crucial role in the FANCA -FAAP20 interaction and is required for integrity of the fanconi anemia pathway. The finding of the FANCA c.3446_3449dupCCCT mutation in two unrelated FA patients with Romani ethnicity from Macedonia and Kosovo suggests it is a founder mutation in the Romani population living in the Balkan region.

  10. A founder large deletion mutation in Xeroderma pigmentosum-Variant form in Tunisia: implication for molecular diagnosis and therapy.

    Science.gov (United States)

    Ben Rekaya, Mariem; Laroussi, Nadia; Messaoud, Olfa; Jones, Mariem; Jerbi, Manel; Naouali, Chokri; Bouyacoub, Yosra; Chargui, Mariem; Kefi, Rym; Fazaa, Becima; Boubaker, Mohamed Samir; Boussen, Hamouda; Mokni, Mourad; Abdelhak, Sonia; Zghal, Mohamed; Khaled, Aida; Yacoub-Youssef, Houda

    2014-01-01

    Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of the POLH gene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to the POLH gene with a founder haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a 3926 bp deletion compared to control individuals. Sequence analysis demonstrates that this deletion has occurred between two Alu-Sq2 repetitive sequences in the same orientation, respectively, in introns 9 and 10. We suggest that this mutation POLH NG_009252.1: g.36847_40771del3925 is caused by an equal crossover event that occurred between two homologous chromosomes at meiosis. These results allowed us to develop a simple test based on a simple PCR in order to screen suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be underestimated and clinical diagnosis is usually later. Cascade screening of this founder mutation by PCR in regions with high frequency of XP provides a rapid and cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa.

  11. A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain.

    Science.gov (United States)

    Callén, Elsa; Casado, José A; Tischkowitz, Marc D; Bueren, Juan A; Creus, Amadeu; Marcos, Ricard; Dasí, Angeles; Estella, Jesús M; Muñoz, Arturo; Ortega, Juan J; de Winter, Johan; Joenje, Hans; Schindler, Detlev; Hanenberg, Helmut; Hodgson, Shirley V; Mathew, Christopher G; Surrallés, Jordi

    2005-03-01

    Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure and cancer predisposition. Here we have identified Spanish Gypsies as the ethnic group with the world's highest prevalence of FA (carrier frequency of 1/64-1/70). DNA sequencing of the FANCA gene in 8 unrelated Spanish Gypsy FA families after retroviral subtyping revealed a homozygous FANCA mutation (295C>T) leading to FANCA truncation and FA pathway disruption. This mutation appeared specific for Spanish Gypsies as it is not found in other Gypsy patients with FA from Hungary, Germany, Slovakia, and Ireland. Haplotype analysis showed that Spanish Gypsy patients all share the same haplotype. Our data thus suggest that the high incidence of FA among Spanish Gypsies is due to an ancestral founder mutation in FANCA that originated in Spain less than 600 years ago. The high carrier frequency makes the Spanish Gypsies a population model to study FA heterozygote mutations in cancer.

  12. [Max Isserlin, Kantian orientation at Königsberg, psychotherapist with Kraepelin, founder of child psychiatry at Munich, emigrant to Britain].

    Science.gov (United States)

    Peters, U H

    2002-01-01

    This account of the life and work of Max Isserlin (1879 - 1941) wants to be a reminder of a German-Jewish fate next to Kraepelin and as a forced emigrant. Immediately after his studies at Königsberg Isserlin in 1903 came to Kraepelin at Heidelberg, later he followed him to Munich. All his life he kept a Kantian orientation and defended Kraepelin's positions out of this background. Kraepelin entrusted to him all of psychotherapy, theory and practice, which Isserlin for at least 18 years gave courses of in Kraepelin's department. His textbook of psychotherapy thus transmissions Kraepelins convictions about this topic also. During World War I Isserlin was the head of a field-hospital for brain damaged soldiers and continued working this way after the end of the war. Finally he became the founder of child psychiatry in Munich, until he was forced to leave Germany for Britain with a heavy heart.

  13. Jean-Alfred Fournier - the founder of the European venereology and dermatology (on the one hundredth death anniversary

    Directory of Open Access Journals (Sweden)

    O. A. Kisteneva

    2014-01-01

    Full Text Available The article presents a life story of a great French dermatologist and venereologist, one of the founders of the theory of syphilis Jean-Alfred Fournier (1832-1914. It provides data on the published works by Jean-Alfred Fournier, some of which earned him a doctoral degree. It also provides data on Fournier’s election as a member of the French Academy of Medicine in 1879 as well as on the founding of the French Society of Dermatology and Syphiligraphy by Fournier and other French dermatologists in 1889. The article defines the contribution made by Fournier to the development of venereology and practical medicine in the second half of the 19th century and early 20th century.

  14. Fragile X founder effect and distribution of CGG repeats among the mentally retarded population of Andalusia, South Spain

    Directory of Open Access Journals (Sweden)

    Yolanda de Diego

    2002-01-01

    Full Text Available Fragile X syndrome is the most common inherited form of mental retardation. We investigated the prevalence of the Fragile X syndrome in the population with mental retardation of unknown etiology in Andalusia, South Spain. We analyzed 322 unrelated patients (280 males and 42 females, and found a fragile X syndrome frequency of 6.5%. Among the non-fragile X chromosomes, the 29 CGG repeat was the most common allele. At the linked microsatellite DXS548 locus, we found a new allele which we called "allele 10" (17 CA. Similar to other south European populations, allele 2 (25 CA at the DXS548 locus and the fragile X allele were in linkage disequilibrium supporting the idea of a common founder chromosome predisposing to the CGG expansion.

  15. Novel Founder Mutation in FANCA Gene (c.3446_3449dupCCCT Among Romani Patients from the Balkan Region

    Directory of Open Access Journals (Sweden)

    Marija Dimishkovska

    2018-02-01

    Full Text Available Background: Fanconi anemia is a rare autosomal recessive or X-linked disorder characterised by clinical and genetic heterogeneity. Most fanconi anemia patients harbour homozygous or double heterozygous mutations in the FANCA (60-65%, FANCC (10-15%, FANCG (~10% or FANCD2 (3-6% genes. We have already reported the FANCA variant c.190–256_283+1680del2040dupC as a founder mutation among Macedonian fanconi anemia patients of Gypsy-like ethnic origin. Here, we present a novel FANCA mutation in two patients from Macedonia and Kosovo. Case Report: The novel FANCA mutation c.3446_3449dupCCCT was identified in two fanconi anemia patients with Romany ethnicity; a 2-year-old girl from Macedonia who is a compound heterozygote for a previously reported FANCA c.190-256_283+1680del2040dupC and the novel mutation and a 10-year-old girl from Kosovo who is a homozygote for the novel FANCA c.3446_3449dupCCCT mutation. The novel mutation is located in exon 35 in the FAAP20-binding domain which plays a crucial role in the FANCA-FAAP20 interaction and is required for integrity of the fanconi anemia pathway. Conclusion: The finding of the FANCA c.3446_3449dupCCCT mutation in two unrelated FA patients with Romani ethnicity from Macedonia and Kosovo suggests it is a founder mutation in the Romani population living in the Balkan region

  16. The CHEK2 del5395 is a founder mutation without direct effects for cancer risk in the latvian population

    Directory of Open Access Journals (Sweden)

    Plonis J

    2015-12-01

    Full Text Available Our objective was to determine: 1 whether the checkpoint kinase 2 (CHEK2 del5395 (g.27417113-27422508 del, NC_000022.11 is a founder mutation in the Latvian population, 2 if there is an association between CHEK2 del5395 mutation and cancer risk, and 3 and whether the CHEK2 del5395 mutation impacts cancer predisposition in Chernobyl disaster liquidators (the civil and military personnel who were called upon to deal with consequences of the 1986 nuclear disaster as well as geriatric populations. We recruited 438 breast cancer patients, 568 colorectal cancer patients, 399 ovarian cancer patients, 419 prostate cancer patients, 526 healthy blood donors, 480 Chernobyl disaster liquidators and 444 geriatric cancer-free participants. DNA samples were isolated from blood samples and subjected to multiplex polymerase chain reaction (PCR. The truncation of del5395 was estimated by fragment size of the multiplex PCR.All groups were compared to the healthy blood donors using Fisher’s exact test. All p values were two-sided and the odds ratios (OR calculated by two-by-two table. In cancer groups, the del5395 mutation was most frequently observed in the ovarian cancer group (1.00%, OR = 1.32. In control groups, the del5395 mutation was most frequent (0.76% in the healthy donors, which exceeded its frequency in the Chernobyl liquidators group and the geriatric group by 0.01 and 0.08%, respectively. For all groups, the OR appeared to be >1 only in ovarian cancer patients. However, OR rates showed no statistical significance in either cancer or control groups, with the p value fluctuating within the range of 0.39-1.00. The CHEK2 gene del5395 is a founder mutation in the Latvian population, which, however, does not have a direct impact on genetic predisposition toward colorectal, breast, ovarian and prostate cancer.

  17. HealthSouth's most wanted. Founder and former chairman and CEO Richard Scrushy is indicted for 85 counts of conspiracy, fraud and money laundering.

    Science.gov (United States)

    Piotrowski, Julie

    2003-11-10

    Wake-up call for the industry or an isolated case of corporate chicanery? Healthcare experts are divided on the import of Richard Scrushy's indictment on 85 counts last week in connection with the financial scandal at HealthSouth Corp. The indictment alleges the company founder relied on electronic and telephone surveillance, threats and intimidation to control his accomplices.

  18. Nonsyndromic retinitis pigmentosa is highly prevalent in the Jerusalem region with a high frequency of founder mutations.

    Science.gov (United States)

    Sharon, Dror; Banin, Eyal

    2015-01-01

    Nonsyndromic retinitis pigmentosa (RP) is the most common inherited retinal degeneration, and prevalence of the disease has been reported in populations of American and European origin with a relatively low consanguinity rate. Our aim was to determine the prevalence of nonsyndromic RP in the Jerusalem region, which has a population of about 1 million individuals with a high rate of consanguinity. The patients' clinical data included eye exam findings (visual acuity, anterior segment, and funduscopy) as well as electroretinographic (ERG) testing results under scotopic and photopic conditions. Mutation analysis on a subgroup of patients was performed mainly with candidate gene analysis and homozygosity mapping. We evaluated the medical records of patients with degenerative retinal diseases residing in the Jerusalem region who were examined over the past 20 years in a large tertiary medical center. A total of 453 individuals affected with nonsyndromic RP were diagnosed at our center, according to funduscopic findings and ERG testing. Based on the estimated population size of 945,000 individuals who reside in the vicinity of Jerusalem, the prevalence of nonsyndromic RP in this region is 1:2,086. The prevalence of RP was higher among Arab Muslims (1:1,798) compared to Jews (1:2,230), mainly due to consanguineous marriages that are more common in the Arab Muslim population. To identify the genetic causes of RP in our cohort, we recruited 383 patients from 183 different families for genetic analysis: 70 with autosomal recessive (AR) inheritance, 15 with autosomal dominant, 86 isolate cases, and 12 with an X-linked inheritance pattern. In 64 (35%) of the families, we identified the genetic cause of the disease, and we revised the inheritance pattern of 20 isolate cases to the AR pattern; 49% of the families in our cohort had AR inheritance. Interestingly, in 42 (66%) of the genetically identified families, the cause of disease was a founder mutation. Previous studies

  19. Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2

    Science.gov (United States)

    Haraldsdottir, Sigurdis; Rafnar, Thorunn; Frankel, Wendy L.; Einarsdottir, Sylvia; Sigurdsson, Asgeir; Hampel, Heather; Snaebjornsson, Petur; Masson, Gisli; Weng, Daniel; Arngrimsson, Reynir; Kehr, Birte; Yilmaz, Ahmet; Haraldsson, Stefan; Sulem, Patrick; Stefansson, Tryggvi; Shields, Peter G.; Sigurdsson, Fridbjorn; Bekaii-Saab, Tanios; Moller, Pall H.; Steinarsdottir, Margret; Alexiusdottir, Kristin; Hitchins, Megan; Pritchard, Colin C.; de la Chapelle, Albert; Jonasson, Jon G.; Goldberg, Richard M.; Stefansson, Kari

    2017-01-01

    Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000–2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations. PMID:28466842

  20. Comprehensive population-wide analysis of Lynch syndrome in Iceland reveals founder mutations in MSH6 and PMS2.

    Science.gov (United States)

    Haraldsdottir, Sigurdis; Rafnar, Thorunn; Frankel, Wendy L; Einarsdottir, Sylvia; Sigurdsson, Asgeir; Hampel, Heather; Snaebjornsson, Petur; Masson, Gisli; Weng, Daniel; Arngrimsson, Reynir; Kehr, Birte; Yilmaz, Ahmet; Haraldsson, Stefan; Sulem, Patrick; Stefansson, Tryggvi; Shields, Peter G; Sigurdsson, Fridbjorn; Bekaii-Saab, Tanios; Moller, Pall H; Steinarsdottir, Margret; Alexiusdottir, Kristin; Hitchins, Megan; Pritchard, Colin C; de la Chapelle, Albert; Jonasson, Jon G; Goldberg, Richard M; Stefansson, Kari

    2017-05-03

    Lynch syndrome, caused by germline mutations in the mismatch repair genes, is associated with increased cancer risk. Here using a large whole-genome sequencing data bank, cancer registry and colorectal tumour bank we determine the prevalence of Lynch syndrome, associated cancer risks and pathogenicity of several variants in the Icelandic population. We use colorectal cancer samples from 1,182 patients diagnosed between 2000-2009. One-hundred and thirty-two (11.2%) tumours are mismatch repair deficient per immunohistochemistry. Twenty-one (1.8%) have Lynch syndrome while 106 (9.0%) have somatic hypermethylation or mutations in the mismatch repair genes. The population prevalence of Lynch syndrome is 0.442%. We discover a translocation disrupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ovarian cancer risk. We find thirteen mismatch repair variants of uncertain significance that are not associated with cancer risk. We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.

  1. The end of capitalism and its future: Hegel as founder of the concept of a welfare state

    Directory of Open Access Journals (Sweden)

    Vieweg Klaus

    2017-01-01

    Full Text Available A key part of Hegel’s practical philosophy is his theory of civil society and the idea of a rational regulation of the market. This is the foundation of Hegel’s theory of a social state. The copyright on the notion of a modern society of freedom and a rational, social state belongs to Hegel. Hegel proves himself to be the thinker who until now has provided the most convincing foundation for freedom in modernity. The theoretical foundation and at the same time bone of contention of Hegel’s political thought is to be found in his concept of ethical life (Sittlichkeit, in particular in his theory of civil society. The current shipwreck of deregulated capitalism does not mean the foundering of our journey towards a free society. Nevertheless the deficiencies and unsustainability of both traditional models - socialist collective ownership and market fundamentalism - exhibit two contradictory claims to a share of the wealth of nations. To take up Hegel’s project is, in essence, to aim at a new conception of an environmentally and socially sustainable and just society, and a corresponding world order. It is to further Hegel’s philosophy of freedom.

  2. Who were the male founders of rural Brazilian Afro-derived communities? A proposal based on three populations.

    Science.gov (United States)

    Ribeiro, Guilherme Galvarros Bueno Lobo; Abe-Sandes, Kiyoko; Barcelos, Rejane da Silva Sena; Klautau-Guimarães, Maria de Nazaré; Junior, Wilson Araujo da Silva; Oliveira, Silviene Fabiana de

    2011-03-01

    Brazilian Quilombos are Afro-derived communities founded mainly by fugitive slaves between the 16(th) and 19(th) centuries; they can be recognized today by ancestral and cultural characteristics. Each of these remnant communities, however, has its own particular history, which includes the migration of non-African derived people. The present work presents a proposal for the origin of the male founder in Brazilian quilombos based on Y-haplogroup distribution. Y haplogroups, based on 16 binary markers (92R7, SRY2627, SRY4064, SRY10831.1 and .2, M2, M3, M09, M34, M60, M89, M213, M216, P2, P3 and YAP), were analysed for 98 DNA samples from genetically unrelated men from three rural Brazilian Afro-derived communities-Mocambo, Rio das Rãs and Kalunga-in order to estimate male geographic origin. Data indicated significant differences among these communities. A high frequency of non-African haplogroups was observed in all communities. This observation suggested an admixture process that has occurred over generations and directional mating between European males and African female slaves that must have occurred on farms before the slaves escaped. This means that the admixture occurred before the slaves escaped and the foundation of the quilombo.

  3. Alfred Russel Wallace (1823-1913): the forgotten co-founder of the Neo-Darwinian theory of biological evolution.

    Science.gov (United States)

    Kutschera, Ulrich; Hossfeld, Uwe

    2013-12-01

    The British naturalist Alfred Russel Wallace (1823-1913), who had to leave school aged 14 and never attended university, did extensive fieldwork, first in the Amazon River basin (1848-1852) and then in Southeast Asia (1854-1862). Based on this experience, and after reading the corresponding scientific literature, Wallace postulated that species were not created, but are modified descendants of pre-existing varieties (Sarawak Law paper, 1855). Evolution is brought about by a struggle for existence via natural selection, which results in the adaptation of those individuals in variable populations who survive and reproduce (Ternate essay, 1858). In his monograph Darwinism (1889), and in subsequent publications, Wallace extended the contents of Darwin's Origin of Species (1859) into the Neo-Darwinian theory of biological evolution, with reference to the work of August Weismann (1834-1914). Wallace also became the (co)-founder of biogeography, biodiversity research, astrobiology and evolutionary anthropology. Moreover, he envisioned what was later called the anthropocene (i.e., the age of human environmental destructiveness). However, since Wallace believed in atheistic spiritualism and mixed up scientific facts and supernatural speculations in some of his writings, he remains a controversial figure in the history of biology.

  4. High throughput generation and characterization of replication-competent clade C transmitter-founder simian human immunodeficiency viruses.

    Directory of Open Access Journals (Sweden)

    Debashis Dutta

    Full Text Available Traditional restriction endonuclease-based cloning has been routinely used to generate replication-competent simian-human immunodeficiency viruses (SHIV and simian tropic HIV (stHIV. This approach requires the existence of suitable restriction sites or the introduction of nucleotide changes to create them. Here, using an In-Fusion cloning technique that involves homologous recombination, we generated SHIVs and stHIVs based on epidemiologically linked clade C transmitted/founder HIV molecular clones from Zambia. Replacing vif from these HIV molecular clones with vif of SIVmac239 resulted in chimeric genomes used to generate infectious stHIV viruses. Likewise, exchanging HIV env genes and introducing N375 mutations to enhance macaque CD4 binding site and cloned into a SHIVAD8-EO backbone. The generated SHIVs and stHIV were infectious in TZMbl and ZB5 cells, as well as macaque PBMCs. Therefore, this method can replace traditional methods and be a valuable tool for the rapid generation and testing of molecular clones of stHIV and SHIV based on primary clinical isolates will be valuable to generate rapid novel challenge viruses for HIV vaccine/cure studies.

  5. Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China.

    Science.gov (United States)

    Li, Fan; Ma, Liying; Feng, Yi; Hu, Jing; Ni, Na; Ruan, Yuhua; Shao, Yiming

    2017-06-01

    HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines.

  6. Mutation screening of the HGD gene identifies a novel alkaptonuria mutation with significant founder effect and high prevalence.

    Science.gov (United States)

    Sakthivel, Srinivasan; Zatkova, Andrea; Nemethova, Martina; Surovy, Milan; Kadasi, Ludevit; Saravanan, Madurai P

    2014-05-01

    Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2-dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16 positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU-causing mutation was not identified in these patients. This result indicates that the founder effect and high degree of consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2. The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin. © 2014 John Wiley & Sons Ltd/University College London.

  7. A homozygous founder missense variant in arylsulfatase G abolishes its enzymatic activity causing atypical Usher syndrome in humans.

    Science.gov (United States)

    Khateb, Samer; Kowalewski, Björn; Bedoni, Nicola; Damme, Markus; Pollack, Netta; Saada, Ann; Obolensky, Alexey; Ben-Yosef, Tamar; Gross, Menachem; Dierks, Thomas; Banin, Eyal; Rivolta, Carlo; Sharon, Dror

    2018-01-04

    PurposeWe aimed to identify the cause of disease in patients suffering from a distinctive, atypical form of Usher syndrome.MethodsWhole-exome and genome sequencing were performed in five patients from three families of Yemenite Jewish origin, suffering from distinctive retinal degeneration phenotype and sensorineural hearing loss. Functional analysis of the wild-type and mutant proteins was performed in human fibrosarcoma cells.ResultsWe identified a homozygous founder missense variant, c.133G>T (p.D45Y) in arylsulfatase G (ARSG). All patients shared a distinctive retinal phenotype with ring-shaped atrophy along the arcades engirdling the fovea, resulting in ring scotoma. In addition, patients developed moderate to severe sensorineural hearing loss. Both vision and hearing loss appeared around the age of 40 years. The identified variant affected a fully conserved amino acid that is part of the catalytic site of the enzyme. Functional analysis of the wild-type and mutant proteins showed no basal activity of p.D45Y.ConclusionHomozygosity for ARSG-p.D45Y in humans leads to protein dysfunction, causing an atypical combination of late-onset Usher syndrome. Although there is no evidence for generalized clinical manifestations of lysosomal storage diseases in this set of patients, we cannot rule out the possibility that mild and late-onset symptoms may appear.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.227.

  8. Founder haplotype analysis of Fanconi anemia in the Korean population finds common ancestral haplotypes for a FANCG variant.

    Science.gov (United States)

    Park, Joonhong; Kim, Myungshin; Jang, Woori; Chae, Hyojin; Kim, Yonggoo; Chung, Nack-Gyun; Lee, Jae-Wook; Cho, Bin; Jeong, Dae-Chul; Park, In Yang; Park, Mi Sun

    2015-05-01

    A common ancestral haplotype is strongly suggested in the Korean and Japanese patients with Fanconi anemia (FA), because common mutations have been frequently found: c.2546delC and c.3720_3724delAAACA of FANCA; c.307+1G>C, c.1066C>T, and c.1589_1591delATA of FANCG. Our aim in this study was to investigate the origin of these common mutations of FANCA and FANCG. We genotyped 13 FA patients consisting of five FA-A patients and eight FA-G patients from the Korean FA population. Microsatellite markers used for haplotype analysis included four CA repeat markers which are closely linked with FANCA and eight CA repeat markers which are contiguous with FANCG. As a result, Korean FA-A patients carrying c.2546delC or c.3720_3724delAAACA did not share the same haplotypes. However, three unique haplotypes carrying c.307+1G>C, c.1066C > T, or c.1589_1591delATA, that consisted of eight polymorphic loci covering a flanking region were strongly associated with Korean FA-G, consistent with founder haplotypes reported previously in the Japanese FA-G population. Our finding confirmed the common ancestral haplotypes on the origins of the East Asian FA-G patients, which will improve our understanding of the molecular population genetics of FA-G. To the best of our knowledge, this is the first report on the association between disease-linked mutations and common ancestral haplotypes in the Korean FA population. © 2015 John Wiley & Sons Ltd/University College London.

  9. Recurrent missense mutations in TMEM43 (ARVD5) due to founder effects cause arrhythmogenic cardiomyopathies in the UK and Canada

    KAUST Repository

    Haywood, Annika

    2012-11-15

    AimsAutosomal dominant arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) (in the group of arrhythmogenic cardiomyopathies) is a common cause of sudden cardiac death in young adults. It is both clinically and genetically heterogeneous, with 12 loci (ARVC/D1-12) and eight genes identified, the majority of which encode structural proteins of cardiac desmosomes. The most recent gene identified, TMEM43, causes disease due to a missense mutation in a non-desmosomal gene (p.S358L) in 15 extended families from Newfoundland, Canada. To determine whether mutations in TMEM43 cause ARVC/D and arrhythmogenic cardiomyopathy in other populations, we fully re-sequenced TMEM43 on 143 ARVC/D probands (families) from the UK and 55 probands (from 55 families) from Newfoundland.Methods and resultsBidirectional sequencing of TMEM43 including intron-exon boundaries revealed 33 variants, the majority located in non-coding regions of TMEM43. For the purpose of validation, families of probands with rare, potentially deleterious coding variants were subjected to clinical and molecular follow-up. Three missense variants of uncertain significance (p.R28W, p.E142K, p.R312W) were located in highly conserved regions of the TMEM43 protein. One variant (p.R312W) also co-segregated with relatives showing clinical signs of disease. Genotyping and expansion of the disease-associated haplotype in subjects with the p.R312W variant from Newfoundland, Canada, and the UK suggest common ancestry.ConclusionAlthough the p.R312W variant was found in controls (3/378), identification of an ancestral disease p R312W haplotype suggests that the p.R312W variant is a pathogenic founder mutation. © 2012 The Author.

  10. Recurrent missense mutations in TMEM43 (ARVD5) due to founder effects cause arrhythmogenic cardiomyopathies in the UK and Canada

    KAUST Repository

    Haywood, Annika; Merner, Nancy D.; Hodgkinson, Kathy A.; Houston, Jim; Syrris, Petros; Booth, Valerie; Connors, Sean; Pantazis, Antonios; Quarta, Giovanni; Elliott, Perry; McKenna, William; Young, Terry Lynn

    2012-01-01

    AimsAutosomal dominant arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) (in the group of arrhythmogenic cardiomyopathies) is a common cause of sudden cardiac death in young adults. It is both clinically and genetically heterogeneous, with 12 loci (ARVC/D1-12) and eight genes identified, the majority of which encode structural proteins of cardiac desmosomes. The most recent gene identified, TMEM43, causes disease due to a missense mutation in a non-desmosomal gene (p.S358L) in 15 extended families from Newfoundland, Canada. To determine whether mutations in TMEM43 cause ARVC/D and arrhythmogenic cardiomyopathy in other populations, we fully re-sequenced TMEM43 on 143 ARVC/D probands (families) from the UK and 55 probands (from 55 families) from Newfoundland.Methods and resultsBidirectional sequencing of TMEM43 including intron-exon boundaries revealed 33 variants, the majority located in non-coding regions of TMEM43. For the purpose of validation, families of probands with rare, potentially deleterious coding variants were subjected to clinical and molecular follow-up. Three missense variants of uncertain significance (p.R28W, p.E142K, p.R312W) were located in highly conserved regions of the TMEM43 protein. One variant (p.R312W) also co-segregated with relatives showing clinical signs of disease. Genotyping and expansion of the disease-associated haplotype in subjects with the p.R312W variant from Newfoundland, Canada, and the UK suggest common ancestry.ConclusionAlthough the p.R312W variant was found in controls (3/378), identification of an ancestral disease p R312W haplotype suggests that the p.R312W variant is a pathogenic founder mutation. © 2012 The Author.

  11. Founder representation and effective population size in old versus young breeds-genetic diversity of Finnish and Nordic Spitz.

    Science.gov (United States)

    Kumpulainen, M; Anderson, H; Svevar, T; Kangasvuo, I; Donner, J; Pohjoismäki, J

    2017-10-01

    Finnish Spitz is 130-year-old breed and has been highly popular in Finland throughout its history. Nordic Spitz is very similar to Finnish Spitz by origin and use, but is a relatively recent breed with much smaller population size. To see how breed age and breeding history have influenced the current population, we performed comprehensive population genetic analysis using pedigree data of 28,119 Finnish and 9,009 Nordic Spitzes combined with genomewide single nucleotide polymorphism (SNP) data from 135 Finnish and 110 Nordic Spitzes. We found that the Finnish Spitz has undergone repeated male bottlenecks resulting in dramatic loss of genetic diversity, reflected by 20 effective founders (f a ) and mean heterozygosity (Hz) of 0.313. The realized effective population size in the breed based on pedigree analysis (N¯ec) is 168, whereas the genetic effective population size (N eg ) computed the decay of linkage disequilibrium (r 2 ) is only 57 individuals. Nordic Spitz, although once been near extinction, has not been exposed to similar repeated bottlenecks than Finnish Spitz and had f a of 27 individuals. However, due to the smaller total population size, the breed has also smaller effective population size than Finnish Spitz (N¯ec = 98 and N eg  = 49). Interestingly, the r 2 data show that the effective population size has contracted dramatically since the establishment of the breed, emphasizing the role of breed standards as constrains for the breeding population. Despite the small population size, Nordic Spitz still maintains SNP heterozygosity levels similar to mixed breed dogs (mean Hz = 0.409). Our study demonstrates that although pedigree analyses cannot provide estimates of the present diversity within a breed, the effective population sizes inferred from them correlate with the genotyping results. The genetic relationships of the northern Spitz breeds and the benefits of the open breed registry are discussed. © 2017 Blackwell Verlag GmbH.

  12. Founders Online Metadata

    Data.gov (United States)

    National Archives and Records Administration — CORRESPONDENCE AND OTHER WRITINGS OF SIX MAJOR SHAPERS OF THE UNITED STATES: George Washington, Benjamin Franklin, John Adams (and family), Thomas Jefferson,...

  13. Transmitted/Founder Viruses Rapidly Escape from CD8+ T Cell Responses in Acute Hepatitis C Virus Infection.

    Science.gov (United States)

    Bull, Rowena A; Leung, Preston; Gaudieri, Silvana; Deshpande, Pooja; Cameron, Barbara; Walker, Melanie; Chopra, Abha; Lloyd, Andrew R; Luciani, Fabio

    2015-05-01

    The interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8(+) T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n = 1) or replacement with viral variants leading to establishment of chronic infection (n = 2). CD8(+) T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infection. Higher-magnitude CD8(+) T cell responses were associated with rapid development of immune escape variants at a rate of up to 0.1 per day. Rapid escape from CD8(+) T cell responses has been quantified for the first time in the early phase of primary HCV infection. These rapid escape dynamics were associated with higher-magnitude CD8(+) T cell responses. These findings raise questions regarding optimal selection of immunogens for HCV vaccine development and suggest that detailed analysis of individual epitopes may be required. A major limitation in our detailed understanding of the role of immune response in HCV clearance has been the lack of data on very early primary infection when the transmitted viral variants successfully establish

  14. A Middle Eastern Founder Mutation Expands the Genotypic and Phenotypic Spectrum of Mitochondrial MICU1 Deficiency: A Report of 13 Patients.

    Science.gov (United States)

    Musa, Sara; Eyaid, Wafaa; Kamer, Kimberli; Ali, Rehab; Al-Mureikhi, Mariam; Shahbeck, Noora; Al Mesaifri, Fatma; Makhseed, Nawal; Mohamed, Zakkiriah; AlShehhi, Wafaa Ali; Mootha, Vamsi K; Juusola, Jane; Ben-Omran, Tawfeg

    2018-05-03

    MICU1 encodes a Ca 2+ sensing, regulatory subunit of the mitochondrial uniporter, a selective calcium channel within the organelle's inner membrane. Ca 2+ entry into mitochondria helps to buffer cytosolic Ca 2+ transients and also activates ATP production within the organelle. Mutations in MICU1 have previously been reported in 17 children from nine families with muscle weakness, fatigue, normal lactate, and persistently elevated creatine kinase, as well as variable features that include progressive extrapyramidal signs, learning disabilities, nystagmus, and cataracts. In this study, we report the clinical features of an additional 13 patients from consanguineous Middle Eastern families with recessive mutations in MICU1. Of these patients, 12/13 are homozygous for a novel founder mutation c.553C>T (p.Q185*) that is predicted to lead to a complete loss of function of MICU1, while one patient is compound heterozygous for this mutation and an intragenic duplication of exons 9 and 10. The founder mutation occurs with a minor allele frequency of 1:60,000 in the ExAC database, but in ~1:500 individual in the Middle East. All 13 of these patients presented with developmental delay, learning disability, muscle weakness and easy fatigability, and failure to thrive, as well as additional variable features we tabulate. Consistent with previous cases, all of these patients had persistently elevated serum creatine kinase with normal lactate levels, but they also exhibited elevated transaminase enzymes. Our work helps to better define the clinical sequelae of MICU1 deficiency. Furthermore, our work suggests that targeted analysis of the MICU1 founder mutation in Middle Eastern patients may be warranted.

  15. George de Hevesy (1885-1966). Discoverer of hafnium, founder of radioanalytical chemistry and X-ray fluorescence analysis and father of nuclear medicine

    International Nuclear Information System (INIS)

    Niese, Siegfried

    2017-01-01

    George de Hevesy known as discoverer of hafnium, founder of radioanalytical chemistry and X-ray fluorescence analysis and father of nuclear medicine has done important research work in inorganic, physical and radioanalytical and physiological chemistry as well as in geochemistry, radiation biology and medicine. When he must flee for political reasons from a country he must change his colleagues, his equipments, and the topic of his work. It is extremely surprising that he could receive important results under such circumstances even at an advanced age. (author)

  16. The science and art of learning about cultures: Descriptions, explanations, and reflections In conversation with Sri Sri Ravi Shankar, Founder, Art of Living

    Directory of Open Access Journals (Sweden)

    Ritu Tripathi

    2014-06-01

    Full Text Available National cultural differences pose major obstacles to global business expansion. Managers, therefore, seek to learn more about cultures. Conventional managerial learning mostly draws from descriptive scientific models which have potential drawbacks such as unidimensionality, decontextualisation, and culture-level information. Explanatory models of cultural psychology can help overcome these limitations. Further, insights from a cross-culturally fluent authority provide reflective learnings. Toward this end, I engage in a conversation with Sri Sri Ravi Shankar, the founder of the Art of Living organization, on issues related to cultural identity in the global workplace in the Indian context.

  17. The initial antibody response to HIV-1: induction of ineffective early B cell responses against GP41 by the transmitted/founder virus

    Energy Technology Data Exchange (ETDEWEB)

    Chavez, Leslie L [Los Alamos National Laboratory; Perelson, Alan [Los Alamos National Laboratory

    2008-01-01

    A window of opportunity for immune responses to extinguish HIV -1 exists from the moment of transmission through establishment of the latent pool of HIV -I-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus) but, to date, this period has been logistically difficult to analyze. Studies in non-human primates challenged with chimeric simianhuman immunodeficiency virus have shown that neutralizing antibodies, when present at the time of infection, can prevent virus infection.

  18. Is the c.3G>C mutation in the succinate dehydrogenase subunit D (SDHD) gene due to a founder effect in Chinese head and neck paraganglioma patients?

    Science.gov (United States)

    Zha, Yang; Chen, Xing-ming; Lam, Ching-wan; Lee, Soo-chin; Tong, Sui-fan; Gao, Zhi-qiang

    2011-08-01

    Three Chinese patients with head and neck paragangliomas have been reported to carry the c.3G>C mutation in the succinate dehydrogenase subunit D (SDHD) gene. In addition, in our hospital, two further patients were identified who have the same mutation. It is unclear whether the c.3G>C mutation in Chinese patients is a recurrent mutation or if it is due to a founder effect. We conducted haplotype analysis on these patients to answer this question. Individual case-control study. Germ-line mutations were confirmed in the patients and their families examined in this study using direct sequencing. We also constructed and analyzed haplotypes in four Chinese families. Genotype frequencies were compared to the control group. Three of four families shared the same haplotype, which rarely occurred in the control group. The last family shared a very short area on the physical map with the other three families. There is a founder effect in Chinese head and neck paraganglioma patients carrying the SDHD c.3G>C mutation. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  19. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression

    DEFF Research Database (Denmark)

    Eiberg, Hans; Troelsen, Jesper; Boyd, Mette

    2008-01-01

    The human eye color is a quantitative trait displaying multifactorial inheritance. Several studies have shown that the OCA2 locus is the major contributor to the human eye color variation. By linkage analysis of a large Danish family, we finemapped the blue eye color locus to a 166 Kbp region...... within the HERC2 gene. By association analyses, we identified two SNPs within this region that were perfectly associated with the blue and brown eye colors: rs12913832 and rs1129038. Of these, rs12913832 is located 21.152 bp upstream from the OCA2 promoter in a highly conserved sequence in intron 86...... founder mutation in an OCA2 inhibiting regulatory element as the cause of blue eye color in humans. In addition, an LOD score of Z = 4.21 between hair color and D14S72 was obtained in the large family, indicating that RABGGTA is a candidate gene for hair color....

  20. An USH2A founder mutation is the major cause of Usher syndrome type 2 in Canadians of French origin and confirms common roots of Quebecois and Acadians

    Science.gov (United States)

    Ebermann, Inga; Koenekoop, Robert K; Lopez, Irma; Bou-Khzam, Lara; Pigeon, Renée; Bolz, Hanno J

    2009-01-01

    Congenital hearing loss affects approximately one child in 1000. About 10% of the deaf population have Usher syndrome (USH). In USH, hearing loss is complicated by retinal degeneration with onset in the first (USH1) or second (USH2) decade. In most populations, diagnostic testing is hampered by a multitude of mutations in nine genes. We have recently shown that in French Canadians from Quebec, USH1 largely results from a single USH1C founder mutation, c.216G>A (‘Acadian allele'). The genetic basis of USH2 in Canadians of French descent, however, has remained elusive. Here, we have investigated nine USH2 families from Quebec and New Brunswick (the former Acadia) by haplotype analyses of the USH2A locus and sequencing of the three known USH2 genes. Seven USH2A mutations were identified in eight patients. One of them, c.4338_4339delCT, accounts for 10 out of 18 disease alleles (55.6%). This mutation has previously been reported in an Acadian USH2 family, and it was found in homozygous state in the three Acadians of our sample. As in the case of c.216G>A (USH1C), a common haplotype is associated with c.4338_4339delCT. With a limited number of molecular tests, it will now be possible in these populations to estimate whether children with congenital hearing impairment of different degrees will develop retinal disease – with important clinical and therapeutic implications. USH2 is the second example that reveals a significant genetic overlap between Quebecois and Acadians: in contrast to current understanding, other genetic disorders present in both populations are likely based on common founder mutations as well. PMID:18665195

  1. Posterior microphthalmia and nanophthalmia in Tunisia caused by a founder c.1059_1066insC mutation of the PRSS56 gene.

    Science.gov (United States)

    Said, Mariem Ben; Chouchène, Ebtissem; Salem, Salma Ben; Daoud, Kods; Largueche, Leila; Bouassida, Walid; Benzina, Zeineb; Ayadi, Hammadi; Söderkvist, Peter; Matri, Leila; Hmani-Aifa, Mounira

    2013-10-10

    Congenital microphthalmia (CMIC) is a common developmental ocular disorder characterized by a small, and sometimes malformed, eye. Posterior microphthalmia (PM) and nanophthalmia are two rare subtypes of isolated CMIC characterized by extreme hyperopia due to short axial length and elevated lens/eye volume ratio. While nanophthalmia is associated with a reduced size in both anterior and posterior segments, PM involves a normal-size anterior chamber but a small posterior segment. Several genes encoding transcription and non-transcription regulators have been identified in different forms of CMIC. MFRP gene mutations have, for instance, been associated with nanophthalmia, and mutations in the recently identified PRSS56 gene have been linked to PM. So far, these two forms of CMIC have been associated with 9 mutations in PRSS56. Of particular interest, a c.1059_1066insC mutation has recently been reported in four Tunisian families with isolated PM and one Tunisian family with nanophthalmia. Here, we performed a genome-wide scan using a high density single nucleotide polymorphism (SNP) array 50 K in a large consanguineous Tunisian family (PM7) affected with PM and identified the same causative disease mutation. A total of 24 polymorphic markers spanning the PRSS56 gene in 6 families originating from different regions of Tunisia were analyzed to investigate the origin of the c.1059_1066insC mutation and to determine whether it arose in a common ancestor. A highly significant disease-associated haplotype, spanning across the 146 kb of the 2q37.1 chromosome, was conserved in those families, suggesting that c.1059_1066insC arose from a common founder. The age of the mutation in this haplotype was estimated to be around 1,850 years. The identification of such 'founder effects' may greatly simplify diagnostic genetic screening and lead to better prognostic counseling. © 2013 Elsevier B.V. All rights reserved.

  2. An USH2A founder mutation is the major cause of Usher syndrome type 2 in Canadians of French origin and confirms common roots of Quebecois and Acadians.

    Science.gov (United States)

    Ebermann, Inga; Koenekoop, Robert K; Lopez, Irma; Bou-Khzam, Lara; Pigeon, Renée; Bolz, Hanno J

    2009-01-01

    Congenital hearing loss affects approximately one child in 1000. About 10% of the deaf population have Usher syndrome (USH). In USH, hearing loss is complicated by retinal degeneration with onset in the first (USH1) or second (USH2) decade. In most populations, diagnostic testing is hampered by a multitude of mutations in nine genes. We have recently shown that in French Canadians from Quebec, USH1 largely results from a single USH1C founder mutation, c.216G>A ('Acadian allele'). The genetic basis of USH2 in Canadians of French descent, however, has remained elusive. Here, we have investigated nine USH2 families from Quebec and New Brunswick (the former Acadia) by haplotype analyses of the USH2A locus and sequencing of the three known USH2 genes. Seven USH2A mutations were identified in eight patients. One of them, c.4338_4339delCT, accounts for 10 out of 18 disease alleles (55.6%). This mutation has previously been reported in an Acadian USH2 family, and it was found in homozygous state in the three Acadians of our sample. As in the case of c.216G>A (USH1C), a common haplotype is associated with c.4338_4339delCT. With a limited number of molecular tests, it will now be possible in these populations to estimate whether children with congenital hearing impairment of different degrees will develop retinal disease - with important clinical and therapeutic implications. USH2 is the second example that reveals a significant genetic overlap between Quebecois and Acadians: in contrast to current understanding, other genetic disorders present in both populations are likely based on common founder mutations as well.

  3. A founder mutation in LEPRE1 carried by 1.5% of West Africans and 0.4% of African Americans causes lethal recessive osteogenesis imperfecta.

    Science.gov (United States)

    Cabral, Wayne A; Barnes, Aileen M; Adeyemo, Adebowale; Cushing, Kelly; Chitayat, David; Porter, Forbes D; Panny, Susan R; Gulamali-Majid, Fizza; Tishkoff, Sarah A; Rebbeck, Timothy R; Gueye, Serigne M; Bailey-Wilson, Joan E; Brody, Lawrence C; Rotimi, Charles N; Marini, Joan C

    2012-05-01

    Deficiency of prolyl 3-hydroxylase 1, encoded by LEPRE1, causes recessive osteogenesis imperfecta (OI). We previously identified a LEPRE1 mutation exclusively in African Americans and contemporary West Africans. We hypothesized that this allele originated in West Africa and was introduced to the Americas with the Atlantic slave trade. We aimed to determine the frequency of carriers for this mutation among African Americans and West Africans, and the mutation origin and age. Genomic DNA was screened for the mutation using PCR and restriction digestion, and a custom TaqMan genomic single-nucleotide polymorphism assay. The mutation age was estimated using microsatellites and short tandem repeats spanning 4.2 Mb surrounding LEPRE1 in probands and carriers. Approximately 0.4% (95% confidence interval: 0.22-0.68%) of Mid-Atlantic African Americans carry this mutation, estimating recessive OI in 1/260,000 births in this population. In Nigeria and Ghana, 1.48% (95% confidence interval: 0.95-2.30%) of unrelated individuals are heterozygous carriers, predicting that 1/18,260 births will be affected with recessive OI, equal to the incidence of de novo dominant OI. The mutation was not detected in Africans from surrounding countries. All carriers shared a haplotype of 63-770 Kb, consistent with a single founder for this mutation. Using linkage disequilibrium analysis, the mutation was estimated to have originated between 650 and 900 years before present (1100-1350 CE). We identified a West African founder mutation for recessive OI in LEPRE1. Nearly 1.5% of Ghanians and Nigerians are carriers. The estimated age of this allele is consistent with introduction to North America via the Atlantic slave trade (1501-1867 CE).

  4. 9 July 2008 - Microsoft Co-Founder P. Allen visiting ATLAS control room and underground experimental area with Adviser J. Ellis and IT Department Head W. von Rüden.

    CERN Multimedia

    Maximilien Brice

    2008-01-01

    9 July 2008 - Microsoft Co-Founder P. Allen visiting ATLAS control room and underground experimental area with Adviser J. Ellis and IT Department Head W. von Rüden and guided by ATLAS Collaboration Users S. Goldfarb, P. Nevski and L. Price.

  5. A novel FKRP-related muscular dystrophy founder mutation in South African Afrikaner patients with a phenotype suggestive of a dystrophinopathy

    Directory of Open Access Journals (Sweden)

    M M Mudau

    2017-01-01

    Full Text Available Background. Fukutin-related protein (FKRP muscular dystrophy is an autosomal recessive disorder caused by mutations in the FKRP gene. The condition is often misdiagnosed as a dystrophinopathy. A previously unreported mutation, c.1100T>C in exon 4 of FKRP, had been identified in homozygous form in two white South African (SA Afrikaner patients clinically diagnosed with a dystrophinopathy. Objectives. To investigate whether the c.1100T>C mutation and the common European FKRP mutation c.826C>A are present in other patients of Afrikaner origin with suspected dystrophinopathy, and whether a founder haplotype exists. Methods. The c.1100T>C mutation was initially tested for using an amplification refractory mutation system technique in 45 white SA Afrikaner patients who had tested negative using multiplex ligation probe amplification screening for exonic deletions/duplications in the dystrophin gene. Sequencing analysis was used to confirm the c.1100T>C mutation and screen for the c.826C>A mutation. Two cohorts (each numbering 100 of Afrikaans and other white controls were screened for the c.1100T>C and c.826C>A mutations, respectively. Results. Of the 45 patients, 8 patients (17.8% were homozygous for c.1100T>C, 2 (4.4% were compound heterozygotes for c.1100T>C and c.826C>A, and 1 (2.2% was heterozygous for c.1100T>C with a second unidentified mutation. The c.1100T>C mutation was found in 1/100 controls, but no heterozygotes for the c.826C>A mutation were identified. Linked marker analysis for c.1100T>C showed a common haplotype, suggesting a probable founder mutation in the SA Afrikaner population. Conclusion. FKRP mutations may be relatively common in Afrikaners, and screening should be considered in patients who have a suggestive phenotype and test negative for a dystrophinopathy. This test will be useful for offering diagnostic, carrier and prenatal testing for affected individuals and their families. As FKRP muscular dystrophy is autosomal

  6. Fifty-five years (1955-2010) of the Coagulation Section at Laboratory of Hematology, Sestre milosrdnice University Hospital, and its founder, hematologist Ljubomir Popović.

    Science.gov (United States)

    Stancić, Vladimir; Stancić, Nevenka; Vucelić, Vesna; Lang, Nada; Grbac, Ljiljana

    2011-09-01

    The Coagulation Section at Laboratory of Hematology, Sestre milosrdnice University Hospital, Zagreb, was founded in 1955 by Ljubomir Popović, hematologist and assistant at School of Medicine, University of Zagreb, in cooperation with hard-working laboratory technicians. Apart from papers on hematologic neoplasms, plasmacytoma and lymphoma, Ljubomir Popović published a number of papers in the field of anticoagulant therapy with heparin and oral anticoagulants, some of which are also in use today. After Ljubomir Popović left the Hospital in 1964, the Laboratory was run by Professor Nedjeljko Milić, head of the newly founded Division of Hematology. In 1968, the management of the Laboratory of Hematology was taken over by Biserka Raić, MS, medical biochemist, until her retirement in 2007. Great development in morphological and cytometric studies of blood and blood cells has been paralleled by continuous progress and almost dominating activities in the diagnosis of hemostasis disorders. In the 1970s, Marko Koprcina, hematologist, and Biserka Raić introduced the then latest tests in practice at all Hospital departments. In that golden age of the Coagulation Section, M. Koprcina, B. Raić and their associates transferred their knowledge to all colleagues in the Hospital. Through that collaboration, high standards in the diagnosis of hemostasis disorders were achieved, from which the currently high level of clinical knowledge about coagulation disorders and their treatment has derived, making Sestre milosrdnice University Hospital one of the leading hospitals in this field in the country. By describing development of the Coagulation Section and the life of its founder Ljubomir Popović, the authors tried to provide an answer to the following question: can today's clinicians still have a deciding role in laboratory development, considering that assessments of different phenomena are always initiated by an interested clinician who is trying to interpret and understand

  7. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

    International Nuclear Information System (INIS)

    Kringen, Pedro; Wang, Yun; Dumeaux, Vanessa; Kristensen, Gunnar; Borresen-Dale, Anne-Lise; Dorum, Anne

    2005-01-01

    Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive. DNA was extracted from paraffin embedded formalin fixed tissues for the familial cases, and from fresh frozen specimen from the sporadic cases. All cases were treated at our hospital according to protocol. Mutation analyses of exon 2 – 11 were performed using TTGE, followed by sequencing. Survival rates for BRCA1-familial cases with TP53 mutations were not significantly lower than for familial cases without TP53 mutations (p = 0.25, RR = 1.64, 95% CI [0.71–3.78]). Median age at diagnosis for sporadic (59 years) and familial (49 years) cases differed significantly (p < 0.001) with or without TP53 mutations. Age at diagnosis between the two types of familial carriers were not significantly different, with median age of 47 for 1675delA and 52.5 for 1135insA carriers (p = 0.245). For cases ≥50 years at diagnosis, a trend toward longer survival for sporadic over familial cases was observed (p = 0.08). The opposite trend was observed for cases <50 years at diagnosis. There do not seem to be a protective advantage for familial BRCA1 carriers without TP53 mutations over familial cases with TP53 mutations. However, there seem to be a trend towards initial advantage in survival for familial cases compared to sporadic cases diagnosed before the age of 50 both with and without TP53 mutations. However, this trend diminishes over time and for cases diagnosed ≥50 years the sporadic cases show a trend towards an advantage in survival over familial cases. Although this data set is small, if confirmed, this may be a link in the evidence that the differences in ovarian cancer survival reported, are

  8. The initiation of lateral roots in the primary roots of maize (Zea mays L.) implies a reactivation of cell proliferation in a group of founder pericycle cells.

    Science.gov (United States)

    Alarcón, M Victoria; Lloret, Pedro G; Martín-Partido, Gervasio; Salguero, Julio

    2016-03-15

    The initiation of lateral roots (LRs) has generally been viewed as a reactivation of proliferative activity in pericycle cells that are committed to initiate primordia. However, it is also possible that pericycle founder cells that initiate LRs never cease proliferative activity but rather are displaced to the most distal root zones while undertaking successive stages of LR initiation. In this study, we tested these two alternative hypotheses by examining the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into the DNA of meristematic root cells of Zea mays. According to the values for the length of the cell cycle and values for cell displacement along the maize root, our results strongly suggest that pericycle cells that initiate LR primordia ceased proliferative activity upon exiting the meristematic zone. This finding is supported by the existence of a root zone between 4 and 20mm from the root cap junction, in which neither mitotic cells nor labelled nuclei were observed in phloem pericycle cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population.

    Science.gov (United States)

    Tüysüz, Beyhan; Bayrakli, Fatih; DiLuna, Michael L; Bilguvar, Kaya; Bayri, Yasar; Yalcinkaya, Cengiz; Bursali, Aysegul; Ozdamar, Elif; Korkmaz, Baris; Mason, Christopher E; Ozturk, Ali K; Lifton, Richard P; State, Matthew W; Gunel, Murat

    2008-05-01

    Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital insensitivity to pain with anhidrosis, is an autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated sweat glands, and delayed mental and motor development. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the neurotrophin signaling pathway phosphorylated in response to nerve growth factor, are associated with this disorder. We identified six families from Northern Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these families. Microsatellite and single nucleotide polymorphism (SNP) markers on the Affymetrix 250K chip platform were used to determine the haplotypes for three families harboring the same mutation. Screening for mutations in the NTRK1 gene demonstrated one novel frameshift mutation, two novel nonsense mutations, and three unrelated kindreds with the same splice-site mutation. Genotyping of the three families with the identical splice-site mutation revealed that they share the same haplotype. This report broadens the spectrum of mutations in NTRK1 that cause HSAN IV and demonstrates a founder mutation in the Turkish population.

  10. The History of the Foundation of the Iranian National Blood Transfusion Service in 1974 and the Biography of its Founder; Professor Fereydoun Ala.

    Science.gov (United States)

    Azizi, Mohammad Hossein; Nayernouri, Touraj; Bahadori, Moslem

    2015-06-01

    The history of early attempts of blood transfusion in Iran traces back to the 1940s; however, around three decades later in 1974, the Iranian National Blood Transfusion Service (Sazeman-e Melli-e Enteqal-e Khun-e Iran) was founded by the outstanding hematologist, Professor Fereydoun Ala. The main goals of this centralized organization were to collect blood from healthy voluntary donors, to screen the donated blood and to provide various safe blood products based on scientific and ethical standards. In due course, a new era of blood transfusion service in Iran had begun to such a degree that after more than four decades of its activity, it is now considered the best-developed blood service in the eastern Mediterranean region. Here, a brief historical account of the early blood transfusion efforts and the establishment of the modern Iranian National Blood Transfusion Service in Iran is discussed in addition to the life and career of its founder and first director, Professor Fereydoun Ala.

  11. Eduardo Primo Yúfera, founder of Revista de Agroquímica y Tecnología de Alimentos and pioneer on food science and technology research in Spain.

    Science.gov (United States)

    Ayala-Gascón, M; Aleixandre-Benavent, R; Gandía-Balaguer, A

    2011-12-01

    Eduardo Primo Yúfera was the founder and director of the Instituto de Agroquímica y Tecnología de Alimentos (IATA, 1957-1974) until he was appointed president of the Consejo Superior de Investigaciones Científicas (CSIC). His aim to publicize food science led him to create the Revista de Agroquímica y Tecnología de Alimentos in 1961, the forerunner of this journal, Food Science and Technology International, which he directed until 1977. Of his scientific output, 50% has been published in this journal. He is considered to be the promoter and exponent of Food Science and Technology and Chemical Ecology in Spain as well as the instigator of the country's innovation model (R&D and innovation). In his work, he was able to combine basic research excellence and socially relevant applied research to move both science and society forward. He was an example and inspiration to many colleagues and followers. The aim of this study is to highlight the influence and importance of Primo Yúfera in the formation, development and consolidation of the journal Revista de Agroquímica y Tecnología de Alimentos, and to appraise his scientific contribution to this journal.

  12. BRCA Genetic Screening in Middle Eastern and North African: Mutational Spectrum and Founder BRCA1 Mutation (c.798_799delTT in North African

    Directory of Open Access Journals (Sweden)

    Abdelilah Laraqui

    2015-01-01

    Full Text Available Background. The contribution of BRCA1 mutations to both hereditary and sporadic breast and ovarian cancer (HBOC has not yet been thoroughly investigated in MENA. Methods. To establish the knowledge about BRCA1 mutations and their correlation with the clinical aspect in diagnosed cases of HBOC in MENA populations. A systematic review of studies examining BRCA1 in BC women in Cyprus, Jordan, Egypt, Lebanon, Morocco, Algeria, and Tunisia was conducted. Results. Thirteen relevant references were identified, including ten studies which performed DNA sequencing of all BRCA1 exons. For the latter, 31 mutations were detected in 57 of the 547 patients ascertained. Familial history of BC was present in 388 (71% patients, of whom 50 were mutation carriers. c.798_799delTT was identified in 11 North African families, accounting for 22% of total identified BRCA1 mutations, suggesting a founder allele. A broad spectrum of other mutations including c.68_69delAG, c.181T>G, c.5095C>T, and c.5266dupC, as well as sequence of unclassified variants and polymorphisms, was also detected. Conclusion. The knowledge of genetic structure of BRCA1 in MENA should contribute to the assessment of the necessity of preventive programs for mutation carriers and clinical management. The high prevalence of BC and the presence of frequent mutations of the BRCA1 gene emphasize the need for improving screening programs and individual testing/counseling.

  13. Human mtDNA hypervariable regions, HVR I and II, hint at deep common maternal founder and subsequent maternal gene flow in Indian population groups.

    Science.gov (United States)

    Sharma, Swarkar; Saha, Anjana; Rai, Ekta; Bhat, Audesh; Bamezai, Ramesh

    2005-01-01

    We have analysed the hypervariable regions (HVR I and II) of human mitochondrial DNA (mtDNA) in individuals from Uttar Pradesh (UP), Bihar (BI) and Punjab (PUNJ), belonging to the Indo-European linguistic group, and from South India (SI), that have their linguistic roots in Dravidian language. Our analysis revealed the presence of known and novel mutations in both hypervariable regions in the studied population groups. Median joining network analyses based on mtDNA showed extensive overlap in mtDNA lineages despite the extensive cultural and linguistic diversity. MDS plot analysis based on Fst distances suggested increased maternal genetic proximity for the studied population groups compared with other world populations. Mismatch distribution curves, respective neighbour joining trees and other statistical analyses showed that there were significant expansions. The study revealed an ancient common ancestry for the studied population groups, most probably through common founder female lineage(s), and also indicated that human migrations occurred (maybe across and within the Indian subcontinent) even after the initial phase of female migration to India.

  14. A deep intronic CLRN1 (USH3A) founder mutation generates an aberrant exon and underlies severe Usher syndrome on the Arabian Peninsula.

    Science.gov (United States)

    Khan, Arif O; Becirovic, Elvir; Betz, Christian; Neuhaus, Christine; Altmüller, Janine; Maria Riedmayr, Lisa; Motameny, Susanne; Nürnberg, Gudrun; Nürnberg, Peter; Bolz, Hanno J

    2017-05-03

    Deafblindness is mostly due to Usher syndrome caused by recessive mutations in the known genes. Mutation-negative patients therefore either have distinct diseases, mutations in yet unknown Usher genes or in extra-exonic parts of the known genes - to date a largely unexplored possibility. In a consanguineous Saudi family segregating Usher syndrome type 1 (USH1), NGS of genes for Usher syndrome, deafness and retinal dystrophy and subsequent whole-exome sequencing each failed to identify a mutation. Genome-wide linkage analysis revealed two small candidate regions on chromosome 3, one containing the USH3A gene CLRN1, which has never been associated with Usher syndrome in Saudi Arabia. Whole-genome sequencing (WGS) identified a homozygous deep intronic mutation, c.254-649T > G, predicted to generate a novel donor splice site. CLRN1 minigene-based analysis confirmed the splicing of an aberrant exon due to usage of this novel motif, resulting in a frameshift and a premature termination codon. We identified this mutation in an additional two of seven unrelated mutation-negative Saudi USH1 patients. Locus-specific markers indicated that c.254-649T > G CLRN1 represents a founder allele that may significantly contribute to deafblindness in this population. Our finding underlines the potential of WGS to uncover atypically localized, hidden mutations in patients who lack exonic mutations in the known disease genes.

  15. Interview with Mia Katigbak (co-founder and artistic producing director of NAATCO).Breaking Racial and Ethnic Stereotypes on the American Stage: National Asian American Theatre Company’s 25th Anniversary

    OpenAIRE

    Medalle, Rovie Herrera

    2016-01-01

    Entretien avec Mia Katigbak, co-fondatrice et directrice artistique de NAATCO (National Asian American Theatre Company). L’entretien, réalisé en août 2015, consistaient en un échange de courriels Interview with Mia Katigbak, co-founder and Artistic Producing Director of NAATCO (National Asian American Theatre Company). The interview was conducted by emails in August 2015

  16. The roles of geography and founder effects in promoting host-associated differentiation in the generalist bogus yucca moth Prodoxus decipiens.

    Science.gov (United States)

    Darwell, C T; Fox, K A; Althoff, D M

    2014-12-01

    There is ample evidence that host shifts in plant-feeding insects have been instrumental in generating the enormous diversity of insects. Changes in host use can cause host-associated differentiation (HAD) among populations that may lead to reproductive isolation and eventual speciation. The importance of geography in facilitating this process remains controversial. We examined the geographic context of HAD in the wide-ranging generalist yucca moth Prodoxus decipiens. Previous work demonstrated HAD among sympatric moth populations feeding on two different Yucca species occurring on the barrier islands of North Carolina, USA. We assessed the genetic structure of P. decipiens across its entire geographic and host range to determine whether HAD is widespread in this generalist herbivore. Population genetic analyses of microsatellite and mtDNA sequence data across the entire range showed genetic structuring with respect to host use and geography. In particular, genetic differentiation was relatively strong between mainland populations and those on the barrier islands of North Carolina. Finer scale analyses, however, among sympatric populations using different host plant species only showed significant clustering based on host use for populations on the barrier islands. Mainland populations did not form population clusters based on host plant use. Reduced genetic diversity in the barrier island populations, especially on the derived host, suggests that founder effects may have been instrumental in facilitating HAD. In general, results suggest that the interplay of local adaptation, geography and demography can determine the tempo of HAD. We argue that future studies should include comprehensive surveys across a wide range of environmental and geographic conditions to elucidate the contribution of various processes to HAD. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  17. The founders of the ININ

    International Nuclear Information System (INIS)

    Bulbulian, S.

    2006-01-01

    The Mexican government sent the constituent law of the National Commission of Nuclear Energy (CNEN) at December 31, 1955. This classification enters in validity the January 1, 1956. However the Commission began to work in the last months 1956. This institution development two main activities: 1. A program of training on techniques with radioisotopes and nuclear instrumentation and 2. The creation of specialized programs and laboratories. Very important persons in the CNEN were the members of the Commission, the Dr. Manuel Sandoval Vallarta, the Dr. Nabor Carrillo Flores and the Atty. Jose Maria Ortiz Tirado, President of this institution. (Author)

  18. G1738R is a BRCA1 founder mutation in Greek breast/ovarian cancer patients: evaluation of its pathogenicity and inferences on its genealogical history.

    Science.gov (United States)

    Anagnostopoulos, Theodore; Pertesi, Maroulio; Konstantopoulou, Irene; Armaou, Sofia; Kamakari, Smaragda; Nasioulas, George; Athanasiou, Athanassios; Dobrovic, Alex; Young, Mary-Anne; Goldgar, David; Fountzilas, George; Yannoukakos, Drakoulis

    2008-07-01

    heterogeneity in the Greek population, the identification of a frequent founder mutation greatly facilitates genetic screening.

  19. Deep genetic divergences among Indo-Pacific populations of the coral reef sponge Leucetta chagosensis (Leucettidae): founder effects, vicariance, or both?

    Science.gov (United States)

    Wörheide, Gert; Epp, Laura S; Macis, Luciana

    2008-01-26

    An increasing number of studies demonstrate that genetic differentiation and speciation in the sea occur over much smaller spatial scales than previously appreciated given the wide distribution range of many morphologically defined coral reef invertebrate species and the presumed dispersal-enhancing qualities of ocean currents. However, knowledge about the processes that lead to population divergence and speciation is often lacking despite being essential for the understanding, conservation, and management of marine biodiversity. Sponges, a highly diverse, ecologically and economically important reef-invertebrate taxon, exhibit spatial trends in the Indo-West Pacific that are not universally reflected in other marine phyla. So far, however, processes generating those unexpected patterns are not understood. We unraveled the phylogeographic structure of the widespread Indo-Pacific coral reef sponge Leucetta chagosensis across its known geographic range using two nuclear markers: the rDNA internal transcribed spacers (ITS 1&2) and a fragment of the 28S gene, as well as the second intron of the ATP synthetase beta subunit-gene (ATPSb-iII). This enabled the detection of several deeply divergent clades congruent over both loci, one containing specimens from the Indian Ocean (Red Sea and Maldives), another one from the Philippines, and two other large and substructured NW Pacific and SW Pacific clades with an area of overlap in the Great Barrier Reef/Coral Sea. Reciprocally monophyletic populations were observed from the Philippines, Red Sea, Maldives, Japan, Samoa, and Polynesia, demonstrating long-standing isolation. Populations along the South Equatorial Current in the south-western Pacific showed isolation-by-distance effects. Overall, the results pointed towards stepping-stone dispersal with some putative long-distance exchange, consistent with expectations from low dispersal capabilities. We argue that both founder and vicariance events during the late Pliocene and

  20. Deep genetic divergences among Indo-Pacific populations of the coral reef sponge Leucetta chagosensis (Leucettidae: Founder effects, vicariance, or both?

    Directory of Open Access Journals (Sweden)

    Epp Laura S

    2008-01-01

    founder and vicariance events during the late Pliocene and Pleistocene were responsible to varying degrees for generating the deep phylogeographic structure. This structure was perpetuated largely as a result of the life history of L. chagosensis, resulting in high levels of regional isolation. Reciprocally monophyletic populations constitute putative sibling (cryptic species, while population para- and polyphyly may indicate incipient speciation processes. The genetic diversity and biodiversity of tropical Indo-Pacific sponges appears to be substantially underestimated since the high level of genetic divergence is not necessarily manifested at the morphological level.

  1. TP53 mutation p.R337H in gastric cancer tissues of a 12-year-old male child - evidence for chimerism involving a common mutant founder haplotype: case report

    International Nuclear Information System (INIS)

    Silva, Edaise M da; W Achatz, Maria Isabel; Martel-Planche, Ghyslaine; Montagnini, André L; Olivier, Magali; Prolla, Patricia A; Hainaut, Pierre; Soares, Fernando A

    2011-01-01

    Gastric adenocarcinoma is rare in children and adolescents, with about 17 cases under age 21 in the world's literature. We report a case of invasive well-differentiated metastatic gastric cancer in a Brazilian 12-year-old boy without documented familial history of cancer. The patient, diagnosed with metastatic disease, died seven months after surgery. DNA from intra-surgical specimens revealed a TP53 mutation at codon 337 (p.R337H) in samples with neoplastic cells (dysplasia, tumor and metastasis) but not in non-transformed cells (incomplete intestinal metaplasia and non-involved celiac lymph node). In all mutation-positive tissues, p.R337H occurred on the same background, a founder allele identified by a specific haplotype previously described in Brazilian Li-Fraumeni syndrome patients. The same mutant haplotype, corresponding to a founder mutation present in 0.3% of the general population in Southern Brazil, was found in the genome of the father. Presence of this inherited haplotype in the tumor as well as in the father's germline, suggests a rare case of microchimerism in this patient, who may have harbored a small number of mutant cells originating in another individual, perhaps a dizygotic twin that died early in gestation. This case represents one of the earliest ages at diagnosis of gastric cancer ever reported. It shows that cancer inheritance can occur in the absence of an obvious germline mutation, calling for caution in assessing early cancers in populations with common founder mutations such as p.R337H in Southern Brazil

  2. Differential and correlation analyses of microarray gene expression data in the CEPH Utah families

    DEFF Research Database (Denmark)

    Tan, Qihua; Zhao, Jinghua; Li, Shuxia

    2008-01-01

    -regulated genes identifies cell-cell signaling as an important functional category implicated in human aging. Sex-dependent gene expression is characterized by genes that may escape X-inactivation and, most interestingly, such a pattern is not affected by the aging process. Analysis on sibship correlation on gene...... expression revealed a large number of significant genes suggesting the importance of a genetic mechanism in regulating transcriptional activities. In addition, we observe an interesting pattern of sibship correlation on gene expression that increases exponentially with the mean of gene expression reflecting...

  3. Invertebrate neuroscience and CephsInAction at the Mediterranean Society for Neuroscience Meeting Cagliari 2015.

    Science.gov (United States)

    Holden-Dye, Lindy; Fiorito, Graziano; Ponte, Giovanna

    2015-12-01

    Invertebrate neuroscience, and in particular cephalopod research, is well represented in the Mediterranean region. Therefore, the recent meeting of the Mediterranean Society for Neuroscience in Santa Margherita di Pula, Sardinia (12-15 June 2015) provided an excellent opportunity for invertebrate contributions. Furthermore, the Chair of an EU COST Action for cephalopod research (FA1301; www.cephsinaction.org ), Giovanna Ponte, together with Graziano Fiorito from the Stazione Zoologica, Naples, aligned a meeting of research groups working in the field of cephalopod neurophysiology from across Europe to coincide with the neuroscience meeting. This provided an exciting forum for exchange of ideas. Here we provide brief highlights of both events and an explanation of the activities of the COST Action for the broader invertebrate neuroscience community.

  4. 18 June 2012 - DST Global Founder Y. Milner signing the guest book with Head of International Relations F. Pauss; visiting the AD facility in building 193 with AEGIS Collaboration Spokesperson M. Doser and Adviser for the Russian Federation T. Kurtyka. Managing Director I. Osborne also present with Mrs J. Milner and DST Global A. Lebedkina.

    CERN Multimedia

    Maximilien Brice

    2012-01-01

    18 June 2012 - DST Global Founder Y. Milner signing the guest book with Head of International Relations F. Pauss; visiting the AD facility in building 193 with AEGIS Collaboration Spokesperson M. Doser and Adviser for the Russian Federation T. Kurtyka. Managing Director I. Osborne also present with Mrs J. Milner and DST Global A. Lebedkina.

  5. 25 June 2010 - Founder Chairman of the Japanese Science and Technology in Society Forum K. Omi signing the guest book with Head of International Relations F. Pauss, Adviser J. Ellis and Director-General R. Heuer; in the ATLAS visitor centre with Former Collaboration Spokesperson P. Jenni.

    CERN Multimedia

    2010-01-01

    25 June 2010 - Founder Chairman of the Japanese Science and Technology in Society Forum K. Omi signing the guest book with Head of International Relations F. Pauss, Adviser J. Ellis and Director-General R. Heuer; in the ATLAS visitor centre with Former Collaboration Spokesperson P. Jenni.

  6. 90-letnij yubilej osnovatelya IAI Petra Grigor'evicha Kulikovskogo %t The founder of "Studies in the history of astronomy" Dr. P. G. Kulikovsky: to his 90th birthday

    Science.gov (United States)

    Eremeeva, A. I.; Laerova, N. B.; Samus', N. N.

    On June 13, 2000, Moscow astronomers congratulated personally P. G. Kulikovsky, the renowned Russian astronomer and teacher of astronomy on his birthday. Born in Kiev in a family with noble Polish and French roots, he graduated from Moscow University in 1938 and worked at Sternberg Astronomical Institute and the Department of Astronomy of Moscow University. His main scientific interests are Galactic astronomy and history of astronomy. Kulikovsky was one of the pioneers of astronomical electrophotometry in the Soviet Union. He was most active in studies of variable stars, investigated connections of their statistical properties with those of the corresponding stars systems. Being a brilliant teacher, he lectured successfully on astronomical subjects in Moscow University. Friends also know him as a talented musician and composer, an author of many piano plays. Kulikovsky has done very much as an organizer of Soviet systematic researches on the history of astronomy. He is the author of many papers on the subject, the founder of the corresponding commission of the USSR Astronomical Council. Kulikovsky was an active member of the IAU, he served as President of the IAU Commission 41 (History of Astronomy) in 1958 - 1964.

  7. Founder effect and estimation of the age of the c.892C>T (p.Arg298Cys) mutation in LMNA associated to Charcot-Marie-Tooth subtype CMT2B1 in families from North Western Africa.

    Science.gov (United States)

    Hamadouche, T; Poitelon, Y; Genin, E; Chaouch, M; Tazir, M; Kassouri, N; Nouioua, S; Chaouch, A; Boccaccio, I; Benhassine, T; De Sandre-Giovannoli, A; Grid, D; Lévy, N; Delague, V

    2008-09-01

    CMT2B1, an axonal subtype (MIM 605588) of the Charcot-Marie-Tooth disease, is an autosomal recessive motor and sensory neuropathy characterized by progressive muscular and sensory loss in the distal extremities with chronic distal weakness. The genetic defect associated with the disease is, to date, a unique homozygous missense mutation, p.Arg298Cys (c.892C>T), in the LMNA gene. So far, this mutation has only been found in affected individuals originating from a restricted region of North Western Africa (northwest of Algeria and east of Morocco), strongly suggesting a founder effect. In order to address this hypothesis, genotyping of both STRs and intragenic SNPs was performed at the LMNA locus, at chromosome 1q21.2-q21.3, in 42 individuals affected with CMT2B1 from 25 Algerian families. Our results indicate that the affected individuals share a common ancestral haplotype in a region of about 1.0 Mb (1 cM) and that the most recent common ancestor would have lived about 800-900 years ago (95% confidence interval: 550 to 1300 years).

  8. Genome-wide analysis in Brazilian Xavante Indians reveals low degree of admixture.

    Science.gov (United States)

    Kuhn, Patricia C; Horimoto, Andréa R V Russo; Sanches, José Maurício; Vieira Filho, João Paulo B; Franco, Luciana; Fabbro, Amaury Dal; Franco, Laercio Joel; Pereira, Alexandre C; Moises, Regina S

    2012-01-01

    Characterization of population genetic variation and structure can be used as tools for research in human genetics and population isolates are of great interest. The aim of the present study was to characterize the genetic structure of Xavante Indians and compare it with other populations. The Xavante, an indigenous population living in Brazilian Central Plateau, is one of the largest native groups in Brazil. A subset of 53 unrelated subjects was selected from the initial sample of 300 Xavante Indians. Using 86,197 markers, Xavante were compared with all populations of HapMap Phase III and HGDP-CEPH projects and with a Southeast Brazilian population sample to establish its population structure. Principal Components Analysis showed that the Xavante Indians are concentrated in the Amerindian axis near other populations of known Amerindian ancestry such as Karitiana, Pima, Surui and Maya and a low degree of genetic admixture was observed. This is consistent with the historical records of bottlenecks experience and cultural isolation. By calculating pair-wise F(st) statistics we characterized the genetic differentiation between Xavante Indians and representative populations of the HapMap and from HGDP-CEPH project. We found that the genetic differentiation between Xavante Indians and populations of Ameridian, Asian, European, and African ancestry increased progressively. Our results indicate that the Xavante is a population that remained genetically isolated over the past decades and can offer advantages for genome-wide mapping studies of inherited disorders.

  9. Analysis of TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 in autosomal recessive congenital ichthyosis from Galicia (NW Spain): evidence of founder effects.

    Science.gov (United States)

    Rodríguez-Pazos, L; Ginarte, M; Fachal, L; Toribio, J; Carracedo, A; Vega, A

    2011-10-01

      Mutations in six genes have been identified in autosomal recessive congenital ichthyosis (ARCI). To date, few studies have analysed the spectrum of these mutations in specific populations. We have studied the characteristics of patients with ARCI in Galicia (NW Spain). Methods  We recruited patients by contacting all dermatology departments of Galicia and the Spanish patient organization for ichthyosis. TGM1, ALOX12B, ALOXE3, NIPAL4 and CYP4F22 were analysed in the patients and their relatives. We identified 23 patients with ARCI and estimated a prevalence of 1 : 122 000. Twenty of the patients were studied. Seventeen of them were clinically categorized as having lamellar ichthyosis (LI) and three as having congenital ichthyosiform erythroderma (CIE). TGM1 and ALOXE3 mutations were identified in 12/16 (75%) probands whereas no ALOX12B, NIPAL4 and CYP4F22 mutations were found. TGM1 mutations were found in 11/13 (85%) of LI probands. ALOXE3 mutations were identified in a single patient with CIE. Remarkably, mutations p.Arg760X, p.Asp408ValfsX21 and c.984+1G>A of TGM1 were present in six, four and two families, accounting for 41%, 23% and 14% of all TGM1 mutant alleles, respectively. The high percentage of patients with the same TGM1 mutations, together with the high number of homozygous probands (64%), indicates the existence of a strong founder effect in our population. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

  10. Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences.

    Science.gov (United States)

    Love, Tanzy M T; Thurston, Sally W; Keefer, Michael C; Dewhurst, Stephen; Lee, Ha Youn

    2010-06-01

    The prominent role of antiviral cytotoxic CD8(+) T-lymphocytes (CD8-TL) in containing the acute viremia of human and simian immunodeficiency viruses (HIV-1 and SIV) has rationalized the development of T-cell-based vaccines. However, the presence of escape mutations in the acute stage of infection has raised a concern that accelerated escape from vaccine-induced CD8-TL responses might undermine vaccine efficacy. We reanalyzed previously published data of 101,822 viral genomes of three CD8-TL epitopes, Nef(103-111)RM9 (RM9), Tat(28-35)SL8 (SL8), and Gag(181-189)CM9 (CM9), sampled by ultradeep pyrosequencing from eight macaques. Multiple epitope variants appeared during the resolution of acute viremia, followed by the predominance of a single mutant epitope. By fitting a mathematical model, we estimated the first acute escape rate as 0.36 day(-1) within escape-prone epitopes, RM9 and SL8, and the chronic escape rate as 0.014 day(-1) within the CM9 epitope. Our estimate of SIV acute escape rates was found to be comparable to very early HIV-1 escape rates. The timing of the first escape was more highly correlated with the timing of the peak CD8-TL response than with the magnitude of the CD8-TL response. The transmitted epitope decayed more than 400 times faster during the acute viral decline stage than predicted by a neutral evolution model. However, the founder epitope persisted as a minor population even at the viral set point; in contrast, the majority of acute escape epitopes were completely cleared. Our results suggest that a reservoir of SIV infection is preferentially formed by virus with the transmitted epitope.

  11. Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect.

    Science.gov (United States)

    Barashkov, Nikolay A; Dzhemileva, Lilya U; Fedorova, Sardana A; Teryutin, Fedor M; Posukh, Olga L; Fedotova, Elvira E; Lobov, Simeon L; Khusnutdinova, Elza K

    2011-09-01

    Hereditary forms of hearing impairment (HI) caused by GJB2 (Cx26) mutations are the frequent sensory disorders registered among newborns in various human populations. In this study, we present data on the molecular, audiological and population features of autosomal recessive deafness 1A (DFNB1A) associated with the donor splicing site IVS1+1G>A mutation of GJB2 gene in Yakut population isolate of the Sakha Republic (Yakutia) located in Eastern Siberia (Russian Federation). The Yakut population exhibits high frequency of some Mendelian disorders, which are rare in other populations worldwide. Mutational analysis of GJB2 gene in 86 unrelated Yakut patients with congenital HI without other clinical features has been performed. In this study, we registered a large cohort of Yakut patients homozygous for the IVS1+1G>A mutation (70 unrelated deaf subjects in total). Detailed audiological analysis of 40 deaf subjects with genotype IVS1+1G>A/IVS1+1G>A revealed significant association of this genotype with mostly symmetrical bilateral severe to profound HI (85% severe-to-profound HI versus 15% mild-to-moderate HI, PA mutation (11.7%) has been found in Yakut population. Reconstruction of 140 haplotypes with IVS1+1G>A mutation demonstrates the common origin of all mutant chromosomes found in Yakuts. The age of mutation was estimated to be approximately 800 years. These findings characterize Eastern Siberia as the region with the most extensive accumulation of the IVS1+1G>A mutation in the world as a result of founder effect.

  12. Physicians founders of orthopedic surgery in Serbia

    Directory of Open Access Journals (Sweden)

    Bumbaširević Marko

    2004-01-01

    Full Text Available The beginnings of the development of orthopedic surgery in Serbia have been related to the name of Dr Nikola Krstic and his first radiography of the hand in 1908. The foundation of the Orthopedic Ward, led by Dr Nikola Krstic, within the General State Hospital in Belgrade, in 1919, marks the definition of orthopedics as a separate branch of surgery. In addition to Dr Nikola Krstic, Dr Borivoje Lalovic and Temp. Docent Dr Borivoje Gradojevic, who published the first orthopedics textbook in Serbian in 1934, also worked at the orthopedic ward between the two world wars. The work at the orthopedic ward, which grew into a clinic in 1947, was continued by Prof. Dr Milos Simovic, Prof. Dr Svetislav Stojanovic and Prof, dr Ljubisa Boric. Their successors would have high achievements: Prof. Dr Zivojin Bumbasirevic became the only orthopedist who was a regular member of the Serbian Academy of Sciences and Arts, and Chief of Staff Dr Predrag Klisic and Prof. Dr Branko Radulovic provide impetus for further development of orthopedics by founding Specialist Orthopedics Hospital "Banjica".

  13. Founder lines for improved citrus biotechnology

    Science.gov (United States)

    This article discusses the research needed to develop the RMCE strategy and molecular assays for site-specific recombinases as tools for genome manipulation. Explanation of genetic engineering used to generate transgenic citrus plants to exhibit a novel phenotype, but not to contain the recombinase...

  14. Founders of fish culture - European origins

    Science.gov (United States)

    Fish, F.F.

    1936-01-01

    Just where true fish culture appeared in history depends entirely upon what one considers fish culture to be. If the transportation of fishes from regions of plenty to those of few is to be regarded as fish culture - as it is by some even today - then this story should start in remotest antiquity and deal with an amazing series of failures. However, fish culture to be classed as a science must include far more than mere transportation, it must include a deliberate effort on the part of man to master a technique of fish raising which will yield results far superior to Nature's. Accordingly, the wheel of history must be spun forward to the fifteenth century, A. D., when man first conceived the idea that with care and exactitude, he could improve upon Nature. The fish cultural efforts of the Chinese, the Egyptians, the Greeks, and the Romans may be skipped over in a hurry, for they represented little more than the transportation and rearing of wild fish. With the renaissance of modern civilization in Europe came the birth of scientific fish culture.

  15. Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.

    Directory of Open Access Journals (Sweden)

    Nicholas F Parrish

    Full Text Available Sexual transmission of human immunodeficiency virus type 1 (HIV-1 most often results from productive infection by a single transmitted/founder (T/F virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20 and chronic (n = 20 Env constructs as well as full-length T/F (n = 6 and chronic (n = 4 infectious molecular clones (IMCs. We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently.

  16. Mutación fundadora en una familia argentina con cáncer colorrectal hereditario Detection of a founder mutation in an Argentine family with hereditary non polyposis colorectal cancer

    Directory of Open Access Journals (Sweden)

    Laura Gómez

    2010-02-01

    Full Text Available El cáncer colorrectal hereditario no poliposo (CCHNP se relaciona con mutaciones en los genes reparadores de ADN (MLH1, MSH2 y MSH6. La mayoría de estas alteraciones son familia-específicas y su detección suele requerir la secuenciación completa de los genes relacionados. Se detectó una mutación puntual (2269-2270insT en el último codón del gen MLH1 en familias de un área del norte de Italia (Reggio Emilia y su origen se considera debido a un efecto fundador. En este trabajo presentamos una familia mendocina con CCHNP portadora de la misma mutación, cuyos ancestros eran oriundos de Reggio Emilia. Para la detección de la mutación se diseñó una estrategia basada en PCR y posterior corte enzimático. La mutación fue hallada en tres integrantes de la familia estudiada, dos de los cuales no presentaban sintomatología clínica. Estos pacientes fueron seguidos preventivamente mediante colonoscopias. La metodología utilizada en nuestro laboratorio fue específica y sensible para la detección de una mutación previamente registrada y permitió realizar el diagnóstico genético molecular en el país, evitando el envío de muestras al extranjero. Es de importancia destacar que el diagnóstico genético pre-sintomático de cáncer hereditario, enfocado desde un grupo multidisciplinario de profesionales, permite un mejor seguimiento y apoyo a las familias afectadas.Hereditary non polyposis colorectal cancer (HNPCC has been related to mutations in the DNA mismatch repair genes (MLH1, MSH2 y MSH6. Mutation detection analysis requires the complete sequencing of these genes, given the high frequency of family-specific alterations. A point mutation (2269- 2270insT in the last codon of the MLH1 gene has been detected in families from a northern region of Italy (Reggio Emilia.Given that this alteration was registered only in people from this region, it has been considered a founder mutation. In this work, we present an Argentine HNPCC family

  17. Cephalopod biology and care, a COST FA1301 (CephsInAction) training school: anaesthesia and scientific procedures.

    Science.gov (United States)

    Lopes, Vanessa M; Sampaio, Eduardo; Roumbedakis, Katina; Tanaka, Nobuaki K; Carulla, Lucía; Gambús, Guillermo; Woo, Theodosia; Martins, Catarina P P; Penicaud, Virginie; Gibbings, Colette; Eberle, Jessica; Tedesco, Perla; Fernández, Isabel; Rodríguez-González, Tania; Imperadore, Pamela; Ponte, Giovanna; Fiorito, Graziano

    2017-09-01

    Cephalopods are the sole invertebrates included in the list of regulated species following the Directive 2010/63/EU. According to the Directive, achieving competence through adequate training is a requisite for people having a role in the different functions (article 23) as such carrying out procedures on animals, designing procedures and projects, taking care of animals, killing animals. Cephalopod Biology and Care Training Program is specifically designed to comply with the requirements of the "working document on the development of a common education and training framework to fulfil the requirements under the Directive 2010/63/EU". The training event occurred at the ICM-CSIC in Barcelona (Spain) where people coming from Europe, America and Asia were instructed on how to cope with regulations for the use of cephalopod molluscs for scientific purposes. The training encompasses discussion on the guidelines for the use and care of animals and their welfare with particular reference to procedures that may be of interest for neuroscience. Intensive discussion has been carried out during the training sessions with focus on behavioural studies and paradigms, welfare assessment, levels of severity of scientific procedures, animal care, handling, transport, individual identification and marking, substance administration, anaesthesia, analgesia and humane killing.

  18. Çanakkale Muharebelerimde Cephede ve Cephe Dışında Sağlık Hizmetleri

    Directory of Open Access Journals (Sweden)

    Ahmet ESENKAYA

    2011-04-01

    Full Text Available It is essential to know not only the shooting-war in the combats occurred in different fronts in the Gallipoli peninsula like Seddülbahir, Arıburnu, Anafartalar and Suvla, but also how the medical services such as hospital was operated in those fronts. With launching the Gallipoli campaign, the entente states aimed at a front which would last very shortly and bring many gains. However, their all expectations came to naught. The Gallipoli became a long-duration battle-front and resulted in more casualties than expected. On the other hand, that situation was a resurrection for Turkish people. Nevertheless, the price of the victory was very high. Due to long-term battle, there were so many injuries as much as the number of deaths. The case of injury was accompanied by pediculosis, malaria, cholera, dysentery, paratyphoid, typhus, icterus, inflammation and scorbutic. Besides, the war environment also brought about some other health problems among soldiers. These were in general insomnia, asthenia, irregular heartbeats and deafness. Despite all these problems, hygenic measures were carried out sensitively. The Turkish Medical Department averted any imminent spread of infectious disease among the army which was deployed in a narrow area. In 9 months, 110.220 injuries, 70.939 patients and those who needed sick leave were sent to the hospitals of "Menzil" and "Kızılay". In this period, 48.268 patients and 22.619 injuries were treated at hospitals. Surprisingly, the deathrate at hospitals was low. Only 11.6 per cent of patients and 2.7 per cent of injuries were lost. The hospitals of the fifth army were dominantly in østanbul. When the hospitals reached full capacity, the army and Kızılay began to use the public buildings such as schools as hospitals, just like the Balkan wars. Since most of their students were in the battle, the medical schools, Gülhane and østanbul, interrupted their education and became additional military hospitals. This health service was carried out under the authority of the chief physician of the command of Istanbul along with the domestic health committees, stretching over øzmit, Eskiúehir and Konya, in addition to the whole eastern Thrace. To transport the patients and injuries, it was tried to use a variety of land and sea vehicles as much as possible. The volunteers of charities, such as "The Consumption of National Women Association" (østihlak-ı Milli Kadınlar Cemiyeti, "the Association of Kızılay", "The Associations of the Turkish Hearts" (Türk Ocakları Cemiyeti and "The Associations of the Navy" (Donanma Cemiyetleri, and the nun teachers and nurses from non-Muslim civils worked at those hospitals. Moreover, the wives of the civil and military superior persons served voluntarily as nurse. It is an indispensible necessity of the scientific method to make the next generations known about these unnamed and humble muslim and non-muslim doctors of the war who assumed a hard task by serving in a great effort in a quite difficult battle zone, or at least to immortalize them by giving their names to medical institutions. In the end, this study is a modest essay. Although a number of primary sources have been used for this study, it may have some shortcomings in many aspects, due to the inadequacy of the materials.

  19. United Kingdom Shadow Secretary of State for Universities and Skills David Willetts MP (centre) in front of the CMS detector with (from left to right) A. Barr, Partner and Founder, Matterhorn Investment Management LLP P. Bate, S. Harper, M. Willetts, T. Virdee, J. Ellis, CMS Spokesperson G. Tonelli, CMS Technical Coordinator A. Ball and (front) Partner, Caravel Capital H. Hsueh and P. Wells. Monday 4th January 2010

    CERN Multimedia

    Maximilien Brice; Point 5

    2010-01-01

    United Kingdom Shadow Secretary of State for Universities and Skills David Willetts MP (centre) in front of the CMS detector with (from left to right) A. Barr, Partner and Founder, Matterhorn Investment Management LLP P. Bate, S. Harper, M. Willetts, T. Virdee, J. Ellis, CMS Spokesperson G. Tonelli, CMS Technical Coordinator A. Ball and (front) Partner, Caravel Capital H. Hsueh and P. Wells. Monday 4th January 2010

  20. Muhsin Ertuğrul: Türk Sinemasının Kurucusu mu Yoksa Günah Keçisi mi? / Muhsin Ertuğrul: The Founder or the Scapegoat of Turkish Cinema?

    Directory of Open Access Journals (Sweden)

    Seçkin SEVİM

    2016-10-01

    koymaktır. / Muhsin Ertuğrul (1892-1979 shaped the genetic codes of Turkish cinema with his films he shot in the early decades of the Rebuplic. The literature about Ertuğrul is dominated by Nijat Özön’s critics. Critics that are influenced by Özön’s arguments, held Ertuğrul responsible for the negativities of Turkish cinema. Alim Şerif Onaran’s studies reduced the effect of biased critics about Ertuğrul to some extent. However, the difficulties of struggling in a severe poverty and being a precursor did not prevent Ertuğrul from being considered as a scapegoat. Muhsin Ertuğrul’s theatrical identity supersedes his filmmaker identity as many historians of cinema stated before. Ertuğrul managed to go beyond average only in a few of his films. Even if his cinema heritage can be criticised in many ways, his effort for founding of Turkish cinema cannot be underestimated. Muhsin Ertuğrul has an exceptional place in the history of Turkish cinema because in severe poverty he managed to establish the cinema, which is the most technological branch of arts. Muhsin Ertuğrul’s films can be watched as a reflection of the Kemalist modernisation project. Ertuğrul was a man of culture who struggled to realize the revolutions of the Republic with self-devotion. He was not only the man who made the Turkish women appear in the silver screen but also he became a representative of the ideals of the Rebuplic in field of art during all his life. For this purpose, he was obliged to undertake many missions such as teaching, directing, criticising, acting and translating at the same time. He laid the foundations of theatre and cinema in a country where fighting against epidemic diseases and educating its population at least in a level of primary school were only priorities. Thus, the aim of this study is to put forward the founder role of Muhsin Ertuğrul in Turkish cinema.

  1. Florence Nightingale: Apontamentos sobre a fundadora da Enfermagem Moderna Florence Nightingale: Apuntes sobre la fundadora de la Enfermería Moderna Florence Nightingale: Notes on the founder of Modern Nursing

    Directory of Open Access Journals (Sweden)

    Lúcia Marlene Macário Lopes

    2010-12-01

    amigos y conocidos distinguidos y redactó cerca de 200 obras repartidas entre libros, informes y panfletos, que tuvieron un profundo impacto en la salud y en la reorganización de los servicios de salud. Su obra fue de tal forma revolucionaria y avanzada, que le permitió un alcance mundial, considerado, aún hoy, piedra angular en la profesionalización de la Enfermería.Ahead of her time, although conservative, Florence Nightingale popularized the practice of nursing, allowing the establishment of a new profession for women. A well-educated and cultured woman, she used her knowledge and status to influence health and education policy in her time. She provided nursing care to patients in the battlefields of the Crimea (1854-1856, validating the profession of nursing and setting her on the path to being a status icon and legend. This article is a selected compilation of the literature that aims to honor and make known the path of the person who is considered the founder of modern nursing. Over 90 years of life, Florence Nightingale wrote about 20.000 letters to friends and distinguished acquaintances and wrote about 200 papers, including books, pamphlets and reports, which had a profound impact on health and the reorganization of health services. Her work was revolutionary and advanced in a way that had global outreach, and is still considered nowadays a cornerstone of the professionalization of nursing.

  2. The BARD1 Cys557Ser variant and breast cancer risk in Iceland.

    Directory of Open Access Journals (Sweden)

    Simon N Stacey

    2006-07-01

    of contemporary carriers lived in a single county in the southeast of Iceland and that all carriers shared a SNP haplotype, which is suggestive of a founder event. Cys557Ser was found on the same SNP haplotype background in the HapMap Project CEPH sample of Utah residents.Our findings suggest that BARD1 Cys557Ser is an ancient variant that confers risk of single and multiple primary breast cancers, and this risk extends to carriers of the BRCA2 999del5 mutation.

  3. Backing the Founders: The Case for Unalienable Individual Rights

    Directory of Open Access Journals (Sweden)

    Tibor R. Machan

    2010-12-01

    Full Text Available Many may benefit from revisiting the natural rights support for the fully free society even though the case is on record in several books and numerous scholarly pieces. Here I provide a sketch of that support, with a plethora of references for those who would like to explore the full case.The basic point is that adult human beings are moral agents and as such require in their communities respect for–and at times expert protection of–their individual natural rights. This is what gives rise to a polity of very limited government or law. Like referees at a game, whoever maintains and defends the law must stick to that job and not stray into other projects lest the work become corrupted. Such a society will not guarantee good conduct or prosperity but will have the best chance at these.

  4. A founder project: marketing the domestication baseline for forest trees

    Science.gov (United States)

    C. G. Williams; Floyd E. Bridgwater; C. Dana Nelson

    2004-01-01

    One of the most apparent benefits of forest genomics programmes is to provide genotypic information on the original selections of tree improvement programmes worldwide. In many breeding programmes, brances from these selections were grafted onto seedlings and the grafted seedlings composed the first seed orchards for planting programmes. with advanced generation...

  5. Horia Hulubei, father founder of the Institute of Atomic Physics

    International Nuclear Information System (INIS)

    Stratan, G.

    1999-01-01

    Horia Hulubei (b. November 15, 1896, Jassy, d. November 22, 1972, Bucharest) enrolled in 1915 at the University of Jassy, but his studies were interrupted by the WW I. He volunteered first on the Eastern Front, and then in France as a fighter pilot. Wounded and decorated with Legion d'Honneur, he came back to Romania and worked in the field of civil aviation. He graduated in 1926 from the same University with Magna cum Laudae. In 1927, Hulubei went in Paris with a fellowship at the Physical Chemistry Laboratory of Sorbonne and took his Ph. D. in 1933 with Jean Perrin in the field of X-rays spectroscopy, a domain in which he became one of the best specialists of the time. His papers treat a large area of subjects from the multiple Compton effect (predicted and experimentally discovered by him), Raman spectra, the X-ray spectra of gases (obtained for the first time by him in collaboration with Mademoiselle Yvette Cauchois), the identification of elements by X spectroscopy etc. Winner of two prizes of Paris Academy of Sciences, he was elected Corresponding Member of this prestigious French institution. He was also a Directeur de Recherches at the French National Centre of Scientific Research (CNRS). Back in Romania at the beginning of WW II, Hulubei became Professor of Physics, and in 1941, Rector of Bucharest University. After the war, Professor Hulubei dedicated himself to the organization of Romanian research in the field of Physics. The foundation of the Institute of Atomic Physics (IAP) in 1949 in Bucharest was the realization of his dream to build a modern institution of Western type in his own country, tightly connected with the rest of scientific world by international cooperation. Horia Hulubei was practically removed from his directorship of IAP in 1968, following his nomination in a honorary duty, but he remained in a permanent contact with the people formed by him and with the directions of research initiated by him and continued by his followers. The celebration of the Centennial of his birth in 1996 and the commemoration of 25 years from his death in 1997 have shown that the Romanian scientific community has a vivid remembrance of Horia Hulubei, as a great scientist and organizer of Science, ardent patriot and outstanding example for younger generations. (author)

  6. Genomewide association study identifies no major founder variant in ...

    Indian Academy of Sciences (India)

    2013-12-10

    Dec 10, 2013 ... variant in Caucasian moyamoya disease ... 1Department of Health and Environmental Sciences, Kyoto University Graduate ... a low prevalence in European countries (Goto and Yonekawa. 1992; Kuroda and Houkin 2008). We have found that the p.R4810K variant in the ring finger protein 213 (RNF213).

  7. Galileo, Descartes, and Newton - founders of the language of physics

    Czech Academy of Sciences Publication Activity Database

    Kvasz, Ladislav

    2012-01-01

    Roč. 62, č. 6 (2012), s. 519-614 ISSN 0323-0465 Institutional support: RVO:67985955 Keywords : Galilean physics * Cartesian physics * Newtonian Physics * language of physics Subject RIV: AA - Philosophy ; Religion Impact factor: 1.333, year: 2012

  8. Case for nuclear power. Founders Award Lecture, November 18, 1976

    International Nuclear Information System (INIS)

    Benedict, M.

    1976-01-01

    In the three years since the oil embargo, there have been many proposals for greater utilization of our domestic energy resources, but discouragingly slow progress toward adopting them. President Ford's generally sensible energy message of February, 1976 failed to gain the support of a Democratic Congress. Now that the elections are over with the President-Elect and Congress from the same party, it is not too much to hope that a national energy policy will be formulated that will provide for the future energy needs reliably, at an acceptable cost, with low environmental impact and with minimal risk of interruption from overseas. The author proposes to show how increased reliance on nuclear energy can contribute to these goals. Nuclear power plants using light water reactors now have a capacity of 42,000 MW and generate about nine percent of the electricity used in the United States. In some parts of the country 40 percent of the electricity now comes from nuclear plants. By the late 1980s reactors now in operation, under construction, and on order will have a capacity of over 208,000 MW, about 30 percent of the total U.S. capacity expected at that time. If the further projected expansion of nuclear capacity takes place, over 400,000 MW of nuclear power should be in operation by the end of the century, generating around 50 percent of U.S. electricity. The incentives for this increased adoption of nuclear power are its lower cost, the security of its fuel supply, and its lower impact on human health and the environment compared with oil and coal

  9. Gregor Mendel, OSA (1822-1884), founder of scientific genetics.

    Science.gov (United States)

    Dunn, P M

    2003-11-01

    Gregor Mendel, an Augustinian monk and part-time school teacher, undertook a series of brilliant hybridisation experiments with garden peas between 1857 and 1864 in the monastery gardens and, using statistical methods for the first time in biology, established the laws of heredity, thereby establishing the discipline of genetics.

  10. [Charles Robert Darwin: the great founder of scientific evolutionism].

    Science.gov (United States)

    Liang, Qian-Jin; Bin, Jie; Zhang, Gen-Fa

    2009-12-01

    Today, we celebrated 200 years since Charles Darwin, one of the world's most creative and influential thinkers, was born. And there happens to be the 150th anniversary of the publication of his famous book, On the Origin of Species. It is verified that On the Origin of Species is an immortal classic book and is still guiding the study of anagenesis in life science as the development of natural science from then on, and even though most of the ideas in the book are well-known at the present age. In the article, we recall the brilliance and predomination life of Darwin, a great sage with rich scientific achievements, review briefly the novel discoveries and theories after him in the field, and then elucidate the focal points and perspectiveas in near future study of evolution.

  11. [Baron Dominique-Jean Larrey: the founder of urological traumatology].

    Science.gov (United States)

    Hatzinger, M; Ameijenda, C; Lent, V; Sohn, M

    2012-12-01

    Dominique-Jean Larrey (1766-1842) was Surgeon-in-Chief of the Grande Army under Napoleon Bonaparte (1769-1821) and personal physician of the Emperor. Against the opposition of the traditionalists he introduced the "ambulances volantes", the so-called flying ambulances. The aim was the medical treatment of the injured soldiers immediately on the battlefield. This revolutionary treatment led to a benefit not only for the own soldiers, but also for the wounded enemies. His innovation in the field of immediate assistance of wounded persons, together with Larreys' outstanding medical competence, saved thousands of soldiers lives on the battlefield of the Napoleonic wars. His memories concerning the military campaigns, have been even up to the 20th century one of the standard works of modern military surgery. He had as well great interest in urolological injuries of the urinary system and their conservative and operative care. Up to these days, his work shows a surprising actuality and perfect anatomic understanding. In a time without anaesthetics, antibiotics and under primitive circumstances, Larrey and his collegues accomplished surgical feats. Larreys flying ambulances were copied by many different countries. The American Mobile Army Surgical Hospital (M.A.S.H) is clearly based on his thoughts and ideals. In our opinion he is the father of the modern war surgery as well the urological traumatology. Georg Thieme Verlag KG Stuttgart · New York.

  12. Entrepreneurial Founder Effects in the Growth of Regional Clusters

    DEFF Research Database (Denmark)

    Dahl, Michael Slavensky; Pedersen, Christian Ø. R.; Dalum, Bent

    How can the growth of regional clusters be explained? This paper studies in great detail the growth of the wireless communication cluster in Northern Denmark. Unlike the dominant theories, we argue that initial success of the first firms are the main driving force behind the generation of new firms...

  13. [Max Hirsch founder of rheumatology in Germany: banished and murdered].

    Science.gov (United States)

    Keitel, W

    2014-08-01

    The Jewish physician and scientist Dr. Max Hirsch (1875-1941) made a substantial contribution to consolidation of the foundations of his professional discipline, balneology, and in particular developed the social aspects. He recognized the economic significance of diseases of the musculoskeletal system very early on and gathered important ideas from abroad. Together with the department head in the Prussian Ministry of Education and Cultural Affairs, the Privy Councillor Prof. Dr. Eduard Dietrich and later alone, he was editor of various balneological journals. He worked as general secretary of the Deutsche Gesellschaft für Rheumatologie (German Society of Rheumatology) from the beginning of its existence (1927) and created the publication series Veröffentlichungen der Deutschen Gesellschaft für Rheumabekämpfung (Publications of the German Society against Rheumatism) and Rheuma-Jahrbuch (Annual review of rheumatology) in 1929, 1930 and 1931 and organized seven rheumatology congresses up to 1933. After the accession to power of the National Socialists, Max Hirsch and Eduard Dietrich were deposed from office. Hirsch emigrated to Latvia via Switzerland and the Soviet Union with his wife and one son where they were murdered in the course of the Jewish pogrom. The second son escaped with his family to Sweden.

  14. Miguel Angel Matute, founder and promoter of scientific culture

    Directory of Open Access Journals (Sweden)

    Giovanni L. Villalón-García

    2017-06-01

    Full Text Available Miguel Ángel Matute Peña is one of the highest voices of the Universidad de Oriente. His professional performance is characterized to extend several fields of the knowledge where he left a good mark of theorist depth, command of the contents, professional exemplarity and the acting as a teacher that marked the interest of the students to know more about the science that he explained. In this work, the author states the main arguments that demonstrate the role that teacher Matute Peña had in the foundation of the Schools of Physics and Sociology, his leadership in the philosophical studies of Mathematics and in the boarding of the field studies in the communities of Santiago de Cuba, between other aspects.

  15. Microsoft founder opens the Windows of the micro-world

    CERN Multimedia

    2009-01-01

    On Monday 8 June Bill Gates came to CERN for a short visit along with his son Rory. The Bulletin managed to grab a few words with him and discovered how much he appreciates (and supports) fundamental science. After meeting CERN Director-General Rolf Heuer, Gates and his son were given an introduction to CERN by Sergio Bertolucci, Director for Research, and then had a tour of the LHC tunnel, the Control Centre and SM18 with Mike Lamont before heading down to the CMS cavern guided by Jim Virdee, CMS Spokesperson, and Wolfram Zeuner.Millions of kids around the world dream of becoming the next Bill Gates, but Gates’ own son may well dream of becoming a physicist. "One of the reasons we wanted to come here is because Rory, my 10-year-old son, has shown a real interest in physics", explains Gates. "Rory has received some extra home-schooling in science. A lot of what we’ve been discussing has been building up to actually being able to s...

  16. Genomewide association study identifies no major founder variant in ...

    Indian Academy of Sciences (India)

    Young onset (<15 year). 14. –. Adult onset (≤15 year). 24. –. Clinical symptoms. Cerebral infarction. 18. –. TIAb. 6. –. Stroke. 3. –. Headache. 4. –. Hemorrhage. 1. –. Epilepsy. 2. –. Asymptomatic. 1. –. Otherc. 3. –. Clinical status. Bilateral. 35. –. Unilateral. 3. –. aSD, standard deviation; bTIA, transient ischemic attack; cother, ...

  17. A putative founder effect for Parkinson's disease in South African ...

    African Journals Online (AJOL)

    arose in German immigrants from the Volga river region in the 17th century,[1] and in PD ... be most useful to identify individuals who are genetically at risk for developing ... A major advantage of genetic studies is not only that they identify the ...

  18. George de Hevesy (1885 - 1966), founder of radioanalytical chemistry

    International Nuclear Information System (INIS)

    Niese, S.

    2006-01-01

    George de Hevesy has founded Radioanalytical Chemistry and Nuclear Medicine, discovered the element hafnium and first separated stable isotopes. For all these different important achievements he was nominated for the Nobel Prize. On occasion of his discovery of activation analysis 70 years ago his life and work will be illustrated. (author)

  19. Satyendranath Bose: Co-Founder of Quantum Statistics

    Science.gov (United States)

    Blanpied, William A.

    1972-01-01

    Satyendranath Bose was first to prove Planck's Law by using ideal quantum gas. Einstein credited Bose for this first step in the development of quantum statistical mechanics. Bose did not realize the importance of his work, perhaps because of peculiar academic settings in India under British rule. (PS)

  20. Population genetic testing for cancer susceptibility: founder mutations to genomes.

    Science.gov (United States)

    Foulkes, William D; Knoppers, Bartha Maria; Turnbull, Clare

    2016-01-01

    The current standard model for identifying carriers of high-risk mutations in cancer-susceptibility genes (CSGs) generally involves a process that is not amenable to population-based testing: access to genetic tests is typically regulated by health-care providers on the basis of a labour-intensive assessment of an individual's personal and family history of cancer, with face-to-face genetic counselling performed before mutation testing. Several studies have shown that application of these selection criteria results in a substantial proportion of mutation carriers being missed. Population-based genetic testing has been proposed as an alternative approach to determining cancer susceptibility, and aims for a more-comprehensive detection of mutation carriers. Herein, we review the existing data on population-based genetic testing, and consider some of the barriers, pitfalls, and challenges related to the possible expansion of this approach. We consider mechanisms by which population-based genetic testing for cancer susceptibility could be delivered, and suggest how such genetic testing might be integrated into existing and emerging health-care structures. The existing models of genetic testing (including issues relating to informed consent) will very likely require considerable alteration if the potential benefits of population-based genetic testing are to be fully realized.

  1. The founders of the ININ; Los fundadores del ININ

    Energy Technology Data Exchange (ETDEWEB)

    Bulbulian, S [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2006-07-01

    The Mexican government sent the constituent law of the National Commission of Nuclear Energy (CNEN) at December 31, 1955. This classification enters in validity the January 1, 1956. However the Commission began to work in the last months 1956. This institution development two main activities: 1. A program of training on techniques with radioisotopes and nuclear instrumentation and 2. The creation of specialized programs and laboratories. Very important persons in the CNEN were the members of the Commission, the Dr. Manuel Sandoval Vallarta, the Dr. Nabor Carrillo Flores and the Atty. Jose Maria Ortiz Tirado, President of this institution. (Author)

  2. The founder of the Friends Foundation--Tessie Soi.

    Science.gov (United States)

    Topurua, Ore

    2013-01-01

    Tessie Soi is well known in Papua New Guinea and beyond for her work with HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients, including through the Friends Foundation, an organization that focuses on helping families affected by HIV and AIDS. This article explores Tessie's early life and childhood, providing insight into some of the values she learned from her parents. Providing details about the Friends Foundation and the Orphan Buddy Systems program, a program Tessie established to support AIDS orphans, the article offers insight into Tessie's beliefs and compassion, simultaneously highlighting the value she places on her family.

  3. Overoptimism among Founders: The Role of Information and Motivation

    NARCIS (Netherlands)

    I. Verheul (Ingrid); M.A. Carree (Martin)

    2008-01-01

    textabstractThis study empirically investigates factors that influence overoptimism across nascent entrepreneurs. We distinguish between two main groups of determinants (information, motivation) and three types of overoptimism (income, psychological burden, leisure time). Findings indicate that

  4. A worldwide survey of human male demographic history based on Y-SNP and Y-STR data from the HGDP-CEPH populations

    NARCIS (Netherlands)

    W. Shi (Wentao); Q. Ayub (Qasim); M. Vermeulen (Mark); R.G. Shao (Rong Guang); S.B. Zuniga (Sofia); K. van der Gaag (Kristiaan); P. de Knijff (Peter); M.H. Kayser (Manfred); Y. Xue (Yali); C. Tyler-Smith (Chris)

    2010-01-01

    textabstractWe have investigated human male demographic history using 590 males from 51 populations in the Human Genome Diversity Project-Centre d'Étude du Polymorphisme Humain worldwide panel, typed with 37 Y-chromosomal Single Nucleotide Polymorphisms and 65 Y-chromosomal Short Tandem Repeats and

  5. Comparison of multipoint linkage analyses for quantitative traits in the CEPH data: parametric LOD scores, variance components LOD scores, and Bayes factors.

    Science.gov (United States)

    Sung, Yun Ju; Di, Yanming; Fu, Audrey Q; Rothstein, Joseph H; Sieh, Weiva; Tong, Liping; Thompson, Elizabeth A; Wijsman, Ellen M

    2007-01-01

    We performed multipoint linkage analyses with multiple programs and models for several gene expression traits in the Centre d'Etude du Polymorphisme Humain families. All analyses provided consistent results for both peak location and shape. Variance-components (VC) analysis gave wider peaks and Bayes factors gave fewer peaks. Among programs from the MORGAN package, lm_multiple performed better than lm_markers, resulting in less Markov-chain Monte Carlo (MCMC) variability between runs, and the program lm_twoqtl provided higher LOD scores by also including either a polygenic component or an additional quantitative trait locus.

  6. A single-tube 27-plex SNP assay for estimating individual ancestry and admixture from three continents.

    Science.gov (United States)

    Wei, Yi-Liang; Wei, Li; Zhao, Lei; Sun, Qi-Fan; Jiang, Li; Zhang, Tao; Liu, Hai-Bo; Chen, Jian-Gang; Ye, Jian; Hu, Lan; Li, Cai-Xia

    2016-01-01

    A single-tube multiplex assay of a small set of ancestry-informative markers (AIMs) for effectively estimating individual ancestry and admixture is an ideal forensic tool to trace the population origin of an unknown DNA sample. We present a newly developed 27-plex single nucleotide polymorphism (SNP) panel with highly robust and balanced differential power to perfectly assign individuals to African, European, and East Asian ancestries. Evaluating 968 previously described intercontinental AIMs from three HapMap population genotyping datasets (Yoruban in Ibadan, Nigeria (YRI); Utah residents with Northern and Western European ancestry from the Centre de'Etude du Polymorphism Humain (CEPH) collection (CEU); and Han Chinese in Beijing, China (CHB)), the best set of markers was selected on the basis of Hardy-Weinberg equilibrium (p > 0.00001), population-specific allele frequency (two of three δ values >0.5), according to linkage disequilibrium (r (2) ancestry of the 11 populations in the HapMap project. Then, we tested the 27-plex SNP assay with 1164 individuals from 17 additional populations. The results demonstrated that the SNP panel was successful for ancestry inference of individuals with African, European, and East Asian ancestry. Furthermore, the system performed well when inferring the admixture of Eurasians (EUR/EAS) after analyzing admixed populations from Xinjiang (Central Asian) as follows: Tajik (68:27), Uyghur (49:46), Kirgiz (40:57), and Kazak (36:60). For individual analyses, we interpreted each sample with a three-ancestry component percentage and a population match probability sequence. This multiplex assay is a convenient and cost-effective tool to assist in criminal investigations, as well as to correct for the effects of population stratification for case-control studies.

  7. An unusual haplotype structure on human chromosome 8p23 derived from the inversion polymorphism.

    Science.gov (United States)

    Deng, Libin; Zhang, Yuezheng; Kang, Jian; Liu, Tao; Zhao, Hongbin; Gao, Yang; Li, Chaohua; Pan, Hao; Tang, Xiaoli; Wang, Dunmei; Niu, Tianhua; Yang, Huanming; Zeng, Changqing

    2008-10-01

    Chromosomal inversion is an important type of genomic variations involved in both evolution and disease pathogenesis. Here, we describe the refined genetic structure of a 3.8-Mb inversion polymorphism at chromosome 8p23. Using HapMap data of 1,073 SNPs generated from 209 unrelated samples from CEPH-Utah residents with ancestry from northern and western Europe (CEU); Yoruba in Ibadan, Nigeria (YRI); and Asian (ASN) samples, which were comprised of Han Chinese from Beijing, China (CHB) and Japanese from Tokyo, Japan (JPT)-we successfully deduced the inversion orientations of all their 418 haplotypes. In particular, distinct haplotype subgroups were identified based on principal component analysis (PCA). Such genetic substructures were consistent with clustering patterns based on neighbor-joining tree reconstruction, which revealed a total of four haplotype clades across all samples. Metaphase fluorescence in situ hybridization (FISH) in a subset of 10 HapMap samples verified their inversion orientations predicted by PCA or phylogenetic tree reconstruction. Positioning of the outgroup haplotype within one of YRI clades suggested that Human NCBI Build 36-inverted order is most likely the ancestral orientation. Furthermore, the population differentiation test and the relative extended haplotype homozygosity (REHH) analysis in this region discovered multiple selection signals, also in a population-specific manner. A positive selection signal was detected at XKR6 in the ASN population. These results revealed the correlation of inversion polymorphisms to population-specific genetic structures, and various selection patterns as possible mechanisms for the maintenance of a large chromosomal rearrangement at 8p23 region during evolution. In addition, our study also showed that haplotype-based clustering methods, such as PCA, can be applied in scanning for cryptic inversion polymorphisms at a genome-wide scale.

  8. [ELIE METCHNIKOFF--THE FOUNDER OF LONGEVITY SCIENCE AND A FOUNDER OF MODERN MEDICINE: IN HONOR OF THE 170TH ANNIVERSARY].

    Science.gov (United States)

    Stambler, I S

    2015-01-01

    The years 2015-2016 mark a double anniversary--the 170th anniversary of birth and the 100th anni- versary of death--of one of the greatest Russian scientists, a person that may be considered a founding figure of modern immunology, aging and longevity science--Elie Metchnikoff (May 15, 1845-July 15, 1916). At this time of the rapid aging of the world population and the rapid development of technologies that may ameliorate degenerative aging processes, Metchnikoff's pioneering contribution to the search for anti-aging and healthspan-extending means needs to be recalled and honored.

  9. IDENTIFIKASI IKAN CUPANG (Betta imbelis TRANSGENIK FOUNDER MEMBAWA GEN PENYANDI HORMON PERTUMBUHAN; Identification of Transgenic Founder Betta Fish (Betta imbelis Carry Growth Hormone Gene.

    Directory of Open Access Journals (Sweden)

    Eni Kusrini

    2017-01-01

    Full Text Available Penelitian dilakukan untuk mengidentifikasi keberhasilan introduksi gen penyandi hormon pertumbuhan (Growth Hormone, GH pada induk F-0 ikan Betta imbellis. Ikan transgenik F-0 dibuat dengan menggunakan metode transfeksi. Identifikasi dilakukan menggunakan metode RT-PCR. RNA total diekstraksi dari embrio pooled sample hasil persilangan induk transgenik dan non-transgenik. Berdasarkan analisis ekspresi gen pada embrio juga menunjukkan adanya aktivitas ekspresi gen GH pada semua perlakuan dibandingkan dengan kontrol (embrio hasil persilangan non-transgenik x non-transgenik. Jumlah individu induk F-0 yang membawa gen GH eksogen berdasarkan analisis PCR dengan DNA template dari sirip ekor adalah sebanyak 16%. Individu positif membawa gen GH eksogen tersebut dibesarkan lebih lanjut untuk memproduksi Betta imbellis transgenik F-1. Kandidat ikan transgenik jantan F-0 dikawinkan dengan ikan non-transgenik betina, sedangkan transgenik F-0 betina dikawinkan dengan non-transgenik jantan. Sebanyak 30-50 butir embrio hasil pemijahan F-0 digabung, kemudian DNA genom diekstrak. Sebagian embrio digunakan untuk ekstraksi RNA total untuk analisis ekspresi mRNA GH eksogen. Hasil analisis PCR menunjukkan bahwa semua sampel embrio dari induk transgenik F-0 dapat terdeteksi gen GH eksogen, sedangkan untuk kontrol (non-transgenik tidak terdeteksi. Ekspresi mRNA juga terdeteksi pada embrio F-1. Dengan demikian, metode transfeksi embrio Betta imbellis efektif digunakan untuk menghasilkan ikan transgenik, dan sangat berpotensi menghasilkan individu F-1 Betta imbellis dengan pertumbuhan lebih cepat. The study was conducted to identify the successful introduction of the growth hormone gene (Growth Hormone, GH on the F-0 Betta imbellis broodstock. The F-0 transgenic fish was made through transfection methods. Identification was done using RT-PCR method. Total RNA was extracted from pooled embryos sample. Based on the analysis of gene expression in embryos also showed activity GH gene expression in all treatments compared to the control (non-transgenic x non-transgenic. The number of individuals F-0 which carried exogenous GH gene by PCR analysis of the DNA template of the tail fin was as much as 16%. Positive individuals carried the exogenous GH gene raised further to produce transgenic F-1 B. imbellis. Candidate of transgenic F-0 males fish were mated with non-transgenic female fish, whereas the transgenic F-0 females were mated with non-transgenic males. The 30-50 embryos obtained were combined, then their genomic DNA were extracted. Some of the embryos was used for the extraction of total RNA for analysis of mRNA expression of GH exogenous. The PCR analysis showed that all samples of embryos from the transgenic F-0 broodstock could be detected, whereas for the control (non-transgenic was not detected. mRNA expression was also detected in embryos of F-1. The average weight of the F-0 broodstocks were 1.55 g and a total length was 12.97 cm. Thus, the transfection methods through betta embryos peaceful effectively generated transgenic fish, and potentially produced fast growth of individuals F-1 Betta imbellis.

  10. Creator of Economic Opera, Founder and Reformer of Economic School – the Rector Paul Bran

    Directory of Open Access Journals (Sweden)

    Ghenadie Ciobanu

    2014-05-01

    Full Text Available Phd. Prof. Paul Bran (1940-2006, during the mandates of rector of the Bucharest University of Economic Studies (1996-2004 and beyond, although financier proved close to the Faculty of Commerce. In 2001, at the jubilee of the uninterrupted operation of the faculty, he stated: We join alumni, students and professors of the Faculty of Commerce to pay tribute to the work of learning and education that takes place here and to honor those who have established and then strengthened higher economic education in trade, marketing, tourism and commodity. I am convinced that the reputation of the Bucharest University of Economic Studies is due mainly to the quality of the activities taking place in departments and laboratories of the Faculty of Commerce.” On another occasion, the dedication on a book, he wrote: “Because tourism lives by money and money through tourism.” There are only two instances, seemingly unimportant, but which can be multiplied to the whole of his professional career of over four decades, and they shows us the Professor and Rector Paul Bran – both charismatic and effective – as a friend of the Faculty of Commerce. “Sincere congratulations and best wishes on the first issue of the journal Amfiteatru Economic,” said Rector Paul Bran, visionary, on the cover of the first issue of our publication, in 1999.

  11. African therapy for a fractured world(view): The life of founder bishop ...

    African Journals Online (AJOL)

    2015-06-26

    Jun 26, 2015 ... spirit-matter worldview. Read online: ... liturgical rituals to be found in this church, and his life story, or rather stories, are also still exercising that role after ..... Indians, Blacks and others, and that is where they met each other.

  12. Founder effect in 20 Afrikaner kindreds with pse·udoxanthoma ...

    African Journals Online (AJOL)

    1991-01-05

    Jan 5, 1991 ... geographical reasons the Mrikaner is an isolate population. Department of Medical Genealogy, Institute for Biostatis- tics ofthe South Mrican Medical Research Council, Parow- vallei, CP. M. TORRINGTON, D. PHIL. Department of Human Genetics and MRC Unit for. Inherited Skeletal Disorders, University ...

  13. High genetic diversity and absence of founder effects in a worldwide aquatic invader.

    Science.gov (United States)

    Lejeusne, Christophe; Saunier, Alice; Petit, Nicolas; Béguer, Mélanie; Otani, Michio; Carlton, James T; Rico, Ciro; Green, Andy J

    2014-07-24

    The introduced oriental shrimp Palaemon macrodactylus has recently become widespread in temperate estuaries worldwide. However, this recent worldwide spread outside of its native range arises after a previous introduction to the US Pacific coast, where it was restricted for more than 30 years. Using a phylogeographic approach, the present work investigates the genetic history of the invasion of this decapod worldwide. Japan acted as the main native source area for worldwide introduced populations, but other native areas (likely South Korea and China) may act as source populations as well. The recently introduced European and NW Atlantic populations result from colonization from both Japan and an unknown area of the native range, although colonization from the NE Pacific could not be ruled out. Most introduced populations had higher haplotypic diversity than most native populations. P. macrodactylus has a strong potential to become one of the most widespread introduced species and may become the dominant estuarine shrimp in Europe. The ecological and economic consequences of this invasion remain to be thoroughly evaluated.

  14. Social Entrepreneurship As Competence For Founders Of Social Enterprises In Romania And The Netherlands

    NARCIS (Netherlands)

    Joop Vinke; Loredana Orhei; S. Nandram

    2013-01-01

    Social entrepreneurship is currently at an early stage of knowledge development, both on the European Continent, as well as internationally. To a large extent, studies originate from theory, are based on small-scale individual case studies or have identified social entrepreneurship based on an

  15. A homozygous PMS2 founder mutation with an attenuated constitutional mismatch repair deficiency phenotype.

    Science.gov (United States)

    Li, Lili; Hamel, Nancy; Baker, Kristi; McGuffin, Michael J; Couillard, Martin; Gologan, Adrian; Marcus, Victoria A; Chodirker, Bernard; Chudley, Albert; Stefanovici, Camelia; Durandy, Anne; Hegele, Robert A; Feng, Bing-Jian; Goldgar, David E; Zhu, Jun; De Rosa, Marina; Gruber, Stephen B; Wimmer, Katharina; Young, Barbara; Chong, George; Tischkowitz, Marc D; Foulkes, William D

    2015-05-01

    Inherited mutations in DNA mismatch repair genes predispose to different cancer syndromes depending on whether they are mono-allelic or bi-allelic. This supports a causal relationship between expression level in the germline and phenotype variation. As a model to study this relationship, our study aimed to define the pathogenic characteristics of a recurrent homozygous coding variant in PMS2 displaying an attenuated phenotype identified by clinical genetic testing in seven Inuit families from Northern Quebec. Pathogenic characteristics of the PMS2 mutation NM_000535.5:c.2002A>G were studied using genotype-phenotype correlation, single-molecule expression detection and single genome microsatellite instability analysis. This PMS2 mutation generates a de novo splice site that competes with the authentic site. In homozygotes, expression of the full-length protein is reduced to a level barely detectable by conventional diagnostics. Median age at primary cancer diagnosis is 22 years among 13 NM_000535.5:c.2002A>G homozygotes, versus 8 years in individuals carrying bi-allelic truncating mutations. Residual expression of full-length PMS2 transcript was detected in normal tissues from homozygotes with cancers in their 20s. Our genotype-phenotype study of c.2002A>G illustrates that an extremely low level of PMS2 expression likely delays cancer onset, a feature that could be exploited in cancer preventive intervention. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Founders, Finding, Being Found: Women's Wisdom in Teaching and Learning in Theology and Religion

    Science.gov (United States)

    Hess, Lisa M.; Brosmer, Mary Pierce; Moore, Mary Elizabeth Mullino

    2015-01-01

    This is an edited transcript of a conversation between two founding women on the delights and demands of teaching and learning within and beyond traditional institutional life, facilitated by Lisa M. Hess of the journal's Editorial Board. The conscious feminine practices of a women's writing school, Women Writing for (a) Change (Cincinnati, Ohio),…

  17. A Dutch Fanconi Anemia FANCC Founder Mutation in Canadian Manitoba Mennonites

    NARCIS (Netherlands)

    de Vries, Yne; Lwiwski, Nikki; Levitus, Marieke; Kuyt, Bertus; Israels, Sara J.; Arwert, Fré; Zwaan, Michel; Greenberg, Cheryl R.; Alter, Blanche P.; Joenje, Hans; Meijers-Heijboer, Hanne

    2012-01-01

    Fanconi anemia (FA) is a recessive DNA instability disorder associated with developmental abnormalities, bone marrow failure, and a predisposition to cancer. Based on their sensitivity to DNA cross-linking agents, FA cells have been assigned to 15 complementation groups, and the associated genes

  18. Commemorating Geoffrey Raisman: a great neuroscientist and one of the founders of neurorestoratology and the IANR

    Directory of Open Access Journals (Sweden)

    Li Y

    2018-03-01

    Full Text Available Ying Li,1 Pawel Tabakow,2 Daqing Li,1 Hongyun Huang3 On behalf of the International Association of Neurorestoratology 1Spinal Repair Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, UK; 2Department of Neurosurgery, Wroclaw Medical University, Wroclaw, Poland; 3Institute of Neurorestoratology, General Hospital of Armed Police Forces, Beijing, People’s Republic of China One year ago (January 27, 2017, the sad news that Life Honorary President of the International Association of Neurorestoratology (IANR, Geoffrey Raisman (Figure 1 had passed away shocked all our association members. We could hardly hide our grief. Besides expressing our grief and condolences to his wife, Vivian; his daughter, Ruth; and all his family, the Core Administration members communicated among each other via email and made a proposal to rename the Youth Forum of the Annual Conference, to the Raisman Youth Forum of the Annual Conference. The fourth IANR Council Board meeting in Argentina on September 29, 2017 approved this motion, and decided to establish the Raisman Neurorestoratology Foundation and to write an article commemorating him to be published in the Journal of Neurorestoratology. This commemorative article is divided into three parts: 1 his students and colleagues Daqing Li and Ying Li introduce his life and work; 2 his collaborating partner Pawel Tabakow introduces the process of their clinical trial; and 3 Hongyun Huang on behalf of the IANR introduces Geoffrey Raisman’s contribution to neurorestoratology and IANR. All individuals in the included images have provided written informed consent for the images to be published. 

  19. 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 stu...... understanding of BHD syndrome and management of BHD patients.Journal of Human Genetics advance online publication, 13 October 2016; doi:10.1038/jhg.2016.118....

  20. [Doctor Levi B. Salmans, founder of The Good Samaritan sanitarium in Guanajuato].

    Science.gov (United States)

    Olivier-Toledo, Carlos; Viesca-Treviño, Carlos

    2016-01-01

    In this research we focus on the medical evangelist Levi B. Salmans, and The Good Samaritan sanitarium. Doctor Salmans lived in Mexico for about 50 years (1885-1935). During the first part of his stay, he was devoted to found churches and Methodist schools. However, from 1891 he took a turn in his career by founding dispensaries in different towns of Guanajuato to create, in 1899, the private charity association for the sick and infirm The Good Samaritan. His intense, intellectual, and practical work led him to create health journals, to train nurses, and to promote physiotherapies in accordance with the science advances of that time. By itself, this research shows that the history of medicine in Mexico still has long way to go and that Protestant communities, in favor of modernity and scientific knowledge, took a big part in shaping the history of this discipline in Mexico.

  1. Family Business Succession: Founders from Disadvantaged Communities in South Africa--An Exploratory Study

    Science.gov (United States)

    Isaacs, Eslyn B. H.; Friedrich, Christian

    2011-01-01

    It is estimated that 50-70% of all South African businesses are family-owned and that these businesses form the backbone of the South African economy, their qualities providing stability and resilience in the changing society of the nation. Succession is one of the biggest challenges for family business owners. Research shows that only 33% of all…

  2. From concept to certification; interview with AD&C co-founder and CEO Marcus Basien

    NARCIS (Netherlands)

    L'Ortye, J.; Spranger, L.

    2013-01-01

    Before any aircraft concept takes to the sky, air travel authorities require the aircraft be certified. One would expect a big organisation like EASA would function like a centralised verification authority. However, small companies like Aircraft Design & Certification Ltd. offer certification

  3. The Founder's Lecture 2009: advances in imaging of osteoporosis and osteoarthritis

    International Nuclear Information System (INIS)

    Link, Thomas Marc

    2010-01-01

    The objective of this review article is to provide an update on new developments in imaging of osteoporosis and osteoarthritis over the past three decades. A literature review is presented that summarizes the highlights in the development of bone mineral density measurements, bone structure imaging, and vertebral fracture assessment in osteoporosis as well as MR-based semiquantitative assessment of osteoarthritis and quantitative cartilage matrix imaging. This review focuses on techniques that have impacted patient management and therapeutic decision making or that potentially will affect patient care in the near future. Results of pertinent studies are presented and used for illustration. In summary, novel developments have significantly impacted imaging of osteoporosis and osteoarthritis over the past three decades. (orig.)

  4. Social Entrepreneurship Competence: Evidence from Founders of Social Enterprises in Romania

    NARCIS (Netherlands)

    Loredana Orhei; Joop Vinke; S. Nandram

    2014-01-01

    Social entrepreneurship has been defined until now by borrowing insights from commercial, Schumpeterian entrepreneurship as well as a new way of looking at non-profit work (Peredo and McLean, 2006; Short et al., 2009). Inspired by the use of a competence perspective to define entrepreneurship

  5. Virtual School Startups: Founder Processes in American K-12 Public Virtual Schools

    Science.gov (United States)

    Taylor, Brett D.; McNair, Delores E.

    2018-01-01

    Traditional school districts do not have a lot of experience with virtual schools and have lost students to state and charter virtual schools. To retain students and offer alternative learning opportunities, more public districts are starting their own virtual schools. This study was an examination of foundational processes at three California…

  6. Distribution and medical impact of loss-of-function variants in the Finnish founder population

    NARCIS (Netherlands)

    Lim, Elaine T.; Würtz, Peter; Havulinna, Aki S.; Palta, Priit; Tukiainen, Taru; Rehnström, Karola; Esko, Tõnu; Mägi, Reedik; Inouye, Michael; Lappalainen, Tuuli; Chan, Yingleong; Salem, Rany M.; Lek, Monkol; Flannick, Jason; Sim, Xueling; Manning, Alisa; Ladenvall, Claes; Bumpstead, Suzannah; Hämäläinen, Eija; Aalto, Kristiina; Maksimow, Mikael; Salmi, Marko; Blankenberg, Stefan; Ardissino, Diego; Shah, Svati; Horne, Benjamin; McPherson, Ruth; Hovingh, Gerald K.; Reilly, Muredach P.; Watkins, Hugh; Goel, Anuj; Farrall, Martin; Girelli, Domenico; Reiner, Alex P.; Stitziel, Nathan O.; Kathiresan, Sekar; Gabriel, Stacey; Barrett, Jeffrey C.; Lehtimäki, Terho; Laakso, Markku; Groop, Leif; Kaprio, Jaakko; Perola, Markus; McCarthy, Mark I.; Boehnke, Michael; Altshuler, David M.; Lindgren, Cecilia M.; Hirschhorn, Joel N.; Metspalu, Andres; Freimer, Nelson B.; Zeller, Tanja; Jalkanen, Sirpa; Koskinen, Seppo; Raitakari, Olli; Durbin, Richard; MacArthur, Daniel G.; Salomaa, Veikko; Ripatti, Samuli; Daly, Mark J.; Palotie, Aarno

    2014-01-01

    Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent

  7. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects.

    Directory of Open Access Journals (Sweden)

    Jinglan Zhang

    2016-04-01

    Full Text Available Genetic leukoencephalopathies (gLEs are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS. The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES, we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G, as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026. VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting and CORVET (class C core vacuole/endosome tethering protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway.

  8. Professor Horia Hulubei, the father founder of the Institute of Atomic Physics

    International Nuclear Information System (INIS)

    Stratan, G.

    2000-01-01

    A hero of WW 1, Horia Hulubei (b. November 15, 1896, d. November 22, 1972), was one of the most prominent Romanian scientists of all time, leader and teacher of several generations of Romanian scientists during more than four decades. Graduated from Jassy University, he took his PhD. in Paris with Marie Curie and Jean Perrin in 1933. A few years later, Horia Hulubei was nominated Directeur de Recherches at the French National Centre of Scientific Research and elected Corresponding Member of Paris Academy of Sciences. Back in Romania, Hulubei was nominated professor and Rector of Bucharest University (1941). Professor Hulubei had a broad field of interests, from Classical to Atomic and Nuclear Physics, but his main achievements are connected with the Physics of X-rays (the first spectra of noble gases, the multiple Compton effect, the search for elements 87 and 85, etc.). The Institute of Atomic Physics (IPA) in Bucharest (1949) was the third research institution founded and directed by him. Following Hulubei's initial design, IPA was, and, in spite of the past and actual difficulties, remains, the flagship of Romanian scientific research. Along the years, IPA influenced beneficially the development of the post-war Romania and established many collaborations abroad. (author)

  9. Sister Mary Emil Penet, I.H.M.: Founder of the Sister Formation Conference

    Science.gov (United States)

    Glisky, Joan

    2006-01-01

    Mary Emil Penet, I.H.M., (1916-2001) used her talents and charisma to shape the first national organization of American women religious, the Sister Formation Conference (SFC; 1954-1964), facilitating the integrated intellectual, spiritual, psychological, and professional development of vowed women religious. In the decade preceding Vatican II, her…

  10. Contribution of CYP1B1 mutations and founder effect to primary congenital glaucoma in Mexico.

    Science.gov (United States)

    Zenteno, Juan Carlos; Hernandez-Merino, Elena; Mejia-Lopez, Herlinda; Matías-Florentino, Margarita; Michel, Norma; Elizondo-Olascoaga, Celia; Korder-Ortega, Vincent; Casab-Rueda, Homero; Garcia-Ortiz, Jose Elias

    2008-01-01

    The frequency of primary congenital glaucoma (PCG)-causing CYP1B1 mutations varies importantly among distinct populations, ranging from 20% in Indonesians and Japanese to about 100% among the Saudi Arabians and Slovakian Gypsies. Thus, the molecular characterization of large groups of PCG from different ethnic backgrounds is important to establish the actual CYP1B1 contribution in specific populations. In this work, the molecular analysis of the CYP1B1 gene in a group of Mexican PCG patients is reported. Thirty unrelated Mexican patients fulfilling the clinical criteria for PCG were included. Two cases were familial and with proven consanguinity, originating from distinct regions of the country. Polymerase chain reaction amplification and direct automated sequencing of the CYP1B1 coding region was performed in each participating subject. An identical pathogenic CYP1B1 mutation was demonstrated in 2 unrelated PCG subjects. The mutation consisted of a homozygous G to A transition at nucleotide position 1505 in exon 3, which predicted a substitution of glutamic acid for lysine at residue 387 of the protein (E387K). In the remaining 28 PCG subjects, no deleterious mutations were identified. Both subjects with the E387K mutation shared a same haplotype for 5 CYP1B1 intragenic single nucleotide polymorphisms, indicating a common origin of the allele. Mexican patients with PCG are rarely (less than 10%) due to CYP1B1 mutations. Available data indicate that most of the non-Brazilian Latin American PCG patients investigated to date are not due to CYP1B1 defects. Populations with low incidence of CYP1B1 mutations are appropriate candidates for the identification of novel PCG-causing genes.

  11. Monod as the founder of a new discipline: local and international contexts.

    Science.gov (United States)

    de Chadarevian, Soraya

    2015-06-01

    Monod gained stature as an experimentalist and theorist as well as a discipline builder. The essay reviews the intimate connection of the intellectual and institutional projects in his career. A brief comparison with the development of the new science of molecular biology across the English Channel highlights the commonalities and specificities of the disciplinary projects in France and Britain and the role that individuals like Monod played in their formation. The article argues that there was not a single path that led to the rise of molecular biology. Rather individual initiatives and historical contingencies very much shaped local outcomes. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  12. On the Founder of the Skripou Church: Literary Trends in the Milieu of Photius

    Directory of Open Access Journals (Sweden)

    Oscar Prieto-Domínguez

    2013-02-01

    Full Text Available Leo’s dedicatory poem, inscribed in 873/4, with its classical allusions has affinities with the culture and circle of Photius, and so the author may be the protospatharios Leo addressed in Photius ep. 209.

  13. Founders hope new venture-capital fund will spur medical, biotechnology research

    Science.gov (United States)

    Gray, Charlotte

    1995-01-01

    Lack of a coherent industrial strategy and venture capital have hindered scientific researchers in Canada, but the Canadian Medical Discoveries Fund (CMDF) Inc. hopes to change that. Under the leadership of Dr. Henry Friesen, president of the Medical Research Council of Canada, and Dr. Calvin Stiller, head of the multiorgan transplant unit at University Hospital, London, Ont., the new fund proposes to invest in promising medical and biotechnology research companies in Canada. The research council's peerreview system gives the new fund scientific credibility.

  14. Density of founder cells affects spatial pattern formation and cooperation in Bacillus subtilis biofilms

    NARCIS (Netherlands)

    van Gestel, Jordi; Weissing, Franz J.; Kuipers, Oscar P.; Kovacs, Akos T.

    2014-01-01

    In nature, most bacteria live in surface-attached sedentary communities known as biofilms. Biofilms are often studied with respect to bacterial interactions. Many cells inhabiting biofilms are assumed to express 'cooperative traits', like the secretion of extracellular polysaccharides (EPS). These

  15. Founder event and its effect on genetic variation in translocated populations of noble crayfish (Astacus astacus)

    Czech Academy of Sciences Publication Activity Database

    Bláha, M.; Žurovcová, Martina; Kouba, A.; Policar, T.; Kozák, P.

    2016-01-01

    Roč. 57, č. 1 (2016), s. 99-106 ISSN 1234-1983 Grant - others:European Fund(CZ) CZ.1.07/2.3.00/30.0049; European Fund(CZ) CZ1.05/2.1.00/01.0024; GA ČR(CZ) GAP505/12/0545 Institutional support: RVO:60077344 Keywords : bottleneck * conservation * homozygote excess Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.655, year: 2016 http://link.springer.com/article/10.1007%2Fs13353-015-0296-3

  16. Friedrich Robert Helmert, founder of modern geodesy, on the occasion of the centenary of his death

    Science.gov (United States)

    Ihde, Johannes; Reinhold, Andreas

    2017-08-01

    Friedrich Robert Helmert died in Potsdam in 1917 at the age of 74 after serving for over 30 years as director of the Royal Prussian Geodetic Institute and of the Central Bureau of the Internationale Erdmessung, the forerunner of today's International Association of Geodesy. He dedicated his life and his scientific career to the field of geodesy. His teachings on theoretical and physical geodesy were incorporated into university curricula around the world and hence into international endeavours to measure planet Earth. The purpose of this article is to illustrate the impact he has had on the development of modern geodesy and on the related sciences.

  17. African therapy for a fractured world(view): The life of founder bishop ...

    African Journals Online (AJOL)

    ... is in essence aimed at healing in all its multifaceted dimensions, which includes healing from physical ailments, 'healing' from barrenness, healing from spirit possession to healing as (re-)incorporation of an individual into the larger group, the healing of a nation as well as healing from a dualistic spirit-matter worldview.

  18. Fragile X founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Chiurazzi, P.; Genuardi, M.; Kozak, L.; Neri, G. [Universita Cattolica and Centro Ricerche per la Disabilita Mentale e Motoria, Roma (Italy)] [and others

    1996-07-12

    A total of 137 fragile X and 235 control chromosomes from various regions of Italy were haplotyped by analyzing two neighbouring marker microsatellites, FRAXAC1 and DXS548. The number of CGG repeats at the 5{prime} end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some {open_quotes}major{close_quotes} haplotypes and fragile X was observed, while other {open_quotes}minor{close_quotes} haplotypes may have originated by subsequent mutation at the marker microsatellite loci and/or recombination between them. Recent evidence suggests that the initial mechanism leading to CGG instability might consist of rare (10{sup -6/-7}) CGG repeat slippage events and/or loss of a stabilizing AGG via A-to-C transversion. Also, the apparently high variety of fragile X chromosomes may be partly due to the relatively high mutation rate (10{sup -4/-5}) of the microsatellite markers used in haplotyping. Our fragile X sample also showed a higher than expected heterozygosity when compared to the control sample and we suggest that this might be explained by the chance occurrence of the few founding events on different chromosomes, irrespective of their actual frequency in the population. Alternatively, a local mechanism could enhance the microsatellite mutation rate only on fragile X chromosomes, or fragile X mutations might occur more frequently on certain background haplotypes. 59 refs., 4 figs.

  19. Local-scale invasion pathways and small founder numbers in introduced Sacramento pikeminnow (Ptychocheilus grandis)

    Science.gov (United States)

    Andrew P. Kinziger; Rodney J. Nakamoto; Bret C. Harvey

    2014-01-01

    Given the general pattern of invasions with severe ecological consequences commonly resulting from multiple introductions of large numbers of individuals on the intercontinental scale, we explored an example of a highly successful, ecologically significant invader introduced over a short distance, possibly via minimal propagule pressure. The Sacramento pikeminnow (

  20. Marian Smoluchowski as the founder of the physics of stochastic phenomena

    International Nuclear Information System (INIS)

    Chandrasekhar, S.

    1989-01-01

    This paper present a discussion on Marian Smoluchowski, the originator (along with Einstein) of the theory of Brownian motion; who gave the correct interpretation of the phenomenon of critical opalescence. The author focuses on a series of papers which Smoluchowski wrote in which the foundations of the modern theory of stochastic processes were laid and the related paradoxes of Loschmidt and Zermelo were discussed

  1. Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population

    Science.gov (United States)

    Arenas, I. A.; Tremblay, J.; Deslauriers, B.; Sandoval, J.; Šeda, O.; Gaudet, D.; Merlo, E.; Kotchen, T.; Cowley, A. W.

    2013-01-01

    Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation. PMID:23269701

  2. Founder-specific inbreeding depression affects racing performance in Thoroughbred horses.

    Science.gov (United States)

    Todd, Evelyn T; Ho, Simon Y W; Thomson, Peter C; Ang, Rachel A; Velie, Brandon D; Hamilton, Natasha A

    2018-04-18

    The Thoroughbred horse has played an important role in both sporting and economic aspects of society since the establishment of the breed in the 1700s. The extensive pedigree and phenotypic information available for the Thoroughbred horse population provides a unique opportunity to examine the effects of 300 years of selective breeding on genetic load. By analysing the relationship between inbreeding and racing performance of 135,572 individuals, we found that selective breeding has not efficiently alleviated the Australian Thoroughbred population of its genetic load. However, we found evidence for purging in the population that might have improved racing performance over time. Over 80% of inbreeding in the contemporary population is accounted for by a small number of ancestors from the foundation of the breed. Inbreeding to these ancestors has variable effects on fitness, demonstrating that an understanding of the distribution of genetic load is important in improving the phenotypic value of a population in the future. Our findings hold value not only for Thoroughbred and other domestic breeds, but also for small and endangered populations where such comprehensive information is not available.

  3. Founders lecture 2007. Metabolic bone disease: what has changed in 30 years?

    Energy Technology Data Exchange (ETDEWEB)

    Sundaram, Murali [Cleveland Clinic, Diagnostic Radiology, MSK, Cleveland, OH (United States)

    2009-09-15

    To provide an update on imaging of metabolic bone disease based on new developments, findings, and changing practices over the past 30 years. Literature review of osteoporosis, osteomalacia, renal osteodystrophy, Paget's disease, bisphosphonates, with an emphasis on imaging. Cited references and pertinent findings. Significant developments have occurred in the imaging of metabolic bone disease over the past 30 years. (orig.)

  4. Ancestry dependent DNA methylation and influence of maternal nutrition.

    Directory of Open Access Journals (Sweden)

    Khyobeni Mozhui

    Full Text Available There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112 and European American (EA; N = 91 participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood. Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition--specifically, plasma levels of vitamin D and folate during pregnancy--on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC. Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome.

  5. Extent and distribution of linkage disequilibrium in the Old Order Amish.

    Science.gov (United States)

    Van Hout, Cristopher V; Levin, Albert M; Rampersaud, Evadnie; Shen, Haiqing; O'Connell, Jeffrey R; Mitchell, Braxton D; Shuldiner, Alan R; Douglas, Julie A

    2010-02-01

    Knowledge of the extent and distribution of linkage disequilibrium (LD) is critical to the design and interpretation of gene mapping studies. Because the demographic history of each population varies and is often not accurately known, it is necessary to empirically evaluate LD on a population-specific basis. Here we present the first genome-wide survey of LD in the Old Order Amish (OOA) of Lancaster County Pennsylvania, a closed population derived from a modest number of founders. Specifically, we present a comparison of LD between OOA individuals and US Utah participants in the International HapMap project (abbreviated CEU) using a high-density single nucleotide polymorphism (SNP) map. Overall, the allele (and haplotype) frequency distributions and LD profiles were remarkably similar between these two populations. For example, the median absolute allele frequency difference for autosomal SNPs was 0.05, with an inter-quartile range of 0.02-0.09, and for autosomal SNPs 10-20 kb apart with common alleles (minor allele frequency > or =0.05), the LD measure r(2) was at least 0.8 for 15 and 14% of SNP pairs in the OOA and CEU, respectively. Moreover, tag SNPs selected from the HapMap CEU sample captured a substantial portion of the common variation in the OOA ( approximately 88%) at r(2) > or =0.8. These results suggest that the OOA and CEU may share similar LD profiles for other common but untyped SNPs. Thus, in the context of the common variant-common disease hypothesis, genetic variants discovered in gene mapping studies in the OOA may generalize to other populations. 2009 Wiley-Liss, Inc.

  6. The use of genome-wide eQTL associations in lymphoblastoid cell lines to identify novel genetic pathways involved in complex traits.

    Directory of Open Access Journals (Sweden)

    Josine L Min

    Full Text Available The integrated analysis of genotypic and expression data for association with complex traits could identify novel genetic pathways involved in complex traits. We profiled 19,573 expression probes in Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs from 299 twins and correlated these with 44 quantitative traits (QTs. For 939 expressed probes correlating with more than one QT, we investigated the presence of eQTL associations in three datasets of 57 CEU HapMap founders and 86 unrelated twins. Genome-wide association analysis of these probes with 2.2 m SNPs revealed 131 potential eQTLs (1,989 eQTL SNPs overlapping between the HapMap datasets, five of which were in cis (58 eQTL SNPs. We then tested 535 SNPs tagging the eQTL SNPs, for association with the relevant QT in 2,905 twins. We identified nine potential SNP-QT associations (P<0.01 but none significantly replicated in five large consortia of 1,097-16,129 subjects. We also failed to replicate previous reported eQTL associations with body mass index, plasma low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels derived from lymphocytes, adipose and liver tissue. Our results and additional power calculations suggest that proponents may have been overoptimistic in the power of LCLs in eQTL approaches to elucidate regulatory genetic effects on complex traits using the small datasets generated to date. Nevertheless, larger tissue-specific expression data sets relevant to specific traits are becoming available, and should enable the adoption of similar integrated analyses in the near future.

  7. Founder virus population related to route of virus transmission: a determinant of intrahost human immunodeficiency virus type 1 evolution?

    NARCIS (Netherlands)

    Lukashov, V. V.; Goudsmit, J.

    1997-01-01

    We and others have shown that in individual human immunodeficiency virus type 1 (HIV-1) infection, the adaptive evolution of HIV-1 is influenced by host immune competence. In this study, we tested the hypothesis that in addition to selective forces operating within the host, transmission bottlenecks

  8. A Novel Founder Mutation in MYBPC3: Phenotypic Comparison With the Most Prevalent MYBPC3 Mutation in Spain.

    Science.gov (United States)

    Sabater-Molina, María; Saura, Daniel; García-Molina Sáez, Esperanza; González-Carrillo, Josefa; Polo, Luis; Pérez-Sánchez, Inmaculada; Olmo, María Del Carmen; Oliva-Sandoval, María José; Barriales-Villa, Roberto; Carbonell, Pablo; Pascual-Figal, Domigo; Gimeno, Juan R

    2017-02-01

    Mutations in MYBPC3 are the cause of hypertrophic cardiomyopathy (HCM). Although most lead to a truncating protein, the severity of the phenotype differs. We describe the clinical phenotype of a novel MYBPC3 mutation, p.Pro108Alafs*9, present in 13 families from southern Spain and compare it with the most prevalent MYBPC3 mutation in this region (c.2308+1 G>A). We studied 107 relatives of 13 index cases diagnosed as HCM carriers of the p.Pro108Alafs*9 mutation. Pedigree analysis, clinical evaluation, and genotyping were performed. A total of 54 carriers of p.Pro108Alafs*9 were identified, of whom 39 had HCM. There were 5 cases of sudden death in the 13 families. Disease penetrance was greater as age increased and HCM patients were more frequently male and developed disease earlier than female patients. The phenotype was similar in p.Pro108Alafs*9 and in c.2308+1 G>A, but differences were found in several risk factors and in survival. There was a trend toward a higher left ventricular mass in p.Pro108Alafs*9 vs c.2308+1G>A. Cardiac magnetic resonance revealed a similar extent and pattern of fibrosis. The p.Pro108Alafs*9 mutation is associated with HCM, high penetrance, and disease onset in middle age. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Finding the founder of Stockholm - A kinship study based on Y-chromosomal, autosomal and mitochondrial DNA

    DEFF Research Database (Denmark)

    Malmström, Helena; Vretemark, Maria; Tillmar, Andreas

    2012-01-01

    -chromosomal and autosomal SNPs and compared the results with haplogroup frequencies of modern Swedes to investigate paternal relations. Possible maternal kinship was investigated by deep FLX-sequencing of overlapping mtDNA amplicons. The authenticity of the sequences was examined using data from independent extractions......, massive clonal data, the c-statistics, and real-time quantitative data. We show that the males carry the same Y-chromosomal haplogroup and thus we cannot reject a father-son type of relation. Further, as shown by the mtDNA analyses, none of the individuals are maternally related. We conclude...

  10. A novel founder BBS1 mutation explains a unique high prevalence of Bardet-Biedl syndrome in the Faroe Islands

    DEFF Research Database (Denmark)

    Hjortshøj, T Duelund; Grønskov, K; Brøndum-Nielsen, K

    2009-01-01

    Bardet-Biedl syndrome is a multiorgan disease presenting with retinitis pigmentosa leading to blindness. The aim of the study was to investigate the genetic background of Bardet-Biedl syndrome in the Faroe Island. It was hypothesised that a common genetic background for the syndrome would be found....

  11. Jean-Martin Charcot and art: relationship of the "founder of neurology" with various aspects of art.

    Science.gov (United States)

    Bogousslavsky, Julien; Boller, François

    2013-01-01

    Jean-Martin Charcot (1825-1893), the "father of neurology" in France and much beyond, was also the man who established academic psychiatry in Paris, differentiating it from clinical alienism. In his teaching, he used artistic representations from previous centuries to illustrate the historical developments of hysteria, mainly with the help of his pupil Paul Richer. Charcot liked to draw portraits (in particular, sketches of colleagues during boring faculty meetings and students' examinations), caricatures of himself and others, church sculptures, landscapes, soldiers, etc. He also used this skill in his clinical and scientific work; he drew histological or anatomic specimens, as well as patients' features and demeanor. His most daring artistic experiments were drawing under the influence of hashish. Charcot's tastes in art were conservative; he displayed no affinity for the avant-gardes of his time, including impressionism, or for contemporary musicians, such as César Franck or Hector Berlioz. Léon Daudet, son of Charcot's former friend and famous writer Alphonse Daudet, described Charcot's home as a pseudo-gothic kitsch accumulation of heteroclite pieces of furniture and materials. However, as Henry Meige wrote a few years after his mentor's death, Charcot the artist remains "inseparable from Charcot the physician." © 2013 Elsevier B.V. All rights reserved.

  12. Herbert Aldersmith (1847-1918): Christ's Hospital medical officer and co-founder of the Medical Officers of Schools Association.

    Science.gov (United States)

    Hoskins, Trevor

    2008-02-01

    Herbert Aldersmith spent his entire working life, from the age of 23 years until his retirement at 65 years, as Resident Medical Officer to Christ's Hospital School. It was a crucial period in the school's history, from the overdue reforms of the late Victorian era to its historic move from the City of London to Sussex in 1902. He became an acknowledged authority on ringworm and also published extensively on the other great interest of his life, the British-Israel Society. He was the prime mover in founding the first-ever professional association of school doctors in 1884.

  13. Four USH2A founder mutations underlie the majority of Usher syndrome type 2 cases among non-Ashkenazi Jews.

    Science.gov (United States)

    Auslender, Noa; Bandah, Dikla; Rizel, Leah; Behar, Doron M; Shohat, Mordechai; Banin, Eyal; Allon-Shalev, Stavit; Sharony, Reuven; Sharon, Dror; Ben-Yosef, Tamar

    2008-06-01

    Type 2 Usher syndrome (USH2) is a recessively inherited disorder, characterized by the combination of early onset, moderate-to-severe, sensorineural hearing loss, and vision impairment due to retinitis pigmentosa. From 74% to 90% of USH2 cases are caused by mutations of the USH2A gene. USH2A is composed of 72 exons, encoding for usherin, an extracellular matrix protein, which plays an important role in the development and maintenance of neurosensory cells in both retina and cochlea. To date, over 70 pathogenic mutations of USH2A have been reported in individuals of various ethnicities. Many of these mutations are rare private mutations segregating in single families. The aim of the current work was to investigate the genetic basis for USH2 among Jews of various origins. We found that four USH2A mutations (c.239-240insGTAC, c.1000C>T, c.2209C>T, and c.12067-2A>G) account for 64% of mutant alleles underlying USH2 in Jewish families of non-Ashkenazi descent. Considering the very large size of the USH2A gene and the high number of mutations detected in USH2 patients worldwide, our findings have significant implications for genetic counseling and carrier screening in various Jewish populations.

  14. Frank Robert Tangherlini — the Founder of an Alternative Relativistic Kinematics (On the Occasion of His 85th Birthday

    Directory of Open Access Journals (Sweden)

    Malykin G. B.

    2009-01-01

    Full Text Available Already fifty years ago, Frank Robert Tangherlini, an American theoretical physicist, suggested an original procedure which, targeting the synchronization of clocks located in two different inertial reference frames of the space, was di erent from that Einstein had introduced. As a result of these, Tangherlini had deduced the so-called the Tangher- lini transformations, which are a sort of the transformations of the spatial coordinates and time being moved from one inertial reference frame into another one. The Tangher- lini transformations differ from the Lorentz transformations (which can be meant clas- sic ones in the theory of relativity and, in particular, suggest the velocity of light to be anisotropic in a moving inertial reference frame. The Tangherlini transformations be- ing applied provide adequate explanations to all well-known interference experiments checking of the Special Theory of Relativity.

  15. A founder effect for p47(phox)Trp193Ter chronic granulomatous disease in Kavkazi Jews

    NARCIS (Netherlands)

    de Boer, Martin; Tzur, Shay; van Leeuwen, Karin; Dencher, Paula C. D.; Skorecki, Karl; Wolach, Baruch; Gavrieli, Ronit; Nasidze, Ivane; Stoneking, Mark; Tanck, Michael W. T.; Roos, Dirk

    2015-01-01

    Chronic granulomatous disease (CGD) is a rare congenital immune deficiency caused by mutations in any of the five genes encoding NADPH oxidase subunits. One of these genes is NCF1, encoding the p47(phox) protein. A group of 39 patients, 14 of whom are of Kavkazi Jewish descent, was investigated for

  16. V.V. Davydov – the founder of significant scientific school and director of the Psychological Institute

    Directory of Open Access Journals (Sweden)

    Rubtsov V.V.

    2015-11-01

    Full Text Available The article presents the stages of biography of the famous Russian psychologist Davydov, who was a brilliant leader of a large scientific group, director of the Psychological Institute of the RAE. The content of the work of Davydov’s scientific schools is based upon the three proverbial whales that define its theoretical, methodological and didactical boundaries: the theory of content generalization and con cept formation, psychological theory of learning activity and the system of developmental teaching. The article also outlines the results of researches conducted by V.V. Davydov’s scientific group. It is demon strated that for evaluating the effectivity of learning activity, the systems of assessment of theoretical thinking and its components (such as analysis, reflection, planning, systemic characteristics of thinking were elaborated for different object matter. Also the scientific group elaborated the criteria for assessing the levels of learning activity development, as a whole as well as its separate components. The scientific school of V.V. Davydov is a living and evolving organism. The disciples and followers of Davydov conduct empirical research that bring his ideas to life. The article analyzes the philosophical, methodological and psychological foundations of Davydov’s scientific school. The content of Davydov’s debates with Vygotsky concerning the mechanisms of theo retical generalization is outlined. Davydov’s point of view is illustrated by large empirical evidence

  17. OCA1 in different ethnic groups of india is primarily due to founder mutations in the tyrosinase gene.

    NARCIS (Netherlands)

    Chaki, M.; Sengupta, M.S.; Mukhopadhyay, A.; Subba Rao, I.; Majumder, P.P.; Das, M.; Samanta, S.; Ray, K.

    2006-01-01

    Oculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders characterized by an abnormally low amount of melanin in the eyes, skin and hair, and associated with common developmental abnormalities of the eye. Defects in the tyrosinase gene (TYR) cause a common type of OCA,

  18. Why Traditional Expository Teaching-Learning Approaches May Founder? An Experimental Examination of Neural Networks in Biology Learning

    Science.gov (United States)

    Lee, Jun-Ki; Kwon, Yong-Ju

    2011-01-01

    Using functional magnetic resonance imaging (fMRI), this study investigates and discusses neurological explanations for, and the educational implications of, the neural network activations involved in hypothesis-generating and hypothesis-understanding for biology education. Two sets of task paradigms about biological phenomena were designed:…

  19. Founder effect in the Horn of Africa for an insulin receptor mutation that may impair receptor recycling

    DEFF Research Database (Denmark)

    Raffan, E; Soos, M A; Rocha, N

    2011-01-01

    Genetic insulin receptoropathies are a rare cause of severe insulin resistance. We identified the Ile119Met missense mutation in the insulin receptor INSR gene, previously reported in a Yemeni kindred, in four unrelated patients with Somali ancestry. We aimed to investigate a possible genetic...

  20. Thirty-two years of Acta Neophilologica - with gratitude to its founder and editor Professor Janez Stanonik

    Directory of Open Access Journals (Sweden)

    Mirko Jurak

    2000-12-01

    Full Text Available In spring this year Professor Janez Stanonik decided to retire as the Editor of the scholarly journal Acta Neophilologica, which he founded in 1968 and edited for thirty-two years. I endeavoured to help him with the material side of the journal from the very beginning until1995; since then this task has been performed by the present Associate Editor. At the time when Janez Stanonik began publishing this journal, his main aim was to make our research work in Western European and American literature better known to scholars all over the world. However, in a few years' time the journal also became open to scholars from other countries and other fields, particularly in areas connected with Slovene literature and culture, Slovene immigrant literature, and linguistics. I believe that this approach gave the journal a new openness and that it enriched its quality, therefore I intend to follow this policy in the future too.

  1. On the number of New World founders: a population genetic portrait of the peopling of the Americas.

    Science.gov (United States)

    Hey, Jody

    2005-06-01

    The founding of New World populations by Asian peoples is the focus of considerable archaeological and genetic research, and there persist important questions on when and how these events occurred. Genetic data offer great potential for the study of human population history, but there are significant challenges in discerning distinct demographic processes. A new method for the study of diverging populations was applied to questions on the founding and history of Amerind-speaking Native American populations. The model permits estimation of founding population sizes, changes in population size, time of population formation, and gene flow. Analyses of data from nine loci are consistent with the general portrait that has emerged from archaeological and other kinds of evidence. The estimated effective size of the founding population for the New World is fewer than 80 individuals, approximately 1% of the effective size of the estimated ancestral Asian population. By adding a splitting parameter to population divergence models it becomes possible to develop detailed portraits of human demographic history. Analyses of Asian and New World data support a model of a recent founding of the New World by a population of quite small effective size.

  2. Integrating new Storage Technologies into EOS

    Science.gov (United States)

    Peters, Andreas J.; van der Ster, Dan C.; Rocha, Joaquim; Lensing, Paul

    2015-12-01

    The EOS[1] storage software was designed to cover CERN disk-only storage use cases in the medium-term trading scalability against latency. To cover and prepare for long-term requirements the CERN IT data and storage services group (DSS) is actively conducting R&D and open source contributions to experiment with a next generation storage software based on CEPH[3] and ethernet enabled disk drives. CEPH provides a scale-out object storage system RADOS and additionally various optional high-level services like S3 gateway, RADOS block devices and a POSIX compliant file system CephFS. The acquisition of CEPH by Redhat underlines the promising role of CEPH as the open source storage platform of the future. CERN IT is running a CEPH service in the context of OpenStack on a moderate scale of 1 PB replicated storage. Building a 100+PB storage system based on CEPH will require software and hardware tuning. It is of capital importance to demonstrate the feasibility and possibly iron out bottlenecks and blocking issues beforehand. The main idea behind this R&D is to leverage and contribute to existing building blocks in the CEPH storage stack and implement a few CERN specific requirements in a thin, customisable storage layer. A second research topic is the integration of ethernet enabled disks. This paper introduces various ongoing open source developments, their status and applicability.

  3. The effect of cephalosporin usage on the occurrence of ESCs producing E. coli in pig herds

    DEFF Research Database (Denmark)

    Dalhoff Andersen, Vibe; Jensen, Vibeke Frøkjær; Agersø, Yvonne

    in 19 pig herds which have had five to fourteen prescriptions of ceph. and 20 pig herds without prescribed ceph. in a previous 12 month period. The 39 herds were all integrated and represent typical Danish pig farms. The occurrence of ESCs producing E. coli in the herds were tested in a total of 9...... pooled samples per herd. A pig herd was considered positive if one or more of the nine samples contained ESCs producing E. coli. Initially, the association between usages of ceph. and occurrence of ESCs producing E. coli in the pig herds was analyzed using logistic regression, and the effect was adjusted...... of ESCs producing E. coli was estimated as risk ratio(RR). The results showed that consumption of ceph. increased the risk of occurrence of ESCs producing E. coli significantly with a RR of 5 (95% CI: 2-11). This demonstrates that ceph. usage significant affect the occurrence of ESCs resistance...

  4. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

    LENUS (Irish Health Repository)

    Trompet, Stella

    2011-10-06

    Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER\\/PHASE project and second show that the PROSPER\\/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer\\'s instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE\\/APOC1; LDLR; FADS2\\/FEN1; HMGCR; PSRC1\\/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER\\/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof

  5. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmacogenetic analyses

    Directory of Open Access Journals (Sweden)

    Stott David J

    2011-10-01

    Full Text Available Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5. The top SNP (rs445925, chromosome 19 with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19 with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof

  6. Integrating new Storage Technologies into EOS

    CERN Document Server

    Peters, Andreas J; Rocha, Joaquim; Lensing, Paul

    2015-01-01

    The EOS[1] storage software was designed to cover CERN disk-only storage use cases in the medium-term trading scalability against latency. To cover and prepare for long-term requirements the CERN IT data and storage services group (DSS) is actively conducting R&D; and open source contributions to experiment with a next generation storage software based on CEPH[3] and ethernet enabled disk drives. CEPH provides a scale-out object storage system RADOS and additionally various optional high-level services like S3 gateway, RADOS block devices and a POSIX compliant file system CephFS. The acquisition of CEPH by Redhat underlines the promising role of CEPH as the open source storage platform of the future. CERN IT is running a CEPH service in the context of OpenStack on a moderate scale of 1 PB replicated storage. Building a 100+PB storage system based on CEPH will require software and hardware tuning. It is of capital importance to demonstrate the feasibility and possibly iron out bottlenecks and blocking issu...

  7. [Eugène-Humbert Guitard, 1884-1976, initiator of the Société d' histoire de la pharmacie and founder of its bulletin].

    Science.gov (United States)

    Julien, Pierre

    2003-01-01

    In 1913, the year when he publishes Deux siècles de presse au service de la pharmacie et cinquante ans de , Guitard creates the histoire de la pharmacie > (he is its genuine father, and not Charles Buchet) and starts its Bulletin (subsequently Revue) the editorship of which he will handle half a century. The author focuses on the striking features of his outstanding personality (acchivist, librarian, curator of a museum, expert at writing, bookseller, printer and publisher, hellenist, professor of history of pharmacy, journalist, columnist, musician, art-lover, urbanist, active defender of our cultural legacy) and the remarkable qualities of his four great works of history of pharmacy.

  8. The Norwegian PMS2 founder mutation c.989-1G > T shows high penetrance of microsatellite instable cancers with normal immunohistochemistry.

    Science.gov (United States)

    Grindedal, Eli Marie; Aarset, Harald; Bjørnevoll, Inga; Røyset, Elin; Mæhle, Lovise; Stormorken, Astrid; Heramb, Cecilie; Medvik, Heidi; Møller, Pål; Sjursen, Wenche

    2014-01-01

    Using immunohistochemistry (IHC) to select cases for mismatch repair (MMR) genetic testing, we failed to identify a large kindred with the deleterious PMS2 mutation c.989-1G > T. The purpose of the study was to examine the sensitivity of IHC and microsatellite instability-analysis (MSI) to identify carriers of the mutation, and to estimate its penetrance and expressions. All carriers and obligate carriers of the mutation were identified. All cancer diagnoses were confirmed. IHC and MSI-analysis were performed on available tumours. Penetrances of cancers included in the Amsterdam and the Bethesda Criteria, for MSI-high tumours and MSI-high and low tumours were calculated by the Kaplan-Meier algorithm. Probability for co-segregation of the mutation and cancers by chance was 0.000004. Fifty-six carriers or obligate carriers were identified. There was normal staining for PMS2 in 15/18 (83.3%) of tumours included in the AMS1/AMS2/Bethesda criteria. MSI-analysis showed that 15/21 (71.4%) of tumours were MSI-high and 4/21 (19.0%) were MSI-low. Penetrance at 70 years was 30.6% for AMS1 cancers (colorectal cancers), 42.8% for AMS2 cancers, 47.2% for Bethesda cancers, 55.6% for MSI-high and MSI-low cancers and 52.2% for MSI-high cancers. The mutation met class 5 criteria for pathogenicity. IHC was insensitive in detecting tumours caused by the mutation. Penetrance of cancers that displayed MSI was 56% at 70 years. Besides colorectal cancers, the most frequent expressions were carcinoma of the endometrium and breast in females and stomach and prostate in males.

  9. Locating a Prostate Cancer Susceptibility Gene on the X Chromosome by Linkage Disequilibrium Mapping Using Three Founder Populations in Quebec and Switzerland

    Science.gov (United States)

    2006-09-01

    Gordon PH, Wang Q, Puisieux, A, Foulkes WD and Trifiro M. Polymorphisms and HNPCC: PMS2 -MLH1 protein interactions diminished by ‘single nucleotide...and PMS2 responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Genes Chromosomes Cancer, 44 (2): 123-38, 2005. 120. Soravia C

  10. A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals With Autosomal Recessive Retinitis Pigmentosa

    NARCIS (Netherlands)

    Van Schil, Kristof; Klevering, B. Jeroen; Leroy, Bart P.; Pott, Jan Willem R.; Bandah-Rozenfeld, Dikla; Zonneveld-Vrieling, Marijke N.; Sharon, Dror; den Hollander, Anneke I.; Cremers, Frans P. M.; De Baere, Elfride; Collin, Rob W. J.; van den Born, L. Ingeborgh

    PURPOSE. To identify mutations in FAM161A underlying autosomal recessive retinitis pigmentosa (arRP) in the Dutch and Belgian populations and to investigate whether common FAM161A-associated phenotypic features could be identified. METHODS. Homozygosity mapping, amplification-refractory mutation

  11. A novel MERTK deletion is a common founder mutation in the Faroe Islands and is responsible for a high proportion of retinitis pigmentosa cases

    DEFF Research Database (Denmark)

    Ostergaard, Elsebet; Duno, Morten; Batbayli, Mustafa

    2011-01-01

    The aim of the study was to elucidate the genetic background of retinitis pigmentosa (RP) in a Faroe Islands population, a genetic isolate in the North Atlantic Ocean.......The aim of the study was to elucidate the genetic background of retinitis pigmentosa (RP) in a Faroe Islands population, a genetic isolate in the North Atlantic Ocean....

  12. Clinical Expression and New SPINK5 Splicing Defects in Netherton Syndrome : Unmasking a Frequent Founder Synonymous Mutation and Unconventional Intronic Mutations

    NARCIS (Netherlands)

    Lacroix, Matthieu; Lacaze-Buzy, Laetitia; Furio, Laetitia; Tron, Elodie; Valari, Manthoula; Van der Wier, Gerda; Bodemer, Christine; Bygum, Anette; Bursztejn, Anne-Claire; Gaitanis, George; Paradisi, Mauro; Stratigos, Alexander; Weibel, Lisa; Deraison, Celine; Hovnanian, Alain

    Netherton syndrome (NS) is a severe skin disease caused by loss-of-function mutations in SPINK5 (serine protease inhibitor Kazal-type 5) encoding the serine protease inhibitor LEKTI (lympho-epithelial Kazal type-related inhibitor). Here, we disclose new SPINK5 defects in 12 patients, who presented a

  13. Clinical characteristics and premorbid variables in childhood-onset schizophrenia: a descriptive study of twelve cases from a schizophrenia founder population.

    Science.gov (United States)

    Maydell, R J; van der Walt, C; Roos, J L; Scribante, L; Ladikos, A

    2009-05-01

    To analyze clinical and demographic data of childhood-onset (12 years and younger) schizophrenia patients collected for a genetic study in schizophrenia, undertaken nationally in South Africa, using multiple parameters. Patients with an onset of schizophrenia at 12 years or younger, were included. From the Diagnostic Interview for Genetic Studies (DIGS), patients' information and summary report data was tabulated and analyzed. Specific subgroups were further compared. This sub-population of 12 subjects was further compared with a group of the adult sample. Of the 12 patients recruited, prominent results were: male to female ratio of 1:1; all had insidious onset of psychosis; a third had all 3 multidimensional impairment (MDI) symptoms; all patients that received ADHD treatment had ADHD treatment failure; two thirds had milestone delay; 58% had birth complications; a third were predominantly bottle fed; 42% had family history of schizophrenia; a third had family history of other major psychiatric conditions; all patients had at least one non-psychotic deviant behaviour (NPDB); no patient used cannabis; all delusions were paranoid; 92% had school achievement difficulty and a third had treatment resistance. Gender comparison included: earlier onset of psychosis in females; all females had aggression versus a third of males; more females had school achievement difficulty than males; males had more treatment resistance. Patients with MDI, compared to the sample average had: earlier onset of non-psychotic deviant behaviour; lower school drop-out rate; less social difficulty and no treatment resistance. The results compare well to previous research on this topic. The new concepts introduced by the present study require further investigation.

  14. Variants of mtDNA among islanders of the lake Titicaca: highest frequency of haplotype B1 and evidence of founder effect

    OpenAIRE

    Sandoval, José; Delgado, Bedsabé; Rivas, Luis; Bonilla, Bertha; Nugent, Daniel; Fujita, Ricardo

    2004-01-01

    Los polimorfismos del ADN mitocondrial son herramientas en el estudio comparativo de poblaciones modernas y antiguas. Entre los más usados están los haplotipos mitocondriales basados en RFLP (polimorfismo de longitud de fragmentos de restricción) y un sistema de inserción /deleción. El presente estudio establece la frecuencia de estos haplotipos y compara un total de 144 individuos representativos de las islas Taquile y Amantaní (lengua quechua) y de las islas de Los Uros y Anapia (lengua aym...

  15. Carlo Moreschi (1876-1921): co-founder of the journal "La Medicina del Lavoro" and often forgotten pioneer of modern medicine.

    Science.gov (United States)

    Riva, M A; Smith, D R; Cesana, G

    2011-01-01

    Carlo Moreschi (1876-1921) was founding co-editor of the journal "Il Lavoro" (now known as "La Medicina del Lavoro"), together with Luigi Devoto in 1901. Despite this fact, many of his pioneering contributions to 20th century scientific debate are not well known outside Italy. The aim of this paper therefore was to recall Moreschi' achievements and the groundbreaking work of this remarkable Italian physician. A comprehensive analysis was conducted on scientific papers written by Carlo Moreschi between 1901 and 1920, extending the investigation to his original manuscripts and private correspondence with family and colleagues. Careful examination of Moreschi's work reveals several studies in the field of social medicine, epidemiology of infectious diseases, general pathology and oncology. In particular, his main interest in haematology and immunology enabled Moreschi to be one of the first to understand the mechanisms of complement fixation and the formation pathways ofantiglobulin sera. In this manner, Moreschi significantly contributed to the work of Wassermann regarding the diagnosis of syphilis, as well as contributing to the discovery of the "antiglobulin test", first described by Coombs in 1945. Furthermore, Moreschi co-founded "Il Lavoro" and "Haematologica", the oldest journals in their respective fields. According to Devoto, Moreschi can be remembered as the archetype modern researcher and clinician. His role in the 20th century scientific debate and his pioneering work in the field of immunology and haematology, that are often forgotten due to his premature death, deserve to be reconsidered and re-assessed by the Italian and international scientific community.

  16. Centenary of the birth of Bernhard Sann - the founder of modern mining research; Bernhard Sann - dem Begruender der modernen Bergbauforschung zum 100. Geburtstag

    Energy Technology Data Exchange (ETDEWEB)

    Scherschel, Manfred; Pasche, Eckart

    2010-05-15

    When Bernhard Sann was offered a position at the RWTH Aachen in 1961 not only was the Institute for Mining Science II - mechanical extraction technology and mining equipment - established, but the foundation stone was also laid for modern mining research. On the occasion of the centenary of the birth of its first director, Professor Dr.-Ing. Dr. Mont. Dr. techn. Dr. E.h. Bernhard Sann, some lifetime achievements of this natural scientist will be remembered on 16 June. As a teacher he warned of the need to cultivate the basic subjects and as a researcher he endeavoured to implement the results of his investigations in practice, be it in extraction and ventilation technology in the mining industry or in the aircraft industry. (orig.)

  17. A founder synonymous COL7A1 mutation in three Danish families with dominant dystrophic epidermolysis bullosa pruriginosa identifies exonic regulatory sequences required for exon 87 splicing

    DEFF Research Database (Denmark)

    Covaciu, C; Grosso, F; Pisaneschi, E

    2011-01-01

    Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) (OMIM 604129) represents a distinct variant within the DEB clinical spectrum. It is characterized by intense pruritus and distinctive nodular prurigo-like and/or hypertrophic lichenoid lesions mainly localized on the arms, legs and upper shoul...

  18. Clinical Expression and New SPINK5 Splicing Defects in Netherton Syndrome: Unmasking a Frequent Founder Synonymous Mutation and Unconventional Intronic Mutations

    DEFF Research Database (Denmark)

    Lacroix, Matthieu; Lacaze-Buzy, Laetitia; Furio, Laetitia

    2012-01-01

    a clinical triad suggestive of NS with variations in inter- and intra-familial disease expression. We identified a new and frequent synonymous mutation c.891C>T (p.Cys297Cys) in exon 11 of the 12 NS patients. This mutation disrupts an exonic splicing enhancer sequence and causes out-of-frame skipping of exon...

  19. Vasily shervinsky – Russian Doctor, scientist, therapeutist and pathologist, Honored scientist of the RSFSR and the founder of the Russian Endocrinology school

    OpenAIRE

    Ivanova, N.

    2013-01-01

    Шервинский Василий Дмитриевич ? русский врач, ученый, терапевт и патолог, заслуженный деятель науки РСФСР и основоположник русской эндокринологии.

  20. A BRCA2 mutation incorrectly mapped in the original BRCA2 reference sequence, is a common West Danish founder mutation disrupting mRNA splicing

    DEFF Research Database (Denmark)

    Thomassen, Mads; Pedersen, Inge Søkilde; Vogel, Ida

    2011-01-01

    Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose carriers to breast and ovarian cancer. The authors have identified a mutation in BRCA2, 7845+1G>A (c.7617+1G>A), not previously regarded as deleterious because of incorrect mapping of the splice junction in the originally...... published genomic reference sequence. This reference sequence is generally used in many laboratories and it maps the mutation 16 base pairs inside intron 15. However, according to the recent reference sequences the mutation is located in the consensus donor splice sequence. By reverse transcriptase analysis......, loss of exon 15 in the final transcript interrupting the open reading frame was demonstrated. Furthermore, the mutation segregates with a cancer phenotype in 18 Danish families. By genetic analysis of more than 3,500 Danish breast/ovarian cancer risk families, the mutation was identified as the most...

  1. Recurrent and founder mutations in the Netherlands Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia

    NARCIS (Netherlands)

    van der Zwaag, P. A.; Cox, M. G. P. J.; van der Werf, C.; Wiesfeld, A. C. P.; Jongbloed, J. D. H.; Dooijes, D.; Bikker, H.; Jongbloed, R.; Suurmeijer, A. J. H.; van den Berg, M. P.; Hofstra, R. M. W.; Hauer, R. N. W.; Wilde, A. A. M.; van Tintelen, J. P.

    2010-01-01

    Background. Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiac disease with reduced penetrance and a highly variable expression. Mutations in the gene encoding the plakophilin-2 gene (PKP2) are detected in about 50% of ARVC/D patients. The p. Arg79X mutation

  2. The application of business models to medical research: interviews with two founders of directed-philanthropy foundations. Interview with Scott Johnson and Don Listwin by Kathryn A. Phillips.

    Science.gov (United States)

    Scott, Johnson; Listwin, Don

    2007-01-01

    A new trend in research funding has emerged: directed philanthropy, in which the donor plays an active, hands-on role in managing the research by applying a "business model." Although such efforts now represent only a small portion of foundation funding, they have potentially far-reaching implications because (1) the approach of using a business model is being applied more broadly and (2) the success or failure of these efforts may portend the fate of larger translational efforts. The author conducted interviews with Scott Johnson of the Myelin Repair Foundation and Don Listwin of the Canary Foundation in the fall of 2006.

  3. A Founder Mutation in MYO7A Underlies a Significant Proportion of Usher Syndrome in Indigenous South Africans: Implications for the African Diaspora.

    Science.gov (United States)

    Roberts, Lisa; George, Siddiqah; Greenberg, Jacquie; Ramesar, Raj S

    2015-10-01

    Research over the past 25 years at the University of Cape Town has led to the identification of causative mutations in 17% of the 1416 families in the Retinal Degenerative Diseases (RDD) biorepository in South Africa. A low rate of mutation detection has been observed in patients of indigenous African origin, hinting at novel genes and mutations in this population. Recently, however, data from our translational research program showed two unrelated indigenous African families with Usher syndrome (USH), with the same homozygous MYO7A mutation. Therefore, the extent to which this mutation contributes toward the disease burden in South Africa was investigated. Cohorts of unrelated indigenous South African probands with different RDD diagnoses were tested for the MYO7A c.6377delC mutation. Familial cosegregation analysis was performed for homozygous probands, clinical data were evaluated, and SNP haplotypes were analyzed. This homozygous MYO7A mutation underlies a remarkable 43% of indigenous African USH cases investigated in this study, the majority of which (60%) were diagnosed clinically with Type 2 USH. All homozygotes shared a common haplotype. This mutation does not appear to cause nonsyndromic vision loss. Of interest is the origin of this common mutation relevant to the Bantu population migration into southern Africa. Further investigation of the phenotype may elucidate the disease biology, and perhaps reveal a larger cohort with the same mutation, with which to assess the impact of environmental and genetic modifiers and evaluate therapeutic trials.

  4. Professor Ernst Bresslau, founder of the Zoology Departments at the Universities of Cologne and Sao Paulo: lessons to learn from his life history.

    Science.gov (United States)

    Pflüger, Hans-Joachim

    2017-06-01

    In this article, the life history of the founding father of the departments of Zoology at the Universities of Cologne and Sao Paulo, Prof. Ernst Bresslau, is described on occasion of the establishing of the "Ernst Bresslau Guest Professorship" at the University of Cologne. His main scientific achievements are discussed, in particular his research on the evolutionary origin of the mammary apparatus, in addition to his broad interest in biological topics. Among the many technical advancements that he introduced was the micro slow-motion camera developed together with the Zeiss Company which allowed to film ciliary beats at high speeds. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Higher prevalence of OCA1 in an ethnic group of eastern India is due to a founder mutation in the tyrosinase gene.

    NARCIS (Netherlands)

    Chaki, M.; Mukhopadhyay, A.; Chatterjee, S.; Das, M.; Samanta, S.; Ray, K.

    2005-01-01

    PURPOSE: Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders characterized by deficient synthesis of melanin pigment and associated with common developmental abnormalities of the eye. It is one of the major causes of childhood blindness in India. The disease is common among an

  6. Recurrent and founder mutations in the Netherlands Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia

    NARCIS (Netherlands)

    van der Zwaag, P. A.; Cox, M. G. P. J.; van der Werf, C.; Wiesfeld, A. C. P.; Jongbloed, J. D. H.; Dooijes, D.; Bikker, H.; Jongbloed, R.; Suurmeijer, A. J. H.; van den Berg, M. P.; Hofstra, R. M. W.; Hauer, R. N. W.; Wilde, A. A. M.; van Tintelen, J. P.

    Background. Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiac disease with reduced penetrance and a highly variable expression. Mutations in the gene encoding the plakophilin-2 gene (PKP2) are detected in about 50% of ARVC/D patients. The p. Arg79X mutation

  7. One hundred years since the birth of academician Dimitar Arsov, founder and nestor of the modern internal medicine in the Republic of Macedonia.

    Science.gov (United States)

    Polenaković, M

    2013-01-01

    Dimitar Arsov was born in Kriva Palanka on September 28, 1908 and died on July 2, 1974 in Skopje; he had finished elementary education in Kriva Palanka, high school (1922-1926) in Kumanovo, Macedonia and Col-lege of Medicine (1926-1932), Ph. D. University of Paris, Sorbone, France, 1936. He returned to Macedonia in 1937. In 1947 he was elected and Assistant Professor and in 1950 a Docent at the Faculty of Medicine in Skopje. He was appointed Director of the Clinic of Medicine and Head of the Chair of Internal Medicine, who served at those positions in the period 1952-74. In 1958 he was elected Professor of Internal Medicine. The first habilitation of the Medical Faculty in Skopje was defended by D. Arsov in 1954, titled: "The Effects of the Intravenous Epinephrine on the Hypersplenism of Malaria and Cala-Azar". On August 18, 1967, D. Arsov was elected Full Member and also the first member in the field of medicine of the Macedonian Academy of Sciences and Arts. The excellent experience in the work with the patients, precise observation of the symptoms and syndromes of the diseases in each patient, knowing the most advanced therapy at that time enabled D. Arsov to make conclusion for possibility of new therapy and gave him the material for writing scientific papers. In the first half of the 50s, during his regular work, Arsov discovers a new, internationally recognized therapy for rheumatism. Patients of both Cala-Azar and inflammatory rheumatism were treated with small doses of adrenaline therapy and they felt drastic decrease in rheumatism inflammation within one week. This therapy was used a couple of years in several countries around the world. He participated in the undergraduate and graduate studies. He contributed to the development of 2,240 graduated doctors and under his management over 300 doctors specialized in internal medicine and became specialists internists. Under his management, numerous habilitations and dissertations in internal medicine were finished. He contributed also to the development of 25 assistants, 5 docents, 5 full-time professors in internal medicine at the Medical Faculty in Skopje. He has published more than 200 papers from different areas of internal medicine, of which 36 are on the PubMed. He has published 5 books on internal medicine for students and doctors. He was a President and member of several Macedonian medical associations, as well as of medical associations of former Yugoslavia. He was awarded with the highest awards of former Yugoslavia and Macedonia. He was also awarded with international awards, such as: Doctor Honoris Causa by the University in Besancon and Honor and Medal from the City Assembly of Besancon (France). During his management of the Internal clinic the University Internal clinic developed eight different sub-specialist departments: Cardiology, Pneumology, Rheumatology, Nephrology, Hematology, Gastroenterology and Endocrinology with metabolism and Clinical biochemical laboratory. The fast development of subspecialties has led to development of separate clinics for each subspecialty in 1975, so only the Chair of Internal Medicine remained as a connection between the subspecialties for education and scientific research. He was a prolific scientist who after World War II wrote the first scientific and specialist papers and books in the field of internal medicine in Macedonia. He created a school of internal medicine. The scientific and uncompromised attitude towards the expert truth are weaved in the unforgettable face of the Academician Prof. D-r. Dimitar Arsov, scientist, teacher, and doctor. With his vast work in healing the sick and preventing the diseases in the Republic of Macedonia, he became the cornerstone of modern medicine in the Republic of Macedonia. Thus, he truly deserves to be the doyen of internal medicine, one of the leading, most important persons in medicine of the 20th century in our country. Today, his honorary name appears on: Clinic of Rheumatology at the Medical Faculty in Skopje, Medical Center in Kriva Palanka, Scientific Club of the student organization of the Medical Faculty in Skopje.

  8. Founders' Weekend. North Country Workshop on Science, Technology and the Undergraduate Curriculum. Proceedings (Potsdam, New York, November 9-10, 1984).

    Science.gov (United States)

    State Univ. of New York, Potsdam. Coll. at Potsdam.

    Proceedings of the North Country Workshop on Science, Technology, and the Undergraduate Curriculum are presented. The Sloan Foundation's call for reform of the liberal arts and coverage of mathematics, science, and technology is noted in welcoming remarks by State University of New York, Potsdam, President Humphrey Tonkin. Stephen H. Cutcliffe…

  9. Professor Eugen Cerkovnikov (1904-1985): the founder of the Chemical and Biochemical Institute of the Rijeka University School of Medicine.

    Science.gov (United States)

    Milin, Cedomila

    2008-01-01

    Professor Eugen Cerkovnikov, PhD (Kamenska, Russia, 1904- Rijeka, Croatia 1985) graduated in chemical technology from the Faculty of Engineering in Zagreb in 1929. His first job was at the School of Medicine in Paris in 1930, and then he moved to Zagreb to the Department of Organic Chemistry of the Faculty of Engineering run by our Nobel Prize winner Vladimir Prelog (1935-1938). There he took his PhD degree with a dissertation on piperidine gamma derivatives. From 1938 to 1947 he was a research associate at an institute established by the pharmaceutical company Kastel (later Pliva). This is when he became a lecturer at the Faculty of Pharmacy in Zagreb and the first director of the Institute of Organic Chemistry, established in 1946/47. In 1948 he became reader, and in 1956 (full) professor. In 1957 he moved to the newly established School of Medicine in Rijeka, and set up the Institute of Chemistry and Biochemistry. He ran the Institute until retirement in 1975. He was the second dean of the Rijeka University School of Medicine and a pioneer of quantum chemistry and medical cybernetics in undergraduate and (post)graduate courses. His scientific work consists of over 200 papers published at home and abroad, 60 professional papers, 20 book reviews, three works of translation, and 27 volumes of lecture notes. In 1958, professor Cerkovnikov established the Croatian Chemical Society and the Rijeka and Istria branches of the nation's Association of Chemists and Chemical Engineers, chairing them until 1974. In addition, he was one of the founding fathers, and the first chair of the Health Culture Studies Association in Rijeka (that preceded today's Croatian Scientific Society for the History of Health Culture), established in 1965.

  10. A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome.

    Science.gov (United States)

    Ballew, Bari J; Joseph, Vijai; De, Saurav; Sarek, Grzegorz; Vannier, Jean-Baptiste; Stracker, Travis; Schrader, Kasmintan A; Small, Trudy N; O'Reilly, Richard; Manschreck, Chris; Harlan Fleischut, Megan M; Zhang, Liying; Sullivan, John; Stratton, Kelly; Yeager, Meredith; Jacobs, Kevin; Giri, Neelam; Alter, Blanche P; Boland, Joseph; Burdett, Laurie; Offit, Kenneth; Boulton, Simon J; Savage, Sharon A; Petrini, John H J

    2013-08-01

    Dyskeratosis congenita (DC) is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH) is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ) ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1.

  11. A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome.

    Directory of Open Access Journals (Sweden)

    Bari J Ballew

    2013-08-01

    Full Text Available Dyskeratosis congenita (DC is a heterogeneous inherited bone marrow failure and cancer predisposition syndrome in which germline mutations in telomere biology genes account for approximately one-half of known families. Hoyeraal Hreidarsson syndrome (HH is a clinically severe variant of DC in which patients also have cerebellar hypoplasia and may present with severe immunodeficiency and enteropathy. We discovered a germline autosomal recessive mutation in RTEL1, a helicase with critical telomeric functions, in two unrelated families of Ashkenazi Jewish (AJ ancestry. The affected individuals in these families are homozygous for the same mutation, R1264H, which affects three isoforms of RTEL1. Each parent was a heterozygous carrier of one mutant allele. Patient-derived cell lines revealed evidence of telomere dysfunction, including significantly decreased telomere length, telomere length heterogeneity, and the presence of extra-chromosomal circular telomeric DNA. In addition, RTEL1 mutant cells exhibited enhanced sensitivity to the interstrand cross-linking agent mitomycin C. The molecular data and the patterns of inheritance are consistent with a hypomorphic mutation in RTEL1 as the underlying basis of the clinical and cellular phenotypes. This study further implicates RTEL1 in the etiology of DC/HH and immunodeficiency, and identifies the first known homozygous autosomal recessive disease-associated mutation in RTEL1.

  12. New RAB3GAP1 mutations in patients with Warburg Micro Syndrome from different ethnic backgrounds and a possible founder effect in the Danish

    DEFF Research Database (Denmark)

    Morris-Rosendahl, Deborah J; Segel, Reeval; Born, A Peter

    2010-01-01

    Warburg Micro Syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism. We have found...... and may aid the differential diagnosis of Micro Syndrome for patients in the future. All patients had postnatal microcephaly, micropthalmia, microcornia, bilateral congenital cataracts, short palpebral fissures, optic atrophy, severe mental retardation, and congenital hypotonia with subsequent spasticity....... Only one patient had microcephaly at birth, highlighting the fact that congenital microcephaly is not a consistent feature of Micro syndrome. Analysis of the brain magnetic resonance imagings (MRIs) revealed a consistent pattern of polymicrogyria in the frontal and parietal lobes, wide sylvian fissures...

  13. Northern Slavs from Serbia do not show a founder effect at autosomal and Y-chromosomal STRs and retain their paternal genetic heritage.

    Science.gov (United States)

    Rębała, Krzysztof; Veselinović, Igor; Siváková, Daniela; Patskun, Erika; Kravchenko, Sergey; Szczerkowska, Zofia

    2014-01-01

    Studies on Y-chromosomal markers revealed significant genetic differentiation between Southern and Northern (Western and Eastern) Slavic populations. The northern Serbian region of Vojvodina is inhabited by Southern Slavic Serbian majority and, inter alia, Western Slavic (Slovak) and Eastern Slavic (Ruthenian) minorities. In the study, 15 autosomal STR markers were analysed in unrelated Slovaks, Ruthenians and Serbs from northern Serbia and western Slovakia. Additionally, Slovak males from Serbia were genotyped for 17 Y-chromosomal STR loci. The results were compared to data available for other Slavic populations. Genetic distances for autosomal markers revealed homogeneity between Serbs from northern Serbia and Slovaks from western Slovakia and distinctiveness of Serbian Slovaks and Ruthenians. Y-STR variation showed a clear genetic departure of the Slovaks and Ruthenians inhabiting Vojvodina from their Serbian neighbours and genetic similarity to the Northern Slavic populations of Slovakia and Ukraine. Admixture estimates revealed negligible Serbian paternal ancestry in both Northern Slavic minorities of Vojvodina, providing evidence for their genetic isolation from the Serbian majority population. No reduction of genetic diversity at autosomal and Y-chromosomal markers was found, excluding genetic drift as a reason for differences observed at autosomal STRs. Analysis of molecular variance detected significant population stratification of autosomal and Y-chromosomal microsatellites in the three Slavic populations of northern Serbia, indicating necessity for separate databases used for estimations of frequencies of autosomal and Y-chromosomal STR profiles in forensic casework. Our results demonstrate that regarding Y-STR haplotypes, Serbian Slovaks and Ruthenians fit in the Eastern European metapopulation defined in the Y chromosome haplotype reference database. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Israel L. Bershtein (1908-2000 — the Founder of the Theory of Fluctuations in Self-Oscillating Systems (In Commemorating the 100th Birthday Anniversary

    Directory of Open Access Journals (Sweden)

    Malykin G. B.

    2009-01-01

    Full Text Available Israel L. Bershtein (1908-2000 was one of the famous radio physicists in the world. He had constructed the theory of amplitude and frequency fluctuations for the electromagnetic wave generators working in the radio and optical scales. He also had developed numerous methods for precise measurement of the fluctuations, which also can be applied to ultimate small mechanical displacements. Besides these he was the first person among the scientists, who had registered the Sagnac effect at radiowaves.

  15. Utilizing linkage disequilibrium information from Indian Genome ...

    Indian Academy of Sciences (India)

    Using LD information derived from Indian Genome Variation database (IGVdb) on populations .... Line diagram represents the SNPs selected in Indian (upper panel) and CEPH .... out procedure for extracting DNA from human nucleated cells.

  16. Data storage as a service

    OpenAIRE

    Tomšič, Jan

    2016-01-01

    The purpose of the thesis was comparison of interfaces to network attached file systems and object storage. The thesis describes network file system and mounting procedure in Linux operating system. Object storage and distributed storage systems are explained with examples of usage. Amazon S3 is an example of object store with access trough REST interface. Ceph, a system for distributed object storage, is explained in detail, and a Ceph cluster was deployed for the purpose of this thesis. Cep...

  17. Population and genomic lessons from genetic analysis of two Indian populations.

    Science.gov (United States)

    Juyal, Garima; Mondal, Mayukh; Luisi, Pierre; Laayouni, Hafid; Sood, Ajit; Midha, Vandana; Heutink, Peter; Bertranpetit, Jaume; Thelma, B K; Casals, Ferran

    2014-10-01

    Indian demographic history includes special features such as founder effects, interpopulation segregation, complex social structure with a caste system and elevated frequency of consanguineous marriages. It also presents a higher frequency for some rare mendelian disorders and in the last two decades increased prevalence of some complex disorders. Despite the fact that India represents about one-sixth of the human population, deep genetic studies from this terrain have been scarce. In this study, we analyzed high-density genotyping and whole-exome sequencing data of a North and a South Indian population. Indian populations show higher differentiation levels than those reported between populations of other continents. In this work, we have analyzed its consequences, by specifically assessing the transferability of genetic markers from or to Indian populations. We show that there is limited genetic marker portability from available genetic resources such as HapMap or the 1,000 Genomes Project to Indian populations, which also present an excess of private rare variants. Conversely, tagSNPs show a high level of portability between the two Indian populations, in contrast to the common belief that North and South Indian populations are genetically very different. By estimating kinship from mates and consanguinity in our data from trios, we also describe different patterns of assortative mating and inbreeding in the two populations, in agreement with distinct mating preferences and social structures. In addition, this analysis has allowed us to describe genomic regions under recent adaptive selection, indicating differential adaptive histories for North and South Indian populations. Our findings highlight the importance of considering demography for design and analysis of genetic studies, as well as the need for extending human genetic variation catalogs to new populations and particularly to those with particular demographic histories.

  18. Comparing genetic variants detected in the 1000 genomes project ...

    Indian Academy of Sciences (India)

    Single-nucleotide polymorphisms (SNPs) determined based on SNP arrays from the international HapMap consortium (HapMap) and the genetic variants detected in the 1000 genomes project (1KGP) can serve as two references for genomewide association studies (GWAS). We conducted comparative analyses to provide ...

  19. A worldwide phylogeography for the human X chromosome.

    Directory of Open Access Journals (Sweden)

    Simone S Santos-Lopes

    Full Text Available BACKGROUND: We reasoned that by identifying genetic markers on human X chromosome regions where recombination is rare or absent, we should be able to construct X chromosome genealogies analogous to those based on Y chromosome and mitochondrial DNA polymorphisms, with the advantage of providing information about both male and female components of the population. METHODOLOGY/PRINCIPAL FINDINGS: We identified a 47 Kb interval containing an Alu insertion polymorphism (DXS225 and four microsatellites in complete linkage disequilibrium in a low recombination rate region of the long arm of the human X chromosome. This haplotype block was studied in 667 males from the HGDP-CEPH Human Genome Diversity Panel. The haplotypic diversity was highest in Africa (0.992+/-0.0025 and lowest in the Americas (0.839+/-0.0378, where no insertion alleles of DXS225 were observed. Africa shared few haplotypes with other geographical areas, while those exhibited significant sharing among themselves. Median joining networks revealed that the African haplotypes were numerous, occupied the periphery of the graph and had low frequency, whereas those from the other continents were few, central and had high frequency. Altogether, our data support a single origin of modern man in Africa and migration to occupy the other continents by serial founder effects. Coalescent analysis permitted estimation of the time of the most recent common ancestor as 182,000 years (56,700-479,000 and the estimated time of the DXS225 Alu insertion of 94,400 years (24,300-310,000. These dates are fully compatible with the current widely accepted scenario of the origin of modern mankind in Africa within the last 195,000 years and migration out-of-Africa circa 55,000-65,000 years ago. CONCLUSIONS/SIGNIFICANCE: A haplotypic block combining an Alu insertion polymorphism and four microsatellite markers on the human X chromosome is a useful marker to evaluate genetic diversity of human populations and

  20. [Štampar's contemporary Josip Šilović: the founder of the Colonization fund for orphans from hunger-stricken Croatian areas and the Fund for orphans of Croatian emigrants during World War I].

    Science.gov (United States)

    Szabo, Agneza

    2015-11-01

    This article gives a brief review of the scientific, academic, and political activity of Josip Šilović, and most importantly of his humanitarian work. He will be remembered for saving thousands of children who lost their fathers or brothers to World War I and who were left to starve to death. To this end Šilović and his associates established several funds and organisations, most notably Narodna zaštita. He continued with his humanitarian activities until he died in Zagreb in 1939.

  1. Combined gating and trafficking defect in Kv11.1 manifests as a malignant long QT syndrome phenotype in a large Danish p.F29L founder family

    DEFF Research Database (Denmark)

    Kanters, Jørgen K.; Skibsbye, Lasse; Hedley, Paula L.

    2015-01-01

    Background: Congenital long QT syndrome (LQTS) is a hereditary cardiac channelopathy characterized by delayedventricular repolarization, syncope, torsades de pointes and sudden cardiac death. Thirty-three members of fi ve apparently‘ unrelated ’Danish families carry the KCNH2:c.87C A; p.F29L...

  2. Dr Edward Macgowan (1795-1860), a long-term pioneer physician in mid-nineteenth century Jerusalem: founder and director of the first modern hospital in the Holy Land.

    Science.gov (United States)

    Lev, Efraim; Perry, Yaron

    2008-02-01

    At the age of 46, Dr Edward Macgowan, by now a well-established physician, joined the ranks of the London Society for Promoting Christianity among the Jews with the aim of establishing the first modern hospital in Palestine. For the first six months of 1842, Macgowan established his work among the Jerusalem population on a regular basis and managed to establish a close relationship with the Jewish community and some of its leaders in Jerusalem. On 12 December 1844, the Jews' Hospital was opened in Jerusalem and became a source of great pride for the missionaries. Edward Macgowan died in Jerusalem after 18 years of service and was buried in the Protestant cemetery in his beloved city.

  3. [Ol'ha Petrivna Chepinoha--a founder of investigations of nucleic acids in biochemistry in Ukraine. To the 100th anniversary of birthday, 1.07.1907--27.04.1983].

    Science.gov (United States)

    Vynohradova, R P

    2008-01-01

    Olga Petrivna Chepinoga, doctor of science (biology), senior scientific worker, was born on July 1, 1907, in Kyiv. She graduated from the 1st Kyiv Medical Institute (1927-1931). In 1931-1935 she worked at various medical institutions of Ukraine. In 1935 O. P. Chepinoga was employed by the Institute of Biochemistry of the National Academy of Sciences of the Ukr.SSR as a laborant, then as an assistant, junior and senior scientific worker. In 1940 O. P. Chepinoga defended a thesis for a Candidate's degree, and from 1941 she was given a rank of the senior scientific worker. During the Great Patriotic War she served in the armed forces of the Soviet Army (1941-1945) as a medical officer in the rank of captain. In 1944-1963 she worked at the Instutute of Biochemistry of the AS of the Ukr.SSR as a senior scientific worker, and in 1963-1965 headed the Laboratory of Nucleic Acids. In 1952 O. P. Chepinoga defended a thesis for Doctor's degree in biology On Biologic Role of Nucleic Acids. Investigations of O. P. Chepinoga were first devoted to oxidation processes in muscles in various physiologic conditions, physico-chemical properties of myosin and its ATPase activity. Since 1948 her scientific interests had been concentrating on studying the biologic role and metabolism of nucleic acids, their transformation in the organism in norm and in pathological states. She was the first to find that various proteins interacted with DNA molecule. The highest activity of DNAse and RNAse was revealed in the organs which permanently synthesize proteins (liver, spleen, pancreas). Under quantitative undifferentiated growth of malignant tumors (Brown-Pierse carcinoma and Crocker sarcoma) the great part belongs to the process of DNA disintegrations; DNAse activity increases considerably in the animal and human blood that is not observed at other somatic diseases and is of great diagnostic value. Considerable shifts in DNAse activity at various pathologies were not found. The enrichment of transport RNA with methyl groups with chemical modifications does not disturb the integrity of the polynucleotide chain and secondary structure but decreases their acceptor activity. O. P. Chepinoga has published 100 scientific works including one monograph and one handbook. Two candidate's theses were defended under her supervision. She was awarded the medals For Courage, For the Victory over Germany in the Great Patriotic War of 1941-1945 and numerous jubilee medals.

  4. Wu Shangshi: One of the outstanding founders of Chinese modern geography%吴尚时对中国近代地理学的贡献与学术思想探讨

    Institute of Scientific and Technical Information of China (English)

    陈吉余; 吴超羽; 司徒尚纪

    2017-01-01

    Wu Shangshi (1904-1947) is considered one of the outstanding modem geographers emerging in the early 20th century in China.It is partly a result of the introduction of modem sciences from the West.Wu graduated as a gold medalist in Sun Yat-sen University (SYU) in 1928.He was then granted scholarship to study geography in France.He studied at the University of Lyon and the University of Grenoble under the supervision of A.Allix,M.Pardé and R.Blanchard,who was one of the best known students of V.de la Blanche.In 1934,Wu finished his study in France and returned to SYU to serve as a professor of geography.He was head of the department in 1939-1945,the most difficult and perilous period during the Japanese invasion.The university moved constantly to flee the flames of war.The thousands of miles across south and south-west China became Wu's research field.To continue one's work under such circumstances required an extraordinary determination and dedication to science.Excessive hard work in tough environments ruined his health.Wu died in 1947 at the age of 43.Among the second generation of Chinese modem geographers,Wu was a rare example of an integrated geographer.He combined comprehensive and complex geographic thought with a balanced approach between holistic perspective and detailed research.In addition,he possessed an outstanding ability to conduct field work.As such,many of his research findings have withstood the test of time and remain relevant to this day.For instance,Wu proposed "one belt and three arcs" to summarize the distribution of the mountain ranges in China.On the long debates of the stratigraphic sequence of the red bed formations "Danxia" and "Nanxiong",Wu suggested an alternative viewpoint that the two formations could be deposited at approximately the same time but in different faces and it has been confirmed by modem geologic investigation some 50 years later.Both contributions were listed on the "Great Geographical Discoveries of China in 100 Years".Wu's pioneering work covered a wide range of disciplines of geography:geomorphology,hydrography,climatology,cartography,regional geography,etc.Most of his research involved a combination of keen observation,incisive logical deduction,broad knowledge and professional instinct.The present paper summarizes Wu's major accomplishments which are scientifically significant to the establishment of modem and contemporary geography in China.It also reveals that Wu's scientific thought and practice can be traced to the French schools of geography and other Western countries.However,his accomplishments cannot be fully appreciated without understanding of the significant role that traditional Chinese culture played in his consciousness.Wu's social connections and educational background could have easily allowed him to move within the power circles and become part of it.Yet he remained upright and forwent opportunities for fame and fortune,choosing Geography as his life's work.Wu was also a renowned educator whose list of students features names such as Luo Kaifu,Zeng Zhaoxuan,Xu Junming etc.The Geography Department in SYU has been being one of the important bases of China's modern geography science,to which Wu's crucial contributions cannot be left unrecognized.A scientific park is under construction by the City Hall of Guangzhou at the site where Wu identified an ancient wave-cut cliff in 1937.Wu'statue placed in the park was designed by the well-known sculptors.%吴尚时(1904-1947)是中国近代地理学重要开创者之一.1928年吴尚时获金牌毕业于中山大学,次年考取公费前往法国学习地理学.他先后就读于里昂大学和格日诺布尔大学,授业于A.阿历克斯,M.巴尔台和R.布朗夏尔等,布氏是维达尔·布拉什知名弟子.1934年吴氏学成归国,任中山大学地理系教授,1939-1945年任地理系主任.时逢日军侵华,学校不断搬迁逃避战火,华南、西南千里迁徙之途成为先生的野外考察路线,这需要非同一般的坚毅意志和对科学的献身精神.先生学术文稿泰半完成于此艰危时期,过度的劳累和极度困苦的环境严重损害了他的健康.1947年,先生去世,年仅43岁.继张相文之后的第二代中国近代地理学家群体中,吴尚时是少有的综合地理学学家.先生所具有的综合与复杂性地理学思想和深厚的部门专业素养,在宏观把握与深入研究之间敏锐地找到恰当切人点和相对整体性以及杰出的野外工作能力,令其许多研究成果经受了科学发展和时间的严酷考验而历久弥新.如提出中国山系“一带三弧”格局、“丹霞南雄层”同时异相说、论证珠江三角洲之存在等.先生的建树涉及地形学、水文地理、气象学、制图学、区域地理等近代地理学各学科.先生的研究工作几乎都是他实地考察,敏锐的观察力,犀利严密的逻辑推理,广博的知识和专业直觉的结合.本文概述吴氏的主要学术成就和对中国近代地理学建立的贡献,对当代地理学仍有其现实意义.吴氏的科学思想与实践可以追溯到法国地理学派的亲炙和欧美地理学派的影响.同样有必要探讨根植于他意识深处的中国传统文化和人文主义的作用.以其社会关系和教育背景,先生不难跻身权贵,然其性刚正不阿,摈弃利禄,选择地理科学作为毕生事业,安贫乐道,穷而益坚.先生亦地理学教育大家,罗开富、曾昭璇、徐俊鸣等地理名家皆出其门下,中山大学地理系成为中国地理学重镇,先生功不可没.目前广州市政府在吴氏于1937年发现古海蚀崖所在建立“七星岗古海蚀遗址科学公园”,并放置先生铜像.

  5. Biblical basics of the Holy Family’s dimension of Christian spirituality according to the teaching of God’s Servant Jean Berthier, founder of the Congregation Missionaries of the Holy Family

    Directory of Open Access Journals (Sweden)

    Adam Józef Sobczyk

    2009-03-01

    Full Text Available The analysis of the biblical basics of the Holy Family’s dimension of Christian spirituality drawn by Jean Berthier shows his impressive knowledge of the Holy Bible. God’ Servant uses many quotations to show biblical grounds for Christ’s imitation according to the pattern of the Holy Family. There are a few virtues of the Holy Family which deserve to be highlighted: trust and obedience to God’s Will, love to God and to neighbor, humility and mortification. Berthier not only enumerates those virtues but also encourages everyone to realize them in everyday life, such as the Holy Family did it.

  6. Florence Nightingale: Apontamentos sobre a fundadora da Enfermagem Moderna Florence Nightingale: Apuntes sobre la fundadora de la Enfermería Moderna Florence Nightingale: Notes on the founder of Modern Nursing

    OpenAIRE

    Lúcia Marlene Macário Lopes; Sandra Maria Pereira dos Santos

    2010-01-01

    Avançada para a sua época, mas ao mesmo tempo conservadora, Florence Nightingale popularizou o exercício da Enfermagem, permitindo o estabelecimento de uma nova profissão para a mulher. Mulher bem formada e culta, recorreu aos seus conhecimentos e estatuto social para influenciar a política de saúde e educação, na sua época. Prestou cuidados de enfermagem aos doentes, durante a Guerra da Crimeia (1854-1856), afirmando a profissão de Enfermagem e dando início à sua caminhada para o estatuto de...

  7. Heritability in the efficiency of nonsense-mediated mRNA decay in humans

    KAUST Repository

    Seoighe, Cathal; Gehring, Christoph A

    2010-01-01

    across tissues and between individuals, with important clinical consequences. Principal Findings: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether

  8. (SNP) assay for population stratification test between eastern Asians

    African Journals Online (AJOL)

    Yomi

    2012-01-03

    Jan 3, 2012 ... program STRUCTURE 2.0, which uses a Markov chain Monte. Carlo (MCMC) algorithm to cluster individuals into different cryptic ... HapMap project. .... Evaluation of the 124-plex SNP typing microarray for forensic testing.

  9. Determining fertility in a bovine subject comprises detecting in a sample from the bovine subject the presence or absence of genetic marker alleles associated with a trait indicative of fertility of the bovine subject and/or off-spring

    DEFF Research Database (Denmark)

    2009-01-01

    NOVELTY - Determining fertility in a bovine subject comprises detecting in a sample from the bovine subject the presence or absence of two or more genetic marker alleles that are associated with a trait indicative of fertility of the bovine subject and/or off-spring. USE - The methods are useful...... for determining fertility in a bovine subject; and selecting bovine subjects for breeding purposes (all claimed). DETAILED DESCRIPTION - Determining fertility in a bovine subject comprises detecting in a sample from the bovine subject the presence or absence of two or more genetic marker alleles...... that are associated with a trait indicative of fertility of the bovine subject and/or off-spring, where the two or more genetic marker alleles are single nucleotide polymorphisms selected from Hapmap60827-rs29019866, ARS-BFGL-NGS-40979, Hapmap47854-BTA-119090, ARS-BFGL-NGS-114679, Hapmap43841-BTA-34601, Hapmap43407...

  10. LIG1 polymorphisms: the Indian scenario

    Indian Academy of Sciences (India)

    2014-08-14

    Aug 14, 2014 ... occurs across this population on social parameters such as income and ..... HapMap database belonging to Chinese (CHB), Japanese. (JPT) ..... was supported by CSIR network projects CMM0016, CMM0018,. NWP0034.

  11. Selection signatures in worldwide sheep populations.

    OpenAIRE

    Fariello, Maria-Ines; Servin, Bertrand; Tosser-Klopp, Gwenola; Rupp, Rachel; Moreno, Carole; San Cristobal, Magali; Boitard, Simon; Drögemüller, Cord; The International Sheep Genomics Consortium, ISGC

    2014-01-01

    The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep popula...

  12. Selection Signatures in Worldwide Sheep Populations

    OpenAIRE

    Fariello, Maria-Ines; Servin, Bertrand; Tosser-Klopp, Gwenola; Rupp, Rachel; Moreno, Carole; Cristobal, Magali San; Boitard, Simon

    2014-01-01

    The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep popula...

  13. Lactase persistence and lipid pathway selection in the Maasai.

    Directory of Open Access Journals (Sweden)

    Kshitij Wagh

    Full Text Available The Maasai are a pastoral people in Kenya and Tanzania, whose traditional diet of milk, blood and meat is rich in lactose, fat and cholesterol. In spite of this, they have low levels of blood cholesterol, and seldom suffer from gallstones or cardiac diseases. Field studies in the 1970s suggested that the Maasai have a genetic adaptation for cholesterol homeostasis. Analysis of HapMap 3 data using Fixation Index (Fst and two metrics of haplotype diversity: the integrated Haplotype Score (iHS and the Cross Population Extended Haplotype Homozygosity (XP-EHH, identified genomic regions and single nucleotide polymorphisms (SNPs as strong candidates for recent selection for lactase persistence and cholesterol regulation in 143-156 founder individuals from the Maasai population in Kinyawa, Kenya (MKK. The non-synonmous SNP with the highest genome-wide Fst was the TC polymorphism at rs2241883 in Fatty Acid Binding Protein 1(FABP1, known to reduce low density lipoprotein and tri-glyceride levels in Europeans. The strongest signal identified by all three metrics was a 1.7 Mb region on Chr2q21. This region contains the genes LCT (Lactase and MCM6 (Minichromosome Maintenance Complex Component involved in lactase persistence, and the gene Rab3GAP1 (Rab3 GTPase-activating Protein Catalytic Subunit, which contains polymorphisms associated with total cholesterol levels in a genome-wide association study of >100,000 individuals of European ancestry. Sanger sequencing of DNA from six MKK samples showed that the GC-14010 polymorphism in the MCM6 gene, known to be associated with lactase persistence in Africans, is segregating in MKK at high frequency (∼58%. The Cytochrome P450 Family 3 Subfamily A (CYP3A cluster of genes, involved in cholesterol metabolism, was identified by Fst and iHS as candidate loci under selection. Overall, our study identified several specific genomic regions under selection in the Maasai which contain polymorphisms in genes associated

  14. Integration of XRootD into the cloud infrastructure for ALICE data analysis

    Science.gov (United States)

    Kompaniets, Mikhail; Shadura, Oksana; Svirin, Pavlo; Yurchenko, Volodymyr; Zarochentsev, Andrey

    2015-12-01

    Cloud technologies allow easy load balancing between different tasks and projects. From the viewpoint of the data analysis in the ALICE experiment, cloud allows to deploy software using Cern Virtual Machine (CernVM) and CernVM File System (CVMFS), to run different (including outdated) versions of software for long term data preservation and to dynamically allocate resources for different computing activities, e.g. grid site, ALICE Analysis Facility (AAF) and possible usage for local projects or other LHC experiments. We present a cloud solution for Tier-3 sites based on OpenStack and Ceph distributed storage with an integrated XRootD based storage element (SE). One of the key features of the solution is based on idea that Ceph has been used as a backend for Cinder Block Storage service for OpenStack, and in the same time as a storage backend for XRootD, with redundancy and availability of data preserved by Ceph settings. For faster and easier OpenStack deployment was applied the Packstack solution, which is based on the Puppet configuration management system. Ceph installation and configuration operations are structured and converted to Puppet manifests describing node configurations and integrated into Packstack. This solution can be easily deployed, maintained and used even in small groups with limited computing resources and small organizations, which usually have lack of IT support. The proposed infrastructure has been tested on two different clouds (SPbSU & BITP) and integrates successfully with the ALICE data analysis model.

  15. Experiment list: ERX329660 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available || sex=female || 1000 Genomes dataset=Pilot2 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/eachData/bw/ER...piens || cell type=lymphoblastoid cell || cell line=NA12878 || population=HapMap CEU || population name=CEPH

  16. Genotyping of PCR-based polymorphisms and linkage-disequilibrium analysis at the NF1 locus

    Energy Technology Data Exchange (ETDEWEB)

    Purandare, S.M.; Viskochil, D.H.; Cawthon, R. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

    1996-07-01

    Six polymorphism across the NF1 gene have been adapted for genotyping through application of PCR-based assays. Three exon-based polymorphisms - at positions 702, 2034, and 10647 in the NF1 cDNA - were genotyped by mutagenically separated PCR (MS-PCR). A fourth polymorphism, DV1.9, is an L1 insertion element in intron 30, and the other two polymorphisms, GXAlu and EVI-20, are short tandem repeats in intron 27b. All the polymorphisms were evaluated in a cohort of 110 CEPH individuals who previously had been analyzed by use of eight RFLPs at the NF1 locus. Pairwise linkage-disequilibrium analyses with the six PCR-based polymorphisms and their flanking markers demonstrated disequilibrium between all tested loci. Genotypes of the four diallelic polymorphisms (702, 2034, 10647, and DV1.9) were also evaluated in cohorts from the CEPH, African, and Japanese populations. The CEPH and Japanese cohorts showed similar heterozygosities and linkage-disequilibrium coefficients. The African cohort showed a higher degree of heterozygosity and lower linkage-disequilibrium values, compared with the CEPH and Japanese cohorts. 36 refs., 2 figs., 3 tabs.

  17. Antibodies to Actin in Autoimmune Neutropenia

    Science.gov (United States)

    1990-02-01

    S) 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Dept of Hematology (If applicable) Div of Medicine ...ceph- standard deviations above the mean value for 20 normal serum alosporins, phenothiazines, antithyroid drugs, antiarrythmic controls reflecting

  18. Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study.

    Science.gov (United States)

    McConville, Thomas Howe; Sullivan, Sean Berger; Gomez-Simmonds, Angela; Whittier, Susan; Uhlemann, Anne-Catrin

    2017-01-01

    Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent public health threat. Intestinal colonization with CRE has been identified as a risk factor for the development of systemic CRE infection, but has not been compared to colonization with third and/or fourth generation cephalosporin-resistant (Ceph-R) Enterobacteriaceae. Moreover, the risk conferred by colonization on adverse outcomes is less clear, particularly in critically ill patients admitted to the intensive care unit (ICU). We carried out a cohort study of consecutive adult patients screened for rectal colonization with CRE or Ceph-R upon ICU entry between April and July 2013. We identified clinical variables and assessed the relationship between CRE or Ceph-R colonization and subsequent systemic CRE infection within 30 days (primary outcome) and all-cause mortality within 90 days (secondary outcome). Among 338 ICU patients, 94 (28%) were colonized with either Ceph-R or CRE. 26 patients developed CRE infection within 30 days of swab collection; 47% (N = 17/36) of CRE-colonized and 3% (N = 2/58) of Ceph-R colonized patients. 36% (N = 13/36) of CRE-colonized patients died within 90 days compared to 31% (N = 18/58) of Ceph-R-colonized and 15% (N = 37/244) of non-colonized patients. In a multivariable analysis, CRE colonization independently predicted development of a systemic CRE infection at 30 days (aOR 10.8, 95% CI2.8-41.9, p = 0.0006); Ceph-R colonization did not (aOR 0.5, 95% CI0.1-3.3, p = 0.5). CRE colonization was associated with increased 90-day mortality in a univariable analysis (p-value 0.001), in a multivariable model, previous hospitalization and medical ICU admission were independent predictors of 90-day mortality whereas CRE colonization approached significance (aOR 2.3, 95% CI1.0-5.3, p = 0.056). Our study highlights the increased risk of CRE infection and mortality in patients with CRE colonization at the time of ICU admission. Future studies are needed to assess how CRE

  19. Chemical composition and immunomodulatory effects of enzymatic protein hydrolysates from common carp (Cyprinus carpio) egg.

    Science.gov (United States)

    Chalamaiah, M; Hemalatha, R; Jyothirmayi, T; Diwan, Prakash V; Bhaskarachary, K; Vajreswari, A; Ramesh Kumar, R; Dinesh Kumar, B

    2015-02-01

    The aim of this study was to prepare protein hydrolysates from underutilized common carp (Cyprinus carpio) egg and to investigate their immunomodulatory effects in vivo. Common carp (Cyprinus carpio) egg (roe) was hydrolysed by pepsin, trypsin, and Alcalase. Chemical composition (proximate, amino acid, mineral and fatty acid compositions) and molecular mass distribution of the three hydrolysates were determined. The carp egg protein hydrolysates (CEPHs) were evaluated for their immunomodulatory effects in BALB/c mice. CEPHs (0.25, 0.5 and 1 g/kg body weight) were orally administered daily to female BALB/c mice (4-6 wk, 18-20 g) for a period of 45 d. After 45 d, mice were sacrificed and different tissues were collected for the immunologic investigations. The three hydrolysates contained high protein content (64%-73%) with all essential amino acids, and good proportion of ω-3 fatty acids, especially docosahexaenoic acid. Molecular mass analysis of hydrolysates confirmed the conversion of large-molecular-weight roe proteins into peptides of different sizes (5-90 kDa). The three hydrolysates significantly enhanced the proliferation of spleen lymphocytes. Pepsin hydrolysate (0.5 g/kg body weight) significantly increased the splenic natural killer cell cytotoxicity, mucosal immunity (secretory immunoglobulin A) in the gut and level of serum immunoglobulin A. Whereas Alcalase hydrolysate induced significant increases in the percentages of CD4+ and CD8+ cells in spleen. The results demonstrate that CEPHs are able to improve the immune system and further reveal that different CEPHs may exert differential influences on the immune function. These results indicate that CEPHs could be useful for several applications in the health food, pharmaceutical, and nutraceutical industries. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Entrepreneurial Choices of Initial Human Capital Endowments and New Venture Success

    DEFF Research Database (Denmark)

    Rocha, Vera; Van Praag, Mirjam; B. Folta, Timothy

    The founder (team)'s human capital is a vital determinant of future firm performance. This is a stylized fact. Less is known about the effect of the human capital of the initial workforce hired by the founder(s). We study the performance consequences of a founder's choice of the initial workforce......'s human capital (quantity and quality), besides the human capital of the founder(s). The analysis is based on matched employer-employee data and covers about 5,300 startups in manufacturing industries founded by individuals coming from employment between 1992 and 2007. We acknowledge that initial hiring...... decisions are endogenous and correlated with the human capital of the founders and the ownership structure of startups (single founder versus team of founders). Given the stickiness of initial choices, human capital decisions at entry turn out to be a close to irreversible matter with significant...

  1. iHAP – integrated haplotype analysis pipeline for characterizing the haplotype structure of genes

    Directory of Open Access Journals (Sweden)

    Lim Yun Ping

    2006-12-01

    Full Text Available Abstract Background The advent of genotype data from large-scale efforts that catalog the genetic variants of different populations have given rise to new avenues for multifactorial disease association studies. Recent work shows that genotype data from the International HapMap Project have a high degree of transferability to the wider population. This implies that the design of genotyping studies on local populations may be facilitated through inferences drawn from information contained in HapMap populations. Results To facilitate analysis of HapMap data for characterizing the haplotype structure of genes or any chromosomal regions, we have developed an integrated web-based resource, iHAP. In addition to incorporating genotype and haplotype data from the International HapMap Project and gene information from the UCSC Genome Browser Database, iHAP also provides capabilities for inferring haplotype blocks and selecting tag SNPs that are representative of haplotype patterns. These include block partitioning algorithms, block definitions, tag SNP definitions, as well as SNPs to be "force included" as tags. Based on the parameters defined at the input stage, iHAP performs on-the-fly analysis and displays the result graphically as a webpage. To facilitate analysis, intermediate and final result files can be downloaded. Conclusion The iHAP resource, available at http://ihap.bii.a-star.edu.sg, provides a convenient yet flexible approach for the user community to analyze HapMap data and identify candidate targets for genotyping studies.

  2. Assessing accuracy of genotype imputation in American Indians.

    Directory of Open Access Journals (Sweden)

    Alka Malhotra

    Full Text Available Genotype imputation is commonly used in genetic association studies to test untyped variants using information on linkage disequilibrium (LD with typed markers. Imputing genotypes requires a suitable reference population in which the LD pattern is known, most often one selected from HapMap. However, some populations, such as American Indians, are not represented in HapMap. In the present study, we assessed accuracy of imputation using HapMap reference populations in a genome-wide association study in Pima Indians.Data from six randomly selected chromosomes were used. Genotypes in the study population were masked (either 1% or 20% of SNPs available for a given chromosome. The masked genotypes were then imputed using the software Markov Chain Haplotyping Algorithm. Using four HapMap reference populations, average genotype error rates ranged from 7.86% for Mexican Americans to 22.30% for Yoruba. In contrast, use of the original Pima Indian data as a reference resulted in an average error rate of 1.73%.Our results suggest that the use of HapMap reference populations results in substantial inaccuracy in the imputation of genotypes in American Indians. A possible solution would be to densely genotype or sequence a reference American Indian population.

  3. Jobs

    DEFF Research Database (Denmark)

    Schubart, Rikke

    2013-01-01

    Review of the movie Jobs (Joshua Michael Stern, 2013), a drama about Steve Jobs, the founder of Apple.......Review of the movie Jobs (Joshua Michael Stern, 2013), a drama about Steve Jobs, the founder of Apple....

  4. Glossary

    Science.gov (United States)

    ... Huntington disease in the Lake Maracaibo region of Venezuela. Related term: founder variant founder variant A pathogenic ... Support Center External link. Please review our privacy policy . NLM NIH DHHS USA.gov National Center for ...

  5. Tests of Cloud Computing and Storage System features for use in H1 Collaboration Data Preservation model

    International Nuclear Information System (INIS)

    Łobodziński, Bogdan

    2011-01-01

    Based on the currently developing strategy for data preservation and long-term analysis in HEP tests of possible future Cloud Computing based on the Eucalyptus Private Cloud platform and the petabyte scale storage open source system CEPH were performed for the H1 Collaboration. Improvements in computing power and strong development of storage systems suggests that a single Cloud Computing resource supported on a given site will be sufficient for analysis requirements beyond the end-date of experiments. This work describes our test-bed architecture which could be applied to fulfill the requirements of the physics program of H1 after the end date of the Collaboration. We discuss the reasons why we choose the Eucalyptus platform and CEPH storage infrastructure as well as our experience with installations and support of these infrastructures. Using our first test results we will examine performance characteristics, noticed failure states, deficiencies, bottlenecks and scaling boundaries.

  6. Cephalopod genomics

    DEFF Research Database (Denmark)

    Albertin, Caroline B.; Bonnaud, Laure; Brown, C. Titus

    2012-01-01

    The Cephalopod Sequencing Consortium (CephSeq Consortium) was established at a NESCent Catalysis Group Meeting, ``Paths to Cephalopod Genomics-Strategies, Choices, Organization,'' held in Durham, North Carolina, USA on May 24-27, 2012. Twenty-eight participants representing nine countries (Austria......, Australia, China, Denmark, France, Italy, Japan, Spain and the USA) met to address the pressing need for genome sequencing of cephalopod mollusks. This group, drawn from cephalopod biologists, neuroscientists, developmental and evolutionary biologists, materials scientists, bioinformaticians and researchers...... active in sequencing, assembling and annotating genomes, agreed on a set of cephalopod species of particular importance for initial sequencing and developed strategies and an organization (CephSeq Consortium) to promote this sequencing. The conclusions and recommendations of this meeting are described...

  7. Influence of nasoalveolar molding on skeletal development in patients with unilateral cleft lip and palate at 5 years of age.

    Science.gov (United States)

    Akarsu-Guven, Bengisu; Arisan, Arda; Ozgur, Figen; Aksu, Muge

    2018-04-01

    The aim of this retrospective study was to assess the influence of presurgical nasoalveolar molding (NAM) on skeletal development in patients with operated unilateral cleft lip and palate at 5 years of age. Lateral cephalometric radiographs of 26 unilateral cleft lip and palate patients who had undergone presurgical NAM (NAM group) and 20 unilateral cleft lip and palate patients who did not have any presurgical NAM (non-NAM group) were analyzed. The radiographs were digitally traced using Quick Ceph Studio software (version 3.5.1.r (1151); Quick Ceph Systems, San Diego, Calif). Independent samples t tests were performed for statistical analysis. No significant differences were observed in sagittal and vertical skeletal measurements between the NAM and non-NAM groups. NAM resulted in no significant difference in skeletal development in unilateral cleft lip and palate patients compared with those without NAM in early childhood. Copyright © 2018. Published by Elsevier Inc.

  8. HindIII identifies a two allele DNA polymorphism of the human cannabinoid receptor gene (CNR)

    Energy Technology Data Exchange (ETDEWEB)

    Caenazzo, L.; Hoehe, M.R.; Hsieh, W.T.; Berrettini, W.H.; Bonner, T.I.; Gershon, E.S. (National Inst. of Health, Bethesda, MD (United States))

    1991-09-11

    HCNR p5, a 0.9 kb BamHI/EcoRI fragment from the human cannabinoid receptor gene inserted into pUC19, was used as probe. The fragment is located in an intron approximately 14 kb 5{prime} of the initiation codon. This fragment is a clean single copy sequence by genomic blotting. Hybridization of human genomic DNA digested with HindIII identified a two allele RFLP with bands at 5.5 (A1) and 3.3 kb (A2). The human cannabinoid receptor gene has been genetically mapped in CEPH reference pedigrees to the centromeric/q region of chromosome 6. In situ hybridization localizes it to 6q14-q15. Codominant segregation has been observed in 26 informative two- and three-generation CEPH pedigrees and in 14 medium-sized disease families.

  9. dCache on Steroids - Delegated Storage Solutions

    Science.gov (United States)

    Mkrtchyan, T.; Adeyemi, F.; Ashish, A.; Behrmann, G.; Fuhrmann, P.; Litvintsev, D.; Millar, P.; Rossi, A.; Sahakyan, M.; Starek, J.

    2017-10-01

    For over a decade, dCache.org has delivered a robust software used at more than 80 Universities and research institutes around the world, allowing these sites to provide reliable storage services for the WLCG experiments as well as many other scientific communities. The flexible architecture of dCache allows running it in a wide variety of configurations and platforms - from a SoC based all-in-one Raspberry-Pi up to hundreds of nodes in a multipetabyte installation. Due to lack of managed storage at the time, dCache implemented data placement, replication and data integrity directly. Today, many alternatives are available: S3, GlusterFS, CEPH and others. While such solutions position themselves as scalable storage systems, they cannot be used by many scientific communities out of the box. The absence of community-accepted authentication and authorization mechanisms, the use of product specific protocols and the lack of namespace are some of the reasons that prevent wide-scale adoption of these alternatives. Most of these limitations are already solved by dCache. By delegating low-level storage management functionality to the above-mentioned new systems and providing the missing layer through dCache, we provide a solution which combines the benefits of both worlds - industry standard storage building blocks with the access protocols and authentication required by scientific communities. In this paper, we focus on CEPH, a popular software for clustered storage that supports file, block and object interfaces. CEPH is often used in modern computing centers, for example as a backend to OpenStack services. We will show prototypes of dCache running with a CEPH backend and discuss the benefits and limitations of such an approach. We will also outline the roadmap for supporting ‘delegated storage’ within the dCache releases.

  10. Global population variability in Qiagen Investigator HDplex STRs.

    Science.gov (United States)

    Phillips, C; Fernandez-Formoso, L; Gelabert-Besada, M; García-Magariños, M; Amigo, J; Carracedo, A; Lareu, M V

    2014-01-01

    Supplementary short tandem repeats (STRs) can be added to forensic analyses if the 15-24 core STRs in routine use fail to give sufficient discrimination power in complex identification or relationship testing scenarios. In this study, 10 of 12 supplementary STRs in the Qiagen Investigator HDplex kit (SE33, D2S1360, D3S1744, D4S2366, D5S2500, D6S474, D7S1517, D8S1132, D10S2325, D21S2055) were genotyped in 941 individuals from the 51 populations of the CEPH Human Genome Diversity Panel (HGDP-CEPH). The other two components of the 12-STR HDplex kit are established STRs D12S391 and D18S51 that we previously genotyped for the HGDP-CEPH panel. We describe the rare alleles identified and outline allele frequency distributions in the seven population groups of the HGDP-CEPH panel. The HDplex STRs novel to forensic application were found to be both highly informative and comparable in their power across all populations studied: at least six of the nine loci showing above average forensic discrimination power in each population group. In some rare instances certain low frequency alleles in D2S1360 were found to overlap in mobility with the neighbouring allele size ranges of D12S391, as well as those of D7S1517 with neighbouring D3S1744 and D10S2325 with neighbouring SE33. Lastly, since expanded five-dye multiplex kits of 20 STRs (Promega Powerplex 21) and 22 STRs (Promega Powerplex Fusion) have recently been introduced, we assess through simulations the increased power to analyse pairwise relationships in deficient pedigrees that can be expected from an optimum kit pair: combining HDplex with either of the above sets to provide 30 or 32 unique STRs and just two overlapping loci. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. MetaSINEs: Broad Distribution of a Novel SINE Superfamily in Animals

    OpenAIRE

    Nishihara, Hidenori; Plazzi, Federico; Passamonti, Marco; Okada, Norihiro

    2016-01-01

    SINEs (short interspersed elements) are transposable elements that typically originate independently in each taxonomic clade (order/family). However, some SINE families share a highly similar central sequence and are thus categorized as a SINE superfamily. Although only four SINE superfamilies (CORE-SINEs, V-SINEs, DeuSINEs, and Ceph-SINEs) have been reported so far, it is expected that new SINE superfamilies would be discovered by deep exploration of new SINEs in metazoan genomes. Here we de...

  12. Integration of XRootD into the cloud infrastructure for ALICE data analysis

    CERN Document Server

    Kompaniets, Mikhail; Svirin, Pavlo; Yurchenko, Volodymyr; Zarochentsev, Andrey

    2015-01-01

    Cloud technologies allow easy load balancing between different tasks and projects. From the viewpoint of the data analysis in the ALICE experiment, cloud allows to deploy software using Cern Virtual Machine (CernVM) and CernVM File System (CVMFS), to run different (including outdated) versions of software for long term data preservation and to dynamically allocate resources for different computing activities, e.g. grid site, ALICE Analysis Facility (AAF) and possible usage for local projects or other LHC experiments.We present a cloud solution for Tier-3 sites based on OpenStack and Ceph distributed storage with an integrated XRootD based storage element (SE). One of the key features of the solution is based on idea that Ceph has been used as a backend for Cinder Block Storage service for OpenStack, and in the same time as a storage backend for XRootD, with redundancy and availability of data preserved by Ceph settings. For faster and easier OpenStack deployment was applied the Packstack solution, which is ba...

  13. The deployment of a large scale object store at the RAL Tier-1

    Science.gov (United States)

    Dewhurst, A.; Johnson, I.; Adams, J.; Canning, B.; Vasilakakos, G.; Packer, A.

    2017-10-01

    Since 2014, the RAL Tier-1 has been working on deploying a Ceph backed object store. The aim is to replace Castor for disk-only storage. This new service must be scalable to meet the data demands of the LHC to 2020 and beyond. As well as offering access protocols the LHC experiments currently use, it must also provide industry standard access protocols. In order to keep costs down the service must use erasure coding rather than replication to ensure data reliability. This paper will present details of the storage service setup, which has been named Echo, as well as the experience gained from running it. The RAL Tier-1 has also been developing XrootD and GridFTP plugins for Ceph. Both plugins are built on top of the same libraries that write striped data into Ceph and therefore data written by one protocol will be accessible by the other. In the long term we hope the LHC experiments will migrate to industry standard protocols, therefore these plugins will only provide the features needed by the LHC experiments. This paper will report on the development and testing of these plugins.

  14. Interview with René Yáñez, artist, co-founder of the Galería de la Raza, San Francisco, CA, USA, August 13, 2001 Entretien avec René Yáñez, artiste, co-fondateur de la Galería de la Raza, San Francisco, CA, Etats-Unis

    Directory of Open Access Journals (Sweden)

    Gérard Selbach

    2009-10-01

    Full Text Available René Yáñez is an all-round visual artist and visionary, now in his sixties. He came out of the Chicano movement of the 70’s and was instrumental in founding the Galería de la Raza in the Mission district of San Francisco. He remained some fifteen years as its director, curating exhibitions, directing and promoting emerging artists of all kinds. He then worked as director of cultural programming at the Mexican Museum until its closure. René Yáñez co-produced Mexican performance artist Astrid H...

  15. Os Tratados de Polícia, fundadores da moderna saúde pública (1707-1856 Los Tratados de Policía, fundadores de la salud pública moderna (1707-1856 Treatises on Medical Police, founders of modern public health (1707-1856

    Directory of Open Access Journals (Sweden)

    Carlos Lousada Subtil

    2012-07-01

    Full Text Available A participação dos enfermeiros no movimento higienista é relativamente recente em relação aos momentos fundadores da moderna saúde pública, a que nos vamos referir. Para o enfermeiro de saúde pública contemporâneo é fundamental, no âmbito das suas atribuições e competências, analisar esses momentos à luz dum quadro conceptual que lhe permita esclarecer-se e estruturar a sua identidade profissional na construção do presente e no delinear do futuro. É objetivo deste trabalho fazer uma breve apresentação de alguns estudos sobre o tema e, sobretudo, analisar e discutir o «Tratado de Conservação da Saúde dos Povos», de Ribeiro Sanches (1756 e o «Tratado de Polícia Médica», de Freitas Soares (1818 que refletem os princípios da ciência de Polícia contidos na obra de Nicolas Delamare (1707, com recurso à metodologia de investigação histórica foucauniana. Aquelas obras ilustram bem a lenta passagem do modelo de governação corporativo para o estadualista, que se iniciou nos finais do Antigo Regime, e prosseguiu, com avanços e recuos, ao longo da monarquia constitucional inaugurada pela revolução de 1820.La participación de los enfermeros en el movimiento higienista es relativamente reciente con respecto a los momentos fundadores de la salud pública moderna a la cual vamos a referirnos. Para el enfermero actual de salud pública es fundamental, dentro del ámbito de sus atribuciones y competencias, analizar dichos movimientos a la luz de un marco conceptual que le permita aclarar y estructurar su identidad profesional en su construcción del presente y en el delinear de su futuro. El objetivo de este trabajo es realizar una breve presentación de algunos de los estudios sobre el tema y, sobre todo, analizar y discutir el «Tratado de Conservação da Saúde dos Povos», de Ribeiro Sanches (1756 y el «Tratado de Polícia Médica», de Freitas Soares (1818, que recogen los principios de la ciencia de Polícia contenidos en la obra de Nicolas Delamare (1707, recurriendo a la metodología de la investigación histórica fouconiana. Estas obras ilustran claramente el lento paso de un modelo de regimiento corporativo hacia uno de tipo estatal, el cual se inició a finales del Antiguo Régimen y siguió, con avances y retrocesos, a lo largo de la monarquía constitucional inaugurada por la revolución de 1820.The participation of nurses in the hygiene movement is relatively recent in relation to the founding moments of modern public health to which we will refer. It is fundamental for contemporary public health nurses, within their role and competences, to analyze those facts within a conceptual framework allowing the clarification and structuring of their professional identity in the construction of the present and sketching of the future. The object of this study is to present briefly some treatises on the topic and, particularly, to analyze and discuss the «Tratado de Conservação da Saúde dos Povos» by Ribeiro Sanches (1756 and the «Tratado de Polícia Médica» by Freitas Soares (1818 that reflect the principles included in Nicolas Delamare’s work (1707. We have used the historical investigation method according to Foucault’s genealogy paradigm. These works provide a good illustration of the slow passage from the model of corporate governance to that of state governance, which began at the end of the Antigo Regime (old regime and continued, with several setbacks, throughout the constitutional monarchy established by the revolution of 1820.

  16. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    NARCIS (Netherlands)

    P.S. de Vries (Paul); D.I. Chasman (Daniel); M. Sabater-Lleal (Maria); M.-H. Chen (Ming-Huei); J.E. Huffman (Jennifer E.); M. Steri (Maristella); W. Tang (Weihong); A. Teumer (Alexander); R.E. Marioni (Riccardo); V. Grossmann (Vera); J.J. Hottenga (Jouke Jan); S. Trompet (Stella); M. Müller-Nurasyid (Martina); J.H. Zhao (Jing Hua); J. Brody (Jennifer); M.E. Kleber (Marcus); X. Guo (Xiuqing); J.J. Wang (Jie Jin); P. Auer (Paul); J. Attia (John); L.R. Yanek (Lisa); T.S. Ahluwalia (Tarunveer Singh); J. Lahti (Jari); C. Venturini (Cristina); T. Tanaka (Toshiko); L.F. Bielak (Lawrence F.); P.K. Joshi (Peter); A. Rocanin-Arjo (Ares); I. Kolcic (Ivana); P. Navarro (Pau); L.M. Rose (Lynda); C. Oldmeadow (Christopher); H. Riess (Helene); J. Mazur (Johanna); S. Basu (Saonli); A. Goel (Anuj); Q. Yang (Qiong); M. Ghanbari (Mohsen); Gonnekewillemsen; A. Rumley (Ann); E. Fiorillo (Edoardo); A.J. de Craen (Anton); A. Grotevendt (Anne); R.A. Scott (Robert); K.D. Taylor (Kent D.); G.E. Delgado (Graciela E.); J. Yao (Jie); A. Kifley (Annette); C. Kooperberg (Charles); Q. Qayyum (Rehan); L. Lopez (Lornam); T.L. Berentzen (Tina L.); K. Räikkönen (Katri); Massimomangino; S. Bandinelli (Stefania); P.A. Peyser (Patricia A.); S. Wild (Sarah); D.-A. Tregouet (David-Alexandre); A.F. Wright (Alan); J. Marten (Jonathan); T. Zemunik (Tatijana); A.C. Morrison (Alanna); B. Sennblad (Bengt); G.H. Tofler (Geoffrey); M.P.M. de Maat (Moniek); E.J.C. de Geus (Eco); G.D. Lowe (Gordon D.); M. Zoledziewska (Magdalena); N. Sattar (Naveed); H. Binder (Harald); U. Völker (Uwe); M. Waldenberger (Melanie); K.-T. Khaw (Kay-Tee); B. McKnight (Barbara); J. Huang (Jian); N.S. Jenny (Nancy); E.G. Holliday (Elizabeth); L. Qi (Lihong); M.G. Mcevoy (Mark G.); D.M. Becker (Diane); J.M. Starr (John); A.-P. Sarin; P.G. Hysi (Pirro); D.G. Hernandez (Dena); M.A. Jhun (Min A.); H. Campbell (Harry); A. Hamsten (Anders); F. Sarin (Fernando); W.L. McArdle (Wendy); P. Eline Slagboom; T. Zeller (Tanja); W. Koenig (Wolfgang); B. Psaty (Brucem); T. Haritunians (Talin); J. Liu (Jingmin); A. Palotie (Aarno); A.G. Uitterlinden (André); D.J. Stott (David J.); A. Hofman (Albert); O.H. Franco (Oscar); O. Polasek (Ozren); I. Rudan (Igor); P.-E. Morange (P.); J.F. Wilson (James F.); S.L. Kardia (Sharon L.r); L. Ferrucci (Luigi); T.D. Spector (Timothy); J.G. Eriksson (Johan G.); T. Hansen (Torben); I.J. Deary (Ian); L.C. Becker (Lewis); R.J. Scott (Rodney); P. Mitchell (Paul); W. März (Winfried); N.J. Wareham (Nick J.); A. Peters (Annette); A. Greinacher (Andreas); P.S. Wild (Philipp S.); J.W. Jukema (Jan Wouter); D.I. Boomsma (Dorret I.); C. Hayward (Caroline); F. Cucca (Francesco); R.P. Tracy (Russell); H. Watkins (Hugh); A.P. Reiner (Alex P.); A.R. Folsom (Aaron); P.M. Ridker (Paul); C.J. O'Donnell (Christopher J.); N.L. Smith (Nicholas L.); D.P. Strachan (David P.); A. Dehghan (Abbas)

    2016-01-01

    textabstractGenome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes

  17. Indian Institute of Science, Bangalore

    Indian Academy of Sciences (India)

    user

    2015-07-04

    Jul 4, 2015 ... About 18% of Indian population speak Dravidian language. Linguistic ... Military conquests by Arabs and Turks. British colonization. Among several ... 132 individuals. 25 populations. 15 states. All the language families. 560,123 SNPs. HGDP & HapMap. PCA - EIGENSOFT. Autosomal SNPs. Affymetrix 6.0 ...

  18. Variation in the Kozak sequence of WNT16 results in an increased translation and is associated with osteoporosis related parameters

    DEFF Research Database (Denmark)

    Hendrickx, Gretl; Boudin, Eveline; Fijałkowski, Igor

    2014-01-01

    on osteoporosis related parameters. Hereto, we performed a WNT16 candidate gene association study in a population of healthy Caucasian men from the Odense Androgen Study (OAS). Using HapMap, five tagSNPs and one multimarker test were selected for genotyping to cover most of the common genetic variation...

  19. Genomic scans for selective sweeps using SNP data

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Williamson, Scott; Kim, Yuseob

    2005-01-01

    of the selection coefficient. To illustrate the method, we apply our approach to data from the Seattle SNP project and to Chromosome 2 data from the HapMap project. In Chromosome 2, the most extreme signal is found in the lactase gene, which previously has been shown to be undergoing positive selection. Evidence...

  20. Planning the Human Variome Project : The Spain Report

    NARCIS (Netherlands)

    Kaput, Jim; Cotton, Richard G. H.; Hardman, Lauren; Watson, Michael; Al Aqeel, Aida I.; Al-Aama, Jumana Y.; Al-Mulla, Fahd; Alonso, Santos; Aretz, Stefan; Auerbach, Arleen D.; Bapat, Bharati; Bernstein, Inge T.; Bhak, Jong; Bleoo, Stacey L.; Bloecker, Helmut; Brenner, Steven E.; Burn, John; Bustamante, Mariona; Calone, Rita; Cambon-Thomsen, Anne; Cargill, Michele; Carrera, Paola; Cavedon, Lawrence; Cho, Yoon Shin; Chung, Yeun-Jun; Claustres, Mireille; Cutting, Garry; Dalgleish, Raymond; den Dunnen, Johan T.; Diaz, Carlos; Dobrowolski, Steven; dos Santos, M. Rosario N.; Ekong, Rosemary; Flanagan, Simon B.; Flicek, Paul; Furukawa, Yoichi; Genuardi, Maurizio; Ghang, Ho; Golubenko, Maria V.; Greenblatt, Marc S.; Hamosh, Ada; Hancock, John M.; Hardison, Ross; Harrison, Terence M.; Hoffmann, Robert; Horaitis, Rania; Howard, Heather J.; Barash, Carol Isaacson; Izagirre, Neskuts; Sijmons, Rolf H.

    The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data

  1. Planning the human variome project: the Spain report

    DEFF Research Database (Denmark)

    Kaput, Jim; Cotton, Richard G H; Hardman, Lauren

    2009-01-01

    The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of dat...

  2. Genetic landscape of the people of India: a canvas for disease gene ...

    Indian Academy of Sciences (India)

    2008-04-09

    Apr 9, 2008 ... (>10 million individuals) and 23 isolated populations, representing a large fraction of the people of India. We observe ... populations not only overlap with the diversity of HapMap populations, but also contain population groups that are genetically ... China has resulted in a rich tapestry of socio-cultural, lin-.

  3. Planning the human variome project: the Spain report.

    NARCIS (Netherlands)

    Kaput, J.; Cotton, R.G.; Hardman, L.; Watson, M.; Aqeel, A.I. Al; Al-Aama, J.Y.; Al-Mulla, F.; Alonso, S.; Aretz, S.; Auerbach, A.D.; Bapat, B.; Bernstein, I.T.; Bhak, J.; Bleoo, S.L.; Blocker, H.; Brenner, S.E.; Burn, J.; Bustamante, M.; Calzone, R.; Cambon-Thomsen, A.; Cargill, M.; Carrera, P.; Cavedon, L.; Cho, Y.S.; Chung, Y.J.; Claustres, M.; Cutting, G.; Dalgleish, R.; Dunnen, J.T. den; Diaz, C.; Dobrowolski, S.; Santos, M.R. dos; Ekong, R.; Flanagan, S.B.; Flicek, P.; Furukawa, Y.; Genuardi, M.; Ghang, H.; Golubenko, M.V.; Greenblatt, M.S.; Hamosh, A.; Hancock, J.M.; Hardison, R.; Harrison, T.M.; Hoffmann, R.; Horaitis, R.; Howard, H.J.; Barash, C.I.; Izagirre, N.; Jung, J.; Kojima, T.; Laradi, S.; Lee, Y.S.; Lee, J.Y.; Gil-da-Silva-Lopes, V.L.; Macrae, F.A.; Maglott, D.; Marafie, M.J.; Marsh, S.G.; Matsubara, Y.; Messiaen, L.M.; Moslein, G.; Netea, M.G.; Norton, M.L.; Oefner, P.J.; Oetting, W.S.; O'Leary, J.C.; Ramirez, A.M. de; Paalman, M.H.; Parboosingh, J.; Patrinos, G.P.; Perozzi, G.; Phillips, I.R.; Povey, S.; Prasad, S.; Qi, M.; Quin, D.J.; Ramesar, R.S.; Richards, C.S.; Savige, J.; Scheible, D.G.; Scott, R.J.; Seminara, D.; Shephard, E.A.; Sijmons, R.H.; Smith, T.D.; Sobrido, M.J.; Tanaka, T.; Tavtigian, S.V.; Taylor, G.R.; Teague, J.; Topel, T.; Ullman-Cullere, M.; Utsunomiya, J.; Kranen, H.J. van; Vihinen, M.; Webb, E.; Weber, T.K.; Yeager, M.

    2009-01-01

    The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data

  4. Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies

    DEFF Research Database (Denmark)

    Li, Yun R.; van Setten, Jessica; Verma, Shefali S.

    2015-01-01

    genome-wide genotyping array, the 'TxArray', comprising approximately 782,000 markers with tailored content for deeper capture of variants across HLA, KIR, pharmacogenomic, and metabolic loci important in transplantation. To test concordance and genotyping quality, we genotyped 85 HapMap samples...

  5. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    DEFF Research Database (Denmark)

    de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria

    2016-01-01

    Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. W...

  6. Genotyping and annotation of Affymetrix SNP arrays

    DEFF Research Database (Denmark)

    Lamy, Philippe; Andersen, Claus Lindbjerg; Wikman, Friedrik

    2006-01-01

    it is indicated that our method is likely to be correct in majority of these cases. In addition, we demonstrate that our method produces more SNPs that are in concordance with Hardy-Weinberg equilibrium than the method by Affymetrix. Finally, we have validated our method on HapMap data and shown...

  7. Geographical structure and differential natural selection among North European populations

    DEFF Research Database (Denmark)

    McEvoy, Brian P; Montgomery, Grant W; McRae, Allan F

    2009-01-01

    polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like...

  8. Heritability, SNP- and gene-based analyses of cannabis use initiation and age at onset

    NARCIS (Netherlands)

    Minica, C.C.; Dolan, C.V.; Hottenga, J.J.; Pool, R.; Fedko, I.O.; Mbarek, H.; Huppertz, C.; Bartels, M.; Boomsma, D.I.; Vink, J.M.

    2015-01-01

    Prior searches for genetic variants (GVs) implicated in initiation of cannabis use have been limited to common single nucleotide polymorphisms (SNPs) typed in HapMap samples. Denser SNPs are now available with the completion of the 1000 Genomes and the Genome of the Netherlands projects. More

  9. Heritability, SNP- and Gene-Based Analyses of Cannabis Use Initiation and Age at Onset

    NARCIS (Netherlands)

    Minica, C.C.; Dolan, C.V.; Hottenga, J.J.; Pool, R.; Fedko, I.O.; Mbarek, H.; Huppertz, C.; Bartels, M.; Boomsma, D.I.; Vink, J.M.

    2015-01-01

    Prior searches for genetic variants (GVs) implicated in initiation of cannabis use have been limited to common single nucleotide polymorphisms (SNPs) typed in HapMap samples. Denser SNPs are now available with the completion of the 1000 Genomes and the Genome of the Netherlands projects. More

  10. MACHIAVELLI DÜŞÜNCESİNDE CUMHURİYETÇİ ÖZGÜRLÜK VE KURUCU LİDER İMGESİ

    OpenAIRE

    ÖZTÜRK, Armağan

    2014-01-01

    In this article, the thoughts of Machiavelli on ethics and politics will be addressed in detail and the republican freedom and founder leader themes will be opened to discussion with regards to the mentioned thought. The main problematic on the base of the discussion is characterized by the issues that what Machiavelli expects from the prince who is the founder of the state; and in this respect whether there is a tension between the founder leader and republican sensibility. Of course, such a...

  11. Shaka Zulu’s Linkage of Strategy and Tactics: An Early Form of Operational Art?

    Science.gov (United States)

    2014-05-22

    Senzangakhona Lineage ........................................................................... 7 Figure 2: Portrait of King Shaka, Founder of the Zulu ...of the Founder of the Zulu Nation (London: Penguin Books, 1955), 65. 13 impi-ebomvu – total war. But treat generously those who submit without war... Founder of the Zulu Nation, 59. 60Ibid., 63. 22 were less than a third of Zwide’s. Despite Shaka’s plea with Dingiswayo to kill Zwide, Dingiswayo

  12. Network Science Center Research Team’s Visit to Kampala, Uganda

    Science.gov (United States)

    2013-07-01

    the intersection of open data, human rights, and African development. Jon is the founder or co- founder of several organizations and initiatives...drove across Kampala to meet with Teddy Ruge, a co- founder of Hive CoLab and a noted Ugandan Social Entrepreneur, and Brian Ndyaguma, the operations...www.netscience.usma.edu 845.938.0804 At Outbox, we were hosted by Richard Zulu , the general manager. Outbox was founded in 2012 and is the newest business incubator

  13. Unravelling starlight: William and Margaret Huggins and the rise of the new astronomy

    National Research Council Canada - National Science Library

    Becker, Barbara J

    2011-01-01

    ...). A pioneer in adapting the spectroscope to new astronomical purposes, William Huggins rose to scientific prominence in London and transformed professional astronomy to become a principal founder...

  14. An integrated genetic, physical, and transcriptional map of chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Scheffer, H.; Kooy, R.F.; Wijngaard, A. [Univ. of Groningen (Netherlands)] [and others

    1994-09-01

    In this study a genetic map containing 20 markers and typed in 40 CEPH families is presented. It includes 7 thusfar untyped microsatellite markers, 7 that have previously been mapped on a subset of 8 CEPH families, one reference marker, D13S71, and three telomeric VNTR markers. Also, 4 intragenic RB1 markers were typed. The markers have an average heterozygosity of 73% (80%, excluding the three RFLPs). The total sex average length of the map is 140 cM. The mean female to male ratio is 1.54. For the non-telomeric part of the chromosome between the markers D13S221 in 13q12 and D13S173 in 13q33-q34, this ratio is 1.99. This ratio is reversed in the telomeric part of the chromosome between D13S173 and D13S234 in distal 13q34, where it is 0.47. A high new mutation frequency of 1% was detected in the (CTTT(T)){sub n} repeat in intron 20 of the RB1 gene. The map has been integrated with 7 microsatellite markers and 2 RFLP markers from CEPH database version 7.0, resulting in a map with 32 markers (28 loci) of chromosome 13q. In addition, a deletion hybrid breakpoint map ordering 50 markers in 18 intervals is constructed. It includes 32 microsatellite markers, 4 genes, 5 STSs, and 9 ESTs. Each of 18 intervals contains at least one microsatellite marker included in the extended genetic map. These data allow a correlation between the genetic and physical map of chromosome 13. New ESTs are currently being identified and localized at this integrated map.

  15. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

    Directory of Open Access Journals (Sweden)

    Blandine Patillon

    Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  16. Two RFLPs in the 5 prime end of the human osteonectin (ON) gene

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, R C; Tsipouras, P [Univ. of Connecticut Health Center Farmington (USA); Young, M F [National Institutes of Health, Bethesda, MD (USA)

    1988-09-26

    On 164 is a 550 base pair cDNA clone at the 5{prime} end of the human osteonectin gene. The insert is an EcoRI fragment inserted into Bluescript. HincII identified a simple two allele polymorphism with a band at either 14 kb or 12.5 kb. TaqI identified a simple two allele polymorphism with a band at either 4.9 or 4.6 kb. 18 and 26 unrelated individuals from the CEPH panel were studied for the HincII and TaqI polymorphisms respectively. Autosomal dominant inheritance was demonstrated in 2 kindreds of 8 individuals for each polymorphism.

  17. Scalable cloud without dedicated storage

    Science.gov (United States)

    Batkovich, D. V.; Kompaniets, M. V.; Zarochentsev, A. K.

    2015-05-01

    We present a prototype of a scalable computing cloud. It is intended to be deployed on the basis of a cluster without the separate dedicated storage. The dedicated storage is replaced by the distributed software storage. In addition, all cluster nodes are used both as computing nodes and as storage nodes. This solution increases utilization of the cluster resources as well as improves fault tolerance and performance of the distributed storage. Another advantage of this solution is high scalability with a relatively low initial and maintenance cost. The solution is built on the basis of the open source components like OpenStack, CEPH, etc.

  18. Evolution of the NFS Filer Service

    CERN Multimedia

    CERN. Geneva; ROUSSEAU, Herve; MASCETTI, Luca

    2015-01-01

    The presentation will give an overview of the operations activities in the IT DSS group on the NFS services and its consolidation with the goal of avoiding proprietary solutions. CERN-IT manages a series of NetApp appliances for NFS applications, the presentation will focus on the Filer history, on a new way to provide NFS-based services using an advanced filesystem like ZFS combined with Ceph (IT-DSS block storage solution for OpenStack) and on the decommissioning strategy of the previous proprietary Filer. The presentation will highlight strengths and weaknesses for each systems and a cost comparison of the different solutions.

  19. Population Analysis of Pharmacogenetic Polymorphisms Related to Acute Lymphoblastic Leukemia Drug Treatment

    Directory of Open Access Journals (Sweden)

    Marcela A. Chiabai

    2012-01-01

    Full Text Available This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in treatment of acute lymphoblastic leukemia (ALL, and to compare the data with data from the HapMap populations. There was significant differentiation between most population pairs, but few associations between genetic ancestry and SNPs in the Brazilian population were observed. AMOVA analysis comparing the Brazilian population to all other populations retrieved from HapMap pointed to a genetic proximity with the European population. These associations point to preclusion of the use of genetic ancestry as a proxy for predicting drug response. In this way, any study aiming to correlate genotype with drug response in the Brazilian population should be based on pharmacogenetic SNP genotypes.

  20. Selection signatures in worldwide sheep populations.

    Science.gov (United States)

    Fariello, Maria-Ines; Servin, Bertrand; Tosser-Klopp, Gwenola; Rupp, Rachel; Moreno, Carole; San Cristobal, Magali; Boitard, Simon

    2014-01-01

    The diversity of populations in domestic species offers great opportunities to study genome response to selection. The recently published Sheep HapMap dataset is a great example of characterization of the world wide genetic diversity in sheep. In this study, we re-analyzed the Sheep HapMap dataset to identify selection signatures in worldwide sheep populations. Compared to previous analyses, we made use of statistical methods that (i) take account of the hierarchical structure of sheep populations, (ii) make use of linkage disequilibrium information and (iii) focus specifically on either recent or older selection signatures. We show that this allows pinpointing several new selection signatures in the sheep genome and distinguishing those related to modern breeding objectives and to earlier post-domestication constraints. The newly identified regions, together with the ones previously identified, reveal the extensive genome response to selection on morphology, color and adaptation to new environments.

  1. Kings Today, Rich Tomorrow

    DEFF Research Database (Denmark)

    Fattoum, Asma

    2013-01-01

    This study investigates the King vs. Rich dilemma that founder-CEOs face at IPO. When undertaking IPO, founders face two options. They can either get rich, but then run the risk of losing the control over their firms; or they can remain kings by introducing defensive mechanisms, but this is likel...

  2. マーケティングのパイオニア : 森永太一郎と鈴木三郎助

    OpenAIRE

    森田, 克徳

    1998-01-01

    This paper attempts to clarify the business activities of Taichiro Morinaga and Saburosuke Suzuki, especially of marketing. The former is the founder of Morinagaseika which was inagurated in 1899, and the latter is the founder of Ajinomoto established in 1908. Morinagaseika is a first-mover in the confectionery industory in Japan and Ajinomoto in the seasoning industory too.

  3. Separation of Powers and the Legislative Power.

    Science.gov (United States)

    Rossum, Ralph A.

    1986-01-01

    Addresses the contribution of separation of powers and checks and balances in resolving the rival defects of democratic ineptitude and majority tyranny as the Founders framed the Constitution. Contends the Founders structured the government so that the three branches could keep each other in their proper places. Discusses Anti- Federalist…

  4. Sanjoy Hazarika

    Indian Academy of Sciences (India)

    Sanjoy Hazarika is the Director, Commonwealth Human Rights Initiative. He was the founder Director, Centre for North-East Studies and Policy Research, Jamia Millia Islamia, New Delhi and also holds Dr Saifuddin Kitchlew Chair. He is the founder and managing trustee of North-East Studies, which runs the pioneering ...

  5. Founding a business inspired by close entrepreneurial ties: Does it matter for survival?

    NARCIS (Netherlands)

    de Jong, J.P.J.; Marsili, O.

    2015-01-01

    Founding a business may be inspired by close entrepreneurial ties, that is, business-owning relatives or friends. We analyze if and when such inspiration is associated with post-entry survival. Drawing on longitudinal data on 942 founders, we find a positive relationship only if founders start by

  6. Generation of transgenic mice producing fungal xylanase in the ...

    African Journals Online (AJOL)

    DR TONUKARI NYEROVWO

    express exogenous digestive enzymes, since a single- stomached animal, such as a pig, can secret .... transgenic founder mice; 1 to15 are fifteen wild-type founder mice; M, marke; β-actin, endogenous control. (C) Identification of transgenic mice by ... 61.48±0.34%), gross energy digestibility (WT vs. TG = 68.79±0.51% vs.

  7. Makit Lld: A Price above Rubies

    DEFF Research Database (Denmark)

    Hockerts, Kai; Jorem, Kaja; Walker Pedersen, Kristina

    2016-01-01

    . The case lends itself, furthermore, to the introduction of a number of other topics related to social entrepreneurship, such as, for example, how to organize a founder team, the ownership structures, and how to plan for the risk of one founder leaving the team. Moreover, the case allows discussing...

  8. Whole genome scan in chickens for quantitative trait loci affecting carcass traits

    NARCIS (Netherlands)

    Kaam, van J.B.C.H.M.; Groenen, M.A.M.; Bovenhuis, H.; Veenendaal, A.; Vereijken, A.L.J.; Arendonk, van J.A.M.

    1999-01-01

    An experiment was conducted to enable quantitative trait loci (QTL) mapping for carcass traits. The population consisted of 10 full-sib families originating from a cross between male and female founders chosen from two different outcross broiler lines. Founder animals, parents, offspring, and

  9. The relationship between male moth density and female mating success in invading populations of Lymantria dispar

    Science.gov (United States)

    Patrick C. Tobin; Ksenia S. Onufrieva; Kevin W. Thorpe

    2012-01-01

    The successful establishment of non-native species in new areas can be affected by many factors including the initial size of the founder population. Populations comprised of fewer individuals tend to be subject to stochastic forces and Allee effects (positive-density dependence), which can challenge the ability of small founder populations to establish in a new area....

  10. Enacted identities in the university spin-off process - bridging an imaginative gap

    DEFF Research Database (Denmark)

    Hannibal, Martin

    2017-01-01

    This paper employs a case study to explore the interdependencies between enacted role identities and behavioural logics of eight inventor-founders embedded in university spin-off venturing. The major tendencies in the findings suggest that the inventor-founders enact their academic role identity ...

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

    OpenAIRE

    Kelsoe, J R

    2004-01-01

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

  12. The CFTR Met 470 allele is associated with lower birth rates in fertile men from a population isolate.

    Directory of Open Access Journals (Sweden)

    Gülüm Kosova

    2010-06-01

    Full Text Available Although little is known about the role of the cystic fibrosis transmembrane regulator (CFTR gene in reproductive physiology, numerous variants in this gene have been implicated in etiology of male infertility due to congenital bilateral absence of the vas deferens (CBAVD. Here, we studied the fertility effects of three CBAVD-associated CFTR polymorphisms, the (TGm and polyT repeat polymorphisms in intron 8 and Met470Val in exon 10, in healthy men of European descent. Homozygosity for the Met470 allele was associated with lower birth rates, defined as the number of births per year of marriage (P = 0.0029. The Met470Val locus explained 4.36% of the phenotypic variance in birth rate, and men homozygous for the Met470 allele had 0.56 fewer children on average compared to Val470 carrier men. The derived Val470 allele occurs at high frequencies in non-African populations (allele frequency = 0.51 in HapMap CEU, whereas it is very rare in African population (Fst = 0.43 between HapMap CEU and YRI. In addition, haplotypes bearing Val470 show a lack of genetic diversity and are thus longer than haplotypes bearing Met470 (measured by an integrated haplotype score [iHS] of -1.93 in HapMap CEU. The fraction of SNPs in the HapMap Phase2 data set with more extreme Fst and iHS measures is 0.003, consistent with a selective sweep outside of Africa. The fertility advantage conferred by Val470 relative to Met470 may provide a selective mechanism for these population genetic observations.

  13. Planning the human variome project: the Spain report.

    OpenAIRE

    Kaput, Jim; Cotton, Richard G H; Hardman, Lauren; Watson, Michael; Al Aqeel, Aida I; Al-Aama, Jumana Y; Al-Mulla, Fahd; Alonso, Santos; Aretz, Stefan; Auerbach, Arleen D; Bapat, Bharati; Bernstein, Inge T; Bhak, Jong; Bleoo, Stacey L; Blöcker, Helmut

    2009-01-01

    The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Because variation in genotype and e...

  14. The Influence of Financial 'Skin in the Game' on New Venture Creation

    DEFF Research Database (Denmark)

    Frid, Casey J.; Wyman, David M.; Gartner, William B.

    2015-01-01

    A common theme in entrepreneurship research is that the founder must be committed inorder for a new venture to succeed. Although investments of time and sweat equity can indicatecommitment, external stakeholders may prefer founders who have made a significant, personalfinancial stake in their nas......A common theme in entrepreneurship research is that the founder must be committed inorder for a new venture to succeed. Although investments of time and sweat equity can indicatecommitment, external stakeholders may prefer founders who have made a significant, personalfinancial stake...... in their nascent ventures. This personal financial commitment is known as “skinin the game.” Founders that invest more of their own money into their ventures signal greater commitment to potential business partners, suppliers, and resource providers.This studyexamines the amount of personal funds invested by 1...

  15. Genetic variations in the Dravidian population of South West coast of India: Implications in designing case-control studies.

    Science.gov (United States)

    D'Cunha, Anitha; Pandit, Lekha; Malli, Chaithra

    2017-06-01

    Indian data have been largely missing from genome-wide databases that provide information on genetic variations in different populations. This hinders association studies for complex disorders in India. This study was aimed to determine whether the complex genetic structure and endogamy among Indians could potentially influence the design of case-control studies for autoimmune disorders in the south Indian population. A total of 12 single nucleotide variations (SNVs) related to genes associated with autoimmune disorders were genotyped in 370 healthy individuals belonging to six different caste groups in southern India. Allele frequencies were estimated; genetic divergence and phylogenetic relationship within the various caste groups and other HapMap populations were ascertained. Allele frequencies for all genotyped SNVs did not vary significantly among the different groups studied. Wright's FSTwas 0.001 per cent among study population and 0.38 per cent when compared with Gujarati in Houston (GIH) population on HapMap data. The analysis of molecular variance results showed a 97 per cent variation attributable to differences within the study population and variation due to differences between castes. Phylogenetic analysis showed a separation of Dravidian population from other HapMap populations and particularly from GIH population. Despite the complex genetic origins of the Indian population, our study indicated a low level of genetic differentiation among Dravidian language-speaking people of south India. Case-control studies of association among Dravidians of south India may not require stratification based on language and caste.

  16. Haplotype mapping of a diploid non-meiotic organism using existing and induced aneuploidies.

    Directory of Open Access Journals (Sweden)

    Melanie Legrand

    2008-01-01

    Full Text Available Haplotype maps (HapMaps reveal underlying sequence variation and facilitate the study of recombination and genetic diversity. In general, HapMaps are produced by analysis of Single-Nucleotide Polymorphism (SNP segregation in large numbers of meiotic progeny. Candida albicans, the most common human fungal pathogen, is an obligate diploid that does not appear to undergo meiosis. Thus, standard methods for haplotype mapping cannot be used. We exploited naturally occurring aneuploid strains to determine the haplotypes of the eight chromosome pairs in the C. albicans laboratory strain SC5314 and in a clinical isolate. Comparison of the maps revealed that the clinical strain had undergone a significant amount of genome rearrangement, consisting primarily of crossover or gene conversion recombination events. SNP map haplotyping revealed that insertion and activation of the UAU1 cassette in essential and non-essential genes can result in whole chromosome aneuploidy. UAU1 is often used to construct homozygous deletions of targeted genes in C. albicans; the exact mechanism (trisomy followed by chromosome loss versus gene conversion has not been determined. UAU1 insertion into the essential ORC1 gene resulted in a large proportion of trisomic strains, while gene conversion events predominated when UAU1 was inserted into the non-essential LRO1 gene. Therefore, induced aneuploidies can be used to generate HapMaps, which are essential for analyzing genome alterations and mitotic recombination events in this clonal organism.

  17. Reliable single chip genotyping with semi-parametric log-concave mixtures.

    Directory of Open Access Journals (Sweden)

    Ralph C A Rippe

    Full Text Available The common approach to SNP genotyping is to use (model-based clustering per individual SNP, on a set of arrays. Genotyping all SNPs on a single array is much more attractive, in terms of flexibility, stability and applicability, when developing new chips. A new semi-parametric method, named SCALA, is proposed. It is based on a mixture model using semi-parametric log-concave densities. Instead of using the raw data, the mixture is fitted on a two-dimensional histogram, thereby making computation time almost independent of the number of SNPs. Furthermore, the algorithm is effective in low-MAF situations.Comparisons between SCALA and CRLMM on HapMap genotypes show very reliable calling of single arrays. Some heterozygous genotypes from HapMap are called homozygous by SCALA and to lesser extent by CRLMM too. Furthermore, HapMap's NoCalls (NN could be genotyped by SCALA, mostly with high probability. The software is available as R scripts from the website www.math.leidenuniv.nl/~rrippe.

  18. Computer simulation of orthognathic surgery with video imaging

    Science.gov (United States)

    Sader, Robert; Zeilhofer, Hans-Florian U.; Horch, Hans-Henning

    1994-04-01

    Patients with extreme jaw imbalance must often undergo operative corrections. The goal of therapy is to harmonize the stomatognathic system and an aesthetical correction of the face profile. A new procedure will be presented which supports the maxillo-facial surgeon in planning the operation and which also presents the patient the result of the treatment by video images. Once an x-ray has been digitized it is possible to produce individualized cephalometric analyses. Using a ceph on screen, all current orthognathic operations can be simulated, whereby the bony segments are moved according to given parameters, and a new soft tissue profile can be calculated. The profile of the patient is fed into the computer by way of a video system and correlated to the ceph. Using the simulated operation the computer calculates a new video image of the patient which presents the expected postoperative appearance. In studies of patients treated between 1987-91, 76 out of 121 patients were able to be evaluated. The deviation in profile change varied between .0 and 1.6mm. A side effect of the practical applications was an increase in patient compliance.

  19. Disk storage at CERN

    CERN Document Server

    Mascetti, L; Chan, B; Espinal, X; Fiorot, A; Labrador, H Gonz; Iven, J; Lamanna, M; Presti, G Lo; Mościcki, JT; Peters, AJ; Ponce, S; Rousseau, H; van der Ster, D

    2015-01-01

    CERN IT DSS operates the main storage resources for data taking and physics analysis mainly via three system: AFS, CASTOR and EOS. The total usable space available on disk for users is about 100 PB (with relative ratios 1:20:120). EOS actively uses the two CERN Tier0 centres (Meyrin and Wigner) with 50:50 ratio. IT DSS also provide sizeable on-demand resources for IT services most notably OpenStack and NFS-based clients: this is provided by a Ceph infrastructure (3 PB) and few proprietary servers (NetApp). We will describe our operational experience and recent changes to these systems with special emphasis to the present usages for LHC data taking, the convergence to commodity hardware (nodes with 200-TB each with optional SSD) shared across all services. We also describe our experience in coupling commodity and home-grown solution (e.g. CERNBox integration in EOS, Ceph disk pools for AFS, CASTOR and NFS) and finally the future evolution of these systems for WLCG and beyond.

  20. Disk storage at CERN

    Science.gov (United States)

    Mascetti, L.; Cano, E.; Chan, B.; Espinal, X.; Fiorot, A.; González Labrador, H.; Iven, J.; Lamanna, M.; Lo Presti, G.; Mościcki, JT; Peters, AJ; Ponce, S.; Rousseau, H.; van der Ster, D.

    2015-12-01

    CERN IT DSS operates the main storage resources for data taking and physics analysis mainly via three system: AFS, CASTOR and EOS. The total usable space available on disk for users is about 100 PB (with relative ratios 1:20:120). EOS actively uses the two CERN Tier0 centres (Meyrin and Wigner) with 50:50 ratio. IT DSS also provide sizeable on-demand resources for IT services most notably OpenStack and NFS-based clients: this is provided by a Ceph infrastructure (3 PB) and few proprietary servers (NetApp). We will describe our operational experience and recent changes to these systems with special emphasis to the present usages for LHC data taking, the convergence to commodity hardware (nodes with 200-TB each with optional SSD) shared across all services. We also describe our experience in coupling commodity and home-grown solution (e.g. CERNBox integration in EOS, Ceph disk pools for AFS, CASTOR and NFS) and finally the future evolution of these systems for WLCG and beyond.

  1. Concept of data storage prototype for Super-C-Tau factory detector

    International Nuclear Information System (INIS)

    Maximov, D.A.

    2017-01-01

    The physics program of experiments at the Super- c τ factory with a peak luminosity of 10 35 cm −2 s −1 leads to high requrements for Data Acquisition and Data Storage systems. Detector data storage is one of the key component of the detector infrastructure, so it must be reliable, highly available and fault tolerant shared storage. It is mostly oriented (from end user point of view) for sequential but mixed read and write operations and is planed to store large data blocks (files). According to CDR of Super-C-Tau factory detector data storage must have very high performance (up to 1 Tbps in both directions simultaneously) and have significant volume (tens and hundreds of Petabytes). It is decided to build a series of prototypes with growing capabilities to investigate storage and neighboring technologies. First prototype of data storage is aimed to develop and test basic components of detector data storage system such as storage devices, networks and software. This prototype is designed to be capable to work with data rate of order 10 Gbps. It is estimated that about 5 modern computers with about 50 disks in total should be enough to archive required performance. The prototype will be based on Ceph storage technology. Ceph is a distributed storage system which allows to create storage solutions with very flexible design, high availability and scalability.

  2. Review of MPH practicum requirements in accredited schools of public health.

    Science.gov (United States)

    Oglesby, Willie H; Alemagno, Sonia A; Zullo, Melissa D; Hartman, Olivia; Smith, Katalin; Smith, Joseph; Buzzelli, Michael

    2013-06-01

    Accreditation criteria by the Council on Education for Public Health (CEPH) state that prior to graduation, Masters of Public Health (MPH) students must demonstrate the application of knowledge and skills through a practice experience, commonly called the "Practicum." The purpose of this research was to review those MPH Practicum requirements. Practicum guidelines from US-based schools of public health that were accredited as of October 2011 were reviewed. Data on each Practicum's level of coordination, timing, and credit and contact hours as well as information about written agreements, preceptors, and how the Practicum was graded were collected. Seventy-four Practicums in 46 accredited schools of public health were reviewed. The majority (85 %) of accredited schools controlled the Practicum at the school-level. Among the Practicums reviewed, most did not require completion of any credit hours or the MPH core courses (57 and 74 %, respectively) prior to starting the Practicum; 82 % required written agreements; 60 % had stated criteria for the approval of preceptors; and 76 % required students to submit a product for grading at the conclusion of the Practicum. The results of this research demonstrate that the majority of accredited schools of public health designed Practicum requirements that reflect some of the criteria established by CEPH; however, issues related to timing, credit and contact hours, and preceptor qualifications vary considerably. We propose that a national dialogue begin among public health faculty and administrators to address these and other findings to standardize the Practicum experience for MPH students.

  3. Block Storage Service: Status and Performance

    CERN Document Server

    Van der Ster, Daniel

    2014-01-01

    This memo summarizes the current status of the Ceph block storage service as it is used for OpenStack Cinder Volumes and Glance Images as of May 2014. We present the block storage activity on the current cluster, measuring IOPS and latencies, and present a cost/benefit analysis of using SSDs to optimize the cost and performance efficiency of the service. During tests in collaboration with IT-CF, we have concluded that by adding SSDs as the synchronous write journals (used to guarantee data durability), we are able increase the IOPS capacity by 4-5 times, at a cost of decreasing the available volume by 20%. Further, the testing has shown that the Ceph implementation is able to operate at the limit of the hardware performance; software-induced performance limitations were not yet observed in either the spinning disk or SSD configurations. In addition, we believe that increasing small write performance with SSDs is applicable only to the block storage use-case; high-bandwidth use-cases such as physics data stora...

  4. Sequence determinants of human microsatellite variability

    Directory of Open Access Journals (Sweden)

    Jakobsson Mattias

    2009-12-01

    Full Text Available Abstract Background Microsatellite loci are frequently used in genomic studies of DNA sequence repeats and in population studies of genetic variability. To investigate the effect of sequence properties of microsatellites on their level of variability we have analyzed genotypes at 627 microsatellite loci in 1,048 worldwide individuals from the HGDP-CEPH cell line panel together with the DNA sequences of these microsatellites in the human RefSeq database. Results Calibrating PCR fragment lengths in individual genotypes by using the RefSeq sequence enabled us to infer repeat number in the HGDP-CEPH dataset and to calculate the mean number of repeats (as opposed to the mean PCR fragment length, under the assumption that differences in PCR fragment length reflect differences in the numbers of repeats in the embedded repeat sequences. We find the mean and maximum numbers of repeats across individuals to be positively correlated with heterozygosity. The size and composition of the repeat unit of a microsatellite are also important factors in predicting heterozygosity, with tetra-nucleotide repeat units high in G/C content leading to higher heterozygosity. Finally, we find that microsatellites containing more separate sets of repeated motifs generally have higher heterozygosity. Conclusions These results suggest that sequence properties of microsatellites have a significant impact in determining the features of human microsatellite variability.

  5. Genome-wide association study identifies major loci for carcass weight on BTA14 in Hanwoo (Korean cattle.

    Directory of Open Access Journals (Sweden)

    Seung Hwan Lee

    Full Text Available This genome-wide association study (GWAS was conducted to identify major loci that are significantly associated with carcass weight, and their effects, in order to provide increased understanding of the genetic architecture of carcass weight in Hanwoo. This genome-wide association study identified one major chromosome region ranging from 23 Mb to 25 Mb on chromosome 14 as being associated with carcass weight in Hanwoo. Significant Bonferroni-corrected genome-wide associations (P<1.52×10(-6 were detected for 6 Single Nucleotide Polymorphic (SNP loci for carcass weight on chromosome 14. The most significant SNP was BTB-01280026 (P = 4.02×10(-11, located in the 25 Mb region on Bos taurus autosome 14 (BTA14. The other 5 significant SNPs were Hapmap27934-BTC-065223 (P = 4.04×10(-11 in 25.2 Mb, BTB-01143580 (P = 6.35×10(-11 in 24.3 Mb, Hapmap30932-BTC-011225 (P = 5.92×10(-10 in 24.8 Mb, Hapmap27112-BTC-063342 (P = 5.18×10(-9 in 25.4 Mb, and Hapmap24414-BTC-073009 (P = 7.38×10(-8 in 25.4 Mb, all on BTA 14. One SNP (BTB-01143580; P = 6.35×10(-11 lies independently from the other 5 SNPs. The 5 SNPs that lie together showed a large Linkage disequilibrium (LD block (block size of 553 kb with LD coefficients ranging from 0.53 to 0.89 within the block. The most significant SNPs accounted for 6.73% to 10.55% of additive genetic variance, which is quite a large proportion of the total additive genetic variance. The most significant SNP (BTB-01280026; P = 4.02×10(-11 had 16.96 kg of allele substitution effect, and the second most significant SNP (Hapmap27934-BTC-065223; P = 4.04×10(-11 had 18.06 kg of effect on carcass weight, which correspond to 44% and 47%, respectively, of the phenotypic standard deviation for carcass weight in Hanwoo cattle. Our results demonstrated that carcass weight was affected by a major Quantitative Trait Locus (QTL with a large effect and by many SNPs with small effects that are normally

  6. Sketching the Global Social Media Landscape = Küresel sosyal medya alanının Avrupa ve Hollanda'ya odaklanarak Taslaklandırılması

    OpenAIRE

    Reijgersberg, Maarten

    2016-01-01

    Maarten Reijgersberg is the founder of and social media architect at RauwCC, social media the Rotterdam way. RauwCC is ranked as the number one social agency in The Netherlands by Emerce 100/2015. Maarten is also the founder of Social Media Week Rotterdam, the largest annual conference on social media and innovation in the Benelux region. Besides his work at RauwCC and Social Media Week Rotterdam, Maarten is the founder of Social Media Signage, the window to your online activity. Social Media...

  7. The Role of Passion and Purpose in Leader Developmental Readiness.

    Science.gov (United States)

    Bronk, Kendall Cotton; McLean, Derrick C

    2016-01-01

    The founder of TOMS Shoes, Blake Mycoskie, and the late Apple cofounder and CEO, Steve Jobs, model the role of passion and purpose in leader developmental readiness. © 2016 Wiley Periodicals, Inc., A Wiley Company.

  8. The man that saw grow the plants

    International Nuclear Information System (INIS)

    Cardona Vallejo, Mateo

    2002-01-01

    The author makes a reminder of the founder of the Botanical Garden in Bogota (Colombia) Enrique Perez Arbelaez, speaks of his life, studies, publications and contributions to the knowledge of the Colombian flora

  9. The Jewish contribution to medicine

    African Journals Online (AJOL)

    1989-07-15

    Jul 15, 1989 ... period of Jewish medicine in Germany included the renowned immunologists ... work in endocrinology where his classic experiment of inducing myxoedema in .... feeding, Alois Epstein (1849 - 1918), the founder of the world-.

  10. 75 FR 24371 - Loyalty Day, 2010

    Science.gov (United States)

    2010-05-05

    ...: individual equality, constitutional liberty, and the rule of law. Over two centuries since our Founders... force that seeks to divide us, finding strength in our diversity and inspiration in the sacrifices of...

  11. CSC9000T A Toll Bell to "Sweat Shops"

    Institute of Scientific and Technical Information of China (English)

    Feng Yuan

    2007-01-01

    @@ CRS:A New Requirement for All "We cannot simply consider doing business is making more money, that's a humiliation to human being." So said Muhammad Yunus, founder of Grameen Bank and who received Nobel Peace Prize 2006.

  12. Peggy Charren: Pioneer TV Activist.

    Science.gov (United States)

    Potter, Rosemary Lee; Charren, Peggy

    1980-01-01

    In this interview, Peggy Charren, the founder and president of Action for Children's Television (ACT), talks about the organization's concerns, goals, and activities, as well as its effect on television programing and commericals intended for children. (Editor/SJL)

  13. Unseen dimensions dialogues in art and science

    CERN Document Server

    2013-01-01

    The interface of art and science was explored by expert speakers and artists including Michael Hoch, founder of the CERN outreach programme, Art@CMS, in a week-long programme at the City of London Boys School in October

  14. Amaldi e Auger, il manager e il poeta

    CERN Document Server

    Amaldi, Ugo

    2004-01-01

    The story of the two scientists, founder fathers of CERN, created 50 years ago; the italian physicist and the colleague from Unesco prevailed in the choice regarding the concurrent idea to upgrade the existing centers

  15. Zur Rolle von Plansprachen im terminologiewissenschaftlichen Werk von Eugen Wuster (The Role of Planned Languages in Eugen Wuster's Work on Terminology Science).

    Science.gov (United States)

    Blanke, Detlev

    1998-01-01

    Discusses the relationship between planned languages and specialized technical languages, with particular reference to Esperanto, and analyzes its significance for several aspects of Eugen Wuster's (the founder of terminology science) work. (Author/VWL)

  16. Emphatie und militaerisches Koennen-zwei Seiten einer Medaille: Rede an der Fuerungsakademie der Bundeswehr am 17. Februar 1999; Ansprache am 17. Februar 1999 zur Erinnerung an den ersten Stabsoffiziergrundlehrgang vor 25 Jahre (Empathy and Military Expertise-Two Sides of the Same Coin: Speech at the Leadership Academy of the Bundeswehr on 17 February 1999; Lecture on 17 February 1999 Remembering the First Staff Officer Training Class 25 Years Ag

    National Research Council Canada - National Science Library

    Scharping, Rudolf

    1999-01-01

    .... He notes that the academy also trains officers from foreign countries. The "empathy" Scharping refers to comes from the founders of the academy, Count Wolf von Baudessin, and is a concept of cooperative security...

  17. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Senior Leadership Team Founder Sylvia Lawry d Cultural Values d Financials Annual Reports Sources of Support d ... Connection About the Society Vision Careers Leadership Cultural Values Financials News Press Room MS Prevalence Charitable Ratings ...

  18. The Islamic Republic of Eastern Turkestan and the Formation of Modern Uyghur Identity in Xinjiang

    National Research Council Canada - National Science Library

    Lee, Joy R

    2006-01-01

    .... Founders of this republic, influenced by Pan-Islamism and Pan-Turkism used it to promote a Turkic-Muslim identity independent from Chinese and Soviet control and unique to the sedentary, oasis-dwellers of Xinjiang...

  19. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Disease T Cells d What Causes MS? Disproved Theories Viruses Clusters d Who Gets MS? Pediatric MS ... Review of Society's Research Programs d Careers d Leadership Board of Directors Senior Leadership Team Founder Sylvia ...

  20. John Dewey--Philosopher and Educational Reformer

    Science.gov (United States)

    Talebi, Kandan

    2015-01-01

    John Dewey was an American philosopher and educator, founder of the philosophical movement known as pragmatism, a pioneer in functional psychology, and a leader of the progressive movement in education in the United States.

  1. Q & A with Ed Tech Leaders: Interview with Clark Aldrich

    Science.gov (United States)

    Shaughnessy, Michael F.; Fulgham, Susan M.

    2016-01-01

    Clark Aldrich is the founder and Managing Partner of Clark Aldrich Designs, and is known as a global education visionary, industry analyst, and speaker. In this interview, he responds to questions about his ideas, his work, and his theories.

  2. Preliminary results of the analysis of the population structure of the ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-18

    Aug 18, 2008 ... the lake based on a small founder population, which though slow in establishing later exploded to become ... was conducted by the Lake Victoria Research Project funded by .... The matrix of pairwise distances obtained was.

  3. Minister Bibeau announces appointments of IDRC's President and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2018-05-04

    May 4, 2018 ... Today the Honourable Marie-Claude Bibeau, Minister of International ... Jean Lebel will strengthen the Centre's position as a global leader on research for ... Shainoor is the founder and managing director of Better Business ...

  4. Michael Bahl | NREL

    Science.gov (United States)

    theoretical mathematics, Western New England University, Springfield, MA B.S. in computer science, University Prior Work Experience Founder, Mobile Makes Sense Senior IT Specialist, IBM Graduate Teaching Assistant

  5. The Cabal Theory in the Nigerian Politics, 1999-2009

    African Journals Online (AJOL)

    User

    2010-10-17

    Oct 17, 2010 ... Keywords: Nigeria, cults, cabal theory, delinquent state. ... sect, cult is not in Western society associated with mainstream Christianity. It has no precise .... of the founders of PC emerged from the impact of the Eagle, a campus.

  6. Behind the cloud: the untold story of how Salesforce.com went from idea to billion-dollar company--and revolutionized an industry

    National Research Council Canada - National Science Library

    Benioff, Marc R; Adler, Carlye

    2009-01-01

    ...? For the first time, Marc Benioff, the visionary founder, chairman and CEO of salesforce.com, tells how he and his team created and used new business, technology, and philanthropic models tailored to this time of extraordinary change...

  7. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Directors Senior Leadership Team Founder Sylvia Lawry d Cultural Values d Financials Annual Reports Sources of Support ... bowel and bladder problems, and problems with cognition (learning and memory or information processing). People with progressive ...

  8. Compassionate Friends

    Science.gov (United States)

    ... sharing comes healing The words of TCF’s Founder, Simon Stephens, resonate with those who have come to ... of what to be thankful of. Thankful? I think not. My life... Read More... Sign Up for ...

  9. Haramaya Law Review - Vol 5, No 1 (2016)

    African Journals Online (AJOL)

    Founders of share companies under the Ethiopian share company law: legal analysis · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Serkalem Eshetie Adinew, 1-32 ...

  10. The Effect of Multiple Paternity on Genetic Diversity of Small Populations during and after Colonisation

    KAUST Repository

    Rafajlović, Marina; Eriksson, Anders; Rimark, Anna; Hintz-Saltin, Sara; Charrier, Gré gory; Panova, Marina; André , Carl; Johannesson, Kerstin; Mehlig, Bernhard

    2013-01-01

    Genetic variation within and among populations is influenced by the genetic content of the founders and the migrants following establishment. This is particularly true if populations are small, migration rate low and habitats arranged in a stepping

  11. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... d Careers d Leadership Board of Directors Senior Leadership Team Founder Sylvia Lawry d Cultural Values d Financials Annual Reports Sources of Support d News d Press Room Events ...

  12. Beginnings and early history of the International Conferences on Magnetic Resonance in Biological Systems: development of the basic ideas in the field.

    Science.gov (United States)

    Jardetzky, Oleg

    2010-09-01

    The early history of the principal meeting in the field of biological NMR spectroscopy, the International Conference on Magnetic Resonance in Biological Systems (ICMRBS), is presented from the perspective of one of the founders. (c) 2010. Published by Elsevier Inc.

  13. Multiple Myeloma Research Foundation

    Science.gov (United States)

    ... MMRF Founder Kathy Giusti named 1 of 100 Visionaries of our time by the Einstein Foundation Learn More September 8, 2017 Tom Brokaw gives inspiring speech at MMRF Leadership Circle Summit on how his life was changed, ...

  14. Download this PDF file

    African Journals Online (AJOL)

    User

    various marketing strategies (M = 3.3); Standards and branding mechanisms of high- quality poultry products .... entrepreneurs pursuing business growth, Journal of Small Business and. Enterprise ... Marketer, Co-founder of ContentMarketer.io.

  15. Revealed Preference Theory, Rationality, and Neoclassical ...

    African Journals Online (AJOL)

    2012-12-17

    Dec 17, 2012 ... cement the claim that capitalist market economics describes the natural and ... one of the founders of the ethical school of thought known as ..... other sciences that deal with human behaviour such as psychology and history.

  16. Commercial Mars Sample Return Architecture

    Science.gov (United States)

    Lenard, R.-X.

    2018-04-01

    Zodiac Planetary Services is a newly-formed company whose three founders together have over 80 years of space and high technology development and legal experience. The company uses IP created by the author covered by patent # 62/523432.

  17. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Fully, Live Well Everyday Matters Resilience: Addressing the Challenges of MS You CAN! Webcasts DVDs Books For ... Review of Society's Research Programs d Careers d Leadership Board of Directors Senior Leadership Team Founder Sylvia ...

  18. Highlight: From factory floor to the middle class: Does labour ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Anindya Chatterjee, IDRC's Regional Director for Asia, offered opening remarks ... Ahmad, founder of Bangladesh's Women Chamber of Commerce; Rafaelita Aldaba, ... and engaging them in the workforce would improve economic outcomes.

  19. Transcending a Patriarchal Past: Teaching the History of Women in Sociology.

    Science.gov (United States)

    Deegan, Mary Jo

    1988-01-01

    Contends that the ideas of early female sociologists are rarely documented in textbooks, classrooms, or historical accounts of the profession. Provides a guide to reference works, autobiographies, and biographies about 10 early female founders of American sociology. (Author/BSR)

  20. A Little Bit of Knowledge Is a Dangerous Thing

    DEFF Research Database (Denmark)

    Toft-Kehler, Rasmus; Wennberg, Karl; Kim, Phillip H.

    2016-01-01

    Existing research has offered conflicting narratives of how entrepreneurial experience influences whether founders will continue working on or disengage from their ventures. We theorize and test how entrepreneurs with varying levels of experience disengage from early-stage companies. Findings...

  1. Genetics Home Reference: mucolipidosis II alpha/beta

    Science.gov (United States)

    ... Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in ... N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population. Clin Genet. 2008 Mar;73( ...

  2. Relapsing-Remitting MS (RRMS)

    Medline Plus

    Full Text Available ... Directors Senior Leadership Team Founder Sylvia Lawry d Cultural Values d Financials Annual Reports Sources of Support ... MS Connection About the Society Vision Careers Leadership Cultural Values Financials News Press Room MS Prevalence Charitable ...

  3. John Whitridge Williams, MD (1866–1931) of Baltimore: pioneer of academic obstetrics

    Science.gov (United States)

    Dunn, P M

    2007-01-01

    Williams was the founder of academic obstetrics in the United States and with his textbook was the recognised leader of this discipline in America during the first 30 years of the 20th century. PMID:17185435

  4. Harvesting Feminist Knowledge for Public Policy: Rebuilding Progress

    International Development Research Centre (IDRC) Digital Library (Canada)

    2011-11-03

    Nov 3, 2011 ... The editors. Devaki Jain is the Founder-Director of the Institute of Social Studies Trust, New Delhi, India. Diane Elson is Professor, Department of Sociology, University of Essex, UK.

  5. Off Course: Restoring Balance between Canadian Society and the ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 janv. 1994 ... The author. Duncan M. Taylor is an assistant professor of environmental studies at the University of Victoria, Victoria, British Columbia. He is a founder and director of Earth Day Canada.

  6. 奥运短讯

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Olympic Games FounderRemembered A seminar to mark the birthday ofPierre de Coubertin,founder of themodern Olympic Games,was held inBeijing on January 1.Jiang Xiaoyu,vice president of theBeijing Olympic Games OrganizingCommittee,senior IOC member HeZhenliang and Olympic historian SunBaoli delivered speeches in memory ofMr.Coubertin who Was born OnJanuary 1,1863.

  7. Crowdinvesting-an alternative financing for German start-up enterprises?

    OpenAIRE

    Schütte, Sven

    2016-01-01

    Creation of young and innovational ventures is becoming more and more attrac-tive for potential business founders, due to beneficial political and economic frame conditions. Nevertheless, the issue of funding the project is concerning most of entrepreneurs: Because relatively weak own financial backings seldom suffice until profitability stage, founders are depending on external financial support in order to cover an arising equity gap. Here, established traditional forms of financing ca...

  8. An Empirical Study of the Relationship between Entrepreneurial Competences and Innovativeness of Successors in Family SMEs

    Directory of Open Access Journals (Sweden)

    Letonja Marina

    2016-12-01

    Full Text Available Background and Purpose: In the recent period, scholarly interest for family entrepreneurship and succession has been increasing while the question of innovative capability of family SMEs and of innovativeness of founders and successors is relatively unexplored. Little is known about the factors, which are positively correlated, or affect innovativeness of successors in family SMEs. This research explores the relationship between entrepreneurial competences of the founders in family SMEs and innovativeness of their successors.

  9. Exploring alternative models for sex-linked quantitative trait loci in outbred populations: application to an iberian x landrace pig intercross.

    OpenAIRE

    Pérez-Enciso, Miguel; Clop, Alex; Folch, Josep M; Sánchez, Armand; Oliver, Maria A; Ovilo, Cristina; Barragán, C; Varona, Luis; Noguera, José L

    2002-01-01

    We present a very flexible method that allows us to analyze X-linked quantitative trait loci (QTL) in crosses between outbred lines. The dosage compensation phenomenon is modeled explicitly in an identity-by-descent approach. A variety of models can be fitted, ranging from considering alternative fixed alleles within the founder breeds to a model where the only genetic variation is within breeds, as well as mixed models. Different genetic variances within each founder breed can be estimated. ...

  10. Financial bootstrapping use in new family ventures and the impact on venture growth

    OpenAIRE

    Helleboogh, David; LAVEREN, Eddy; LYBAERT, Nadine

    2010-01-01

    This paper contributes to the general knowledge of bootstrap financing among new family ventures in two ways. Firstly, this research reveals which human capital characteristics of the owner-manager has an impact on financial bootstrapping use. The empirical results indicate that the use of bootstrapping techniques does not depend upon the family's business founder's education, but that it is a skill which is absorbed from self-employed parents or during the founder's prior work and management...

  11. Do social networks shape the geography of crowdfunding?

    OpenAIRE

    Dejean , Sylvain

    2017-01-01

    Does the distance still matters in a context where digital technologies promised to eliminate distance-related costs? In crowdfunding platforms, the founder of a project and the backers mainly exchange tacit information (trustworthiness and seriousness of the founder, feasibility of a project), challenging the ability of the Internet to abolish the cost of distance. We investigate how the existence of social ties between two geographical areas, by lowering the asymmetry of information, can sh...

  12. Genetic diversity in India and the inference of Eurasian population expansion.

    Science.gov (United States)

    Xing, Jinchuan; Watkins, W Scott; Hu, Ya; Huff, Chad D; Sabo, Aniko; Muzny, Donna M; Bamshad, Michael J; Gibbs, Richard A; Jorde, Lynn B; Yu, Fuli

    2010-01-01

    Genetic studies of populations from the Indian subcontinent are of great interest because of India's large population size, complex demographic history, and unique social structure. Despite recent large-scale efforts in discovering human genetic variation, India's vast reservoir of genetic diversity remains largely unexplored. To analyze an unbiased sample of genetic diversity in India and to investigate human migration history in Eurasia, we resequenced one 100-kb ENCODE region in 92 samples collected from three castes and one tribal group from the state of Andhra Pradesh in south India. Analyses of the four Indian populations, along with eight HapMap populations (692 samples), showed that 30% of all SNPs in the south Indian populations are not seen in HapMap populations. Several Indian populations, such as the Yadava, Mala/Madiga, and Irula, have nucleotide diversity levels as high as those of HapMap African populations. Using unbiased allele-frequency spectra, we investigated the expansion of human populations into Eurasia. The divergence time estimates among the major population groups suggest that Eurasian populations in this study diverged from Africans during the same time frame (approximately 90 to 110 thousand years ago). The divergence among different Eurasian populations occurred more than 40,000 years after their divergence with Africans. Our results show that Indian populations harbor large amounts of genetic variation that have not been surveyed adequately by public SNP discovery efforts. Our data also support a delayed expansion hypothesis in which an ancestral Eurasian founding population remained isolated long after the out-of-Africa diaspora, before expanding throughout Eurasia. © 2010 Xing et al.; licensee BioMed Central Ltd.

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

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    2005-12-01

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

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

    Directory of Open Access Journals (Sweden)

    2005-12-01

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

  15. A TaqI RFLP identified at the retinoblastoma locus on chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Shiang, R; Murray, J C [Univ. of Iowa, Iowa City (USA); Wiggs, J; Dryja, T [Massachusetts Eye and Ear Infirmary, Boston (USA)

    1988-09-26

    Probe D95HS0.5 is a 0.6 kb fragment subcloned into Bluescribe a pUC19 derivative from a bacterio phage library isolated by a cDNA probe of the retinoblastoma gene. The fragment is released with the enzymes HindIII and SaII. TaqI identifies a 2 allele polymorphism with a band at 2.1 kb and 1.8 kb with a frequency of 0.97 and 0.03 respectively. There are no constant bands. The probe was assigned to chromosome 13 using a linkage analysis with retinoblastoma. Co-dominant inheritance was shown in 3 CEPH pedigrees.

  16. An XmnI RFLP detected with a cDNA probe for the CYP2C gene locus on chromosome 10

    Energy Technology Data Exchange (ETDEWEB)

    Gough, A C; Spurr, N K [Clare Hall Laboratories, Herts (England); Meehan, R R; Miles, J S; Wolf, C R [Univ. Department of Biochemistry, Edinburgh (England)

    1989-06-12

    A 700 bp fragment of the cDNA clone for the human cytochrome P450 gene cloned in pUC9 at the PstI restriction site. XmnI detects a two allele polymorphism with bands at 10.00 kb (A1), 4.8 kb (A2) and constants bands at 13.0, 8.3, 4.6, 3.1, 2.8, 2.5, 2.3, 2.2, 1.8 and 1.5 kb. A total of 16 unrelated individuals of Caucasian origin were screened for A1 (.625) and A2 (.375). The probe was assigned to chromosome 10q24.1-q24.3 using a panel of human-rodent somatic cell hybrids and in situ hybridization. Co-dominant inheritance was observed in 3 families from CEPH, K1329 2 K1331 and K1333.

  17. Correlation between genetic and geographic structure in Europe

    DEFF Research Database (Denmark)

    Lao, Oscar; Lu, Timothy T; Nothnagel, Michael

    2008-01-01

    geographic but narrow genomic coverage [1, 2], or vice versa [3-6]. We therefore investigated Affymetrix GeneChip 500K genotype data from 2,514 individuals belonging to 23 different subpopulations, widely spread over Europe. Although we found only a low level of genetic differentiation between subpopulations......, the existing differences were characterized by a strong continent-wide correlation between geographic and genetic distance. Furthermore, mean heterozygosity was larger, and mean linkage disequilibrium smaller, in southern as compared to northern Europe. Both parameters clearly showed a clinal distribution...... Europe. By including the widely used CEPH from Utah (CEU) samples into our analysis, we could show that these individuals represent northern and western Europeans reasonably well, thereby confirming their assumed regional ancestry....

  18. International Network Performance and Security Testing Based on Distributed Abyss Storage Cluster and Draft of Data Lake Framework

    Directory of Open Access Journals (Sweden)

    ByungRae Cha

    2018-01-01

    Full Text Available The megatrends and Industry 4.0 in ICT (Information Communication & Technology are concentrated in IoT (Internet of Things, BigData, CPS (Cyber Physical System, and AI (Artificial Intelligence. These megatrends do not operate independently, and mass storage technology is essential as large computing technology is needed in the background to support them. In order to evaluate the performance of high-capacity storage based on open source Ceph, we carry out the network performance test of Abyss storage with domestic and overseas sites using KOREN (Korea Advanced Research Network. And storage media and network bonding are tested to evaluate the performance of the storage itself. Additionally, the security test is demonstrated by Cuckoo sandbox and Yara malware detection among Abyss storage cluster and oversea sites. Lastly, we have proposed the draft design of Data Lake framework in order to solve garbage dump problem.

  19. A ScaI RFLP demonstrated for the GRO gene on chromosome 4

    Energy Technology Data Exchange (ETDEWEB)

    Beck, J.S.; Murray, J.C. (Univ. of Iowa Hospitals, Iowa City (USA)); Sager, R. (Dana Farber Cancer Institute, Boston, MA (USA))

    1989-11-11

    TC870 is a 0.85 kb fragment running from the EcoRI site 200 pb from the 5{prime} end of the human cDNA subcloned into the EcoRI site of pGEM3. ScaI detects a polymorphism with two variable bands of 19 kb and 16 kb. One strong constant band (14 kb) and two fainter constant bands (5 kb and 3 kb) are also present. The polymorphism type is unknown. GRO has been localized to 4q13-4q21 by somatic cell hybrid analysis and in situ hybridization. Codominant segregation and Hardy-Weinberg equilibrium demonstrated in 20 CEPH families. The probe also was assigned to chromosome 4 with significant linkage to ALB, GC, INP10, MT2P1. GRO may be the same gene as MGSA.

  20. RFLPs for ATP1BL1 (. beta. subunit Na sup + /K sup + ATPase pseudogene) on chromosome 4

    Energy Technology Data Exchange (ETDEWEB)

    Georgiou, C.; Shull, M. (Univ. of Iowa Hospitals, Iowa City (USA)); Lingrel, J.B.; Murray, J.C.; Lane, L.K. (Univ. of Cincinnati College of Medicine, OH (USA))

    1989-11-11

    {beta}51-1(1.4) contains a 1.4kb EcoRI fragment, free of repetitive elements, from the {beta} subunit Na{sup +}/K{sup +} ATPase pseudogene (ATP1BL1). The vector is pUG18. EcoRI identifies 2 allelic bands of 7.0 and 14.0 kb. KpnI identifies 2 allelic bands of 19.0 and 23.0 kb. The probe was localized to chromosome 4 by linkage to chromosome 4 markers (D4S35, KIT) and somatic cell hybrid analysis. Co-dominant segregation was shown in 32 and 16 CEPH families for EcoRI and KpnI respectively.

  1. Lloyd F. Novick, Cynthia B. Morrow, Carole Novick: 21 Public Health Case Studies on Policy & Administration : Wolters Kluwer, Philadelphia, 2018, 368 pp., Paperback, Figures, Tables, Bibliography, Index., $79.99.

    Science.gov (United States)

    Teutsch, Steven M

    2018-03-06

    This review looks at a compilation of 21 case studies edited by Lloyd F. Novick et al. that provide a broad array of real-life public health challenges from infectious disease and chronic disease to development of evidence-based guidelines and a system of accreditation gathered from the experience of many authors-all seasoned public health professionals. Tracking the 2016 CEPH (Council on Education for Public Health) criteria, the cases provide a vehicle for students, public health professionals and others to understand the complexities of competing demands in public health. These case studies may be used as educational tools for a broad range of public health learners but are also intended to appeal to anyone who is interested in public health.

  2. Association study of common variants in the sFRP1 gene region and parameters of bone strength and body composition in two independent healthy Caucasian male cohorts

    DEFF Research Database (Denmark)

    Boudin, Eveline; Piters, Elke; Fransen, Erik

    2012-01-01

    has an influence on bone formation. Therefore this study aimed to investigate the effect of common genetic variation on BMD and bone strength in Caucasian men of different ages. Using HapMap we selected 13 tagSNPs which tag most common genetic variation in and around sFRP1 and we genotyped these SNPs...... parameters. Based on the results of the young cohort we selected three SNPs for further analysis in the complete OAS population. To conclude we tried to replicate the results of two SNPs in an independent population of 994 Belgian men. We found a strong association for rs9694405 with BMI as well in both...

  3. Association between cytochrome CYP17A1, CYP3A4, and CYP3A43 polymorphisms and prostate cancer risk and aggressiveness in a Korean study population

    OpenAIRE

    Han, Jun Hyun; Lee, Yong Seong; Kim, Hae Jong; Lee, Shin Young; Myung, Soon Chul

    2014-01-01

    In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer (PCa) in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 single-nucleotide polymorphism (SNP) database variants detected, 129 were reported in two Asian groups (Han Chinese and Japanese) in the HapMap database. Only 21 polymorphisms o...

  4. Construction of a YAC contig and STS map spanning 2.5 Mbp in Xq25, the critical region for the X-linked lymphoproliferative (XLP) gene

    Energy Technology Data Exchange (ETDEWEB)

    Lanyi, A.; Li, B.F.; Li, S. [Univ. of Nebraska Medical Center, Omaha, NE (United States)] [and others

    1994-09-01

    X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability in Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia or B-cell lymphoma. The XLP gene lies within a 10 cM region in Xq25 between DXS42 and DXS10. Initial chromosome studies revealed an interstitial, cytogenetically visible deletion in Xq25 in one XLP family (43-004). We estimated the size of the Xq25 deletion by dual laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mbp of DNA sequences. To further delineate the deletion we performed a series of pulsed field gel electrophoresis (PFGE) analyses which showed that DXS6 and DXS100, two Xq25-specific markers, are missing from 45-004 DNA. Five yeast artificial chromosomes (YACs) from a chromosome X specific YAC library containing sequences deleted in patient`s 43-004 DNA were isolated. These five YACs did not overlap, and their end fragments were used to screen the CEPH MegaYAC library. Seven YACs were isolated from the CEPH MegaYAC library. They could be arranged into a contig which spans between DXS6 and DXS100. The contig contains a minimum of 2.5 Mbp of human DNA. A total of 12 YAC end clone, lambda subclones and STS probes have been used to order clones within the contig. These reagents were also used in Southern blot and patients showed interstitial deletions in Xq25. The size of these deletions range between 0.5 and 2.5 Mbp. The shortest deletion probably represents the critical region for the XLP gene.

  5. Faculty performance evaluation in accredited U.S. public health graduate schools and programs: a national study.

    Science.gov (United States)

    Gimbel, Ronald W; Cruess, David F; Schor, Kenneth; Hooper, Tomoko I; Barbour, Galen L

    2008-10-01

    To provide baseline data on evaluation of faculty performance in U.S. schools and programs of public health. The authors administered an anonymous Internet-based questionnaire using PHP Surveyor. The invited sample consisted of individuals listed in the Council on Education for Public Health (CEPH) Directory of Accredited Schools and Programs of Public Health. The authors explored performance measures in teaching, research, and service, and assessed how faculty performance measures are used. A total of 64 individuals (60.4%) responded to the survey, with 26 (40.6%) reporting accreditation/reaccreditation by CEPH within the preceding 24 months. Although all schools and programs employ faculty performance evaluations, a significant difference exists between schools and programs in the use of results for merit pay increases and mentoring purposes. Thirty-one (48.4%) of the organizations published minimum performance expectations. Fifty-nine (92.2%) of the respondents counted number of publications, but only 22 (34.4%) formally evaluated their quality. Sixty-two (96.9%) evaluated teaching through student course evaluations, and only 29 (45.3%) engaged in peer assessment. Although aggregate results of teaching evaluation are available to faculty and administrators, this information is often unavailable to students and the public. Most schools and programs documented faculty service activities qualitatively but neither assessed it quantitatively nor evaluated its impact. This study provides insight into how schools and programs of public health evaluate faculty performance. Results suggest that although schools and programs do evaluate faculty performance on a basic level, many do not devote substantial attention to this process.

  6. Phylogeography of haplotypes of five microsatellites located in a low-recombination region of the X chromosome: studies worldwide and in Brazilian populations.

    Science.gov (United States)

    Pereira, Rinaldo Wellerson; Pena, Sérgio D J

    2006-01-01

    We studied five microsatellites (DXS995, DXS8076, DXS8114, DXS1002 and DXS1050) located in a region of very low recombination rate in the long arm of the human X chromosome (Xq13.3-Xq21.3). No recombination was seen in 291 meioses in CEPH families. To test whether haplotypes composed of the five microsatellites could differentiate among distinct human continental populations, we studied an international panel containing 72 males from Africa, Europe, Asia and the America. Haplotypic diversity was very high within these groups and no haplotypes were shared among them. This led to the hope that we might be able to identify continent-specific lineages. However, in a median joining network there was no clear discrimination of the different continental groups. We then tested whether we could identify X chromosomal lineages from different continental origins in Brazilians. We typed 180 white Brazilians from four different geographical regions and examined their proportions of haplotype sharing with Africans, Asians, Europeans and Amerindians. No phylogeographical patterns emerged from the data. Moreover, there were several instances of the same haplotype being shared by many (and in one instance all) groups, suggesting that recombination might be occurring. We thus studied pairwise the level of linkage disequilibrium (LD) between the microsatellites. No detectable linkage disequilibrium between the most external loci DXS995 and DXS1050 was observed. Thus, even though recombination may be absent on short time spans, as seen in the CEPH pedigrees, on a long term basis it occurs often enough to dissipate all linkage disequilibrium. On the other hand, we observed very strong linkage disequilibrium between the pairs DXS995/DXS8076 and DXS1002/DXS8114, raising the possibility of resequencing the segment between them to identify single nucleotide polymorphisms (SNPs) in their intervals. The combination of X-linked microsatellites and SNPs in strong linkage disequilibrium might

  7. Development of a YAC contig covering the minimal region of a CSNB1 locus in Xp11

    Energy Technology Data Exchange (ETDEWEB)

    Boycott, K.M.; Gratton, K.J.; Moore, B.J. [Univ. of Calgary (Canada)] [and others

    1994-09-01

    X-linked congenital stationary night blindness (CSNB1) is an eye disorder that includes impairment of night vision, reduced visual acuity and, in some cases, myopia and congenital nystagmus. Electroretinography reveals a marked reduction of the b-wave in affected individuals suggesting that X-linked CSNB is due to a molecular defect in the bipolar layer of the retina. Based on our studies of a large four generation family with X-linked CSNB, a CSNB1 locus was mapped to a 4-5 cM region at Xp11.23-Xp11.22 bounded telomerically by DXS426 and centromerically by DXS988. Using a panel of radiation and conventional somatic cell hybrids, a detailed map of new and published STSs has been generated for the minimal region of CSNB1. PCR primer pairs for STSs has been generated for the minimal region of CSNB1. PCR primer pairs for twenty-five STSs, including eleven end-clones, were used to isolate YAC clones from CEPH, mega-CEPH, and X chromosome-specific YAC libraries. In total, fifty-two YACs were characterized for STS overlaps and assembled to provide a minimum of 3 Mb of physical coverage in the region between DXS426 and DXS988. Five gaps proximal to SYP are still to be closed. Our physical map suggests the following gene order: Xpter-OTAL1-GF1-DXS1011E-MG81-HUMCRAS2P-SYP-Xcen. STS analysis of the YACs revealed three subregions of the physical map which appear to be particularly susceptible to internal deletions and end-clone analysis demonstrated chimerism in six of seventeen YACs. A physical map of Xp11.23-Xp11.22 will provide a resource for the isolation of candidate genes for the X-linked CSNB gene which maps to this region.

  8. Brain cortical organization in entrepreneurs during a visual Stroop decision task

    Directory of Open Access Journals (Sweden)

    Ortiz-Terán E

    2013-11-01

    Full Text Available Elena Ortiz-Terán,1,4 Agustín Turrero,2 Juan M Santos,3 Peter T Bryant,1 Tomás Ortiz4 1IE Business School, 2Department of Statistics, Universidad Complutense, Madrid, Spain; 3Fundación J Robert Cade and Department of Psychiatry, Universidad Católica de Córdoba, Córdoba, Argentina; 4Department of Psychiatry, Universidad Complutense, Madrid, Spain Abstract: Decision-making in entrepreneurs is a key aspect of their skills, but much about these processes remains unexplained. During a Stroop task, concomitant N200, P300, and N450 event-related potentials were measured in 25 founder entrepreneurs and in age-matched and gender-matched nonfounders/nonentrepreneurs (NFNE. Reaction times were shorter among founder entrepreneurs. The N200 was shorter and N450 larger in founder entrepreneurs. The personalities of both groups were measured using the Temperament and Character Inventory-Revised. Founder entrepreneurs scored significantly higher in novelty-seeking and self-directedness dimensions, as well as in exploratory excitability, impulsiveness, optimism, eagerness, and responsibility subdimensions. Possible interactions among candidate variables to differentiate between founder entrepreneurs versus NFNE were also addressed, and the model including impulsivity, N450 latency, and impulsivity*N450 interaction came up as the best model for discrimination between founder entrepreneurs and NFNE. A shorter N200, mostly associated with bilateral supplementary motor area activation, revealed a faster capability to make decisions when information was noncongruent or blurred. However, the larger N450 revealed a more intense post-evaluation cognitive process happening in founder entrepreneurs and was accompanied by a greater activation of anterior frontal regions. The whole decision-making process consumed more time and resources in founder entrepreneurs, even if its closure was faster. Attention, memory, and alertness, among other factors, have been invoked

  9. Coverage and characteristics of the Affymetrix GeneChip Human Mapping 100K SNP set.

    Directory of Open Access Journals (Sweden)

    2006-05-01

    Full Text Available Improvements in technology have made it possible to conduct genome-wide association mapping at costs within reach of academic investigators, and experiments are currently being conducted with a variety of high-throughput platforms. To provide an appropriate context for interpreting results of such studies, we summarize here results of an investigation of one of the first of these technologies to be publicly available, the Affymetrix GeneChip Human Mapping 100K set of single nucleotide polymorphisms (SNPs. In a systematic analysis of the pattern and distribution of SNPs in the Mapping 100K set, we find that SNPs in this set are undersampled from coding regions (both nonsynonymous and synonymous and oversampled from regions outside genes, relative to SNPs in the overall HapMap database. In addition, we utilize a novel multilocus linkage disequilibrium (LD coefficient based on information content (analogous to the information content scores commonly used for linkage mapping that is equivalent to the familiar measure r2 in the special case of two loci. Using this approach, we are able to summarize for any subset of markers, such as the Affymetrix Mapping 100K set, the information available for association mapping in that subset, relative to the information available in the full set of markers included in the HapMap, and highlight circumstances in which this multilocus measure of LD provides substantial additional insight about the haplotype structure in a region over pairwise measures of LD.

  10. Mixed effects modeling of proliferation rates in cell-based models: consequence for pharmacogenomics and cancer.

    Directory of Open Access Journals (Sweden)

    Hae Kyung Im

    2012-02-01

    Full Text Available The International HapMap project has made publicly available extensive genotypic data on a number of lymphoblastoid cell lines (LCLs. Building on this resource, many research groups have generated a large amount of phenotypic data on these cell lines to facilitate genetic studies of disease risk or drug response. However, one problem that may reduce the usefulness of these resources is the biological noise inherent to cellular phenotypes. We developed a novel method, termed Mixed Effects Model Averaging (MEM, which pools data from multiple sources and generates an intrinsic cellular growth rate phenotype. This intrinsic growth rate was estimated for each of over 500 HapMap cell lines. We then examined the association of this intrinsic growth rate with gene expression levels and found that almost 30% (2,967 out of 10,748 of the genes tested were significant with FDR less than 10%. We probed further to demonstrate evidence of a genetic effect on intrinsic growth rate by determining a significant enrichment in growth-associated genes among genes targeted by top growth-associated SNPs (as eQTLs. The estimated intrinsic growth rate as well as the strength of the association with genetic variants and gene expression traits are made publicly available through a cell-based pharmacogenomics database, PACdb. This resource should enable researchers to explore the mediating effects of proliferation rate on other phenotypes.

  11. Detection of genomic variation by selection of a 9 mb DNA region and high throughput sequencing.

    Directory of Open Access Journals (Sweden)

    Sergey I Nikolaev

    Full Text Available Detection of the rare polymorphisms and causative mutations of genetic diseases in a targeted genomic area has become a major goal in order to understand genomic and phenotypic variability. We have interrogated repeat-masked regions of 8.9 Mb on human chromosomes 21 (7.8 Mb and 7 (1.1 Mb from an individual from the International HapMap Project (NA12872. We have optimized a method of genomic selection for high throughput sequencing. Microarray-based selection and sequencing resulted in 260-fold enrichment, with 41% of reads mapping to the target region. 83% of SNPs in the targeted region had at least 4-fold sequence coverage and 54% at least 15-fold. When assaying HapMap SNPs in NA12872, our sequence genotypes are 91.3% concordant in regions with coverage > or = 4-fold, and 97.9% concordant in regions with coverage > or = 15-fold. About 81% of the SNPs recovered with both thresholds are listed in dbSNP. We observed that regions with low sequence coverage occur in close proximity to low-complexity DNA. Validation experiments using Sanger sequencing were performed for 46 SNPs with 15-20 fold coverage, with a confirmation rate of 96%, suggesting that DNA selection provides an accurate and cost-effective method for identifying rare genomic variants.

  12. Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian Tamil Rheumatoid Arthritis patients.

    Science.gov (United States)

    Muralidharan, Niveditha; Gulati, Reena; Misra, Durga Prasanna; Negi, Vir S

    2018-02-01

    The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR-RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5' nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.

  13. SNPpy--database management for SNP data from genome wide association studies.

    Directory of Open Access Journals (Sweden)

    Faheem Mitha

    Full Text Available BACKGROUND: We describe SNPpy, a hybrid script database system using the Python SQLAlchemy library coupled with the PostgreSQL database to manage genotype data from Genome-Wide Association Studies (GWAS. This system makes it possible to merge study data with HapMap data and merge across studies for meta-analyses, including data filtering based on the values of phenotype and Single-Nucleotide Polymorphism (SNP data. SNPpy and its dependencies are open source software. RESULTS: The current version of SNPpy offers utility functions to import genotype and annotation data from two commercial platforms. We use these to import data from two GWAS studies and the HapMap Project. We then export these individual datasets to standard data format files that can be imported into statistical software for downstream analyses. CONCLUSIONS: By leveraging the power of relational databases, SNPpy offers integrated management and manipulation of genotype and phenotype data from GWAS studies. The analysis of these studies requires merging across GWAS datasets as well as patient and marker selection. To this end, SNPpy enables the user to filter the data and output the results as standardized GWAS file formats. It does low level and flexible data validation, including validation of patient data. SNPpy is a practical and extensible solution for investigators who seek to deploy central management of their GWAS data.

  14. Genes with stable DNA methylation levels show higher evolutionary conservation than genes with fluctuant DNA methylation levels.

    Science.gov (United States)

    Zhang, Ruijie; Lv, Wenhua; Luan, Meiwei; Zheng, Jiajia; Shi, Miao; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Shang, Zhenwei; Duan, Lian; Jiang, Yongshuai

    2015-11-24

    Different human genes often exhibit different degrees of stability in their DNA methylation levels between tissues, samples or cell types. This may be related to the evolution of human genome. Thus, we compared the evolutionary conservation between two types of genes: genes with stable DNA methylation levels (SM genes) and genes with fluctuant DNA methylation levels (FM genes). For long-term evolutionary characteristics between species, we compared the percentage of the orthologous genes, evolutionary rate dn/ds and protein sequence identity. We found that the SM genes had greater percentages of the orthologous genes, lower dn/ds, and higher protein sequence identities in all the 21 species. These results indicated that the SM genes were more evolutionarily conserved than the FM genes. For short-term evolutionary characteristics among human populations, we compared the single nucleotide polymorphism (SNP) density, and the linkage disequilibrium (LD) degree in HapMap populations and 1000 genomes project populations. We observed that the SM genes had lower SNP densities, and higher degrees of LD in all the 11 HapMap populations and 13 1000 genomes project populations. These results mean that the SM genes had more stable chromosome genetic structures, and were more conserved than the FM genes.

  15. Reducing Bias of Allele Frequency Estimates by Modeling SNP Genotype Data with Informative Missingness

    Directory of Open Access Journals (Sweden)

    Wan-Yu eLin

    2012-06-01

    Full Text Available The presence of missing single-nucleotide polymorphism (SNP genotypes is common in genetic data. For studies with low-density SNPs, the most commonly used approach to deal with genotype missingness is to simply remove the observations with missing genotypes from the analyses. This naïve method is straightforward but is appropriate only when the missingness is random. However, a given assay often has a different capability in genotyping heterozygotes and homozygotes, causing the phenomenon of ‘differential dropout’ in the sense that the missing rates of heterozygotes and homozygotes are different. In practice, differential dropout among genotypes exists in even carefully designed studies, such as the data from the HapMap project and the Wellcome Trust Case Control Consortium. In this study, we propose a statistical method to model the differential dropout among different genotypes. Compared with the naïve method, our method provides more accurate allele frequency estimates when the differential dropout is present. To demonstrate its practical use, we further apply our method to the HapMap data and a scleroderma data set.

  16. Genome-wide detection and characterization of positive selection in human populations.

    Science.gov (United States)

    Sabeti, Pardis C; Varilly, Patrick; Fry, Ben; Lohmueller, Jason; Hostetter, Elizabeth; Cotsapas, Chris; Xie, Xiaohui; Byrne, Elizabeth H; McCarroll, Steven A; Gaudet, Rachelle; Schaffner, Stephen F; Lander, Eric S; Frazer, Kelly A; Ballinger, Dennis G; Cox, David R; Hinds, David A; Stuve, Laura L; Gibbs, Richard A; Belmont, John W; Boudreau, Andrew; Hardenbol, Paul; Leal, Suzanne M; Pasternak, Shiran; Wheeler, David A; Willis, Thomas D; Yu, Fuli; Yang, Huanming; Zeng, Changqing; Gao, Yang; Hu, Haoran; Hu, Weitao; Li, Chaohua; Lin, Wei; Liu, Siqi; Pan, Hao; Tang, Xiaoli; Wang, Jian; Wang, Wei; Yu, Jun; Zhang, Bo; Zhang, Qingrun; Zhao, Hongbin; Zhao, Hui; Zhou, Jun; Gabriel, Stacey B; Barry, Rachel; Blumenstiel, Brendan; Camargo, Amy; Defelice, Matthew; Faggart, Maura; Goyette, Mary; Gupta, Supriya; Moore, Jamie; Nguyen, Huy; Onofrio, Robert C; Parkin, Melissa; Roy, Jessica; Stahl, Erich; Winchester, Ellen; Ziaugra, Liuda; Altshuler, David; Shen, Yan; Yao, Zhijian; Huang, Wei; Chu, Xun; He, Yungang; Jin, Li; Liu, Yangfan; Shen, Yayun; Sun, Weiwei; Wang, Haifeng; Wang, Yi; Wang, Ying; Xiong, Xiaoyan; Xu, Liang; Waye, Mary M Y; Tsui, Stephen K W; Xue, Hong; Wong, J Tze-Fei; Galver, Luana M; Fan, Jian-Bing; Gunderson, Kevin; Murray, Sarah S; Oliphant, Arnold R; Chee, Mark S; Montpetit, Alexandre; Chagnon, Fanny; Ferretti, Vincent; Leboeuf, Martin; Olivier, Jean-François; Phillips, Michael S; Roumy, Stéphanie; Sallée, Clémentine; Verner, Andrei; Hudson, Thomas J; Kwok, Pui-Yan; Cai, Dongmei; Koboldt, Daniel C; Miller, Raymond D; Pawlikowska, Ludmila; Taillon-Miller, Patricia; Xiao, Ming; Tsui, Lap-Chee; Mak, William; Song, You Qiang; Tam, Paul K H; Nakamura, Yusuke; Kawaguchi, Takahisa; Kitamoto, Takuya; Morizono, Takashi; Nagashima, Atsushi; Ohnishi, Yozo; Sekine, Akihiro; Tanaka, Toshihiro; Tsunoda, Tatsuhiko; Deloukas, Panos; Bird, Christine P; Delgado, Marcos; Dermitzakis, Emmanouil T; Gwilliam, Rhian; Hunt, Sarah; Morrison, Jonathan; Powell, Don; Stranger, Barbara E; Whittaker, Pamela; Bentley, David R; Daly, Mark J; de Bakker, Paul I W; Barrett, Jeff; Chretien, Yves R; Maller, Julian; McCarroll, Steve; Patterson, Nick; Pe'er, Itsik; Price, Alkes; Purcell, Shaun; Richter, Daniel J; Sabeti, Pardis; Saxena, Richa; Schaffner, Stephen F; Sham, Pak C; Varilly, Patrick; Altshuler, David; Stein, Lincoln D; Krishnan, Lalitha; Smith, Albert Vernon; Tello-Ruiz, Marcela K; Thorisson, Gudmundur A; Chakravarti, Aravinda; Chen, Peter E; Cutler, David J; Kashuk, Carl S; Lin, Shin; Abecasis, Gonçalo R; Guan, Weihua; Li, Yun; Munro, Heather M; Qin, Zhaohui Steve; Thomas, Daryl J; McVean, Gilean; Auton, Adam; Bottolo, Leonardo; Cardin, Niall; Eyheramendy, Susana; Freeman, Colin; Marchini, Jonathan; Myers, Simon; Spencer, Chris; Stephens, Matthew; Donnelly, Peter; Cardon, Lon R; Clarke, Geraldine; Evans, David M; Morris, Andrew P; Weir, Bruce S; Tsunoda, Tatsuhiko; Johnson, Todd A; Mullikin, James C; Sherry, Stephen T; Feolo, Michael; Skol, Andrew; Zhang, Houcan; Zeng, Changqing; Zhao, Hui; Matsuda, Ichiro; Fukushima, Yoshimitsu; Macer, Darryl R; Suda, Eiko; Rotimi, Charles N; Adebamowo, Clement A; Ajayi, Ike; Aniagwu, Toyin; Marshall, Patricia A; Nkwodimmah, Chibuzor; Royal, Charmaine D M; Leppert, Mark F; Dixon, Missy; Peiffer, Andy; Qiu, Renzong; Kent, Alastair; Kato, Kazuto; Niikawa, Norio; Adewole, Isaac F; Knoppers, Bartha M; Foster, Morris W; Clayton, Ellen Wright; Watkin, Jessica; Gibbs, Richard A; Belmont, John W; Muzny, Donna; Nazareth, Lynne; Sodergren, Erica; Weinstock, George M; Wheeler, David A; Yakub, Imtaz; Gabriel, Stacey B; Onofrio, Robert C; Richter, Daniel J; Ziaugra, Liuda; Birren, Bruce W; Daly, Mark J; Altshuler, David; Wilson, Richard K; Fulton, Lucinda L; Rogers, Jane; Burton, John; Carter, Nigel P; Clee, Christopher M; Griffiths, Mark; Jones, Matthew C; McLay, Kirsten; Plumb, Robert W; Ross, Mark T; Sims, Sarah K; Willey, David L; Chen, Zhu; Han, Hua; Kang, Le; Godbout, Martin; Wallenburg, John C; L'Archevêque, Paul; Bellemare, Guy; Saeki, Koji; Wang, Hongguang; An, Daochang; Fu, Hongbo; Li, Qing; Wang, Zhen; Wang, Renwu; Holden, Arthur L; Brooks, Lisa D; McEwen, Jean E; Guyer, Mark S; Wang, Vivian Ota; Peterson, Jane L; Shi, Michael; Spiegel, Jack; Sung, Lawrence M; Zacharia, Lynn F; Collins, Francis S; Kennedy, Karen; Jamieson, Ruth; Stewart, John

    2007-10-18

    With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.

  17. Identification of Diabetic Retinopathy Genes through a Genome-Wide Association Study among Mexican-Americans from Starr County, Texas

    Directory of Open Access Journals (Sweden)

    Yi-Ping Fu

    2010-01-01

    Full Text Available To identify genetic loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas, completed physical examinations including fundus photography for diabetic retinopathy grading. Individuals with moderate-to-severe non-proliferative and proliferative diabetic retinopathy were defined as cases. Direct genotyping was performed using the Affymetrix GeneChip Human Mapping 100 K Set, and SNPs passing quality control criteria were used to impute markers available in HapMap Phase III Mexican population (MXL in Los Angeles, California. Two directly genotyped markers were associated with severe diabetic retinopathy at a P-value less than .0001: SNP rs2300782 (P=6.04×10−5 mapped to an intron region of CAMK4 (calcium/calmodulin-dependent protein kinase IV on chromosome 5, and SNP rs10519765 (P=6.21×10−5 on chromosomal 15q13 in the FMN1 (formin 1 gene. Using well-imputed markers based on the HapMap III Mexican population, we identified an additional 32 SNPs located in 11 chromosomal regions with nominal association with severe diabetic retinopathy at P-value less than .0001. None of these markers were located in traditional candidate genes for diabetic retinopathy or diabetes itself. However, these signals implicate genes involved in inflammation, oxidative stress and cell adhesion for the development and progression of diabetic retinopathy.

  18. Allele and Genotype Distributions of DNA Repair Gene Polymorphisms in South Indian Healthy Population

    Directory of Open Access Journals (Sweden)

    Katiboina Srinivasa Rao

    2014-01-01

    Full Text Available Various DNA repair pathways protect the structural and chemical integrity of the human genome from environmental and endogenous threats. Polymorphisms of genes encoding the proteins involved in DNA repair have been found to be associated with cancer risk and chemotherapeutic response. In this study, we aim to establish the normative frequencies of DNA repair genes in South Indian healthy population and compare with HapMap populations. Genotyping was done on 128 healthy volunteers from South India, and the allele and genotype distributions were established. The minor allele frequency of Xeroderma pigmentosum group A ( XPA G23A, Excision repair cross-complementing 2 ( ERCC2 /Xeroderma pigmentosum group D ( XPD Lys751Gln, Xeroderma pigmentosum group G ( XPG His46His, XPG Asp1104His, and X-ray repair cross-complementing group 1 ( XRCC1 Arg399Gln polymorphisms were 49.2%, 36.3%, 48.0%, 23.0%, and 34.0% respectively. Ethnic variations were observed in the frequency distribution of these polymorphisms between the South Indians and other HapMap populations. The present work forms the groundwork for cancer association studies and biomarker identification for treatment response and prognosis.

  19. LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs

    Directory of Open Access Journals (Sweden)

    Cheng Yu-Huei

    2009-06-01

    Full Text Available Abstract Background Linkage disequilibrium (LD mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from dbSNP/NCBI and HapMap, respectively. Restriction fragment length polymorphism (RFLP enzyme information for SNP genotype is available to all SNP IDs and tag SNPs. Single and multiple SNP inputs are possible in order to perform LD analysis by online retrieval from HapMap and NCBI. An LD statistics section provides D, D', r2, δQ, ρ, and the P values of the Hardy-Weinberg Equilibrium for each SNP marker, and Chi-square and likelihood-ratio tests for the pair-wise association of two SNPs in LD calculation. Finally, 2D and 3D plots, as well as plain-text output of the results, can be selected. Conclusion LD2SNPing thus provides a novel visualization environment for multiple SNP input, which facilitates SNP association studies. The software, user manual, and tutorial are freely available at http://bio.kuas.edu.tw/LD2NPing.

  20. Population specific genetic heterogeneity of familial hypercholesterolemia in South Africa.

    Science.gov (United States)

    Smyth, Natalie; Ramsay, Michèle; Raal, Frederick J

    2018-04-01

    To describe the prevalence and population-specific genetic heterogeneity of familial hypercholesterolemia in South Africa. This review highlights the paucity of data on familial hypercholesterolemia in South Africa, and the urgent need to uncover the mutation profiles in lipid-associated genes, causing an increase in LDL-cholesterol in the different ethnic groups. Case reports and small studies have shown that familial hypercholesterolemia, although apparently uncommon, is present in black Africans. Local founder effects have led to an increased prevalence of familial hypercholesterolemia in several South African populations: Afrikaner founder mutations (c.681 C>G, c.1285 G>A, c.523 G>A), Ashkenazi founder mutation (c.654_656del) and possible Indian founder mutation (c.2054 C>T). Preliminary data in black Africans with elevated LDL-cholesterol identified a possible common mutation, c.137_142del. The South African multiethnic society and well described founder effects emphasize the need for differential approaches to diagnosis and management of familial hypercholesterolemia. Studies involving larger cohorts and inclusive of different ethnicities are paramount to establishing an accurate prevalence of familial hypercholesterolemia in black Africans, not only in South Africa but in the Sub-Saharan African region. It is clear that the estimated world prevalence of one in 250 cannot be generally applied across African populations.