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Sample records for african gene pool

  1. Switchgrass Gene Pools for Conservation and Restoration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Panicum virgatum L. (switchgrass) is a perennial grass native to the North American tallgrass prairie and broadly adapted to the central and eastern USA. Movement of plant materials throughout this region creates the potential of contaminating local gene pools with genes that are not native to a lo...

  2. Decrypting the Mitochondrial Gene Pool of Modern Panamanians

    PubMed Central

    Angerhofer, Norman; Ekins, Jayne E.; Olivieri, Anna; Woodward, Scott R.; Pascale, Juan Miguel; Cooke, Richard; Motta, Jorge; Achilli, Alessandro

    2012-01-01

    The Isthmus of Panama–the narrow neck of land connecting the northern and southern American landmasses–was an obligatory corridor for the Paleo-Indians as they moved into South America. Archaeological evidence suggests an unbroken link between modern natives and their Paleo-Indian ancestors in some areas of Panama, even if the surviving indigenous groups account for only 12.3% of the total population. To evaluate if modern Panamanians have retained a larger fraction of the native pre-Columbian gene pool in their maternally-inherited mitochondrial genome, DNA samples and historical records were collected from more than 1500 volunteer participants living in the nine provinces and four indigenous territories of the Republic. Due to recent gene-flow, we detected ∼14% African mitochondrial lineages, confirming the demographic impact of the Atlantic slave trade and subsequent African immigration into Panama from Caribbean islands, and a small European (∼2%) component, indicating only a minor influence of colonialism on the maternal side. The majority (∼83%) of Panamanian mtDNAs clustered into native pan-American lineages, mostly represented by haplogroup A2 (51%). These findings reveal an overwhelming native maternal legacy in today's Panama, which is in contrast with the overall concept of personal identity shared by many Panamanians. Moreover, the A2 sub-clades A2ad and A2af (with the previously named 6 bp Huetar deletion), when analyzed at the maximum level of resolution (26 entire mitochondrial genomes), confirm the major role of the Pacific coastal path in the peopling of North, Central and South America, and testify to the antiquity of native mitochondrial genomes in Panama. PMID:22675545

  3. Decrypting the mitochondrial gene pool of modern Panamanians.

    PubMed

    Perego, Ugo A; Lancioni, Hovirag; Tribaldos, Maribel; Angerhofer, Norman; Ekins, Jayne E; Olivieri, Anna; Woodward, Scott R; Pascale, Juan Miguel; Cooke, Richard; Motta, Jorge; Achilli, Alessandro

    2012-01-01

    The Isthmus of Panama--the narrow neck of land connecting the northern and southern American landmasses--was an obligatory corridor for the Paleo-Indians as they moved into South America. Archaeological evidence suggests an unbroken link between modern natives and their Paleo-Indian ancestors in some areas of Panama, even if the surviving indigenous groups account for only 12.3% of the total population. To evaluate if modern Panamanians have retained a larger fraction of the native pre-Columbian gene pool in their maternally-inherited mitochondrial genome, DNA samples and historical records were collected from more than 1500 volunteer participants living in the nine provinces and four indigenous territories of the Republic. Due to recent gene-flow, we detected ~14% African mitochondrial lineages, confirming the demographic impact of the Atlantic slave trade and subsequent African immigration into Panama from Caribbean islands, and a small European (~2%) component, indicating only a minor influence of colonialism on the maternal side. The majority (~83%) of Panamanian mtDNAs clustered into native pan-American lineages, mostly represented by haplogroup A2 (51%). These findings reveal an overwhelming native maternal legacy in today's Panama, which is in contrast with the overall concept of personal identity shared by many Panamanians. Moreover, the A2 sub-clades A2ad and A2af (with the previously named 6 bp Huetar deletion), when analyzed at the maximum level of resolution (26 entire mitochondrial genomes), confirm the major role of the Pacific coastal path in the peopling of North, Central and South America, and testify to the antiquity of native mitochondrial genomes in Panama. PMID:22675545

  4. Genetic diversity, plant adaptation regions, and gene pools of switchgrass

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Switchgrass is a perennial grass native to the North American tallgrass prairie and broadly adapted to the central and eastern USA. Movement of plant materials throughout this region creates the potential of contaminating local gene pools with genes that are not native to a locale. The objective o...

  5. Possible effect of biotechnology on plant gene pools in Turkey

    PubMed Central

    Demir, Aynur

    2015-01-01

    The recent rapid developments in biotechnology have made great contributions to the study of plant gene pools. The application of in vitro methods in freeze storage and DNA protection techniques in fast production studies has made major advances. From that aspect, biotechnology is an indispensable means for the protection of plant gene pools, which includes the insurance of sustainable agriculture and development of species. Besides all the positive developments, one of the primary risks posed by the uncontrolled spreading of genetically modified organisms is the possibility for other non-target organisms to be negatively affected. Genes of plant origin should be given priority in this type of studies by taking into consideration such negative effects that may result in disruption of ecological balance and damage to plant genetic pools. Turkey, due to its ecological conditions and history, has a very important position in terms of plant gene pools. This richness ought to be protected without corrupting its natural quality and natural evolution process in order to provide the sources of species that will be required for future sustainable agricultural applications. Thus, attention should be paid to the use of biotechnological methods, which play an important role especially in the protection and use of local and original plant gene pools. PMID:26019612

  6. Detection of African horse sickness virus in Culicoides imicola pools using RT-qPCR.

    PubMed

    de Waal, Tania; Liebenberg, Danica; Venter, Gert J; Mienie, Charlotte Ms; van Hamburg, Huib

    2016-06-01

    African horse sickness (AHS) is an infectious, non-contagious arthropod-borne disease of equids, caused by the African horse sickness virus (AHSV), an orbivirus of the Reoviridae family. It is endemic in sub-Saharan Africa and thought to be the most lethal viral disease of horses. This study focused on detection of AHSV in Culicoides imicola (Diptera: Ceratopogonidae) pools by the application of a RT-qPCR. Midges were fed on AHSV-infected blood. A single blood-engorged female was allocated to pools of unfed nulliparous female midges. Pool sizes varied from 1 to 200. RNA was extracted and prepared for RT-qPCR. The virus was successfully detected and the optimal pool size for the limit of detection of the virus was determined at a range between 1 to 25. Results from this investigation highlight the need for a standardized protocol for AHSV investigation in Culicoides midges especially for comparison among different studies and for the determination of infection rate. PMID:27232141

  7. Conjugative plasmids: vessels of the communal gene pool

    PubMed Central

    Norman, Anders; Hansen, Lars H.; Sørensen, Søren J.

    2009-01-01

    Comparative whole-genome analyses have demonstrated that horizontal gene transfer (HGT) provides a significant contribution to prokaryotic genome innovation. The evolution of specific prokaryotes is therefore tightly linked to the environment in which they live and the communal pool of genes available within that environment. Here we use the term supergenome to describe the set of all genes that a prokaryotic ‘individual’ can draw on within a particular environmental setting. Conjugative plasmids can be considered particularly successful entities within the communal pool, which have enabled HGT over large taxonomic distances. These plasmids are collections of discrete regions of genes that function as ‘backbone modules’ to undertake different aspects of overall plasmid maintenance and propagation. Conjugative plasmids often carry suites of ‘accessory elements’ that contribute adaptive traits to the hosts and, potentially, other resident prokaryotes within specific environmental niches. Insight into the evolution of plasmid modules therefore contributes to our knowledge of gene dissemination and evolution within prokaryotic communities. This communal pool provides the prokaryotes with an important mechanistic framework for obtaining adaptability and functional diversity that alleviates the need for large genomes of specialized ‘private genes’. PMID:19571247

  8. First Detection of Mycobacteria in African Rodents and Insectivores, Using Stratified Pool Screening▿ †

    PubMed Central

    Durnez, Lies; Eddyani, Miriam; Mgode, Georgies F.; Katakweba, Abdul; Katholi, Charles R.; Machang'u, Robert R.; Kazwala, Rudovik R.; Portaels, Françoise; Leirs, Herwig

    2008-01-01

    With the rising number of patients with human immunodeficiency virus (HIV)/AIDS in developing countries, the control of mycobacteria is of growing importance. Previous studies have shown that rodents and insectivores are carriers of mycobacteria. However, it is not clear how widespread mycobacteria are in these animals and what their role is in spreading them. Therefore, the prevalence of mycobacteria in rodents and insectivores was studied in and around Morogoro, Tanzania. Live rodents were trapped, with three types of live traps, in three habitats. Pieces of organs were pooled per habitat, species, and organ type (stratified pooling); these sample pools were examined for the presence of mycobacteria by PCR, microscopy, and culture methods. The mycobacterial isolates were identified using phenotypic techniques and sequencing. In total, 708 small mammals were collected, 31 of which were shrews. By pool prevalence estimation, 2.65% of the animals were carriers of mycobacteria, with a higher prevalence in the urban areas and in Cricetomys gambianus and the insectivore Crocidura hirta. Nontuberculous mycobacteria (Mycobacterium chimaera, M. intracellulare, M. arupense, M. parascrofulaceum, and Mycobacterium spp.) were isolated from C. gambianus, Mastomys natalensis, and C. hirta. This study is the first to report findings of mycobacteria in African rodents and insectivores and the first in mycobacterial ecology to estimate the prevalence of mycobacteria after stratified pool screening. The fact that small mammals in urban areas carry more mycobacteria than those in the fields and that potentially pathogenic mycobacteria were isolated identifies a risk for other animals and humans, especially HIV/AIDS patients, that have a weakened immune system. PMID:18065608

  9. First detection of mycobacteria in African rodents and insectivores, using stratified pool screening.

    PubMed

    Durnez, Lies; Eddyani, Miriam; Mgode, Georgies F; Katakweba, Abdul; Katholi, Charles R; Machang'u, Robert R; Kazwala, Rudovik R; Portaels, Françoise; Leirs, Herwig

    2008-02-01

    With the rising number of patients with human immunodeficiency virus (HIV)/AIDS in developing countries, the control of mycobacteria is of growing importance. Previous studies have shown that rodents and insectivores are carriers of mycobacteria. However, it is not clear how widespread mycobacteria are in these animals and what their role is in spreading them. Therefore, the prevalence of mycobacteria in rodents and insectivores was studied in and around Morogoro, Tanzania. Live rodents were trapped, with three types of live traps, in three habitats. Pieces of organs were pooled per habitat, species, and organ type (stratified pooling); these sample pools were examined for the presence of mycobacteria by PCR, microscopy, and culture methods. The mycobacterial isolates were identified using phenotypic techniques and sequencing. In total, 708 small mammals were collected, 31 of which were shrews. By pool prevalence estimation, 2.65% of the animals were carriers of mycobacteria, with a higher prevalence in the urban areas and in Cricetomys gambianus and the insectivore Crocidura hirta. Nontuberculous mycobacteria (Mycobacterium chimaera, M. intracellulare, M. arupense, M. parascrofulaceum, and Mycobacterium spp.) were isolated from C. gambianus, Mastomys natalensis, and C. hirta. This study is the first to report findings of mycobacteria in African rodents and insectivores and the first in mycobacterial ecology to estimate the prevalence of mycobacteria after stratified pool screening. The fact that small mammals in urban areas carry more mycobacteria than those in the fields and that potentially pathogenic mycobacteria were isolated identifies a risk for other animals and humans, especially HIV/AIDS patients, that have a weakened immune system. PMID:18065608

  10. Combinatorial Pooling Enables Selective Sequencing of the Barley Gene Space

    PubMed Central

    Lonardi, Stefano; Duma, Denisa; Alpert, Matthew; Cordero, Francesca; Beccuti, Marco; Bhat, Prasanna R.; Wu, Yonghui; Ciardo, Gianfranco; Alsaihati, Burair; Ma, Yaqin; Wanamaker, Steve; Resnik, Josh; Bozdag, Serdar; Luo, Ming-Cheng; Close, Timothy J.

    2013-01-01

    For the vast majority of species – including many economically or ecologically important organisms, progress in biological research is hampered due to the lack of a reference genome sequence. Despite recent advances in sequencing technologies, several factors still limit the availability of such a critical resource. At the same time, many research groups and international consortia have already produced BAC libraries and physical maps and now are in a position to proceed with the development of whole-genome sequences organized around a physical map anchored to a genetic map. We propose a BAC-by-BAC sequencing protocol that combines combinatorial pooling design and second-generation sequencing technology to efficiently approach denovo selective genome sequencing. We show that combinatorial pooling is a cost-effective and practical alternative to exhaustive DNA barcoding when preparing sequencing libraries for hundreds or thousands of DNA samples, such as in this case gene-bearing minimum-tiling-path BAC clones. The novelty of the protocol hinges on the computational ability to efficiently compare hundred millions of short reads and assign them to the correct BAC clones (deconvolution) so that the assembly can be carried out clone-by-clone. Experimental results on simulated data for the rice genome show that the deconvolution is very accurate, and the resulting BAC assemblies have high quality. Results on real data for a gene-rich subset of the barley genome confirm that the deconvolution is accurate and the BAC assemblies have good quality. While our method cannot provide the level of completeness that one would achieve with a comprehensive whole-genome sequencing project, we show that it is quite successful in reconstructing the gene sequences within BACs. In the case of plants such as barley, this level of sequence knowledge is sufficient to support critical end-point objectives such as map-based cloning and marker-assisted breeding. PMID:23592960

  11. Demographic factors shaped diversity in the two gene pools of wild common bean Phaseolus vulgaris L.

    PubMed Central

    Mamidi, S; Rossi, M; Moghaddam, S M; Annam, D; Lee, R; Papa, R; McClean, P E

    2013-01-01

    Wild common bean (Phaseolus vulgaris L.) is distributed throughout the Americas from Mexico to northern Argentina. Within this range, the species is divided into two gene pools (Andean and Middle American) along a latitudinal gradient. The diversity of 24 wild common bean genotypes from throughout the geographic range of the species was described by using sequence data from 13 loci. An isolation–migration model was evaluated using a coalescent analysis to estimate multiple demographic parameters. Using a Bayesian approach, Andean and Middle American subpopulations with high percentage of parentages were observed. Over all loci, the Middle American gene pool was more diverse than the Andean gene pool (πsil=0.0089 vs 0.0068). The two subpopulations were strongly genetically differentiated over all loci (Fst=0.29). It is estimated that the two current wild gene pools diverged from a common ancestor ∼111 000 years ago. Subsequently, each gene pool underwent a bottleneck immediately after divergence and lasted ∼40 000 years. The Middle American bottleneck population size was ∼46% of the ancestral population size, whereas the Andean was 26%. Continuous asymmetric gene flow was detected between the two gene pools with a larger number of migrants entering Middle American gene pool from the Andean gene pool. These results suggest that because of the complex population structure associated with the ancestral divergence, subsequent bottlenecks in each gene pool, gene pool-specific domestication and intense selection within each gene pool by breeders; association mapping would best be practised within each common bean gene pool. PMID:23169559

  12. Frozen gene pools - A future for species otherwise destined for extinction

    USGS Publications Warehouse

    Gee, G.F.

    1986-01-01

    Conclusion: Semen banks and ova and embryo banks can be practical methods to maintain gene pools. Gene pool preservation is desperately needed today due to the rapid decline in number of species and their habitat, a matter that is of concern to.biologists, economists, and politicians worldwide. Techniques are available for the cryopreservation of semen from many animals (and embryos from a few mammals) and adaptations of these techniques to other animals should be possible. A frozen gene pool in conjunction with existing programs makes it possible to preserve gene pools at less cost or in.some cases where no other alternative to extinction existed.

  13. The World Gene Pool of Gossypium barbadense L. and Its Improvement

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter describes the improved and unimproved gene pools of Gossypium barbadense. Section one discusses the taxonomic and geographic structure of species diversity. Section two describes the origin and development of modern improved germplasm pools, beginning with Sea Island cottons deve...

  14. Sharp gene pool transition in a population affected by phenotype-based selective hunting

    NASA Astrophysics Data System (ADS)

    Brigatti, E.; Sá Martins, J. S.; Roditi, I.

    2005-06-01

    We use a microscopic model of population dynamics, a modified version of the well known Penna model, to study some aspects of microevolution. This research is motivated by recent reports on the effect of selective hunting on the gene pool of bighorn sheep living in the Ram Mountain region, in Canada. Our model finds a sharp transition in the structure of the gene pool as some threshold for the number of animals hunted is reached.

  15. Ethiopian Genetic Diversity Reveals Linguistic Stratification and Complex Influences on the Ethiopian Gene Pool

    PubMed Central

    Pagani, Luca; Kivisild, Toomas; Tarekegn, Ayele; Ekong, Rosemary; Plaster, Chris; Gallego Romero, Irene; Ayub, Qasim; Mehdi, S. Qasim; Thomas, Mark G.; Luiselli, Donata; Bekele, Endashaw; Bradman, Neil; Balding, David J.; Tyler-Smith, Chris

    2012-01-01

    Humans and their ancestors have traversed the Ethiopian landscape for millions of years, and present-day Ethiopians show great cultural, linguistic, and historical diversity, which makes them essential for understanding African variability and human origins. We genotyped 235 individuals from ten Ethiopian and two neighboring (South Sudanese and Somali) populations on an Illumina Omni 1M chip. Genotypes were compared with published data from several African and non-African populations. Principal-component and STRUCTURE-like analyses confirmed substantial genetic diversity both within and between populations, and revealed a match between genetic data and linguistic affiliation. Using comparisons with African and non-African reference samples in 40-SNP genomic windows, we identified “African” and “non-African” haplotypic components for each Ethiopian individual. The non-African component, which includes the SLC24A5 allele associated with light skin pigmentation in Europeans, may represent gene flow into Africa, which we estimate to have occurred ∼3 thousand years ago (kya). The non-African component was found to be more similar to populations inhabiting the Levant rather than the Arabian Peninsula, but the principal route for the expansion out of Africa ∼60 kya remains unresolved. Linkage-disequilibrium decay with genomic distance was less rapid in both the whole genome and the African component than in southern African samples, suggesting a less ancient history for Ethiopian populations. PMID:22726845

  16. Fishing for Function in the Human Gene Pool.

    PubMed

    Barozzi, Iros; Visel, Axel; Dickel, Diane E

    2016-07-01

    Identification and characterization of causal non-coding variants in human genomes is challenging and requires substantial experimental resources. A new study by Tehranchi et al. describes a cost-effective approach for accurate mapping of molecular quantitative trait loci (QTLs) from pooled samples, a powerful way to link disease-associated changes to molecular functions. PMID:27220646

  17. Microclimatic differentiation of gene pools in the Lobaria pulmonaria symbiosis in a primeval forest landscape.

    PubMed

    Nadyeina, Olga; Dymytrova, Lyudmyla; Naumovych, Anna; Postoyalkin, Sergyi; Werth, Silke; Cheenacharoen, Saran; Scheidegger, Christoph

    2014-11-01

    Population genetics of the tree-colonizing lichen Lobaria pulmonaria were studied in the largest primeval beech forest of Europe, covering 10 000 ha. During an intensive survey of the area, we collected 1522 thallus fragments originating from 483 trees, which were genotyped with eight mycobiont- and 14 photobiont-specific microsatellite markers. The mycobiont and photobiont of L. pulmonaria were found to consist of two distinct gene pools, which are co-existing within small areas of 3-180 ha in a homogeneous beech forest. The small-scale distribution pattern of the symbiotic gene pools show habitat partitioning of lineages associated with either floodplains or mountain forests. Using approximate Bayesian computation (ABC), we dated the divergence of the two fungal gene pools of L. pulmonaria as the Early Pleistocene. Both fungal gene pools survived the Pleistocene glacial cycles in the Carpathians, although possibly in climatically different refugia. Fungal diversification prior to these cycles and the selection of photobionts with different altitudinal distributions explain the current sympatric, but ecologically differentiated habitat partitioning of L. pulmonaria. In addition, the habitat preferences of the mycobiont are determined by other factors and are rather independent of those of the photobiont at the landscape level. The distinct gene pools should be considered evolutionarily significant units and deserve specific conservation priorities in the future, for example gene pool A, which is a Pliocene relict. PMID:25244617

  18. Population history and gene dispersal inferred from spatial genetic structure of a Central African timber tree, Distemonanthus benthamianus (Caesalpinioideae)

    PubMed Central

    Debout, G D G; Doucet, J-L; Hardy, O J

    2011-01-01

    African rainforests have undergone major distribution range shifts during the Quaternary, but few studies have investigated their impact on the genetic diversity of plant species and we lack knowledge on the extent of gene flow to predict how plant species can cope with such environmental changes. Analysis of the spatial genetic structure (SGS) of a species is an effective method to determine major directions of the demographic history of its populations and to estimate the extent of gene dispersal. This study characterises the SGS of an African tropical timber tree species, Distemonanthus benthamianus, at various spatial scales in Cameroon and Gabon. Displaying a large continuous distribution in the Lower Guinea domain, this is a model species to detect signs of past population fragmentation and recolonization, and to estimate the extent of gene dispersal. Ten microsatellite loci were used to genotype 295 adult trees sampled from eight populations. Three clearly differentiated gene pools were resolved at this regional scale and could be linked to the biogeographical history of the region, rather than to physical barriers to gene flow. A comparison with the distribution of gene pools observed for two other tree species living in the same region invalidates the basic assumption that all species share the same Quaternary refuges and recolonization pathways. In four populations, significant and similar patterns of SGS were detected. Indirect estimates of gene dispersal distances (sigma) obtained for three populations ranged from 400 to 1200 m, whereas neighbourhood size estimates ranged from 50 to 110. PMID:20389306

  19. A Bayesian Model for Pooling Gene Expression Studies That Incorporates Co-Regulation Information

    PubMed Central

    Conlon, Erin M.; Postier, Bradley L.; Methé, Barbara A.; Nevin, Kelly P.; Lovley, Derek R.

    2012-01-01

    Current Bayesian microarray models that pool multiple studies assume gene expression is independent of other genes. However, in prokaryotic organisms, genes are arranged in units that are co-regulated (called operons). Here, we introduce a new Bayesian model for pooling gene expression studies that incorporates operon information into the model. Our Bayesian model borrows information from other genes within the same operon to improve estimation of gene expression. The model produces the gene-specific posterior probability of differential expression, which is the basis for inference. We found in simulations and in biological studies that incorporating co-regulation information improves upon the independence model. We assume that each study contains two experimental conditions: a treatment and control. We note that there exist environmental conditions for which genes that are supposed to be transcribed together lose their operon structure, and that our model is best carried out for known operon structures. PMID:23284902

  20. Epistasis in intra- and inter-gene pool crosses of the common bean.

    PubMed

    Borel, J C; Ramalho, M A P; Abreu, A F B

    2016-01-01

    Epistasis has been shown to have an important role in the genetic control of several quantitative traits in the common bean. This study aimed to investigate the occurrence of epistasis in intra- and inter-pool gene crosses of the common bean. Four elite lines adapted to Brazilian conditions were used as parents, two from the Andean gene pool (ESAL 686; BRS Radiante) and two from the Mesoamerican gene pool (BRSMG Majestoso; BRS Valente). Four F2 populations were obtained: "A" (ESAL 686 x BRS Radiante), "B" (BRSMG Majestoso x BRS Valente), "C" (BRS Radiante x BRSMG Majestoso), and "D" (BRS Valente x ESAL 686). A random sample of F2 plants from each population was backcrossed to parents and F1 individuals, according to the triple test cross. Three types of progenies from each population were evaluated in contiguous trials. Seed yield and 100-seed weight were evaluated. Dominance genetic variance was predominant in most cases. However, the estimates of genetic variance may be biased by the occurrence of linkage disequilibrium and epistasis. Epistasis was detected for both traits; however, the occurrence differed among the populations and between the two traits. The results of this study reinforce the hypothesis that epistasis is present in the genetic control of traits in the common bean and suggest that the phenomenon is more frequent in inter-gene pool crosses than in intra-gene pool crosses. PMID:26985920

  1. Genetic diversity, inter-gene pool introgression and nutritional quality of common beans (Phaseolus vulgaris L.) from Central Africa.

    PubMed

    Blair, Matthew W; González, Laura F; Kimani, Paul M; Butare, Louis

    2010-07-01

    The Great Lakes region of Central Africa is a major producer of common beans in Africa. The region is known for high population density and small average farm size. The common bean represents the most important legume crop of the region, grown on over a third of the cultivated land area, and the per capita consumption is among the highest in the world for the food crop. The objective of this study was to evaluate the genetic diversity in a collection of 365 genotypes from the Great Lakes region of Central Africa, including a large group of landraces from Rwanda as well as varieties from primary centers of diversity and from neighboring countries of Central Africa, such as the Democratic Republic of Congo and Uganda, using 30 fluorescently labeled microsatellite markers and automated allele detection. In addition, the landraces were evaluated for their seed iron and zinc concentration to determine if genetic diversity influenced nutritional quality. Principal coordinate and neighbor-joining analyses allowed the separation of the landraces into 132 Andean and 195 Mesoamerican (or Middle American) genotypes with 32 landraces and 6 varieties intermediate between the gene pools and representing inter-gene pool introgression in terms of seed characteristics and alleles. Genetic diversity and the number of alleles were high for the collection, reflecting the preference for a wide range of seed types in the region and no strong commercial class preference, although red, red mottled and brown seeded beans were common. Observed heterozygosity was also high and may be explained by the common practice of maintaining seed and plant mixtures, a coping strategy practiced by Central African farmers to reduce the effects of abiotic and biotic stresses. Finally, nutritional quality differed between the gene pools with respect to seed iron and zinc concentration, while genotypes from the intermediate group were notably high in both minerals. In conclusion, this study has shown that

  2. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    PubMed Central

    Makarova, Kira S.; Omelchenko, Marina V.; Gaidamakova, Elena K.; Matrosova, Vera Y.; Vasilenko, Alexander; Zhai, Min; Lapidus, Alla; Copeland, Alex; Kim, Edwin; Land, Miriam; Mavromatis, Konstantinos; Pitluck, Samuel; Richardson, Paul M.; Detter, Chris; Brettin, Thomas; Saunders, Elizabeth; Lai, Barry; Ravel, Bruce; Kemner, Kenneth M.; Wolf, Yuri I.; Sorokin, Alexander; Gerasimova, Anna V.; Gelfand, Mikhail S.; Fredrickson, James K.; Koonin, Eugene V.; Daly, Michael J.

    2007-01-01

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  3. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    SciTech Connect

    Makarova, Kira S.; Omelchenko, Marina; Gaidamakova, Elena; Matrosova, Vera; Vasilenko, Alexander; Zhai, Min; Lapidus, Alla L.; Copeland, A; Kim, Edwin; Land, Miriam L; Mavromatis, K; Pitluck, Samual; Richardson, P M; Detter, J. Chris; Brettin, Tom; Saunders, Elizabeth H; Lai, Barry; Ravel, Bruce; Kemner, Kenneth M; Wolf, Yuri; Sorokin, Alexei; Gerasimova, Anna; Gelfand, Mikhail; Fredrickson, James K; Koonin, Eugene; Daly, Michael

    2007-01-01

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  4. Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

    SciTech Connect

    Makarova, Kira S.; Omelchenko, Marina V.; Gaidamakova, Elena K.; Matrosova, Vera Y.; Vasilenko, Alexander; Zhai, Min; Lapidus, Alla; Copeland, Alex; Kim, Edwin; Land, Miriam; Mavrommatis, Konstantinos; Pitluck, Samuel; Richardson, Paul M.; Detter, Chris; Brettin, Thomas; Saunders, Elizabeth; Lai, Barry; Ravel, Bruce; Kemner, Kenneth M.; Wolf, Yuri I.; Sorokin, Alexander; Gerasimova, Anna V.; Gelfand, Mikhail S.; Fredrickson, James K.; Koonin, Eugene V.; Daly, Michael J.

    2007-07-24

    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at itsoptimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

  5. The diverse origins of the human gene pool.

    PubMed

    Pääbo, Svante

    2015-06-01

    Analyses of the genomes of Neanderthals and Denisovans, the closest evolutionary relatives of present-day humans, suggest that our ancestors were part of a web of now-extinct populations linked by limited, but intermittent or sometimes perhaps even persistent, gene flow. PMID:25982166

  6. Redox state of plastoquinone pool regulates expression of Arabidopsis thaliana genes in response to elevated irradiance.

    PubMed

    Adamiec, Małgorzata; Drath, Maria; Jackowski, Grzegorz

    2008-01-01

    DNA microarray technology was applied to gain insight into the role of the redox state of PQ pool as a retrograde factor mediating differential expression of Arabidopsis nuclear genes during the acclimation to changing irradiance. DNA microarray chips containing probes corresponding to 24,000 Arabidopsis nuclear genes were screened with cRNA samples prepared from leaves of plants exposed for 5 h to low irradiance (control) vs. medium, high and excessive irradiances (MI, HI and EI, respectively). Six hundred and sixty three genes were differentially expressed as a result of an exposure to at least one elevated irradiance. Among 663 differentially expressed genes a total of 50 were reverted by DCMU--24 ones modulated at medium irradiance, 32 ones modulated at high irradiance and a single one modulated at excessive irradiance. We postulate that their expression is regulated by redox state of plastoquinone (PQ) pool. Thus the PQ-mediated redox regulation of expression of Arabidopsis nuclear genes is probably limited to the irradiance window representing non-stressing conditions. We found that the promoter regions of the PQ-regulated genes contained conserved elements, suggesting transcriptional control by a shared set of trans-acting factors which participate in signal transduction from the redox state of the PQ pool. PMID:18231654

  7. From single-cell to cell-pool transcriptomes: stochasticity in gene expression and RNA splicing.

    PubMed

    Marinov, Georgi K; Williams, Brian A; McCue, Ken; Schroth, Gary P; Gertz, Jason; Myers, Richard M; Wold, Barbara J

    2014-03-01

    Single-cell RNA-seq mammalian transcriptome studies are at an early stage in uncovering cell-to-cell variation in gene expression, transcript processing and editing, and regulatory module activity. Despite great progress recently, substantial challenges remain, including discriminating biological variation from technical noise. Here we apply the SMART-seq single-cell RNA-seq protocol to study the reference lymphoblastoid cell line GM12878. By using spike-in quantification standards, we estimate the absolute number of RNA molecules per cell for each gene and find significant variation in total mRNA content: between 50,000 and 300,000 transcripts per cell. We directly measure technical stochasticity by a pool/split design and find that there are significant differences in expression between individual cells, over and above technical variation. Specific gene coexpression modules were preferentially expressed in subsets of individual cells, including one enriched for mRNA processing and splicing factors. We assess cell-to-cell variation in alternative splicing and allelic bias and report evidence of significant differences in splice site usage that exceed splice variation in the pool/split comparison. Finally, we show that transcriptomes from small pools of 30-100 cells approach the information content and reproducibility of contemporary RNA-seq from large amounts of input material. Together, our results define an experimental and computational path forward for analyzing gene expression in rare cell types and cell states. PMID:24299736

  8. Pooled Sequencing of Candidate Genes Implicates Rare Variants in the Development of Asthma Following Severe RSV Bronchiolitis in Infancy

    PubMed Central

    Torgerson, Dara G.; Giri, Tusar; Druley, Todd E.; Zheng, Jie; Huntsman, Scott; Seibold, Max A.; Young, Andrew L.; Schweiger, Toni; Yin-Declue, Huiqing; Sajol, Geneline D.; Schechtman, Kenneth B; Hernandez, Ryan D.; Randolph, Adrienne G.; Bacharier, Leonard B.; Castro, Mario

    2015-01-01

    Severe infection with respiratory syncytial virus (RSV) during infancy is strongly associated with the development of asthma. To identify genetic variation that contributes to asthma following severe RSV bronchiolitis during infancy, we sequenced the coding exons of 131 asthma candidate genes in 182 European and African American children with severe RSV bronchiolitis in infancy using anonymous pools for variant discovery, and then directly genotyped a set of 190 nonsynonymous variants. Association testing was performed for physician-diagnosed asthma before the 7th birthday (asthma) using genotypes from 6,500 individuals from the Exome Sequencing Project (ESP) as controls to gain statistical power. In addition, among patients with severe RSV bronchiolitis during infancy, we examined genetic associations with asthma, active asthma, persistent wheeze, and bronchial hyperreactivity (methacholine PC20) at age 6 years. We identified four rare nonsynonymous variants that were significantly associated with asthma following severe RSV bronchiolitis, including single variants in ADRB2, FLG and NCAM1 in European Americans (p = 4.6x10-4, 1.9x10-13 and 5.0x10-5, respectively), and NOS1 in African Americans (p = 2.3x10-11). One of the variants was a highly functional nonsynonymous variant in ADRB2 (rs1800888), which was also nominally associated with asthma (p = 0.027) and active asthma (p = 0.013) among European Americans with severe RSV bronchiolitis without including the ESP. Our results suggest that rare nonsynonymous variants contribute to the development of asthma following severe RSV bronchiolitis in infancy, notably in ADRB2. Additional studies are required to explore the role of rare variants in the etiology of asthma and asthma-related traits following severe RSV bronchiolitis. PMID:26587832

  9. Demographic history of Canary Islands male gene-pool: replacement of native lineages by European

    PubMed Central

    Fregel, Rosa; Gomes, Verónica; Gusmão, Leonor; González, Ana M; Cabrera, Vicente M; Amorim, António; Larruga, Jose M

    2009-01-01

    Background The origin and prevalence of the prehispanic settlers of the Canary Islands has attracted great multidisciplinary interest. However, direct ancient DNA genetic studies on indigenous and historical 17th–18th century remains, using mitochondrial DNA as a female marker, have only recently been possible. In the present work, the analysis of Y-chromosome polymorphisms in the same samples, has shed light on the way the European colonization affected male and female Canary Island indigenous genetic pools, from the conquest to present-day times. Results Autochthonous (E-M81) and prominent (E-M78 and J-M267) Berber Y-chromosome lineages were detected in the indigenous remains, confirming a North West African origin for their ancestors which confirms previous mitochondrial DNA results. However, in contrast with their female lineages, which have survived in the present-day population since the conquest with only a moderate decline, the male indigenous lineages have dropped constantly being substituted by European lineages. Male and female sub-Saharan African genetic inputs were also detected in the Canary population, but their frequencies were higher during the 17th–18th centuries than today. Conclusion The European colonization of the Canary Islands introduced a strong sex-biased change in the indigenous population in such a way that indigenous female lineages survived in the extant population in a significantly higher proportion than their male counterparts. PMID:19650893

  10. Comparison of nifH Gene Pools in Soils and Soil Microenvironments with Contrasting Properties

    PubMed Central

    Poly, Franck; Ranjard, Lionel; Nazaret, Sylvie; Gourbière, François; Monrozier, Lucile Jocteur

    2001-01-01

    The similarities and differences in the structures of the nifH gene pools of six different soils (Montrond, LCSA-p, Vernon, Dombes, LCSA-c, and Thysse Kaymor) and five soil fractions extracted from LCSA-c were studied. Bacterial DNA was directly extracted from the soils, and a region of the nifH gene was amplified by PCR and analyzed by restriction. Soils were selected on the basis of differences in soil management, plant cover, and major physicochemical properties. Microenvironments differed on the basis of the sizes of the constituent particles and the organic carbon and clay contents. Restriction profiles were subjected to principal-component analysis. We showed that the composition of the diazotrophic communities varied both on a large scale (among soils) and on a microscale (among microenvironments in LCSA-c soil). Soil management seemed to be the major parameter influencing differences in the nifH gene pool structure among soils by controlling inorganic nitrogen content and its variation. However, physicochemical parameters (texture and total C and N contents) were found to correlate with differences among nifH gene pools on a microscale. We hypothesize that the observed nifH genetic structures resulted from the adaptation to fluctuating conditions (cultivated soil, forest soil, coarse fractions) or constant conditions (permanent pasture soil, fine fractions). We attempted to identify a specific band within the profile of the clay fraction by cloning and sequencing it and comparing it with the gene databases. Unexpectedly, the nifH sequences of the dominant bacteria were most similar to sequences of unidentified marine eubacteria. PMID:11319109

  11. Nucleotide Pool Depletion Induces G-Quadruplex-Dependent Perturbation of Gene Expression

    PubMed Central

    Papadopoulou, Charikleia; Guilbaud, Guillaume; Schiavone, Davide; Sale, Julian E.

    2015-01-01

    Summary Nucleotide pool imbalance has been proposed to drive genetic instability in cancer. Here, we show that slowing replication forks by depleting nucleotide pools with hydroxyurea (HU) can also give rise to both transient and permanent epigenetic instability of a reporter locus, BU-1, in DT40 cells. HU induces stochastic formation of Bu-1low variants in dividing cells, which have lost the H3K4me3 present in untreated cells. This instability is potentiated by an intragenic G quadruplex, which also promotes local H2Ax phosphorylation and transient heterochromatinization. Genome-wide, gene expression changes induced by HU significantly overlap with those resulting from loss of the G4-helicases FANCJ, WRN, and BLM. Thus, the effects of global replication stress induced by nucleotide pool depletion can be focused by local replication impediments caused by G quadruplex formation to induce epigenetic instability and changes in gene expression, a mechanism that may contribute to selectable transcriptional changes in cancer. PMID:26686635

  12. Differential Natural Selection of Human Zinc Transporter Genes between African and Non-African Populations.

    PubMed

    Zhang, Chao; Li, Jing; Tian, Lei; Lu, Dongsheng; Yuan, Kai; Yuan, Yuan; Xu, Shuhua

    2015-01-01

    Zinc transporters play important roles in all eukaryotes by maintaining the rational zinc concentration in cells. However, the diversity of zinc transporter genes (ZTGs) remains poorly studied. Here, we investigated the genetic diversity of 24 human ZTGs based on the 1000 Genomes data. Some ZTGs show small population differences, such as SLC30A6 with a weighted-average FST (WA-FST = 0.015), while other ZTGs exhibit considerably large population differences, such as SLC30A9 (WA-FST = 0.284). Overall, ZTGs harbor many more highly population-differentiated variants compared with random genes. Intriguingly, we found that SLC30A9 was underlying natural selection in both East Asians (EAS) and Africans (AFR) but in different directions. Notably, a non-synonymous variant (rs1047626) in SLC30A9 is almost fixed with 96.4% A in EAS and 92% G in AFR, respectively. Consequently, there are two different functional haplotypes exhibiting dominant abundance in AFR and EAS, respectively. Furthermore, a strong correlation was observed between the haplotype frequencies of SLC30A9 and distributions of zinc contents in soils or crops. We speculate that the genetic differentiation of ZTGs could directly contribute to population heterogeneity in zinc transporting capabilities and local adaptations of human populations in regard to the local zinc state or diets, which have both evolutionary and medical implications. PMID:25927708

  13. [Book review] Fish Gene Pools: preservation of genetic resources in relation to wild fish stocks, edited by N. Ryman

    USGS Publications Warehouse

    Simon, R.C.

    1984-01-01

    Review of: Fish Gene Pools: Preservation of Genetic Resources in Relation to Wild Fish Stocks. Edited by N. Ryman. The Editorial Service/FRN, Box 6710, S-11385, Stockholm, Sweden. 1981. 111 pages. $16.00 (paper).

  14. Phenotype Sequencing: Identifying the Genes That Cause a Phenotype Directly from Pooled Sequencing of Independent Mutants

    PubMed Central

    Harper, Marc A.; Chen, Zugen; Toy, Traci; Machado, Iara M. P.; Nelson, Stanley F.; Liao, James C.; Lee, Christopher J.

    2011-01-01

    Random mutagenesis and phenotype screening provide a powerful method for dissecting microbial functions, but their results can be laborious to analyze experimentally. Each mutant strain may contain 50–100 random mutations, necessitating extensive functional experiments to determine which one causes the selected phenotype. To solve this problem, we propose a “Phenotype Sequencing” approach in which genes causing the phenotype can be identified directly from sequencing of multiple independent mutants. We developed a new computational analysis method showing that 1. causal genes can be identified with high probability from even a modest number of mutant genomes; 2. costs can be cut many-fold compared with a conventional genome sequencing approach via an optimized strategy of library-pooling (multiple strains per library) and tag-pooling (multiple tagged libraries per sequencing lane). We have performed extensive validation experiments on a set of E. coli mutants with increased isobutanol biofuel tolerance. We generated a range of sequencing experiments varying from 3 to 32 mutant strains, with pooling on 1 to 3 sequencing lanes. Our statistical analysis of these data (4099 mutations from 32 mutant genomes) successfully identified 3 genes (acrB, marC, acrA) that have been independently validated as causing this experimental phenotype. It must be emphasized that our approach reduces mutant sequencing costs enormously. Whereas a conventional genome sequencing experiment would have cost $7,200 in reagents alone, our Phenotype Sequencing design yielded the same information value for only $1200. In fact, our smallest experiments reliably identified acrB and marC at a cost of only $110–$340. PMID:21364744

  15. Two endornaviruses show differential infection patterns between gene pools of Phaseolus vulgaris.

    PubMed

    Khankhum, Surasak; Valverde, Rodrigo A; Pastor-Corrales, Marcial A; Osorno, Juan M; Sabanadzovic, Sead

    2015-04-01

    We investigated the occurrence of two plant endornaviruses, Phaseolus vulgaris endornavirus 1 and Phaseolus vulgaris endornavirus 2, in breeding lines, cultivars, landraces, and wild genotypes of common bean (Phaseolus vulgaris) collected from the two centers of common bean domestication: Mesoamerica and the Andes. The two endornaviruses were detected in many genotypes of Mesoamerican origin but rarely in genotypes of Andean origin. The results suggest that these two endornaviruses were introduced into the Mesoamerican modern genotypes during common bean domestication and provide more evidence for the existence of two divergent gene pools of common bean. PMID:25623050

  16. Gene targets of mouse miR-709: regulation of distinct pools

    PubMed Central

    Surendran, Sneha; Jideonwo, Victoria N.; Merchun, Chris; Ahn, Miwon; Murray, John; Ryan, Jennifer; Dunn, Kenneth W.; Kota, Janaiah; Morral, Núria

    2016-01-01

    MicroRNA (miRNA) are short non-coding RNA molecules that regulate multiple cellular processes, including development, cell differentiation, proliferation and death. Nevertheless, little is known on whether miRNA control the same gene networks in different tissues. miR-709 is an abundant miRNA expressed ubiquitously. Through transcriptome analysis, we have identified targets of miR-709 in hepatocytes. miR-709 represses genes implicated in cytoskeleton organization, extracellular matrix attachment, and fatty acid metabolism. Remarkably, none of the previously identified targets in non-hepatic tissues are silenced by miR-709 in hepatocytes, even though several of these genes are abundantly expressed in liver. In addition, miR-709 is upregulated in hepatocellular carcinoma, suggesting it participates in the genetic reprogramming that takes place during cell division, when cytoskeleton remodeling requires substantial changes in gene expression. In summary, the present study shows that miR-709 does not repress the same pool of genes in separate cell types. These results underscore the need for validating gene targets in every tissue a miRNA is expressed. PMID:26743462

  17. First microbiota assessments of children's paddling pool waters evaluated using 16S rRNA gene-based metagenome analysis.

    PubMed

    Sawabe, Toko; Suda, Wataru; Ohshima, Kenshiro; Hattori, Masahira; Sawabe, Tomoo

    2016-01-01

    Insufficient chloric sterilization of children's paddling pool waters increases the risk of diarrheal illness. Therefore, we investigated the microbiota changes after children use pools. First, we applied 16S rRNA gene-based metagenome analysis to understand the dynamics of microbiota in pool water, especially with respect to the bio-contamination by potential pathogens. Proteobacteria were major taxa detected in every pool water sample after children spent time in the pool. In more detail, Gammaproteobacteria comprised the dominant class, which was followed by Betaproteobacteria. Five phyla, Bacteroidetes, Firmicutes, Actinobacteria and Deinococcus-Thermus phyla were minor groups. The pool water microbiota are likely to be a consortium of intestinal and skin microbiota from humans. Interestingly, the ratio of Gammaproteobacteria and Betaproteobacteria differed according to the age of the children who used the pool, which means the pool water was additionally contaminated by soil microbiota as a result of the children's behavior. Furthermore, potential pathogens, such as Campylobacter spp., Comamonas testosteroni and Burkholderia pseudomallei, were also found. Considering the standard plate counts, the abundances of these human pathogens are unlikely to be a sufficiently infectious dose. We suggest the importance of sanitary measures in paddling pool waters to reduce bio-contamination from both humans and the environment. PMID:26671497

  18. Genome-wide signatures of male-mediated migration shaping the Indian gene pool.

    PubMed

    ArunKumar, GaneshPrasad; Tatarinova, Tatiana V; Duty, Jeff; Rollo, Debra; Syama, Adhikarla; Arun, Varatharajan Santhakumari; Kavitha, Valampuri John; Triska, Petr; Greenspan, Bennett; Wells, R Spencer; Pitchappan, Ramasamy

    2015-09-01

    Multiple questions relating to contributions of cultural and demographical factors in the process of human geographical dispersal remain largely unanswered. India, a land of early human settlement and the resulting diversity is a good place to look for some of the answers. In this study, we explored the genetic structure of India using a diverse panel of 78 males genotyped using the GenoChip. Their genome-wide single-nucleotide polymorphism (SNP) diversity was examined in the context of various covariates that influence Indian gene pool. Admixture analysis of genome-wide SNP data showed high proportion of the Southwest Asian component in all of the Indian samples. Hierarchical clustering based on admixture proportions revealed seven distinct clusters correlating to geographical and linguistic affiliations. Convex hull overlay of Y-chromosomal haplogroups on the genome-wide SNP principal component analysis brought out distinct non-overlapping polygons of F*-M89, H*-M69, L1-M27, O2a-M95 and O3a3c1-M117, suggesting a male-mediated migration and expansion of the Indian gene pool. Lack of similar correlation with mitochondrial DNA clades indicated a shared genetic ancestry of females. We suggest that ancient male-mediated migratory events and settlement in various regional niches led to the present day scenario and peopling of India. PMID:25994871

  19. Genomics of crop wild relatives: expanding the gene pool for crop improvement.

    PubMed

    Brozynska, Marta; Furtado, Agnelo; Henry, Robert J

    2016-04-01

    Plant breeders require access to new genetic diversity to satisfy the demands of a growing human population for more food that can be produced in a variable or changing climate and to deliver the high-quality food with nutritional and health benefits demanded by consumers. The close relatives of domesticated plants, crop wild relatives (CWRs), represent a practical gene pool for use by plant breeders. Genomics of CWR generates data that support the use of CWR to expand the genetic diversity of crop plants. Advances in DNA sequencing technology are enabling the efficient sequencing of CWR and their increased use in crop improvement. As the sequencing of genomes of major crop species is completed, attention has shifted to analysis of the wider gene pool of major crops including CWR. A combination of de novo sequencing and resequencing is required to efficiently explore useful genetic variation in CWR. Analysis of the nuclear genome, transcriptome and maternal (chloroplast and mitochondrial) genome of CWR is facilitating their use in crop improvement. Genome analysis results in discovery of useful alleles in CWR and identification of regions of the genome in which diversity has been lost in domestication bottlenecks. Targeting of high priority CWR for sequencing will maximize the contribution of genome sequencing of CWR. Coordination of global efforts to apply genomics has the potential to accelerate access to and conservation of the biodiversity essential to the sustainability of agriculture and food production. PMID:26311018

  20. Evaluation of human gene variant detection in amplicon pools by the GS-FLX parallel Pyrosequencer

    PubMed Central

    Bordoni, Roberta; Bonnal, Raoul; Rizzi, Ermanno; Carrera, Paola; Benedetti, Sara; Cremonesi, Laura; Stenirri, Stefania; Colombo, Alessio; Montrasio, Cristina; Bonalumi, Sara; Albertini, Alberto; Bernardi, Luigi Rossi; Ferrari, Maurizio; De Bellis, Gianluca

    2008-01-01

    Background A new priority in genome research is large-scale resequencing of genes to understand the molecular basis of hereditary disease and cancer. We assessed the ability of massively parallel pyrosequencing to identify sequence variants in pools. From a large collection of human PCR samples we selected 343 PCR products belonging to 16 disease genes and including a large spectrum of sequence variations previously identified by Sanger sequencing. The sequence variants included SNPs and small deletions and insertions (up to 44 bp), in homozygous or heterozygous state. Results The DNA was combined in 4 pools containing from 27 to 164 amplicons and from 8,9 to 50,8 Kb to sequence for a total of 110 Kb. Pyrosequencing generated over 80 million base pairs of data. Blind searching for sequence variations with a specifically designed bioinformatics procedure identified 465 putative sequence variants, including 412 true variants, 53 false positives (in or adjacent to homopolymeric tracts), no false negatives. All known variants in positions covered with at least 30× depth were correctly recognized. Conclusion Massively parallel pyrosequencing may be used to simplify and speed the search for DNA variations in PCR products. Our results encourage further studies to evaluate molecular diagnostics applications. PMID:18842124

  1. The Polynesian gene pool: an early contribution by Amerindians to Easter Island

    PubMed Central

    Thorsby, Erik

    2012-01-01

    It is now generally accepted that Polynesia was first settled by peoples from southeast Asia. An alternative that eastern parts of Polynesia were first inhabited by Amerindians has found little support. There are, however, many indications of a ‘prehistoric’ (i.e. before Polynesia was discovered by Europeans) contact between Polynesia and the Americas, but genetic evidence of a prehistoric Amerindian contribution to the Polynesian gene pool has been lacking. We recently carried out genomic HLA (human leucocyte antigen) typing as well as typing for mitochondrial DNA (mtDNA) and Y chromosome markers of blood samples collected in 1971 and 2008 from reputedly non-admixed Easter Islanders. All individuals carried HLA alleles and mtDNA types previously found in Polynesia, and most of the males carried Y chromosome markers of Polynesian origin (a few had European Y chromosome markers), further supporting an initial Polynesian population on Easter Island. The HLA investigations revealed, however, that some individuals also carried HLA alleles which have previously almost only been found in Amerindians. We could trace the introduction of these Amerindian alleles to before the Peruvian slave trades, i.e. before the 1860s, and provide suggestive evidence that they were introduced already in prehistoric time. Our results demonstrate an early Amerindian contribution to the Polynesian gene pool on Easter Island, and illustrate the usefulness of typing for immunogenetic markers such as HLA to complement mtDNA and Y chromosome analyses in anthropological investigations. PMID:22312048

  2. Saturation of an intra-gene pool linkage map: toward unified consensus linkage map in common bean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Map-based cloning to find genes of interest and marker assisted selection (MAS) requires good genetic maps with high reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers in includin...

  3. Rapid Mutation of Endogenous Zebrafish Genes Using Zinc Finger Nucleases Made by Oligomerized Pool ENgineering (OPEN)

    PubMed Central

    Maeder, Morgan L.; Reyon, Deepak; Sander, Jeffry D.; Peterson, Randall T.; Joung, J. Keith

    2009-01-01

    Background Customized zinc finger nucleases (ZFNs) form the basis of a broadly applicable tool for highly efficient genome modification. ZFNs are artificial restriction endonucleases consisting of a non-specific nuclease domain fused to a zinc finger array which can be engineered to recognize specific DNA sequences of interest. Recent proof-of-principle experiments have shown that targeted knockout mutations can be efficiently generated in endogenous zebrafish genes via non-homologous end-joining-mediated repair of ZFN-induced DNA double-stranded breaks. The Zinc Finger Consortium, a group of academic laboratories committed to the development of engineered zinc finger technology, recently described the first rapid, highly effective, and publicly available method for engineering zinc finger arrays. The Consortium has previously used this new method (known as OPEN for Oligomerized Pool ENgineering) to generate high quality ZFN pairs that function in human and plant cells. Methodology/Principal Findings Here we show that OPEN can also be used to generate ZFNs that function efficiently in zebrafish. Using OPEN, we successfully engineered ZFN pairs for five endogenous zebrafish genes: tfr2, dopamine transporter, telomerase, hif1aa, and gridlock. Each of these ZFN pairs induces targeted insertions and deletions with high efficiency at its endogenous gene target in somatic zebrafish cells. In addition, these mutations are transmitted through the germline with sufficiently high frequency such that only a small number of fish need to be screened to identify founders. Finally, in silico analysis demonstrates that one or more potential OPEN ZFN sites can be found within the first three coding exons of more than 25,000 different endogenous zebrafish gene transcripts. Conclusions and Significance In summary, our study nearly triples the total number of endogenous zebrafish genes successfully modified using ZFNs (from three to eight) and suggests that OPEN provides a reliable

  4. Gene Flow Among Different Teosinte Taxa and Into the Domesticated Maize Gene Pool

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize (Zea mays ssp. mays) was domesticated from one wild species ancestor, the Balsas teosinte (Zea mays ssp. parviglumis) about 9000 years ago. Higher levels of gene diversity are found in teosinte taxa compared to maize following domestication and selection bottlenecks. Diversity in maize can b...

  5. [Comparative Estimate of the Sheep Breed Gene Pools using ISSR Analysis].

    PubMed

    Nesteruk, L V; Makarova, N N; Evsyukov, A N; Svishcheva, G R; Lhasaranov, B B; Stolpovsky, Yu A

    2016-03-01

    Using the ISSR-PCR technique, the genetic structure of nine sheep breeds (Ovis aries) bred on the territories of Russia and Mongolia was examined. Species-specific and breed-specific DNA fragments were identified. For the first time, data on the genetic diversity of Telengit and Buubey sheep breeds were obtained. The main parameters of the genetic diversity and the breed structure were assessed, and the phylogenetic relationships and genetic distances between the studied breeds were determined. Using the method of hierarchical frequency averaging, the prototypal sheep gene pool was reconstructed. The three-tiered analysis of diversity based on the ISSR fingerprinting data showed that 15.8% of variability was found between the breeds, 31.4% of variability was found between the populations within the breeds, and the diversity among the individuals within the populations constituted 52.8%. PMID:27281855

  6. High-density SNP genotyping array for hexaploid wheat and its secondary and tertiary gene pool.

    PubMed

    Winfield, Mark O; Allen, Alexandra M; Burridge, Amanda J; Barker, Gary L A; Benbow, Harriet R; Wilkinson, Paul A; Coghill, Jane; Waterfall, Christy; Davassi, Alessandro; Scopes, Geoff; Pirani, Ali; Webster, Teresa; Brew, Fiona; Bloor, Claire; King, Julie; West, Claire; Griffiths, Simon; King, Ian; Bentley, Alison R; Edwards, Keith J

    2016-05-01

    In wheat, a lack of genetic diversity between breeding lines has been recognized as a significant block to future yield increases. Species belonging to bread wheat's secondary and tertiary gene pools harbour a much greater level of genetic variability, and are an important source of genes to broaden its genetic base. Introgression of novel genes from progenitors and related species has been widely employed to improve the agronomic characteristics of hexaploid wheat, but this approach has been hampered by a lack of markers that can be used to track introduced chromosome segments. Here, we describe the identification of a large number of single nucleotide polymorphisms that can be used to genotype hexaploid wheat and to identify and track introgressions from a variety of sources. We have validated these markers using an ultra-high-density Axiom(®) genotyping array to characterize a range of diploid, tetraploid and hexaploid wheat accessions and wheat relatives. To facilitate the use of these, both the markers and the associated sequence and genotype information have been made available through an interactive web site. PMID:26466852

  7. Pre-breeding for diversification of primary gene pool and genetic enhancement of grain legumes

    PubMed Central

    Sharma, Shivali; Upadhyaya, H. D.; Varshney, R. K.; Gowda, C. L. L.

    2013-01-01

    The narrow genetic base of cultivars coupled with low utilization of genetic resources are the major factors limiting grain legume production and productivity globally. Exploitation of new and diverse sources of variation is needed for the genetic enhancement of grain legumes. Wild relatives with enhanced levels of resistance/tolerance to multiple stresses provide important sources of genetic diversity for crop improvement. However, their exploitation for cultivar improvement is limited by cross-incompatibility barriers and linkage drags. Pre-breeding provides a unique opportunity, through the introgression of desirable genes from wild germplasm into genetic backgrounds readily used by the breeders with minimum linkage drag, to overcome this. Pre-breeding activities using promising landraces, wild relatives, and popular cultivars have been initiated at International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) to develop new gene pools in chickpea, pigeonpea, and groundnut with a high frequency of useful genes, wider adaptability, and a broad genetic base. The availability of molecular markers will greatly assist in reducing linkage drags and increasing the efficiency of introgression in pre-breeding programs. PMID:23970889

  8. Comparison of microsatellite variations between Red Junglefowl and a commercial chicken gene pool.

    PubMed

    Tadano, R; Kinoshita, K; Mizutani, M; Tsudzuki, M

    2014-02-01

    It is assumed that Red Junglefowl (Gallus gallus) is one of the main ancestors of domestic chickens (Gallus gallus domesticus). Differences in microsatellite polymorphisms between Red Junglefowl and modern commercial chickens, which are used for egg and meat production, have not been fully reported. A total of 361 individuals from 1 Red Junglefowl population that has been maintained as a closed flock, 5 final cross-bred commercial layer populations (white-, tinted-, and brown-egg layers), and 2 final cross-bred commercial broiler populations were genotyped for 40 autosomal microsatellite loci. We compared microsatellite variations in Red Junglefowl with those in a commercial chicken gene pool. The contribution of each population to the genetic diversity was also estimated based on the molecular coancestry. In total, 302 distinct alleles were detected in 1 Red Junglefowl and 7 commercial chicken populations, of which 31 alleles (10.3%) were unique to Red Junglefowl, most of which occurred at a high frequency. The genetic differentiation between Red Junglefowl and commercial chickens (pairwise FST) ranged from 0.32 to 0.47. According to the neighbor-joining tree based on the modified Cavalli-Sforza chord distances and the Bayesian clustering analysis, Red Junglefowl was genetically distant from the commercial chicken gene pool tested. In all of the populations analyzed, Red Junglefowl made the highest contribution to genetic diversity. These results suggest that Red Junglefowl has a distinct distribution of microsatellite alleles and that there is a high level of genetic divergence between Red Junglefowl and commercial chickens. PMID:24570452

  9. Distinction between wild and cultivated enset (Ensete ventricosum) gene pools in Ethiopia using RAPD markers.

    PubMed

    Birmeta, Genet; Nybom, Hilde; Bekele, Endashaw

    2004-01-01

    In southwest Ethiopia, the cultivation area of Ensete ventricosum (enset) overlaps with the natural distribution area of this species. Analyses of genetic diversity were undertaken using RAPD to provide information for conservation strategies as well as evidence of possible gene flow between the different gene pools, which can be of interest for future improvement of cultivated enset. The extent of RAPD variation in wild enset was investigated in 5 populations in the Bonga area (Kefficho administrative region) and 9 cultivated clones. Comparisons were also made with some Musa samples of potential relevance for crop improvement. Nine oligonucleotide primers amplified 72 polymorphic loci. Population differentiation was estimated with the Shannon index (G'(ST)=0.10), Nei's G(ST) (0.12) and AMOVA (Phi(ST)=0.12), and appears to be relatively low when compared with outbreeding, perennial species in general. Cluster analysis (UPGMA) and principal component analysis (PCA) similarly indicated low population differentiation, and also demonstrated that cultivated clones essentially clustered distinctly from wild enset samples, suggesting that the present-day cultivated enset clones have been introduced to domestication from a limited number of wild progenitors. In addition, subsequent gene flow between wild and cultivated enset may have been prohibited by differences between modes of propagation and harvesting time; cultivated enset is propagated vegetatively through sucker production and the plant is generally harvested before maturity or flower set, thereby hindering pollination by wild enset or vice versa. A significant correlation was not found between genetic and geographical distances. The relatively high total RAPD diversity suggests that wild enset populations in the Bonga area harbour genetic variability which could potentially act as a source for useful or rare genes in the improvement of cultivated enset. As expected, E. ventricosum was clearly differentiated from

  10. Changes in gravity affect gene expression, protein modulation and metabolite pools of arabidopsis

    NASA Astrophysics Data System (ADS)

    Hampp, R.; Martzivanou, M.; Maier, R. M.; Magel, E.

    ), we investigated samples from sounding rocket experiments (5 min μ g) and show increased transcript levels for signalling proteins. By means of 2-dimensional SDS polyacrylamide gelelectrophoresis, coupled to spot identification after tryptic digest (MALDI-TOF), we further show that metabolic short-term responses can be adjusted by protein phosphorylation/dephosphorylation. Changes in gene expression / protein modulation are mirrored by respective alterations in metabolite pools. (Supported by a grant from the Deutsches Zentrum für Luft- und Raumfahrt (DLR, 50WB0143)).

  11. T cell receptor gene deletion circles identify recent thymic emigrants in the peripheral T cell pool

    PubMed Central

    Kong, Fan-kun; Chen, Chen-lo H.; Six, Adrien; Hockett, Richard D.; Cooper, Max D.

    1999-01-01

    Progenitor cells undergo T cell receptor (TCR) gene rearrangements during their intrathymic differentiation to become T cells. Rearrangements of the variable (V), diversity (D), and joining (J) segments of the TCR genes result in deletion of the intervening chromosomal DNA and the formation of circular episomes as a byproduct. Detection of these extrachromosomal excision circles in T cells located in the peripheral lymphoid tissues has been viewed as evidence for the existence of extrathymic T cell generation. Because all of the T cells in chickens apparently are generated in the thymus, we have employed this avian model to determine the fate of the V(D)J deletion circles. In normal animals we identified TCR Vγ-Jγ and Vβ-Dβ deletion circles in the blood, spleen, and intestines, as well as in the thymus. Thymectomy resulted in the gradual loss of these DNA deletion circles in all of the peripheral lymphoid tissues. A quantitative PCR analysis of Vγ1-Jγ1 and Vβ1-Dβ deletion circles in splenic γδ and Vβ1+ αβ T cells indicated that their numbers progressively decline after thymectomy with a half-life of approximately 2 weeks. Although TCR deletion circles therefore cannot be regarded as reliable indicators of in situ V(D)J rearrangement, measuring their levels in peripheral T cell samples can provide a valuable index of newly generated T cells entering the T cell pool. PMID:9990059

  12. Clines of nuclear DNA markers suggest a largely neolithic ancestry of the European gene pool.

    PubMed

    Chikhi, L; Destro-Bisol, G; Bertorelle, G; Pascali, V; Barbujani, G

    1998-07-21

    Comparisons between archaeological findings and allele frequencies at protein loci suggest that most genes of current Europeans descend from populations that have been expanding in Europe in the last 10, 000 years, in the Neolithic period. Recent mitochondrial data have been interpreted as indicating a much older, Paleolithic ancestry. In a spatial autocorrelation study at seven hypervariable loci in Europe (four microsatellites, two larger, tandem-repeat loci, and a sequence polymorphism) broad clinal patterns of DNA variation were recognized. The observed clines closely match those described at the protein level, in agreement with a possible Near Eastern origin for the ancestral population. Separation times between populations were estimated on the basis of a stepwise mutation model. Even assuming low mutation rates and long generation times, we found no evidence for population splits older than 10,000 years, with the predictable exception of Saami (Lapps). The simplest interpretation of these results is that the current nuclear gene pool largely reflects the westward and northward expansion of a Neolithic group. This conclusion is now supported by purely genetic evidence on the levels and patterns of microsatellite diversity, rather than by correlations of biological and nonbiological data. We argue that many mitochondrial lineages whose origin has been traced back to the Paleolithic period probably reached Europe at a later time. PMID:9671803

  13. Nonblack patients with sickle cell disease have African. beta. sup s gene cluster haplotypes

    SciTech Connect

    Rogers, Z.R.; Powars, D.R.; Williams, W.D. ); Kinney, T.R. ); Schroeder, W.A. )

    1989-05-26

    Of 18 nonblack patients with sickle cell disease, 14 had sickle cell anemia, 2 had hemoglobin SC disease, and 2 had hemoglobin S-{beta}{sup o}-thalassemia. The {beta}{sup s} gene cluster haplotypes that were determined in 7 patients were of African origin and were identified as Central African Republic, Central African Republic minor II, Benin, and Senegal. The haplotype Central African Republic minor II was present on the {beta}{sup o}-thalassemia chromosome in 2 patients. None of 10 patients whose {alpha}-gene status was determined had {alpha}-thalassemia-2. These data strongly support the concept that the {beta}{sup s} gene on chromosome 11 of these individuals is of African origin and that the {alpha}-gene locus on chromosome 16 is of white or native American origin. The clinical severity of the disease in these nonblack patients is appropriate to their haplotype without {alpha}-thalassemia-2 and is comparable with that of black patients. All persons with congenital hemolytic anemia should be examined for the presence of sickle cell disease regardless of physical appearance or ethnic background.

  14. Training Quantitative Thinkers by Using Spreadsheets as Simulation Drivers for Biology Classes: Selective Predation Effect on Prey Gene Pool.

    ERIC Educational Resources Information Center

    Porter, Tom

    1996-01-01

    Describes the use of a spreadsheet in running a hands-on prey/predator simulation that enables students to see the effect of selection pressure on one allele in a gene pool. Discusses setting up and running the simulation, class discussion issues, exploring assumptions, and extensions. (JRH)

  15. Extensive SSR genotyping of potato landraces supports a drastic revaluation of their gene pool structure and classification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cultivated potato is one of the most important food plants worldwide, yet knowledge of the gene pool structure of the native South American landraces remains largely uninvestigated and is controversial. As a result, contrasting taxonomic treatments of the landraces have continued over the last c...

  16. The History of African Gene Flow into Southern Europeans, Levantines, and Jews

    PubMed Central

    Moorjani, Priya; Patterson, Nick; Hirschhorn, Joel N.; Keinan, Alon; Hao, Li; Atzmon, Gil; Burns, Edward; Ostrer, Harry; Price, Alkes L.; Reich, David

    2011-01-01

    Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%–3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%–15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%–5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas. PMID:21533020

  17. The history of African gene flow into Southern Europeans, Levantines, and Jews.

    PubMed

    Moorjani, Priya; Patterson, Nick; Hirschhorn, Joel N; Keinan, Alon; Hao, Li; Atzmon, Gil; Burns, Edward; Ostrer, Harry; Price, Alkes L; Reich, David

    2011-04-01

    Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%-3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%-15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%-5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas. PMID:21533020

  18. Gene-gene interaction between tuberculosis candidate genes in a South African population.

    PubMed

    de Wit, Erika; van der Merwe, Lize; van Helden, Paul D; Hoal, Eileen G

    2011-02-01

    In a complex disease such as tuberculosis (TB) it is increasingly evident that gene-gene interactions play a far more important role in an individual's susceptibility to develop the disease than single polymorphisms on their own, as one gene can enhance or hinder the expression of another gene. Gene-gene interaction analysis is a new approach to elucidate susceptibility to TB. The possibility of gene-gene interactions was assessed, focusing on 11 polymorphisms in nine genes (DC-SIGN, IFN-γ, IFNGR1, IL-8, IL-1Ra, MBL, NRAMP1, RANTES, and SP-D) that have been associated with TB, some repeatedly. An optimal model, which best describes and predicts TB case-control status, was constructed. Significant interactions were detected between eight pairs of variants. The models fitted the observed data extremely well, with p < 0.0001 for all eight models. A highly significant interaction was detected between INFGR1 and NRAMP1, which is not surprising because macrophage activation is greatly enhanced by IFN-γ and IFN-γ response elements that are present in the human NRAMP1 promoter region, providing further evidence for their interaction. This study enabled us to test the theory that disease outcome may be due to interaction of several gene effects. With eight instances of statistically significant gene-gene interactions, the importance of epistasis is clearly identifiable in this study. Methods for studying gene-gene interactions are based on a multilocus and multigene approach, consistent with the nature of complex-trait diseases, and may provide the paradigm for future genetic studies of TB. PMID:20799037

  19. Designing and Evaluating Health Systems Level Hypertension Control Interventions for African-Americans: Lessons from a Pooled Analysis of Three Cluster Randomized Trials

    PubMed Central

    Pavlik, Valory N.; Chan, Wenyaw; Hyman, David J.; Feldman, Penny; Ogedegbe, Gbenga; Schwartz, Joseph E.; McDonald, Margaret; Einhorn, Paula; Tobin, Jonathan N.

    2015-01-01

    Objectives African-Americans (AAs) have a high prevalence of hypertension and their blood pressure (BP) control on treatment still lags behind other groups. In 2004, NHLBI funded five projects that aimed to evaluate clinically feasible interventions to effect changes in medical care delivery leading to an increased proportion of AA patients with controlled BP. Three of the groups performed a pooled analysis of trial results to determine: 1) the magnitude of the combined intervention effect; and 2) how the pooled results could inform the methodology for future health-system level BP interventions. Methods Using a cluster randomized design, the trials enrolled AAs with uncontrolled hypertension to test interventions targeting a combination of patient and clinician behaviors. The 12-month Systolic BP (SBP) and Diastolic BP (DBP) effects of intervention or control cluster assignment were assessed using mixed effects longitudinal regression modeling. Results 2,015 patients representing 352 clusters participated across the three trials. Pooled BP slopes followed a quadratic pattern, with an initial decline, followed by a rise toward baseline, and did not differ significantly between intervention and control clusters: SBP linear coefficient = −2.60±0.21 mmHg per month, p<0.001; quadratic coefficient = 0.167± 0.02 mmHg/month, p<0.001; group by time interaction group by time group x linear time coefficient=0.145 ± 0.293, p=0.622; group x quadratic time coefficient= −0.017 ± 0.026, p=0.525). Results were similar for DBP. The individual sites did not have significant intervention effects when analyzed separately. Conclusion Investigators planning behavioral trials to improve BP control in health systems serving AAs should plan for small effect sizes and employ a “run-in” period in which BP can be expected to improve in both experimental and control clusters. PMID:25808682

  20. Wheat Landraces Are Better Qualified as Potential Gene Pools at Ultraspaced rather than Densely Grown Conditions

    PubMed Central

    Ninou, Elissavet G.; Mylonas, Ioannis G.; Tokatlidis, Ioannis S.

    2014-01-01

    The negative relationship between the yield potential of a genotype and its competitive ability may constitute an obstacle to recognize outstanding genotypes within heterogeneous populations. This issue was investigated by growing six heterogeneous wheat landraces along with a pure-line commercial cultivar under both dense and widely spaced conditions. The performance of two landraces showed a perfect match to the above relationship. Although they lagged behind the cultivar by 64 and 38% at the dense stand, the reverse was true with spaced plants where they succeeded in out-yielding the cultivar by 58 and 73%, respectively. It was concluded that dense stand might undervalue a landrace as potential gene pool in order to apply single-plant selection targeting pure-line cultivars, attributable to inability of plants representing high yielding genotypes to exhibit their capacity due to competitive disadvantage. On the other side, the yield expression of individuals is optimized when density is low enough to preclude interplant competition. Therefore, the latter condition appears ideal to identify the most promising landrace for breeding and subsequently recognize the individuals representing the most outstanding genotypes. PMID:24955427

  1. Echoes from Sepharad: signatures on the maternal gene pool of crypto-Jewish descendants

    PubMed Central

    Nogueiro, Inês; Teixeira, João; Amorim, António; Gusmão, Leonor; Alvarez, Luis

    2015-01-01

    The majority of genetic studies on Jewish populations have been focused on Ashkenazim, and genetic data from the Sephardic original source, the Iberian Peninsula, are particularly scarce. Regarding the mitochondrial genome, the available information is limited to a single Portuguese village, Belmonte, where just two different lineages (a single one corresponding to 93.3%) were found in 30 individuals. Aiming at disclosing the ancestral maternal background of the Portuguese Jewry, we enlarged the sampling to other crypto-Jewish descendants in the Bragança district (NE Portugal). Fifty-seven complete mtDNA genomes were newly sequenced and — in contrast with Belmonte — a high level of diversity was found, with five haplogroups (HV0b, N1, T2b11, T2e and U2e) being putatively identified as Sephardic founding lineages. Therefore — in sharp contrast with Belmonte — these communities have managed to escape the expected inbreeding effects caused by centuries of religious repression and have kept a significant proportion of the Sephardic founder gene pool. This deeper analysis of the surviving Sephardic maternal lineages allowed a much more comprehensive and detailed perspective on the origins and survival of the Sephardic genetic heritage. In line with previously published results on Sephardic paternal lineages, our findings also show a surprising resistance to the erosion of genetic diversity in the maternal lineages. PMID:25074462

  2. Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of circa 2,000 candidate genes in 7,657 African Americans, 1,315 Hi...

  3. Phenotype-Based identification of host genes required for propagation of African swine fever virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    African Swine Fever Virus (ASFV) produces a fatal acute hemorrhagic fever in domesticated pigs that is of worldwide economic importance. Using an expressed sequence tag (EST)-library-based antisense method of random gene inactivation and a phenotypic screen for limitation of ASFV propagation in cul...

  4. PHENOTYPE-BASED IDENTIFICATION OF HOST GENES REQUIRED FOR REPLICATION OF AFRICAN SWINE FEVER VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    African Swine Fever Virus (ASFV) produces a fatal acute hemorrhagic fever in domesticated pigs that potentially is a worldwide economic threat. Using an expressed sequence tag (EST)-library-based antisense method of random gene inactivation and a phenotypic screen for limitation of ASFV replication ...

  5. Role of genetic refuges in the restoration of native gene pools of brown trout.

    PubMed

    Araguas, Rosa M; Sanz, Núria; Fernández, Raquel; Utter, Fred M; Pla, Carles; García-Marín, José-Luis

    2009-08-01

    Captive-bred animals derived from native, alien, or hybrid stocks are often released in large numbers in natural settings with the intention of augmenting harvests. In brown trout (Salmo trutta), stocking with hatchery-reared non-native fish has been the main management strategy used to maintain or improve depleted wild brown trout populations in Iberian and other Mediterranean regions. This measure has become a serious threat to the conservation of native genetic diversity, mainly due to introgressive hybridization. Aware of this risk, the agency responsible for management of brown trout in the eastern Pyrenees (Spain) created "brown trout genetic refuges" to preserve the integrity of brown trout gene pools in this region. Within refuge areas, the prerefuge status with respect to fishing activities has been maintained, but hatchery releases have been banned completely. We evaluated this management strategy through a comparison of the stocking impact on native populations that accounted for stocking histories before and after refuge designations and fishing activities. In particular we examined the relevant scientific, cultural, and political challenges encountered. Despite agency willingness to change fishery policies to balance exploitation and conservation, acceptance of these new policies by anglers and genetic monitoring of refuge populations should also be considered. To improve management supported by genetic refuges, we suggest focusing on areas where the public is more receptive, considering the situation of local native diversity, and monitoring of adjacent introgressed populations. We recommend the use of directional supportive breeding only when a population really needs to be enhanced. In any case, management strategies should be developed to allow for protection within the context of human use. PMID:19183212

  6. Genomic Evidence Establishes Anatolia as the Source of the European Neolithic Gene Pool.

    PubMed

    Omrak, Ayça; Günther, Torsten; Valdiosera, Cristina; Svensson, Emma M; Malmström, Helena; Kiesewetter, Henrike; Aylward, William; Storå, Jan; Jakobsson, Mattias; Götherström, Anders

    2016-01-25

    Anatolia and the Near East have long been recognized as the epicenter of the Neolithic expansion through archaeological evidence. Recent archaeogenetic studies on Neolithic European human remains have shown that the Neolithic expansion in Europe was driven westward and northward by migration from a supposed Near Eastern origin [1-5]. However, this expansion and the establishment of numerous culture complexes in the Aegean and Balkans did not occur until 8,500 before present (BP), over 2,000 years after the initial settlements in the Neolithic core area [6-9]. We present ancient genome-wide sequence data from 6,700-year-old human remains excavated from a Neolithic context in Kumtepe, located in northwestern Anatolia near the well-known (and younger) site Troy [10]. Kumtepe is one of the settlements that emerged around 7,000 BP, after the initial expansion wave brought Neolithic practices to Europe. We show that this individual displays genetic similarities to the early European Neolithic gene pool and modern-day Sardinians, as well as a genetic affinity to modern-day populations from the Near East and the Caucasus. Furthermore, modern-day Anatolians carry signatures of several admixture events from different populations that have diluted this early Neolithic farmer component, explaining why modern-day Sardinian populations, instead of modern-day Anatolian populations, are genetically more similar to the people that drove the Neolithic expansion into Europe. Anatolia's central geographic location appears to have served as a connecting point, allowing a complex contact network with other areas of the Near East and Europe throughout, and after, the Neolithic. PMID:26748850

  7. Multiple cholinergic nicotinic receptor genes affect nicotine dependence risk in African and European Americans

    PubMed Central

    Saccone, Nancy L.; Schwantes-An, Tae-Hwi; Wang, Jen C.; Grucza, Richard A.; Breslau, Naomi; Hatsukami, Dorothy; Johnson, Eric O.; Rice, John P.; Goate, Alison M.; Bierut, Laura J.

    2010-01-01

    Several independent studies show that the chromosome 15q25.1 region, which contains the CHRNA5-CHRNA3-CHRNB4 gene cluster, harbors variants strongly associated with nicotine dependence, other smoking behaviors, lung cancer, and chronic obstructive pulmonary disease. We investigated whether variants in other cholinergic nicotinic receptor subunit (CHRN) genes affect risk for nicotine dependence in a new sample of African-Americans (N = 710). We also analyzed this African-American sample together with a European-American sample (N=2062, 1608 of which have been previously studied), allowing for differing effects in the two populations. Cases are current nicotine-dependent smokers and controls are non-dependent smokers. Variants in or near CHRND-CHRNG, CHRNA7, and CHRNA10 show modest association with nicotine dependence risk in the African-American sample. In addition, CHRNA4, CHRNB3-CHRNA6, and CHRNB1 show association in at least one population. CHRNG and CHRNA4 harbor SNPs that have opposite directions of effect in the two populations. In each of the population samples, these loci substantially increase the trait variation explained, although no loci meet Bonferroni-corrected significance in the African-American sample alone. The trait variation explained by three key associated SNPs in CHRNA5-CHRNA3-CHRNB4 is 1.9% in European-Americans and also 1.9% in African-Americans; this increases to 4.5% in EAs and 7.3% in AAs when we add six variants representing associations at other CHRN genes. Multiple nicotinic receptor subunit genes outside of chromosome 15q25 are likely to be important in the biological processes and development of nicotine dependence, and some of these risks may be shared across diverse populations. PMID:20584212

  8. [Gene pool of Buryats: clinal variability and territorial subdivision based on data of Y-chromosome markers].

    PubMed

    Har'kov, V N; Hamina, K V; Medvedeva, O F; Simonova, K V; Eremina, E R; Stepanov, V A

    2014-02-01

    The structure of the Buryat gene pool has been studied based on the composition and frequency of Y-chromosome haplogroups in eight geographically distant populations. Eleven haplotypes have been found in the Buryat gene pool, two of which are the most frequent (N1cl and C3d). The greatest difference in haplogroup frequencies was fixed between the western and eastern Buryat samples. The evaluation of genetic diversity based on haplotype frequencies revealed that it has low values in most of the samples. The evaluation of the genetic differentiation of the examined samples using an analysis of molecular variance (AMOVA) shows that the Buryat gene pool is highly differentiated by haplotype frequencies. Phylogenetic analysis within haplo-groups N1cl and C3d revealed a strong founder effect, i.e., reduced diversity and starlike phylogeny of the median network of haplotypes that form specific subclusters. The results of a phylogenetic analysis of the haplogroups identified common genetic components for Buryats and Mongols. PMID:25711029

  9. In planta gene expression analysis of Xanthomonas oryzae pathovar oryzae, African strain MAI1

    PubMed Central

    2010-01-01

    Background Bacterial leaf blight causes significant yield losses in rice crops throughout Asia and Africa. Although both the Asian and African strains of the pathogen, Xanthomonas oryzae pv. oryzae (Xoo), induce similar symptoms, they are nevertheless genetically different, with the African strains being more closely related to the Asian X. oryzae pv. oryzicola (Xoc). Results Changes in gene expression of the African Xoo strain MAI1 in the susceptible rice cultivar Nipponbare were profiled, using an SSH Xoo DNA microarray. Microarray hybridization was performed comparing bacteria recovered from plant tissues at 1, 3, and 6 days after inoculation (dai) with bacteria grown in vitro. A total of 710 bacterial genes were found to be differentially expressed, with 407 up-regulated and 303 down-regulated. Expression profiling indicated that less than 20% of the 710 bacterial transcripts were induced in the first 24 h after inoculation, whereas 63% were differentially expressed at 6 dai. The 710 differentially expressed genes were one-end sequenced. 535 sequences were obtained from which 147 non-redundant sequences were identified. Differentially expressed genes were related to metabolism, secretion and transport, pathogen adherence to plant tissues, plant cell-wall degradation, IS elements, and virulence. In addition, various other genes encoding proteins with unknown function or showing no similarity to other proteins were also induced. The Xoo MAI1 non-redundant set of sequences was compared against several X. oryzae genomes, revealing a specific group of genes that was present only in MAI1. Numerous IS elements were also found to be differentially expressed. Quantitative real-time PCR confirmed 86% of the identified profile on a set of 14 genes selected according to the microarray analysis. Conclusions This is the first report to compare the expression of Xoo genes in planta across different time points during infection. This work shows that as-yet-unidentified and

  10. Pooled Enrichment Sequencing Identifies Diversity and Evolutionary Pressures at NLR Resistance Genes within a Wild Tomato Population.

    PubMed

    Stam, Remco; Scheikl, Daniela; Tellier, Aurélien

    2016-01-01

    Nod-like receptors (NLRs) are nucleotide-binding domain and leucine-rich repeats containing proteins that are important in plant resistance signaling. Many of the known pathogen resistance (R) genes in plants are NLRs and they can recognize pathogen molecules directly or indirectly. As such, divergence and copy number variants at these genes are found to be high between species. Within populations, positive and balancing selection are to be expected if plants coevolve with their pathogens. In order to understand the complexity of R-gene coevolution in wild nonmodel species, it is necessary to identify the full range of NLRs and infer their evolutionary history. Here we investigate and reveal polymorphism occurring at 220 NLR genes within one population of the partially selfing wild tomato species Solanum pennellii. We use a combination of enrichment sequencing and pooling ten individuals, to specifically sequence NLR genes in a resource and cost-effective manner. We focus on the effects which different mapping and single nucleotide polymorphism calling software and settings have on calling polymorphisms in customized pooled samples. Our results are accurately verified using Sanger sequencing of polymorphic gene fragments. Our results indicate that some NLRs, namely 13 out of 220, have maintained polymorphism within our S. pennellii population. These genes show a wide range of πN/πS ratios and differing site frequency spectra. We compare our observed rate of heterozygosity with expectations for this selfing and bottlenecked population. We conclude that our method enables us to pinpoint NLR genes which have experienced natural selection in their habitat. PMID:27189991

  11. Pooled Enrichment Sequencing Identifies Diversity and Evolutionary Pressures at NLR Resistance Genes within a Wild Tomato Population

    PubMed Central

    Stam, Remco; Scheikl, Daniela; Tellier, Aurélien

    2016-01-01

    Nod-like receptors (NLRs) are nucleotide-binding domain and leucine-rich repeats containing proteins that are important in plant resistance signaling. Many of the known pathogen resistance (R) genes in plants are NLRs and they can recognize pathogen molecules directly or indirectly. As such, divergence and copy number variants at these genes are found to be high between species. Within populations, positive and balancing selection are to be expected if plants coevolve with their pathogens. In order to understand the complexity of R-gene coevolution in wild nonmodel species, it is necessary to identify the full range of NLRs and infer their evolutionary history. Here we investigate and reveal polymorphism occurring at 220 NLR genes within one population of the partially selfing wild tomato species Solanum pennellii. We use a combination of enrichment sequencing and pooling ten individuals, to specifically sequence NLR genes in a resource and cost-effective manner. We focus on the effects which different mapping and single nucleotide polymorphism calling software and settings have on calling polymorphisms in customized pooled samples. Our results are accurately verified using Sanger sequencing of polymorphic gene fragments. Our results indicate that some NLRs, namely 13 out of 220, have maintained polymorphism within our S. pennellii population. These genes show a wide range of πN/πS ratios and differing site frequency spectra. We compare our observed rate of heterozygosity with expectations for this selfing and bottlenecked population. We conclude that our method enables us to pinpoint NLR genes which have experienced natural selection in their habitat. PMID:27189991

  12. Gene-environment interactions on mental development in African American, Dominican, and Caucasian Mothers and Newborns

    PubMed Central

    Wang, Shuang; Chanock, Stephen; Tang, Deliang; Li, Zhigang; Edwards, Susan; Jedrychowski, Wieslaw; Perera, Frederica P.

    2009-01-01

    The health impact of environmental toxins has gained increasing recognition over the years. Polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) are known to affect nervous system development in children, but no studies have investigated how polymorphisms in PAH metabolic or detoxification genes affect child cognitive development following PAH exposure during pregnancy. In two parallel prospective cohort studies of nonsmoking African American and Dominican mothers and children in New York City and of Caucasian mothers and children in Krakow, Poland, we explored the effect of gene-PAH interaction on child mental development index (MDI), as measured by the Bayley Scales of Infant Development-Revised (BSID-II). Genes known to play important roles in the metabolic activation or detoxification of PAHs were selected. Genetic variations in these genes could influence susceptibility to adverse effects of PAHs in polluted air. We explored the effects of interactions between prenatal PAH exposure and 21 polymorphisms or haplotypes in these genes on MDI at 12, 24, and 36 months among 547 newborns and 806 mothers from three different ethnic groups: African Americans, Dominicans, and Caucasians. PAHs were measured by personal air monitoring of mothers during pregnancy. Significant interaction effects between haplotypes and PAHs were observed in mothers and their newborns in all three ethnic groups after Bonferroni correction for multiple comparisons. The strongest and most consistent effect observed was between PAH and haplotype ACCGGC of the CYP1B1 gene. PMID:19860743

  13. Expression and characterization of the thymidine kinase gene of African swine fever virus.

    PubMed Central

    Martin Hernandez, A M; Tabares, E

    1991-01-01

    The thymidine kinase (TK) gene of African swine fever virus (ASFV) was located within the viral genome by using two degenerate oligonucleotide probes derived from sequences of the vaccinia virus and cellular TK genes. The TK gene was mapped within a 0.72-kbp BglII-XhoI fragment (0.242 to 0.246 map units) derived from a 23.9-kbp SalI-B fragment of the ASFV genome. Identification of this region as the ASFV TK gene was confirmed by expression of TK in Escherichia coli and by the synthesis of active TK in a cell-free system programmed with RNA synthesized in vitro. The sequenced gene for TK includes an open reading frame of 588 nucleotides encoding a protein of 196 amino acids. The deduced amino acid sequence shows 32.4% identity with the TK of vaccinia virus. Images PMID:1987368

  14. Deletion of the zupT gene for a zinc importer influences zinc pools in Cupriavidus metallidurans CH34.

    PubMed

    Herzberg, M; Bauer, L; Nies, D H

    2014-03-01

    Cupriavidus metallidurans strain CH34 accomplishes a high level of transition metal resistance by a combination of rather unspecific transition metal import and controlled efflux of surplus metals. Using the plasmid-free mutant strain AE104 that possesses only a limited number of metal efflux systems, cellular metal pools were identified as counterparts of these transport reactions. At low zinc concentrations strain AE104 took up Zn(II) until the zinc content reached an optimum level of 70,000 Zn(II) per cell in the exponential phase of growth, whereas a ΔzupT mutant lacking the zinc importer ZupT contained only 20,000 Zn(II)/cell, possibly the minimum zinc content. Mutant and parent cells accumulated up to 125,000 Zn(II) per cell at high (100 μM) external zinc concentrations (optimum zinc content). When the mutant strain Δe4, which has all the known genes for zinc efflux systems deleted, was cultivated in the presence of zinc concentrations close to its upper tolerance level (10 μM), these cells contained 250,000 Zn(II) per cell, probably the maximum zinc content. Instead of zinc, 120,000 cobalt or cadmium ions could also fill-up parts of this zinc pool, showing that it is in fact an undefined pool of divalent transition metal cations bound with low substrate specificity. Even when the cells contained sufficient numbers of total zinc, the zinc importer ZupT was required for important cellular processes, indicating the presence of a pool of tightly bound zinc ions, which depends on ZupT for efficient replenishment. The absence of ZupT led to the formation of inclusion bodies, perturbed oxidative stress resistance and decreased efficiency in the synthesis of the zinc-dependent subunit RpoC of the RNA polymerase, leading to RpoC accumulation. Moreover, when a czc allele for a zinc-exporting transenvelope efflux system CzcCBA was constitutively expressed in a ΔzupT mutant, this led to the disappearance of the CzcA protein and the central subunit of the protein

  15. Globin gene-associated restriction-fragment-length polymorphisms in southern African peoples.

    PubMed Central

    Ramsay, M; Jenkins, T

    1987-01-01

    The combination of polymorphic restriction-enzyme sites in the 3' region of the beta-globin gene cluster shows very little variation in southern-African Bantu-speaking black and Kalahari !Kung San populations. The sites of the 5' region, on the other hand, show marked variation, and two common haplotypes are present--the "Negro" type (- - - - +) and the "San" type (- + - - +)--in frequencies of .404 and .106, respectively, in the Bantu-speakers and .262 and .405, respectively, in the San. Twenty of 23 beta s-associated haplotypes in southern-African Bantu-speaking black subjects were the same as that found commonly in the Central African Republic (CAR)--i.e., the "Bantu" type--a finding providing the first convincing biological evidence for the common ancestry of geographically widely separated speakers of languages belonging to the Bantu family. The (-alpha) haplotype has a frequency of .21 in the Venda, .07 in both the Sotho-Tswana and the Nguni, and .06 among the !Kung San. These data are interpreted in the light of Plasmodium falciparum malaria selection and population movements in the African subcontinent. PMID:2891298

  16. Characterization of extractable soil organic matter pools from African Dark Earths (AfDE): A case study in historical biochar and organic waste amendments

    NASA Astrophysics Data System (ADS)

    Fujiu, Manna; Plante, Alain; Ohno, Tsutomu; Solomon, Dawit; Lehmann, Johannes; Fraser, James; Leach, Melissa; Fairhead, James

    2014-05-01

    Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils that were formed from the original highly-weathered infertile yellowish to red Oxisols and Ultisols through an extant but hitherto overlooked climate-smart sustainable soil management system that has long been an important feature of the indigenous West African agricultural repertoire. Studies have demonstrated that ADE soils in general have significantly different organic matter properties compared to adjacent non-DE soils, largely attributable to the presence of high concentrations of ash-derived carbon. Quantification and characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) confirmed substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant or relatively stable, but the goal of the current study was to characterize the presumably labile, more rapidly cycling, pools of C in AfDEs through the characterization of hot water- and pyrophosphate-extractable fractions, referred to as HWEOC and PyroC respectively. Extracts were analyzed for carbon content, as well as composition using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FTICR-MS). The amount of extractable C as a proportion of total soil C was relatively low: less than ~0.8% for HWEOC and 2.8% for PyroC. The proportion of HWEOC did not differ (P = 0.18, paired t-test) between the AfDE and the non-AfDE soils, while the proportions of PyroC were significantly larger (P = 0.001) in the AfDE soils compared to the non-AfDE soils. Preliminary analysis of the EEM/PARAFAC data suggests that AfDE samples had

  17. Association and interaction analysis of variants in CHRNA5/CHRNA3/CHRNB4 gene cluster with nicotine dependence in African and European Americans

    PubMed Central

    Li, Ming D.; Xu, Qing; Lou, Xiang-Yang; Payne, Thomas J; Niu, Tianhua; Ma, Jennie Z.

    2010-01-01

    Several previous genome-wide and targeted association studies revealed that variants in the CHRNA5-CHRNA3-CHRNB4 (CHRNA5/A3/B4) gene cluster on chromosome 15 that encode the α5, α3 and β4 subunits of the nicotinic acetylcholine receptor (nAChRs) are associated with nicotine dependence (ND) in European Americans (EAs) or others of European origin. Considering the distinct linkage disequilibrium patterns in European and other ethnic populations such as African Americans (AAs), it would be interesting to determine whether such associations exist in other ethnic populations. We performed a comprehensive association and interaction analysis of the CHRNA5/A3/B4 cluster in two ethnic samples to investigate the role of variants in the risk for ND, which was assessed by Smoking Quantity, Heaviness Smoking Index, and Fagerström test for ND. Using a family-based association test, we found a nominal association of single nucleotide polymorphisms (SNPs) rs1317286 and rs8040868 in CHRNA3 with ND in the AA and combined AA and EA samples. Furthermore, we found that several haplotypes in CHRNA5 and CHRNA3 are nominally associated with ND in AA, EA, and pooled samples. However, none of these associations remained significant after correction for multiple testing. In addition, we performed interaction analysis of SNPs within the CHRNA5/A3/B4 cluster using the pedigree-based generalized multifactor dimensionality reduction method and found significant interactions within CHRNA3 and among the three subunit genes in the AA and pooled samples. Together, these results indicate that variants within CHRNA3 and among CHRNA5, CHRNA3, and CHRNB4 contribute significantly to the etiology of ND through gene-gene interactions, although the association of each subunit gene with ND is weak in both the AA and EA samples. PMID:19859904

  18. The association between polymorphisms in the leptin receptor gene and risk of breast cancer: a systematic review and pooled analysis.

    PubMed

    Wang, Li-qiang; Shen, Wei; Xu, Lan; Chen, Min-Bin; Gong, Ting; Lu, Pei-Hua; Tao, Guo-Qing

    2012-11-01

    Many epidemiological studies have found that leptin correlates to body fat extent and breast cancer. Leptin exerts its physiological action through the leptin receptor (LEPR). However, published data on the association between LEPR alleles and breast cancer occurrence have led to in contradictory results. A total of 10 studies were identified to the meta-analysis, including 4,644 cases and 5,485 controls for LEPR rs1137101 polymorphism, 5 studies with 2,759 cases and 4,464 controls for rs1137100 polymorphism, and 2 studies for rs8051542, rs8051542, and rs8051542 polymorphisms. The pooled odds ratios (OR) with 95 % confidence intervals (CI) for breast cancer risk associated with LEPR genotypes were estimated. Elevated breast cancer risk was associated with LEPR rs1137101 polymorphism when all studies were pooled in the meta-analysis (allele contrast model: OR = 0.71, 95 % CI = 0.551-0.997). In the stratified analysis by ethnicity, significantly increased risks were also found among Asians for allele contrast model (OR 0.414, 95 % CI 0.312-0.550) and dominant model (OR 0.537, 95 % CI 0.370-0.781); for Africans, significantly increased risks were also found for allele contrast model (OR 0.716, 95 % CI 0.595-0.861), homozygote codominant (OR 0.537, 95 % CI 0.370-0.781) and dominant model (OR 1.595, 95 % CI 1.207-2.108). And significantly elevated breast cancer risk was associated with LEPR rs1137100 polymorphism for allele contrast (OR = 0.666, 95 % CI = 0.603-0.720) and homozygote codominant models (OR = 0.344, 95 % CI = 0.282-0.421). For LEPR rs8179183, rs4655537, and rs3762274 polymorphisms, no significant associations were detected in all comparison models. This pooled analysis suggested that rs1137101 and rs1137100 polymorphisms were significantly correlated with breast cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR rs1137100 variant were low-penetrant risk factors for developing breast cancer. Further, no

  19. High Temperature Inhibits Ascorbate Recycling and Light Stimulation of the Ascorbate Pool in Tomato despite Increased Expression of Biosynthesis Genes

    PubMed Central

    Massot, Capucine; Bancel, Doriane; Lopez Lauri, Félicie; Truffault, Vincent; Baldet, Pierre; Stevens, Rebecca; Gautier, Hélène

    2013-01-01

    Understanding how the fruit microclimate affects ascorbate (AsA) biosynthesis, oxidation and recycling is a great challenge in improving fruit nutritional quality. For this purpose, tomatoes at breaker stage were harvested and placed in controlled environment conditions at different temperatures (12, 17, 23, 27 and 31°C) and irradiance regimes (darkness or 150 µmol m-2 s-1). Fruit pericarp tissue was used to assay ascorbate, glutathione, enzymes related to oxidative stress and the AsA/glutathione cycle and follow the expression of genes coding for 5 enzymes of the AsA biosynthesis pathway (GME, VTC2, GPP, L-GalDH, GLDH). The AsA pool size in pericarp tissue was significantly higher under light at temperatures below 27°C. In addition, light promoted glutathione accumulation at low and high temperatures. At 12°C, increased AsA content was correlated with the enhanced expression of all genes of the biosynthesis pathway studied, combined with higher DHAR and MDHAR activities and increased enzymatic activities related to oxidative stress (CAT and APX). In contrast, at 31°C, MDHAR and GR activities were significantly reduced under light indicating that enzymes of the AsA/glutathione cycle may limit AsA recycling and pool size in fruit pericarp, despite enhanced expression of genes coding for AsA biosynthesis enzymes. In conclusion, this study confirms the important role of fruit microclimate in the regulation of fruit pericarp AsA content, as under oxidative conditions (12°C, light) total fruit pericarp AsA content increased up to 71%. Moreover, it reveals that light and temperature interact to regulate both AsA biosynthesis gene expression in tomato fruits and AsA oxidation and recycling. PMID:24367665

  20. Swimming Pools.

    ERIC Educational Resources Information Center

    Ministry of Housing and Local Government, London (England).

    Technical and engineering data are set forth on the design and construction of swimming pools. Consideration is given to site selection, pool construction, the comparative merits of combining open air and enclosed pools, and alternative uses of the pool. Guidelines are presented regarding--(1) pool size and use, (2) locker and changing rooms, (3)…

  1. Prevalence of betaproteobacterial sequences in nifH gene pools associated with roots of modern rice cultivars.

    PubMed

    Wu, Liqin; Ma, Ke; Lu, Yahai

    2009-01-01

    The diversity and function of nitrogen-fixing bacteria colonizing rice roots are not well understood. A field experiment was conducted to determine the diversity of diazotrophic communities associated with roots of modern rice cultivars using culture-independent molecular analyses of nitrogenase gene (nifH) fragments. Experimental treatments included four modern rice cultivars (Oryza sativa, one Indica, one Japonica and two hybrid rice varieties) and three levels (0, 50, and 100 kg N ha(-1)) of N (urea) fertilizer application. Cloning and sequencing of 103 partial nifH genes showed that a diverse community of diazotrophs was associated with rice roots. However, the nifH gene fragments belonging to betaproteobacteria were dominant, accounting for nearly half of nifH sequences analyzed across the clone libraries. Most of them were similar to nifH fragments retrieved from wild rice and Kallar grass, with Azoarcus spp. being the closest cultured relatives. Alphaproteobacteria were also detected, but their relative abundance in the nifH gene pools was dramatically decreased with N fertilizer application. In addition, a high fraction of nifH gene pools was affiliated with methylotrophs and methane oxidizers. The sequence analysis was consistent with the terminal restriction fragment-length polymorphism (T-RFLP) fingerprinting of the nifH gene fragments, which showed three of four dominant terminal restriction fragments were mainly related to betaproteobacteria based on in silico digestion of nifH sequences. T-RFLP analyses also revealed that the effects of N fertilizer on the nifH gene diversity retrieved from roots varied according to rice cultivars. In summary, the present study revealed the prevalence of betaproteobacterial sequences among the proteobacteria associated with roots of modern rice cultivars. This group of diazotrophs appeared less sensitive to N fertilizer application than diazotrophic alphaproteobacteria. Furthermore, methylotrophs may also play a role

  2. Evolution of African swine fever virus genes related to evasion of host immune response.

    PubMed

    Frączyk, Magdalena; Woźniakowski, Grzegorz; Kowalczyk, Andrzej; Bocian, Łukasz; Kozak, Edyta; Niemczuk, Krzysztof; Pejsak, Zygmunt

    2016-09-25

    African swine fever (ASF) is a notifiable and one of the most complex and devastating infectious disease of pigs, wild boars and other representatives of Suidae family. African swine fever virus (ASFV) developed various molecular mechanisms to evade host immune response including alteration of interferon production by multigene family protein (MGF505-2R), inhibition of NF-κB and nuclear activating factor in T-cells by the A238L protein, or modulation of host defense by CD2v lectin-like protein encoded by EP402R and EP153R genes. The current situation concerning ASF in Poland seems to be stable in comparison to other eastern European countries but up-to-date in total 106 ASF cases in wild boar and 5 outbreaks in pigs were identified. The presented study aimed to reveal and summarize the genetic variability of genes related to inhibition or modulation of infected host response among 67 field ASF isolates collected from wild boar and pigs. The nucleotide sequences derived from the analysed A238L and EP153R regions showed 100% identity. However, minor but remarkable genetic diversity was found within EP402R and MGF505-2R genes suggesting slow molecular evolution of circulating ASFV isolates and the important role of this gene in modulation of interferon I production and hemadsorption phenomenon. The obtained nucleotide sequences of Polish ASFV isolates were closely related to Georgia 2007/1 and Odintsovo 02/14 isolates suggesting their common Caucasian origin. In the case of EP402R and partially in MGF505-2R gene the identified genetic variability was related to spatio-temporal occurrence of particular cases and outbreaks what may facilitate evolution tracing of ASFV isolates. This is the first report indicating identification of genetic variability within the genes related to evasion of host immune system which may be used to trace the direction of ASFV isolates molecular evolution. PMID:27599940

  3. Interethnic diversity of the CD209 (rs4804803) gene promoter polymorphism in African but not American sickle cell disease

    PubMed Central

    Noble, Jenelle A.; Duru, Kimberley C.; Guindo, Aldiouma; Yi, Li; Imumorin, Ikhide G.; Diallo, Dapa A.

    2015-01-01

    Elucidating the genomic diversity of CD209 gene promoter polymorphism could assist in clarifying disease pathophysiology as well as contribution to co-morbidities. CD209 gene promoter polymorphism has been shown to be associated with susceptibility to infection. We hypothesize that CD209 mutant variants occur at a higher frequency among Africans and in sickle cell disease. We analyzed the frequency of the CD209 gene (rs4804803) in healthy control and sickle cell disease (SCD) populations and determined association with disease. Genomic DNA was extracted from blood samples collected from 145 SCD and 231 control Africans (from Mali), 331 SCD and 379 control African Americans and 159 Caucasians. Comparative analysis among and between groups was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Per ethnic diversification, we found significant disparity in genotypic (23.4% versus 16.9% versus 3.2%) and allelic frequencies (48.7% versus 42.1% versus 19.8%) of the homozygote mutant variant of the CD209 (snp 309A/G) gene promoter between Africans, African Americans and Caucasians respectively. Comparative evaluation between disease and control groups reveal a significant difference in genotypic (10.4% versus 23.4%; p = 0.002) and allelic frequencies (39.7% versus 48.7%; p = 0.02) of the homozygote mutant variant in African SCD and healthy controls respectively, an observation that is completely absent among Americans. Comparing disease groups, we found no difference in the genotypic (p = 0.19) or allelic (p = 0.72) frequencies of CD209 homozygote mutant variant between Africans and Americans with sickle cell disease. The higher frequency of CD209 homozygote mutant variants in the African control group reveals a potential impairment of the capacity to mount an immune response to infectious diseases, and possibly delineate susceptibility to or severity of infectious co-morbidities within and between groups. PMID:25755928

  4. Analysis of multiple transcriptomes of the African oil palm (Elaeis guineensis) to identify reference genes for RT-qPCR.

    PubMed

    Xia, Wei; Mason, Annaliese S; Xiao, Yong; Liu, Zheng; Yang, Yaodong; Lei, Xintao; Wu, Xiaoming; Ma, Zilong; Peng, Ming

    2014-08-20

    The African oil palm (Elaeis guineensis), which is grown in tropical and subtropical regions, is a highly productive oil-bearing crop. For gene expression-based analyses such as reverse transcription-quantitative real time PCR (RT-qPCR), reference genes are essential to provide a baseline with which to quantify relative gene expression. Normalization using reliable reference genes is critical in correctly interpreting expression data from RT-qPCR. In order to identify suitable reference genes in African oil palm, 17 transcriptomes of different tissues obtained from NCBI were systematically assessed for gene expression variation. In total, 53 putative candidate reference genes with coefficient of variation values <3.0 were identified: 18 in reproductive tissue and 35 in vegetative tissue. Analysis for enriched functions showed that approximately 90% of identified genes were clustered in cell component gene functions, and 12 out of 53 genes were traditional housekeeping genes. We selected and validated 16 reference genes chosen from leaf tissue transcriptomes by using RT-qPCR in sets of cold, drought and high salinity treated samples, and ranked expression stability using statistical algorithms geNorm, Normfinder and Bestkeeper. Genes encoding actin, adenine phosphoribosyltransferase and eukaryotic initiation factor 4A genes were the most stable genes over the cold, drought and high salinity stresses. Identification of stably expressed genes as reference gene candidates from multiple transcriptome datasets was found to be reliable and efficient, and some traditional housekeeping genes were more stably expressed than others. We provide a useful molecular genetic resource for future gene expression studies in African oil palm, facilitating molecular genetics approaches for crop improvement in this species. PMID:24862192

  5. The Genetics of POAG in Black South Africans: A Candidate Gene Association Study

    PubMed Central

    Williams, Susan E. I.; Carmichael, Trevor R.; Allingham, R. Rand; Hauser, Michael; Ramsay, Michele

    2015-01-01

    Multiple loci have been associated with either primary open angle glaucoma (POAG) or heritable ocular quantitative traits associated with this condition. This study examined the association of these loci with POAG, with central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR) and with diabetes mellitus in a group of black South Africans (215 POAG cases and 214 controls). The population was homogeneous and distinct from other African and European populations. Single SNPs in the MYOC, COL8A2, COL1A1 and ZNF469 gene regions showed marginal associations with POAG. No association with POAG was identified with tagging SNPs in TMCO1, CAV1/CAV2, CYP1B1, COL1A2, COL5A1, CDKN2B/CDKN2BAS-1, SIX1/SIX6 or the chromosome 2p16 regions and there were no associations with CCT or VCDR. However, SNP rs12522383 in WDR36 was associated with diabetes mellitus (p = 0.00008). This first POAG genetic association study in black South Africans has therefore identified associations that require additional investigation in this and other populations to determine their significance. This highlights the need for larger studies in this population if we are to achieve the goal of facilitating early POAG detection and ultimately preventing irreversible blindness from this condition. PMID:25669751

  6. The genetics of POAG in black South Africans: a candidate gene association study.

    PubMed

    Williams, Susan E I; Carmichael, Trevor R; Allingham, R Rand; Hauser, Michael; Ramsay, Michele

    2015-01-01

    Multiple loci have been associated with either primary open angle glaucoma (POAG) or heritable ocular quantitative traits associated with this condition. This study examined the association of these loci with POAG, with central corneal thickness (CCT), vertical cup-to-disc ratio (VCDR) and with diabetes mellitus in a group of black South Africans (215 POAG cases and 214 controls). The population was homogeneous and distinct from other African and European populations. Single SNPs in the MYOC, COL8A2, COL1A1 and ZNF469 gene regions showed marginal associations with POAG. No association with POAG was identified with tagging SNPs in TMCO1, CAV1/CAV2, CYP1B1, COL1A2, COL5A1, CDKN2B/CDKN2BAS-1, SIX1/SIX6 or the chromosome 2p16 regions and there were no associations with CCT or VCDR. However, SNP rs12522383 in WDR36 was associated with diabetes mellitus (p = 0.00008). This first POAG genetic association study in black South Africans has therefore identified associations that require additional investigation in this and other populations to determine their significance. This highlights the need for larger studies in this population if we are to achieve the goal of facilitating early POAG detection and ultimately preventing irreversible blindness from this condition. PMID:25669751

  7. Structure of genetic diversity in the two major gene pools of common bean (Phaseolus vulgaris L., Fabaceae).

    PubMed

    Kwak, Myounghai; Gepts, Paul

    2009-03-01

    Domesticated materials with well-known wild relatives provide an experimental system to reveal how human selection during cultivation affects genetic composition and adaptation to novel environments. In this paper, our goal was to elucidate how two geographically distinct domestication events modified the structure and level of genetic diversity in common bean. Specifically, we analyzed the genome-wide genetic composition at 26, mostly unlinked microsatellite loci in 349 accessions of wild and domesticated common bean from the Andean and Mesoamerican gene pools. Using a model-based approach, implemented in the software STRUCTURE, we identified nine wild or domesticated populations in common bean, including four of Andean and four of Mesoamerican origins. The ninth population was the putative wild ancestor of the species, which was classified as a Mesoamerican population. A neighbor-joining analysis and a principal coordinate analysis confirmed genetic relationships among accessions and populations observed with the STRUCTURE analysis. Geographic and genetic distances in wild populations were congruent with the exception of a few putative hybrids identified in this study, suggesting a predominant effect of isolation by distance. Domesticated common bean populations possessed lower genetic diversity, higher F(ST), and generally higher linkage disequilibrium (LD) than wild populations in both gene pools; their geographic distributions were less correlated with genetic distance, probably reflecting seed-based gene flow after domestication. The LD was reduced when analyzed in separate Andean and Mesoamerican germplasm samples. The Andean domesticated race Nueva Granada had the highest F(ST) value and widest geographic distribution compared to other domesticated races, suggesting a very recent origin or a selection event, presumably associated with a determinate growth habit, which predominates in this race. PMID:19130029

  8. Race structure within the Mesoamerican gene pool of common bean (Phaseolus vulgaris L.) as determined by microsatellite markers.

    PubMed

    Díaz, L M; Blair, M W

    2006-12-01

    Common bean (Phaseolus vulgaris L.) cultivars are distinguished morphologically, agronomically and ecologically into specific races within each of the two gene pools found for the species (Andean and Mesoamerican). The objective of this study was to describe the race structure of the Mesoamerican gene pool using microsatellite markers. A total of 60 genotypes previously described as pertaining to specific Mesoamerican races as well as two Andean control genotypes were analyzed with 52 markers. A total of 267 bands were generated with an average of 5.1 alleles per marker and 0.297 heterozygosity across all microsatellites. Correspondence analysis identified two major groups equivalent to the Mesoamerica race and a group containing both Durango and Jalisco race genotypes. Two outlying individuals were classified as potentially of the Guatemala race although this race does not have a defined structure and previously classified members of this race were classified with other races. Population structure analysis with K = 1-4 agreed with this classification. The genetic diversity based on Nei's index for the entire set of genotypes was 0.468 while this was highest for the Durango-Jalisco group (0.414), intermediate for race Mesoamerica (0.340) and low for race Guatemala (0.262). Genetic differentiation (G (ST)) between the Mesoamerican races was 0.27 while genetic distance and identity showed race Durango and Jalisco individuals to be closely related with high gene flow (N (m)) both between these two races (1.67) and between races Durango and Mesoamerica (1.58). Observed heterozygosity was low in all the races as would be expected for an inbreeding species. The analysis with microsatellite markers identified subgroups, which agreed well with commercial class divisions, and seed size was the main distinguishing factor between the two major groups identified. PMID:17047911

  9. Epidemic Clones, Oceanic Gene Pools, and Eco-LD in the Free Living Marine Pathogen Vibrio parahaemolyticus.

    PubMed

    Cui, Yujun; Yang, Xianwei; Didelot, Xavier; Guo, Chenyi; Li, Dongfang; Yan, Yanfeng; Zhang, Yiquan; Yuan, Yanting; Yang, Huanming; Wang, Jian; Wang, Jun; Song, Yajun; Zhou, Dongsheng; Falush, Daniel; Yang, Ruifu

    2015-06-01

    We investigated global patterns of variation in 157 whole-genome sequences of Vibrio parahaemolyticus, a free-living and seafood associated marine bacterium. Pandemic clones, responsible for recent outbreaks of gastroenteritis in humans, have spread globally. However, there are oceanic gene pools, one located in the oceans surrounding Asia and another in the Mexican Gulf. Frequent recombination means that most isolates have acquired the genetic profile of their current location. We investigated the genetic structure in the Asian gene pool by calculating the effective population size in two different ways. Under standard neutral models, the two estimates should give similar answers but we found a 27-fold difference. We propose that this discrepancy is caused by the subdivision of the species into a hundred or more ecotypes which are maintained stably in the population. To investigate the genetic factors involved, we used 51 unrelated isolates to conduct a genome-wide scan for epistatically interacting loci. We found a single example of strong epistasis between distant genome regions. A majority of strains had a type VI secretion system associated with bacterial killing. The remaining strains had genes associated with biofilm formation and regulated by cyclic dimeric GMP signaling. All strains had one or other of the two systems and none of isolate had complete complements of both systems, although several strains had remnants. Further "top down" analysis of patterns of linkage disequilibrium within frequently recombining species will allow a detailed understanding of how selection acts to structure the pattern of variation within natural bacterial populations. PMID:25605790

  10. A network of autism linked genes stabilizes two pools of synaptic GABAA receptors

    PubMed Central

    Tong, Xia-Jing; Hu, Zhitao; Liu, Yu; Anderson, Dorian; Kaplan, Joshua M

    2015-01-01

    Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABAA receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABAA receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABAA receptors are stabilized by the synaptic adhesion molecules Neurexin and Neuroligin. Inhibitory post-synaptic currents are eliminated in double mutants lacking both scaffolds. Neurexin, Neuroligin, and CASK mutations are all linked to Autism Spectrum Disorders (ASD). Our results suggest that these mutations may directly alter inhibitory transmission, which could contribute to the developmental and cognitive deficits observed in ASD. DOI: http://dx.doi.org/10.7554/eLife.09648.001 PMID:26575289

  11. A network of autism linked genes stabilizes two pools of synaptic GABA(A) receptors.

    PubMed

    Tong, Xia-Jing; Hu, Zhitao; Liu, Yu; Anderson, Dorian; Kaplan, Joshua M

    2015-01-01

    Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABA(A) receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABA(A) receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABA(A) receptors are stabilized by the synaptic adhesion molecules Neurexin and Neuroligin. Inhibitory post-synaptic currents are eliminated in double mutants lacking both scaffolds. Neurexin, Neuroligin, and CASK mutations are all linked to Autism Spectrum Disorders (ASD). Our results suggest that these mutations may directly alter inhibitory transmission, which could contribute to the developmental and cognitive deficits observed in ASD. PMID:26575289

  12. Association of genes with physiological functions by comparative analysis of pooled expression microarray data.

    PubMed

    Chen, Iuan-bor D; Rathi, Vinay K; DeAndrade, Diana S; Jay, Patrick Y

    2013-01-15

    The physiological functions of a tissue in the body are carried out by its complement of expressed genes. Genes that execute a particular function should be more specifically expressed in tissues that perform the function. Given this premise, we mined public microarray expression data to build a database of genes ranked by their specificity of expression in multiple organs. The database permitted the accurate identification of genes and functions known to be specific to individual organs. Next, we used the database to predict transcriptional regulators of brown adipose tissue (BAT) and validated two candidate genes. Based upon hypotheses regarding pathways shared between combinations of BAT or white adipose tissue (WAT) and other organs, we identified genes that met threshold criteria for specific or counterspecific expression in each tissue. By contrasting WAT to the heart and BAT, the two most mitochondria-rich tissues in the body, we discovered a novel function for the transcription factor ESRRG in the induction of BAT genes in white adipocytes. Because the heart and other estrogen-related receptor gamma (ESRRG)-rich tissues do not express BAT markers, we hypothesized that an adipocyte co-regulator acts with ESRRG. By comparing WAT and BAT to the heart, brain, kidney and skeletal muscle, we discovered that an isoform of the transcription factor sterol regulatory element binding transcription factor 1 (SREBF1) induces BAT markers in C2C12 myocytes in the presence of ESRRG. The results demonstrate a straightforward bioinformatic strategy to associate genes with functions. The database upon which the strategy is based is provided so that investigators can perform their own screens. PMID:23170034

  13. Resolution of the African hominoid trichotomy by use of a mitochondrial gene sequence

    SciTech Connect

    Ruvolo, M.; Disotell, T.R.; Allard, M.W. ); Brown, W.M. ); Honeycutt, R.L. )

    1991-02-15

    Mitochondrial DNA sequences encoding the cytochrome oxidase subunit II gene have been determined for five primate species, siamang (Hylobates syndactylus), lowland gorilla (Gorilla gorilla), pygmy chimpanzee (Pan paniscus), crab-eating macaque (Macaca fascicularis), and green monkey (Cercopithecus aethiops), and compared with published sequences of other primate and nonprimate species. Comparisons of cytochrome oxidase subunit II gene sequences provide clear-cut evidence from the mitochondrial genome for the separation of the African ape trichotomy into two evolutionary lineages, one leading to gorillas and the other to humans and chimpanzees. Several different tree-building methods support this same phylogenetic tree topology. The comparisons also yield trees in which a substantial length separates the divergence point of gorillas from that of humans and chimpanzees, suggesting that the lineage most immediately ancestral to humans and chimpanzees may have been in existence for a relatively long time.

  14. DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia.

    PubMed

    Ashktorab, Hassan; Daremipouran, M; Goel, Ajay; Varma, Sudhir; Leavitt, R; Sun, Xueguang; Brim, Hassan

    2014-04-01

    The identification of genes that are differentially methylated in colorectal cancer (CRC) has potential value for both diagnostic and therapeutic interventions specifically in high-risk populations such as African Americans (AAs). However, DNA methylation patterns in CRC, especially in AAs, have not been systematically explored and remain poorly understood. Here, we performed DNA methylome profiling to identify the methylation status of CpG islands within candidate genes involved in critical pathways important in the initiation and development of CRC. We used reduced representation bisulfite sequencing (RRBS) in colorectal cancer and adenoma tissues that were compared with DNA methylome from a healthy AA subject's colon tissue and peripheral blood DNA. The identified methylation markers were validated in fresh frozen CRC tissues and corresponding normal tissues from AA patients diagnosed with CRC at Howard University Hospital. We identified and validated the methylation status of 355 CpG sites located within 16 gene promoter regions associated with CpG islands. Fifty CpG sites located within CpG islands-in genes ATXN7L1 (2), BMP3 (7), EID3 (15), GAS7 (1), GPR75 (24), and TNFAIP2 (1)-were significantly hypermethylated in tumor vs. normal tissues (P<0.05). The methylation status of BMP3, EID3, GAS7, and GPR75 was confirmed in an independent, validation cohort. Ingenuity pathway analysis mapped three of these markers (GAS7, BMP3 and GPR) in the insulin and TGF-β1 network-the two key pathways in CRC. In addition to hypermethylated genes, our analysis also revealed that LINE-1 repeat elements were progressively hypomethylated in the normal-adenoma-cancer sequence. We conclude that DNA methylome profiling based on RRBS is an effective method for screening aberrantly methylated genes in CRC. While previous studies focused on the limited identification of hypermethylated genes, ours is the first study to systematically and comprehensively identify novel hypermethylated

  15. A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans

    PubMed Central

    Palmer, Nicholette D.; McDonough, Caitrin W.; Hicks, Pamela J.; Roh, Bong H.; Wing, Maria R.; An, S. Sandy; Hester, Jessica M.; Cooke, Jessica N.; Bostrom, Meredith A.; Rudock, Megan E.; Talbert, Matthew E.; Lewis, Joshua P.; Ferrara, Assiamira; Lu, Lingyi; Ziegler, Julie T.; Sale, Michele M.; Divers, Jasmin; Shriner, Daniel; Adeyemo, Adebowale; Rotimi, Charles N.; Ng, Maggie C. Y.; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.

    2012-01-01

    African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10−8). SNP rs7560163 (P = 7.0×10−9, OR (95% CI) = 0.75 (0.67–0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10−5) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations. PMID:22238593

  16. A genome-wide association search for type 2 diabetes genes in African Americans.

    PubMed

    Palmer, Nicholette D; McDonough, Caitrin W; Hicks, Pamela J; Roh, Bong H; Wing, Maria R; An, S Sandy; Hester, Jessica M; Cooke, Jessica N; Bostrom, Meredith A; Rudock, Megan E; Talbert, Matthew E; Lewis, Joshua P; Ferrara, Assiamira; Lu, Lingyi; Ziegler, Julie T; Sale, Michele M; Divers, Jasmin; Shriner, Daniel; Adeyemo, Adebowale; Rotimi, Charles N; Ng, Maggie C Y; Langefeld, Carl D; Freedman, Barry I; Bowden, Donald W; Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Morris, Andrew P; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Langenberg, Claudia; Hofmann, Oliver M; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Couper, David J; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Perry, John R B; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L; Morris, Andrew D; Palmer, Colin N A; Pramstaller, Peter P; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J; Watanabe, Richard M; Abecasis, Goncalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Hu, Frank B; Meigs, James B; Pankow, James S; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Inês; Florez, Jose C; Frayling, Timothy M; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I; Soranzo, Nicole; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Mägi, Reedik; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Henneman, Peter; Dehghan, Abbas; Hottenga, Jouke Jan; Song, Kijoung; Goel, Anuj; Egan, Josephine M; Lajunen, Taina; Doney, Alex; Kanoni, Stavroula; Cavalcanti-Proença, Christine; Kumari, Meena; Timpson, Nicholas J; Zabena, Carina; Ingelsson, Erik; An, Ping; O'Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ariyurek, Yavuz; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Bergmann, Sven; Bochud, Murielle; Bonnefond, Amélie; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Crisponi, Laura; Day, Ian N M; de Geus, Eco J C; Delplanque, Jerome; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Frants, Rune; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Grundy, Scott; Gwilliam, Rhian; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Hicks, Andrew A; Hillman, David R; Hingorani, Aroon D; Hui, Jennie; Hung, Joe; Jula, Antti; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Mahley, Robert; Mangino, Massimo; Manning, Alisa K; Martínez-Larrad, María Teresa; McAteer, Jarred B; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Mukherjee, Sutapa; Naitza, Silvia; Neville, Matthew J; Oostra, Ben A; Orrù, Marco; Pakyz, Ruth; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L; Perola, Markus; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Psaty, Bruce M; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sijbrands, Eric J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tanaka, Toshiko; Tönjes, Anke; Uitterlinden, André G; van Dijk, Ko Willems; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Ward, Kim L; Watkins, Hugh; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Loos, Ruth J F; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Silander, Kaisa; Salomaa, Veikko; Smith, George Davey; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Dedoussis, George V; Serrano-Ríos, Manuel; Lind, Lars; Palmer, Lyle J; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pramstaller, Peter Paul; Wright, Alan F; Stumvoll, Michael; Hamsten, Anders; Buchanan, Thomas A; Valle, Timo T; Rotter, Jerome I; Siscovick, David S; Penninx, Brenda W J H; Boomsma, Dorret I; Deloukas, Panos; Spector, Timothy D; Ferrucci, Luigi; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Waterworth, Dawn M; Vollenweider, Peter; Peltonen, Leena; Mooser, Vincent; Sladek, Robert

    2012-01-01

    African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations. PMID:22238593

  17. Differential gene expression between African American and European American colorectal cancer patients.

    PubMed

    Jovov, Biljana; Araujo-Perez, Felix; Sigel, Carlie S; Stratford, Jeran K; McCoy, Amber N; Yeh, Jen Jen; Keku, Temitope

    2012-01-01

    The incidence and mortality of colorectal cancer (CRC) is higher in African Americans (AAs) than other ethnic groups in the U. S., but reasons for the disparities are unknown. We performed gene expression profiling of sporadic CRCs from AAs vs. European Americans (EAs) to assess the contribution to CRC disparities. We evaluated the gene expression of 43 AA and 43 EA CRC tumors matched by stage and 40 matching normal colorectal tissues using the Agilent human whole genome 4x44K cDNA arrays. Gene and pathway analyses were performed using Significance Analysis of Microarrays (SAM), Ten-fold cross validation, and Ingenuity Pathway Analysis (IPA). SAM revealed that 95 genes were differentially expressed between AA and EA patients at a false discovery rate of ≤5%. Using IPA we determined that most prominent disease and pathway associations of differentially expressed genes were related to inflammation and immune response. Ten-fold cross validation demonstrated that following 10 genes can predict ethnicity with an accuracy of 94%: CRYBB2, PSPH, ADAL, VSIG10L, C17orf81, ANKRD36B, ZNF835, ARHGAP6, TRNT1 and WDR8. Expression of these 10 genes was validated by qRT-PCR in an independent test set of 28 patients (10 AA, 18 EA). Our results are the first to implicate differential gene expression in CRC racial disparities and indicate prominent difference in CRC inflammation between AA and EA patients. Differences in susceptibility to inflammation support the existence of distinct tumor microenvironments in these two patient populations. PMID:22276153

  18. A Nonessential African Swine Fever Virus Gene UK Is a Significant Virulence Determinant in Domestic Swine

    PubMed Central

    Zsak, L.; Caler, E.; Lu, Z.; Kutish, G. F.; Neilan, J. G.; Rock, D. L.

    1998-01-01

    Sequence analysis of the right variable genomic region of the pathogenic African swine fever virus (ASFV) isolate E70 revealed a novel gene, UK, that is immediately upstream from the previously described ASFV virulence-associated gene NL-S (L. Zsak, Z. Lu, G. F. Kutish, J. G. Neilan, and D. L. Rock, J. Virol. 70:8865–8871, 1996). UK, transcriptionally oriented toward the right end of the genome, predicts a protein of 96 amino acids with a molecular mass of 10.7 kDa. Searches of genetic databases did not find significant similarity between UK and other known genes. Sequence analysis of the UK genes from several pathogenic ASFVs from Europe, the Caribbean, and Africa demonstrated that this gene was highly conserved among diverse pathogenic isolates, including those from both tick and pig sources. Polyclonal antibodies raised against the UK protein specifically precipitated a 15-kDa protein from ASFV-infected macrophage cell cultures as early as 2 h postinfection. A recombinant UK gene deletion mutant, ΔUK, and its revertant, UK-R, were constructed from the E70 isolate to study gene function. Although deletion of UK did not affect the growth characteristics of the virus in macrophage cell cultures, ΔUK exhibited reduced virulence in infected pigs. While mortality among parental E70- or UK-R-infected animals was 100%, all ΔUK-infected pigs survived infection. Fever responses were comparable in E70-, UK-R-, and ΔUK-infected groups; however, ΔUK-infected animals exhibited significant, 100- to 1,000-fold, reductions in viremia titers. These data indicate that the highly conserved UK gene of ASFV, while being nonessential for growth in macrophages in vitro, is an important viral virulence determinant for domestic pigs. PMID:9444996

  19. A nonessential African swine fever virus gene UK is a significant virulence determinant in domestic swine.

    PubMed

    Zsak, L; Caler, E; Lu, Z; Kutish, G F; Neilan, J G; Rock, D L

    1998-02-01

    Sequence analysis of the right variable genomic region of the pathogenic African swine fever virus (ASFV) isolate E70 revealed a novel gene, UK, that is immediately upstream from the previously described ASFV virulence-associated gene NL-S (L. Zsak, Z. Lu, G. F. Kutish, J. G. Neilan, and D. L. Rock, J. Virol. 70:8865-8871, 1996). UK, transcriptionally oriented toward the right end of the genome, predicts a protein of 96 amino acids with a molecular mass of 10.7 kDa. Searches of genetic databases did not find significant similarity between UK and other known genes. Sequence analysis of the UK genes from several pathogenic ASFVs from Europe, the Caribbean, and Africa demonstrated that this gene was highly conserved among diverse pathogenic isolates, including those from both tick and pig sources. Polyclonal antibodies raised against the UK protein specifically precipitated a 15-kDa protein from ASFV-infected macrophage cell cultures as early as 2 h postinfection. A recombinant UK gene deletion mutant, deltaUK, and its revertant, UK-R, were constructed from the E70 isolate to study gene function. Although deletion of UK did not affect the growth characteristics of the virus in macrophage cell cultures, deltaUK exhibited reduced virulence in infected pigs. While mortality among parental E70- or UK-R-infected animals was 100%, all deltaUK-infected pigs survived infection. Fever responses were comparable in E70-, UK-R-, and deltaUK-infected groups; however, deltaUK-infected animals exhibited significant, 100- to 1,000-fold, reductions in viremia titers. These data indicate that the highly conserved UK gene of ASFV, while being nonessential for growth in macrophages in vitro, is an important viral virulence determinant for domestic pigs. PMID:9444996

  20. Targeted high-throughput growth hormone 1 gene sequencing reveals high within-breed genetic diversity in South African goats.

    PubMed

    Ncube, K T; Mdladla, K; Dzomba, E F; Muchadeyi, F C

    2016-06-01

    This study assessed the genetic diversity in the growth hormone 1 gene (GH1) within and between South African goat breeds. Polymerase chain reaction-targeted gene amplification together with Illumina MiSeq next-generation sequencing (NGS) was used to generate the full length (2.54 kb) of the growth hormone 1 gene and screen for SNPs in the South African Boer (SAB) (n = 17), Tankwa (n = 15) and South African village (n = 35) goat populations. A range of 27-58 SNPs per population were observed. Mutations resulting in amino acid changes were observed at exons 2 and 5. Higher within-breed diversity of 97.37% was observed within the population category consisting of SA village ecotypes and the Tankwa goats. Highest pairwise FST values ranging from 0.148 to 0.356 were observed between the SAB and both the South African village and Tankwa feral goat populations. Phylogenetic analysis indicated nine genetic clusters, which reflected close relationships between the South African populations and the other international breeds with the exception of the Italian Sarda breeds. Results imply greater potential for within-population selection programs, particularly with SA village goats. PMID:26919178

  1. Distinct cholesterogenic and lipidogenic gene expression patterns in ovarian cancer - a new pool of biomarkers

    PubMed Central

    Pampalakis, Georgios; Politi, Angeliki-Louiza; Papanastasiou, Anastasios; Sotiropoulou, Georgia

    2015-01-01

    Cancer cells display different metabolic requirements compared to nonmalignant cells imposed by their need for rapid proliferation. Alterations in cellular metabolic pathways of lipid and cholesterol synthesis have been linked to tumorigenesis and cancer progression but have not been exploited in clinical diagnosis. Here, the expression of genes related to cholesterol/lipid metabolism was measured with semiquantitative and real-time RT-PCR in RNA isolated from normal, benign and cancer ovarian tissues. We found that both SREBF2 and its target gene DHCR7 are downregulated in ovarian cancer tissues. On the contrary, SREBF1c and its target SCD1 were upregulated. The steroidogenesis regulator PDE8B was found downregulated. Oncomine analysis supported these findings, and further revealed that in ovarian cancers, the SREBF1-regulated lipidogenic pathway is activated while the SREBF2-regulated cholesterogenic pathway is repressed based on expression profiles of HMGCR and DHCR7. In conclusion, we show that ovarian cancer cells display distinct lipidogenic and cholesterogenic gene expression profiles with potential applications in the development of new biomarkers and/or treatment of ovarian cancer. Reduced cholesterol and enhanced lipid synthesis and SCD1 expression may provide an explanation for the previously reported increased membrane fluidity of ovarian cancer cells, a finding that merits further investigation. PMID:26807200

  2. Light intensity regulation of cab gene transcription is signaled by the redox state of the plastoquinone pool.

    PubMed Central

    Escoubas, J M; Lomas, M; LaRoche, J; Falkowski, P G

    1995-01-01

    The eukaryotic green alga Dunaliella tertiolecta acclimates to decreased growth irradiance by increasing cellular levels of light-harvesting chlorophyll protein complex apoproteins associated with photosystem II (LHCIIs), whereas increased growth irradiance elicits the opposite response. Nuclear run-on transcription assays and measurements of cab mRNA stability established that light intensity-dependent changes in LHCII are controlled at the level of transcription. cab gene transcription in high-intensity light was partially enhanced by reducing plastoquinone with 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU), whereas it was repressed in low-intensity light by partially inhibiting the oxidation of plastoquinol with 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB). Uncouplers of photosynthetic electron transport and inhibition of water splitting had no effect on LHCII levels. These results strongly implicate the redox state of the plastoquinone pool in the chloroplast as a photon-sensing system that is coupled to the light-intensity regulation of nuclear-encoded cab gene transcription. The accumulation of cellular chlorophyll at low-intensity light can be blocked with cytoplasmically directed phosphatase inhibitors, such as okadaic acid, microcystin L-R, and tautomycin. Gel mobility-shift assays revealed that cells grown in high-intensity light contained proteins that bind to the promoter region of a cab gene carrying sequences homologous to higher plant light-responsive elements. On the basis of these experimental results, we propose a model for a light intensity signaling system where cab gene expression is reversibly repressed by a phosphorylated factor coupled to the redox status of plastoquinone through a chloroplast protein kinase. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7479759

  3. Simultaneous analysis of the bidirectional African cassava mosaic virus promoter activity using two different luciferase genes.

    PubMed

    Frey, P M; Schärer-Hernández, N G; Fütterer, J; Potrykus, I; Puonti-Kaerlas, J

    2001-03-01

    The expression of geminivirus genes is controlled by bidirectional promoters which are located in the large intergenic region of the circular DNA genomes and specifically regulated by virus encoded proteins. In order to study the simultaneous regulation of both orientations of the DNA A and DNA B promoters of African cassava mosaic virus (ACMV), they were cloned between two different luciferase genes with the firefly luciferase gene in complementary-sense and the Renilla luciferase gene in virion-sense orientation. The regulation of the ACMV promoters by proteins encoded by the complete DNA A, as well as by the individually expressed transactivator (TrAP) or replication-associated (Rep) proteins was assessed in tobacco and cassava protoplasts using dual luciferase assays. In addition, the regulation of the DNA A promoter integrated into tobacco genome was also assessed. The results show that TrAP activates virion-sense expression strongly both in cassava and tobacco protoplasts, but not in transgenic tobacco plants. In contrast to this, DNA A encoded proteins activate virion-sense expression both in protoplasts and in transgenic plants. At the same time they reduce the expression of the complementary-sense Rep gene on DNA A but activate the expression of the complementary-sense movement protein (MPB) gene on DNA B. The degree of MBP activation is higher in cassava than in tobacco protoplasts, indicating that the plant host also influences the promoter strength. Transient transformation experiments using linearized DNA indicate that the different regulation of the ACMV DNA A promoter in protoplasts and transgenic plants could be due to different DNA curvature in free plasmids and in genes integrated in plant genomic DNA. PMID:11324760

  4. Elevated Resistin Gene Expression in African American Estrogen and Progesterone Receptor Negative Breast Cancer

    PubMed Central

    Vallega, Karin A.; Liu, NingNing; Myers, Jennifer S.; Yu, Kaixian; Sang, Qing-Xiang Amy

    2016-01-01

    Introduction African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women. Methods Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values. Results Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer. Conclusion Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA

  5. Immune-Related Functions of the Hivep Gene Family in East African Cichlid Fishes

    PubMed Central

    Diepeveen, Eveline T.; Roth, Olivia; Salzburger, Walter

    2013-01-01

    Immune-related genes are often characterized by adaptive protein evolution. Selection on immune genes can be particularly strong when hosts encounter novel parasites, for instance, after the colonization of a new habitat or upon the exploitation of vacant ecological niches in an adaptive radiation. We examined a set of new candidate immune genes in East African cichlid fishes. More specifically, we studied the signatures of selection in five paralogs of the human immunodeficiency virus type I enhancer-binding protein (Hivep) gene family, tested their involvement in the immune defense, and related our results to explosive speciation and adaptive radiation events in cichlids. We found signatures of long-term positive selection in four Hivep paralogs and lineage-specific positive selection in Hivep3b in two radiating cichlid lineages. Exposure of the cichlid Astatotilapia burtoni to a vaccination with Vibrio anguillarum bacteria resulted in a positive correlation between immune response parameters and expression levels of three Hivep loci. This work provides the first evidence for a role of Hivep paralogs in teleost immune defense and links the signatures of positive selection to host–pathogen interactions within an adaptive radiation. PMID:24142922

  6. Deep Sequencing of the Nicastrin Gene in Pooled DNA, the Identification of Genetic Variants That Affect Risk of Alzheimer's Disease

    PubMed Central

    Lupton, Michelle K.; Proitsi, Petroula; Danillidou, Makrina; Tsolaki, Magda; Hamilton, Gillian; Wroe, Richard; Pritchard, Megan; Lord, Kathryn; Martin, Belinda M.; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Harold, Denise; Hollingworth, Paul; Lovestone, Simon; Powell, John F.

    2011-01-01

    Nicastrin is an obligatory component of the γ-secretase; the enzyme complex that leads to the production of Aβ fragments critically central to the pathogenesis of Alzheimer's disease (AD). Analyses of the effects of common variation in this gene on risk for late onset AD have been inconclusive. We investigated the effect of rare variation in the coding regions of the Nicastrin gene in a cohort of AD patients and matched controls using an innovative pooling approach and next generation sequencing. Five SNPs were identified and validated by individual genotyping from 311 cases and 360 controls. Association analysis identified a non-synonymous rare SNP (N417Y) with a statistically higher frequency in cases compared to controls in the Greek population (OR 3.994, CI 1.105–14.439, p = 0.035). This finding warrants further investigation in a larger cohort and adds weight to the hypothesis that rare variation explains some of genetic heritability still to be identified in Alzheimer's disease. PMID:21364883

  7. Discovery of nucleotide polymorphisms in the Musa gene pool by Ecotilling.

    PubMed

    Till, Bradley J; Jankowicz-Cieslak, Joanna; Sági, László; Huynh, Owen A; Utsushi, Hiroe; Swennen, Rony; Terauchi, Ryohei; Mba, Chikelu

    2010-11-01

    Musa (banana and plantain) is an important genus for the global export market and in local markets where it provides staple food for approximately 400 million people. Hybridization and polyploidization of several (sub)species, combined with vegetative propagation and human selection have produced a complex genetic history. We describe the application of the Ecotilling method for the discovery and characterization of nucleotide polymorphisms in diploid and polyploid accessions of Musa. We discovered over 800 novel alleles in 80 accessions. Sequencing and band evaluation shows Ecotilling to be a robust and accurate platform for the discovery of polymorphisms in homologous and homeologous gene targets. In the process of validating the method, we identified two single nucleotide polymorphisms that may be deleterious for the function of a gene putatively important for phototropism. Evaluation of heterozygous polymorphism and haplotype blocks revealed a high level of nucleotide diversity in Musa accessions. We further applied a strategy for the simultaneous discovery of heterozygous and homozygous polymorphisms in diploid accessions to rapidly evaluate nucleotide diversity in accessions of the same genome type. This strategy can be used to develop hypotheses for inheritance patterns of nucleotide polymorphisms within and between genome types. We conclude that Ecotilling is suitable for diversity studies in Musa, that it can be considered for functional genomics studies and as tool in selecting germplasm for traditional and mutation breeding approaches. PMID:20589365

  8. Intraclass diversification of immunoglobulin heavy chain genes in the African lungfish.

    PubMed

    Zhang, Tianyi; Tacchi, Luca; Wei, Zhiguo; Zhao, Yaofeng; Salinas, Irene

    2014-05-01

    Lungfish (Dipnoi) are the closest living relatives to tetrapods, and they represent the transition from water to land during vertebrate evolution. Lungfish are armed with immunoglobulins (Igs), one of the hallmarks of the adaptive immune system of jawed vertebrates, but only three Ig forms have been characterized in Dipnoi to date. We report here a new diversity of Ig molecules in two African lungfish species (Protopterus dolloi and Protopterus annectens). The African lungfish Igs consist of three IgMs, two IgWs, three IgNs, and an IgQ, where both IgN and IgQ originated evidently from the IgW lineage. Our data also suggest that the IgH genes in the lungfish are organized in a transiting form from clusters (IgH loci in cartilaginous fish) to a translocon configuration (IgH locus in tetrapods). We propose that the intraclass diversification of the two primordial gnathostome Ig classes (IgM and IgW) as well as acquisition of new isotypes (IgN and IgQ) has allowed lungfish to acquire a complex and functionally diverse Ig repertoire to fight a variety of microorganisms. Furthermore, our results support the idea that "tetrapod-specific" Ig classes did not evolve until the vertebrate adaptation to land was completed ~360 million years ago. PMID:24676685

  9. Intraclass diversification of immunoglobulin heavy chain genes in the African lungfish

    PubMed Central

    Zhang, Tianyi; Tacchi, Luca; Wei, Zhiguo

    2015-01-01

    Lungfish (Dipnoi) are the closest living relatives to tetrapods, and they represent the transition from water to land during vertebrate evolution. Lungfish are armed with immunoglobulins (Igs), one of the hallmarks of the adaptive immune system of jawed vertebrates, but only three Ig forms have been characterized in Dipnoi to date. We report here a new diversity of Ig molecules in two African lungfish species (Protopterus dolloi and Protopterus annectens). The African lungfish Igs consist of three IgMs, two IgWs, three IgNs, and an IgQ, where both IgN and IgQ originated evidently from the IgW lineage. Our data also suggest that the IgH genes in the lungfish are organized in a transiting form from clusters (IgH loci in cartilaginous fish) to a translocon configuration (IgH locus in tetrapods). We propose that the intraclass diversification of the two primordial gnathostome Ig classes (IgM and IgW) as well as acquisition of new isotypes (IgN and IgQ) has allowed lungfish to acquire a complex and functionally diverse Ig repertoire to fight a variety of microorganisms. Furthermore, our results support the idea that “tetrapod-specific” Ig classes did not evolve until the vertebrate adaptation to land was completed ∼360 million years ago. PMID:24676685

  10. African Swine Fever Virus Multigene Family 360 and 530 Genes Affect Host Interferon Response

    PubMed Central

    Afonso, C. L.; Piccone, M. E.; Zaffuto, K. M.; Neilan, J.; Kutish, G. F.; Lu, Z.; Balinsky, C. A.; Gibb, T. R.; Bean, T. J.; Zsak, L.; Rock, D. L.

    2004-01-01

    African swine fever virus (ASFV) multigene family 360 and 530 (MGF360/530) genes affect viral growth in macrophage cell cultures and virulence in pigs (L. Zsak, Z. Lu, T. G. Burrage, J. G. Neilan, G. F. Kutish, D. M. Moore, and D. L. Rock, J. Virol. 75:3066-3076, 2001). The mechanism by which these novel genes affect virus-host interactions is unknown. To define MGF360/530 gene function, we compared macrophage transcriptional responses following infection with parental ASFV (Pr4) and an MGF360/530 deletion mutant (Pr4Δ35). A swine cDNA microarray containing 7,712 macrophage cDNA clones was used to compare the transcriptional profiles of swine macrophages infected with Pr4 and Pr4Δ35 at 3 and 6 h postinfection (hpi). While at 3 hpi most (7,564) of the genes had similar expression levels in cells infected with either virus, 38 genes had significantly increased (>2.0-fold, P < 0.05) mRNA levels in Pr4Δ35-infected macrophages. Similar up-regulation of these genes was observed at 6 hpi. Viral infection was required for this induced transcriptional response. Most Pr4Δ35 up-regulated genes were part of a type I interferon (IFN) response or were genes that are normally induced by double-stranded RNA and/or viral infection. These included monocyte chemoattractant protein, transmembrane protein 3, tetratricopeptide repeat protein 1, a ubiquitin-like 17-kDa protein, ubiquitin-specific protease ISG43, an RNA helicase DEAD box protein, GTP-binding MX protein, the cytokine IP-10, and the PKR activator PACT. Differential expression of IFN early-response genes in Pr4Δ35 relative to Pr4 was confirmed by Northern blot analysis and real-time PCR. Analysis of IFN-α mRNA and secreted IFN-α levels at 3, 8, and 24 hpi revealed undetectable IFN-α in mock- and Pr4-infected macrophages but significant IFN-α levels at 24 hpi in Pr4Δ35-infected macrophages. The absence of IFN-α in Pr4-infected macrophages suggests that MGF360/530 genes either directly or indirectly suppress a type

  11. African swine fever virus multigene family 360 and 530 genes affect host interferon response.

    PubMed

    Afonso, C L; Piccone, M E; Zaffuto, K M; Neilan, J; Kutish, G F; Lu, Z; Balinsky, C A; Gibb, T R; Bean, T J; Zsak, L; Rock, D L

    2004-02-01

    African swine fever virus (ASFV) multigene family 360 and 530 (MGF360/530) genes affect viral growth in macrophage cell cultures and virulence in pigs (L. Zsak, Z. Lu, T. G. Burrage, J. G. Neilan, G. F. Kutish, D. M. Moore, and D. L. Rock, J. Virol. 75:3066-3076, 2001). The mechanism by which these novel genes affect virus-host interactions is unknown. To define MGF360/530 gene function, we compared macrophage transcriptional responses following infection with parental ASFV (Pr4) and an MGF360/530 deletion mutant (Pr4 Delta 35). A swine cDNA microarray containing 7,712 macrophage cDNA clones was used to compare the transcriptional profiles of swine macrophages infected with Pr4 and Pr4 Delta 35 at 3 and 6 h postinfection (hpi). While at 3 hpi most (7,564) of the genes had similar expression levels in cells infected with either virus, 38 genes had significantly increased (>2.0-fold, P < 0.05) mRNA levels in Pr4 Delta 35-infected macrophages. Similar up-regulation of these genes was observed at 6 hpi. Viral infection was required for this induced transcriptional response. Most Pr Delta 35 up-regulated genes were part of a type I interferon (IFN) response or were genes that are normally induced by double-stranded RNA and/or viral infection. These included monocyte chemoattractant protein, transmembrane protein 3, tetratricopeptide repeat protein 1, a ubiquitin-like 17-kDa protein, ubiquitin-specific protease ISG43, an RNA helicase DEAD box protein, GTP-binding MX protein, the cytokine IP-10, and the PKR activator PACT. Differential expression of IFN early-response genes in Pr4 Delta 35 relative to Pr4 was confirmed by Northern blot analysis and real-time PCR. Analysis of IFN-alpha mRNA and secreted IFN-alpha levels at 3, 8, and 24 hpi revealed undetectable IFN-alpha in mock- and Pr4-infected macrophages but significant IFN-alpha levels at 24 hpi in Pr4 Delta 35-infected macrophages. The absence of IFN-alpha in Pr4-infected macrophages suggests that MGF360/530 genes

  12. Rpv10: a new locus from the Asian Vitis gene pool for pyramiding downy mildew resistance loci in grapevine.

    PubMed

    Schwander, Florian; Eibach, Rudolf; Fechter, Iris; Hausmann, Ludger; Zyprian, Eva; Töpfer, Reinhard

    2012-01-01

    A population derived from a cross between grapevine breeding strain Gf.Ga-52-42 and cultivar 'Solaris' consisting of 265 F1-individuals was genetically mapped using SSR markers and screened for downy mildew resistance. Quantitative trait locus (QTL) analysis revealed two strong QTLs on linkage groups (LGs) 18 and 09. The locus on LG 18 was found to be identical with the previously described locus Rpv3 and is transmitted by Gf.Ga-52-42. 'Solaris' transmitted the resistance-related locus on LG 09 explaining up to 50% of the phenotypic variation in the population. This downy mildew resistance locus is named Rpv10 for resistance to Plasmopara viticola. Rpv10 was initially introgressed from Vitis amurensis, a wild species of the Asian Vitis gene pool. The one-LOD supported confidence interval of the QTL spans a section of 2.1 centi Morgan (cM) corresponding to 314 kb in the reference genome PN40024 (12x). Eight resistance gene analogues (RGAs) of the NBS-LRR type and additional resistance-linked genes are located in this region of PN40024. The F1 sub-population which contains the Rpv3 as well as the Rpv10 locus showed a significantly higher degree of resistance, indicating additive effects by pyramiding of resistance loci. Possibilities for using the resistance locus Rpv10 in a grapevine breeding programme are discussed. Furthermore, the marker data revealed 'Severnyi' × 'Muscat Ottonel' as the true parentage for the male parent of 'Solaris'. PMID:21935694

  13. Resistance gene pool to co-trimoxazole in non-susceptible Nocardia strains

    PubMed Central

    Valdezate, Sylvia; Garrido, Noelia; Carrasco, Gema; Villalón, Pilar; Medina-Pascual, María J.; Saéz-Nieto, Juan A.

    2015-01-01

    The soil-borne pathogen Nocardia sp. causes severe cutaneous, pulmonary, and central nervous system infections. Against them, co-trimoxazole (SXT) constitutes the mainstay of antimicrobial therapy. However, some Nocardia strains show resistance to SXT, but the underlying genetic basis is unknown. We investigated the presence of genetic resistance determinants and class 1–3 integrons in 76 SXT-resistant Nocardia strains by PCR and sequencing. By E test, these clinical strains showed SXT minimum inhibitory concentrations of ≥32:608 mg/L (ratio of 1:19 for trimethoprim: sulfamethoxazole). They belonged to 12 species, being the main representatives Nocardia farcinica (32%), followed by N. flavorosea (6.5%), N. nova (11.8%), N. carnea (10.5%), N. transvalensis (10.5%), and Nocardia sp. (6.5%). The prevalence of resistance genes in the SXT-resistant strains was as follows: sul1 and sul2 93.4 and 78.9%, respectively, dfrA(S1) 14.7%, blaTEM-1 and blaZ 2.6 and 2.6%, respectively, VIM-2 1.3%, aph(3′)-IIIa 40.8%, ermA, ermB, mefA, and msrD 2.6, 77.6, 14.4, and 5.2%, respectively, and tet(O), tet(M), and tet(L) 48.6, 25.0, and 3.9%, respectively. Detected amino acid changes in GyrA were not related to fluoroquinolone resistance, but probably linked to species polymorphism. Class 1 and 3 integrons were found in 93.42 and 56.57% strains, respectively. Class 2 integrons and sul3 genes were not detected. Other mechanisms, different than dfrA(S1), dfrD, dfrF, dfrG, and dfrK, could explain the strong trimethoprim resistance shown by the other 64 strains. For first time, resistance determinants commonly found in clinically important bacteria were detected in Nocardia sp. sul1, sul2, erm(B), and tet(O) were the most prevalent in the SXT-resistant strains. The similarity in their resistome could be due to a common genetic platform, in which these determinants are co-transferred. PMID:25972856

  14. Swimming in the deep end of the gene pool: global population structure of an oceanic giant.

    PubMed

    Bradshaw, Corey J A

    2007-12-01

    Despite the impression held by some that few biological mysteries remain, even evocative species such as humpback whales (Megaptera novaeangliae), white sharks (Carcharodon carcharias) and green turtles (Chelonia mydas) have poorly documented movement patterns, reproductive strategies and population dynamics despite years of dedicated research. This is largely due to the difficulty of observing wide-ranging marine species over the majority of their life cycle. The advent of powerful tracking devices has certainly improved our understanding, but it is usually only with molecular tools that the nature of population structure becomes apparent. In this issue of Molecular Ecology, Castro and colleagues have provided the first global-scale assessment of population structure for the largest fish--whale sharks (Rhincodon typus). Whale sharks can reach lengths > 12 m and are a popular tourist attraction at places where they aggregate, yet for most of their life cycle, we know little indeed of where they go and how they interact with other populations. Previous tracking studies imply a high dispersal capacity, but only now have Castro and colleagues demonstrated high gene flow and haplotype diversity among the major ocean basins where they are found. PMID:17944855

  15. Phenotype-Based Identification of Host Genes Required for Replication of African Swine Fever Virus†

    PubMed Central

    Chang, Annie C. Y.; Zsak, Laszlo; Feng, Yanan; Mosseri, Ronen; Lu, Quan; Kowalski, Paul; Zsak, Aniko; Burrage, Thomas G.; Neilan, John G.; Kutish, Gerald F.; Lu, Zhiqiang; Laegreid, Will; Rock, Daniel L.; Cohen, Stanley N.

    2006-01-01

    African swine fever virus (ASFV) produces a fatal acute hemorrhagic fever in domesticated pigs that potentially is a worldwide economic threat. Using an expressed sequence tag (EST) library-based antisense method of random gene inactivation and a phenotypic screen for limitation of ASFV replication in cultured human cells, we identified six host genes whose cellular functions are required by ASFV. These included three loci, BAT3 (HLA-B-associated transcript 3), C1qTNF (C1q and tumor necrosis factor-related protein 6), and TOM40 (translocase of outer mitochondrial membrane 40), for which antisense expression from a tetracycline-regulated promoter resulted in reversible inhibition of ASFV production by >99%. The effects of antisense transcription of the BAT3 EST and also of expression in the sense orientation of this EST, which encodes amino acid residues 450 to 518 of the mature BAT3 protein, were investigated more extensively. Sense expression of the BAT3 peptide, which appears to reversibly interfere with BAT3 function by a dominant negative mechanism, resulted in decreased synthesis of viral DNA and proteins early after ASFV infection, altered transcription of apoptosis-related genes as determined by cDNA microarray analysis, and increased cellular sensitivity to staurosporine-induced apoptosis. Antisense transcription of BAT3 reduced ASFV production without affecting abundance of the virus macromolecules we assayed. Our results, which demonstrate the utility of EST-based functional screens for the detection of host genes exploited by pathogenic viruses, reveal a novel collection of cellular genes previously not known to be required for ASFV infection. PMID:16912318

  16. Phenotype-based identification of host genes required for replication of African swine fever virus.

    PubMed

    Chang, Annie C Y; Zsak, Laszlo; Feng, Yanan; Mosseri, Ronen; Lu, Quan; Kowalski, Paul; Zsak, Aniko; Burrage, Thomas G; Neilan, John G; Kutish, Gerald F; Lu, Zhiqiang; Laegreid, Will; Rock, Daniel L; Cohen, Stanley N

    2006-09-01

    African swine fever virus (ASFV) produces a fatal acute hemorrhagic fever in domesticated pigs that potentially is a worldwide economic threat. Using an expressed sequence tag (EST) library-based antisense method of random gene inactivation and a phenotypic screen for limitation of ASFV replication in cultured human cells, we identified six host genes whose cellular functions are required by ASFV. These included three loci, BAT3 (HLA-B-associated transcript 3), C1qTNF (C1q and tumor necrosis factor-related protein 6), and TOM40 (translocase of outer mitochondrial membrane 40), for which antisense expression from a tetracycline-regulated promoter resulted in reversible inhibition of ASFV production by >99%. The effects of antisense transcription of the BAT3 EST and also of expression in the sense orientation of this EST, which encodes amino acid residues 450 to 518 of the mature BAT3 protein, were investigated more extensively. Sense expression of the BAT3 peptide, which appears to reversibly interfere with BAT3 function by a dominant negative mechanism, resulted in decreased synthesis of viral DNA and proteins early after ASFV infection, altered transcription of apoptosis-related genes as determined by cDNA microarray analysis, and increased cellular sensitivity to staurosporine-induced apoptosis. Antisense transcription of BAT3 reduced ASFV production without affecting abundance of the virus macromolecules we assayed. Our results, which demonstrate the utility of EST-based functional screens for the detection of host genes exploited by pathogenic viruses, reveal a novel collection of cellular genes previously not known to be required for ASFV infection. PMID:16912318

  17. Molecular Analysis of South African Ovine Herpesvirus 2 Strains Based on Selected Glycoprotein and Tegument Genes

    PubMed Central

    Doboro, Fulufhelo Amanda; Njiro, Stephen; Sibeko-Matjila, Kgomotso; Van Vuuren, Moritz

    2016-01-01

    Ovine herpesvirus 2 (OvHV-2), is the causative agent of sheep-associated malignant catarrhal fever (SA-MCF), a generally fatal disease of cattle and other captive wild ruminants. Information on the OvHV-2 strains circulating in South Africa (SA) and other African countries with regard to genetic structure and diversity, and pattern of distribution is not available. This study aimed to characterize the OvHV-2 strains circulating in SA using selected genes encoding glycoproteins and tegument proteins. To establish the genetic diversity of OvHV-2 strains, four genes, Ov 7, Ov 8 ex2, ORF 27 and ORF 73 were selected for analysis by PCR and DNA sequencing. Nucleotide and amino acid multiple sequence analyses revealed two genotypes for ORF 27 and ORF 73, and three genotypes for Ov 7 and Ov 8 ex2, randomly distributed throughout the regions. Ov 7 and ORF 27 nucleotide sequence analysis revealed variations that distinguished SA genotypes from those of reference OvHV-2 strains. Epitope mapping analysis showed that mutations identified from the investigated genes are not likely to affect the functions of the gene products, particularly those responsible for antibody binding activities associated with B-cell epitopes. Knowledge of the extent of genetic diversity existing among OvHV-2 strains has provided an understanding on the distribution patterns of OvHV-2 strains or genotypes across the regions of South Africa. This can facilitate the management of SA-MCF in SA, in terms of introduction of control measures or safe practices to monitor and control OvHV-2 infection. The products encoded by the Ov 7, Ov 8 ex2 and ORF 27 genes are recommended for evaluation of their coded proteins as possible antigens in the development of an OvHV-2 specific serodiagnostic assay. PMID:27002629

  18. Polymorphisms of Estrogen Metabolism-Related Genes and Prostate Cancer Risk in Two Populations of African Ancestry

    PubMed Central

    Emeville, Elise; Ferdinand, Séverine; Punga, Augustin; Lufuma, Simon; Blanchet, Pascal; Romana, Marc; Multigner, Luc

    2016-01-01

    Background Estrogens are thought to play a critical role in prostate carcinogenesis. It has been suggested that polymorphisms of genes encoding enzymes involved in estrogen metabolism are risk factors for prostate cancer. However, few studies have been performed on populations of African ancestry, which are known to have a high risk of prostate cancer. Objective We investigated whether functional polymorphisms of CYP17, CYP19, CYP1B1, COMT and UGT1A1 affected the risk of prostate cancer in two different populations of African ancestry. Methods In Guadeloupe (French West Indies), we compared 498 prostate cancer patients and 565 control subjects. In Kinshasa (Democratic Republic of Congo), 162 prostate cancer patients were compared with 144 controls. Gene polymorphisms were determined by the SNaPshot technique or short tandem repeat PCR analysis. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results The AA genotype and the A allele of rs4680 (COMT) appeared to be inversely associated with the risk of prostate cancer in adjusted models for both Afro-Caribbean and native African men. For the A allele, a significant inverse association was observed among cases with low-grade Gleason scores and localized clinical stage, in both populations. Conclusions These preliminary results support the hypothesis that polymorphisms of genes encoding enzymes involved in estrogen metabolism may modulate the risk of prostate cancer in populations of African ancestry. PMID:27074016

  19. Orchestration of Neuronal Differentiation and Progenitor Pool Expansion in the Developing Cortex by SoxC Genes

    PubMed Central

    Chen, Chao; Lee, Garrett A.; Pourmorady, Ariel; Sock, Elisabeth

    2015-01-01

    As the cerebral cortex forms, specialized molecular cascades direct the expansion of progenitor pools, the differentiation of neurons, or the maturation of discrete neuronal subtypes, together ensuring that the correct amounts and classes of neurons are generated. In several neural systems, the SoxC transcriptional regulators, particularly Sox11 and Sox4, have been characterized as functioning exclusively and redundantly in promoting neuronal differentiation. Using the mouse cerebral cortex as a model, Sox11 and Sox4 were examined in the formation of the most complex part of the mammalian brain. Anticipated prodifferentiation roles were observed. Distinct expression patterns and mutant phenotypes, however, reveal that Sox11 and Sox4 are not redundant in the cortex, but rather act in overlapping and discrete populations of neurons. In particular, Sox11 acts in early-born neurons; binding to its partner protein, Neurogenin1, leads to selective targeting and transactivation of a downstream gene, NeuroD1. In addition to neuronal expression, Sox4 was unexpectedly expressed in intermediate progenitor cells, the transit amplifying cell of the cerebral cortex. Sox4 mutant analyses reveal a requirement for Sox4 in IPC specification and maintenance. In intermediate progenitors, Sox4 partners with the proneural gene Neurogenin2 to activate Tbrain2 and then with Tbrain2 to maintain this cell fate. This work reveals an intricately structured molecular architecture for SoxC molecules, with Sox11 acting in a select set of cortical neurons and Sox4 playing an unanticipated role in designating secondary progenitors. PMID:26203155

  20. Renin angiotensinogen system gene polymorphisms and essential hypertension among people of West African descent: a systematic review.

    PubMed

    Reiter, L M; Christensen, D L; Gjesing, A P

    2016-08-01

    This systematic review investigates the high level of hypertension found among urban dwellers in West Africa and in the West African Diaspora in the Americas in relation to variants within the genes encoding the renin angiotensinogen system. For comparison, the results from the Caucasian populations are reviewed as well. Through a PubMed search, 1252 articles were identified and 28 eligible articles assessed in detail of which 13 included a Caucasian population. The results suggest that among the people of West African descent and among the people of Caucasian descent, hypertension is partly related to a number of single nucleotide polymorphisms (SNPs) and haplotypes in the renin gene, the angiotensinogen gene, the angiotensinogen I-converting enzyme gene and the angiotensinogen II type 1 receptor gene. Concordance between these two populations was found for some SNPs. However, for others, it was found that the SNPs associating with hypertension and the disease allele frequencies differed between these populations. Understanding the importance of these variants in a modern life setting may assist our understanding of the increased risk of developing hypertension among West Africans. Because of inconsistency in the results, low statistical power and methodological differences between studies, these results can only be taken as indicative of an association. PMID:26607294

  1. Gene Fusion Analysis in the Battle against the African Endemic Sleeping Sickness

    PubMed Central

    Trimpalis, Philip; Koumandou, Vassiliki Lila; Pliakou, Evangelia; Anagnou, Nicholas P.; Kossida, Sophia

    2013-01-01

    The protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping sickness in humans, which can be lethal if untreated. Most available pharmacological treatments for the disease have severe side-effects. The purpose of this analysis was to detect novel protein-protein interactions (PPIs), vital for the parasite, which could lead to the development of drugs against this disease to block the specific interactions. In this work, the Domain Fusion Analysis (Rosetta Stone method) was used to identify novel PPIs, by comparing T. brucei to 19 organisms covering all major lineages of the tree of life. Overall, 49 possible protein-protein interactions were detected, and classified based on (a) statistical significance (BLAST e-value, domain length etc.), (b) their involvement in crucial metabolic pathways, and (c) their evolutionary history, particularly focusing on whether a protein pair is split in T. brucei and fused in the human host. We also evaluated fusion events including hypothetical proteins, and suggest a possible molecular function or involvement in a certain biological process. This work has produced valuable results which could be further studied through structural biology or other experimental approaches so as to validate the protein-protein interactions proposed here. The evolutionary analysis of the proteins involved showed that, gene fusion or gene fission events can happen in all organisms, while some protein domains are more prone to fusion and fission events and present complex evolutionary patterns. PMID:23874788

  2. Climate-driven range shifts explain the distribution of extant gene pools and predict future loss of unique lineages in a marine brown alga.

    PubMed

    Assis, J; Serrão, E A; Claro, B; Perrin, C; Pearson, G A

    2014-06-01

    The climate-driven dynamics of species ranges is a critical research question in evolutionary ecology. We ask whether present intraspecific diversity is determined by the imprint of past climate. This is an ongoing debate requiring interdisciplinary examination of population genetic pools and persistence patterns across global ranges. Previously, contrasting inferences and predictions have resulted from distinct genomic coverage and/or geographical information. We aim to describe and explain the causes of geographical contrasts in genetic diversity and their consequences for the future baseline of the global genetic pool, by comparing present geographical distribution of genetic diversity and differentiation with predictive species distribution modelling (SDM) during past extremes, present time and future climate scenarios for a brown alga, Fucus vesiculosus. SDM showed that both atmospheric and oceanic variables shape the global distribution of intertidal species, revealing regions of persistence, extinction and expansion during glacial and postglacial periods. These explained the distribution and structure of present genetic diversity, consisting of differentiated genetic pools with maximal diversity in areas of long-term persistence. Most of the present species range comprises postglacial expansion zones and, in contrast to highly dispersive marine organisms, expansions involved only local fronts, leaving distinct genetic pools at rear edges. Besides unravelling a complex phylogeographical history and showing congruence between genetic diversity and persistent distribution zones, supporting the hypothesis of niche conservatism, range shifts and loss of unique genetic diversity at the rear edge were predicted for future climate scenarios, impoverishing the global gene pool. PMID:24766057

  3. Comparative analysis of a putative tuberculosis-susceptibility gene, MC3R, and pseudogene sequences in cattle, African buffalo, hyena, rhinoceros and other African bovids and ruminants.

    PubMed

    Müller, A; Möller, M; Adams, L A; Warren, R M; Hoal, E G; van Helden, P D

    2012-01-01

    Studies in humans have suggested the possible involvement of melanocortin-3-receptor (MC3R) and other components of the central melanocortin system in host defense against mycobacteria. We report a genomic DNA nucleotide sequence highly homologous to human MC3R in several bovids and non-bovid African wildlife species. Nucleotide sequence analysis indicates that the orthologous genes of cattle and buffalo are highly homologous (89.4 and 90%, respectively) to the human MC3R gene. Sequence results also identified a typical non-functional, duplicated pseudogene, MC3RP, in 7 species from the family Bovidae. No pseudogene was found in animals outside Bovidae. The presence of the pseudogene in tuberculosis-susceptible species could have possible immunomodulatory effects on susceptibility to bovine tuberculosis infection, as well as a considerable influence on energy metabolism and food conversion efficiency. PMID:22286663

  4. The role of GHR and IGF1 genes in the genetic determination of African pygmies' short stature.

    PubMed

    Becker, Noémie S A; Verdu, Paul; Georges, Myriam; Duquesnoy, Philippe; Froment, Alain; Amselem, Serge; Le Bouc, Yves; Heyer, Evelyne

    2013-06-01

    African pygmies are at the lower extreme of human variation in adult stature and many evolutionary hypotheses have been proposed to explain this phenotype. We showed in a recent study that the difference in average stature of about 10 cm observed between contemporary pygmies and neighboring non-pygmies has a genetic component. Nevertheless, the genetic basis of African pygmies' short stature remains unknown. Using a candidate-gene approach, we show that intronic polymorphisms in GH receptor (GHR) and insulin-like growth factor 1 (IGF1) genes present outlying values of the genetic distance between Baka pygmies and their non-pygmy Nzimé neighbors. We further show that GHR and IGF1 genes have experienced divergent natural selection pressures between pygmies and non-pygmies throughout evolution. In addition, these SNPs are associated with stature in a sample composed of 60 pygmies and 30 non-pygmies and this association remains significant when correcting for population structure for the GHR locus. We conclude that the GHR and IGF1 genes may have a role in African pygmies' short stature. The use of phenotypically contrasted populations is a promising strategy to identify new variants associated with complex traits in humans. PMID:23047741

  5. Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans.

    PubMed

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2015-01-01

    Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:26417403

  6. Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans

    PubMed Central

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2015-01-01

    Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women’s Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:26417403

  7. Genetic variation of the whole ICAM4 gene in Caucasians and African Americans

    PubMed Central

    Srivastava, Kshitij; Almarry, Noorah Salman; Flegel, Willy A.

    2014-01-01

    Background Landsteiner-Wiener (LW) is the human blood group system no. 16, which comprises 2 antithetical antigens, LWa and LWb and the high prevalence antigen LWab. LW is encoded by the Intracellular Adhesion Molecule 4 (ICAM4) gene. The ICAM4 protein is part of the Rhesus complex in the red cell membrane and is involved in cell-cell adhesion. Methods We developed a method to sequence the whole 1.9 kb ICAM4 gene from genomic DNA in 1 amplicon. We determined the nucleotide sequence of exons 1 to 3, the 2 introns and 402 bp 5′-UTR and 347 bp 3′-UTR in 97 Caucasian and 91 African American individuals. Results Seven variant ICAM4 alleles were found, distinct from the wild type ICAM4 allele (GenBank KF712272), known as LW*05 and encoding LWa. An effect of the LWa/LWb amino acid substitution on the protein structure was predicted by 2 of the 3 computational modeling programs used. Conclusions We describe a practical approach for sequencing and determining the ICAM4 alleles using genomic DNA. LW*05 is the ancestral allele, which had also been observed in a Neandertal sample. All 7 variant alleles are immediate derivatives of the prevalent LW*05 and caused by 1 single nucleotide polymorphism (SNP) in each allele. Our data were consistent with the NHLBI GO Exome Sequencing Project (ESP) and the dbSNP databases, as all SNPs had been observed before. Our study has the advantage over the other databases in that it adds haplotype (allele) information for the ICAM4 gene, clinically relevant in the field of transfusion medicine. PMID:24673173

  8. Centromere protein B of African green monkey cells: gene structure, cellular expression, and centromeric localization.

    PubMed Central

    Yoda, K; Nakamura, T; Masumoto, H; Suzuki, N; Kitagawa, K; Nakano, M; Shinjo, A; Okazaki, T

    1996-01-01

    Centromere protein B (CENP-B) is a centromeric DNA-binding protein which recognizes a 17-bp sequence (CENP-B box) in human and mouse centromeric satellite DNA. The African green monkey (AGM) is phylogenetically closer to humans than mice and is known to contain large amounts of alpha-satellite DNA, but there has been no report of CENP-B boxes or CENP-B in the centromere domains of its chromosomes. To elucidate the AGM CENP-B-CENP-B box interaction, we have analyzed the gene structure, expression, biochemical properties, and centromeric localization of its CENP-B. The amino acid sequence deduced from the cloned AGM CENP-B gene was established to be highly homologous to that of human and mouse CENP-B. In particular, the DNA binding and homodimer formation domains demonstrated 100% identity to their human and mouse counterparts. Immunoblotting and DNA mobility shift analyses revealed CENP-B to be expressed in AGM cell lines. As predicted from the gene structure, the AGM CENP-B in the cell extracts exhibited the same DNA binding specificity and homodimer forming activity as human CENP-B. By indirect immunofluorescent staining of AGM mitotic cells with anti-CENP-B antibodies, a centromere-specific localization of AGM CENP-B could be demonstrated. We also isolated AGM alpha-satellite DNA with a CENP-B box-like sequence with CENP-B affinity. These results not only prove that CENP-B functionally persists in AGM cells but also suggest that the AGM genome contains the recognition sequences for CENP-B (CENP-B boxes with the core recognition sequence or CENP-B box variants) in centromeric satellite DNA. PMID:8756674

  9. Pool Purification

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Caribbean Clear, Inc. used NASA's silver ion technology as a basis for its automatic pool purifier. System offers alternative approach to conventional purification chemicals. Caribbean Clear's principal markets are swimming pool owners who want to eliminate chlorine and bromine. Purifiers in Caribbean Clear System are same silver ions used in Apollo System to kill bacteria, plus copper ions to kill algae. They produce spa or pool water that exceeds EPA Standards for drinking water.

  10. The contribution of Escherichia coli from human and animal sources to the integron gene pool in coastal waters

    PubMed Central

    Moura, Alexandra; Araújo, Susana; Alves, Marta S.; Henriques, Isabel; Pereira, Anabela; Correia, António C. M.

    2014-01-01

    To understand the contribution of animal- and human-derived fecal pollution sources in shaping integron prevalence and diversity in beach waters, 414 Escherichia coli strains were collected from beach waters (BW, n = 166), seagull feces (SF, n = 179), and wastewaters (WW, n = 69), on the World Biosphere Reserve of the Berlenga Island, Portugal. Statistical differences were found between the prevalence of integrons in BW (21%) and WW (10%), but not between BW and SF (19%). The majority of integrase-positive (intI+)-strains affiliated to commensal phylogroups B1 (37%), A0 (24%), and A1 (20%). Eighteen different gene cassette arrays were detected, most of them coding for resistances to aminoglycosides, trimethoprim, chloramphenicol, and quaternary ammonia compounds. Common arrays were found among strains from different sources. Multi-resistance to three or more different classes of antibiotics was observed in 89, 82, and 57% of intI+-strains from BW, SF and WW, respectively. Plasmids were detected in 79% of strains (60/76) revealing a high diversity of replicons in all sources, mostly belonging to IncF (Frep, FIA, and FIB subgroups), IncI1, IncN, IncY, and IncK incompatibility groups. In 20% (15/76) of strains, integrons were successfully mobilized through conjugation to E. coli CV601. Results obtained support the existence of a diverse integron pool in the E. coli strains from this coastal environment, associated with different resistance traits and plasmid incompatibility groups, mainly shaped by animal fecal pollution inputs. These findings underscore the role of wild life in dissemination of integrons and antibiotic resistance traits in natural environments. PMID:25161650

  11. Pilus Gene Pool Variation and the Virulence of Corynebacterium diphtheriae Clinical Isolates during Infection of a Nematode

    PubMed Central

    Broadway, Melissa M.; Rogers, Elizabeth A.; Chang, Chungyu; Huang, I-Hsiu; Dwivedi, Prabhat; Yildirim, Suleyman; Schmitt, Michael P.; Das, Asis

    2013-01-01

    Toxigenic Corynebacterium diphtheriae strains cause diphtheria in humans. The toxigenic C. diphtheriae isolate NCTC13129 produces three distinct heterotrimeric pili that contain SpaA, SpaD, and SpaH, making up the shaft structure. The SpaA pili are known to mediate bacterial adherence to pharyngeal epithelial cells. However, to date little is known about the expression of different pili in various clinical isolates and their importance in bacterial pathogenesis. Here, we characterized a large collection of C. diphtheriae clinical isolates for their pilin gene pool by PCR and for the expression of the respective pilins by immunoblotting with antibodies against Spa pilins. Consistent with the role of a virulence factor, the SpaA-type pili were found to be prevalent among the isolates, and most significantly, corynebacterial adherence to pharyngeal epithelial cells was strictly correlated with isolates that were positive for the SpaA pili. By comparison, the isolates were heterogeneous for the presence of SpaD- and SpaH-type pili. Importantly, using Caenorhabditis elegans as a model host for infection, we show here that strain NCTC13129 rapidly killed the nematodes, the phenotype similar to isolates that were positive for toxin and all pilus types. In contrast, isogenic mutants of NCTC13129 lacking SpaA-type pili or devoid of toxin and SpaA pili exhibited delayed killing of nematodes with similar kinetics. Consistently, nontoxigenic or toxigenic isolates that lack one, two, or all three pilus types were also attenuated in virulence. This work signifies the important role of pili in corynebacterial pathogenesis and provides a simple host model to identify additional virulence factors. PMID:23772071

  12. Domestication of the neotropical tree Chrysophyllum cainito from a geographically limited yet genetically diverse gene pool in Panama

    PubMed Central

    Petersen, Jennifer J; Parker, Ingrid M; Potter, Daniel

    2014-01-01

    Species in the early stages of domestication, in which wild and cultivated forms co-occur, provide important opportunities to develop and test hypotheses about the origins of crop species. Chrysophyllum cainito (Sapotaceae), the star apple or caimito, is a semidomesticated tree widely cultivated for its edible fruits; it is known to be native to the neotropics, but its precise geographic origins have not been firmly established. Here, we report results of microsatellite marker analyses supporting the hypothesis that the center of domestication for caimito was the Isthmus of Panama, a region in which few crop species are believed to have originated, despite its importance as a crossroads for the dispersal of domesticated plants between North and South America. Our data suggest that caimito was domesticated in a geographically restricted area while incorporating a diverse gene pool. These results refute the generally accepted Antillean origin of caimito, as well as alternative hypotheses that the species was domesticated independently in the two areas or over a broad geographic range including both. Human-mediated dispersal from Panama to the north and east was accompanied by strong reductions in both genotypic and phenotypic diversity. Within Panama, cultivated and wild trees show little neutral genetic divergence, in contrast to striking phenotypic differentiation in fruit and seed traits. In addition to providing a rare example of data that support the hypothesis of a narrow geographic origin on the Isthmus of Panama for a now widespread cultivated plant species, this study is one of the first investigations of the origins of an edible species of the large pantropical family Sapotaceae. PMID:25035796

  13. Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals

    PubMed Central

    Matsui, Atsushi; Touhara, Kazushige

    2014-01-01

    Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species—reflecting the respective species' lifestyles—and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory. PMID:25053675

  14. Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals.

    PubMed

    Niimura, Yoshihito; Matsui, Atsushi; Touhara, Kazushige

    2014-09-01

    Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species--reflecting the respective species' lifestyles--and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼ 2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory. PMID:25053675

  15. Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations

    PubMed Central

    Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L.; Nalls, Michael A.; Sung, Yun Ju; Tayo, Bamidele O.; Sun, Yan V.; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D.; Young, J. Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L.; Andrews, Jeanette S.; Smith, Jennifer A.; Faul, Jessica D.; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S.; Musani, Solomon K.; Srinivasan, Sathanur; Velez Edwards, Digna R.; Wang, Heming; Becker, Lewis C.; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I.; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W.; Evans, Michele K.; Guo, Xiuqing; Garcia, Melissa E.; Jensen, Rich; Keller, Margaux F.; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W.; Moore, Jason H.; Morrison, Alanna C.; Mosley, Thomas H.; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F.; Ridker, Paul M.; Salako, Babatunde; Singleton, Andrew B.; Shriner, Daniel; Taylor, Kent D.; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M.; Yanek, Lisa R.; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N.; Howard, Virginia J.; Karczewsk, Konrad J.; Lanktree, Matthew B.; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Jeon, Jae-Pil; Kim, Sung Soo; Han, Bok-Ghee; Cho, Yoon Shin; Sim, Xueling; Tay, Wan Ting; Ong, Rick Twee Hee; Seielstad, Mark; Liu, Jian Jun; Aung, Tin; Wong, Tien Yin; Teo, Yik Ying; Tai, E. Shyong; Chen, Chien-Hsiun; Chang, Li-ching; Chen, Yuan-Tsong; Wu, Jer-Yuarn; Kelly, Tanika N.; Gu, Dongfeng; Hixson, James E.; Sung, Yun Ju; He, Jiang; Tabara, Yasuharu; Kokubo, Yoshihiro; Miki, Tetsuro; Iwai, Naoharu; Kato, Norihiro; Takeuchi, Fumihiko; Katsuya, Tomohiro; Nabika, Toru; Sugiyama, Takao; Zhang, Yi; Huang, Wei; Zhang, Xuegong; Zhou, Xueya; Jin, Li; Zhu, Dingliang; Psaty, Bruce M.; Schork, Nicholas J.; Weir, David R.; Rotimi, Charles N.; Sale, Michele M.; Harris, Tamara; Kardia, Sharon L.R.; Hunt, Steven C.; Arnett, Donna; Redline, Susan; Cooper, Richard S.; Risch, Neil J.; Rao, D.C.; Rotter, Jerome I.; Chakravarti, Aravinda; Reiner, Alex P.; Levy, Daniel; Keating, Brendan J.; Zhu, Xiaofeng

    2013-01-01

    High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10−8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability. PMID:23972371

  16. Systematic analysis of RNAi reports identifies dismal commonality at gene-level & reveals an unprecedented enrichment in pooled shRNA screens

    PubMed Central

    Bhinder, Bhavneet; Djaballah, Hakim

    2013-01-01

    RNA interference (RNAi) has opened promising avenues to better understand gene function. Though many RNAi screens report on the identification of genes, very few, if any, have been further studied and validated. Data discrepancy is emerging as one of RNAi main pitfalls. We reasoned that a systematic analysis of lethality-based screens, since they score for cell death, would examine the extent of hit discordance at inter-screen level. To this end, we developed a methodology for literature mining and overlap analysis of several screens using both siRNA and shRNA flavors, and obtained 64 gene lists censoring an initial list of 7,430 nominated genes. We further performed a comparative analysis first at a global level followed by hit re-assessment under much more stringent conditions. To our surprise, none of the hits overlapped across the board even for PLK1, which emerged as a strong candidate in siRNA screens; but only marginally in the shRNA ones. Furthermore, EIF5B emerges as the most common hit only in the shRNA screens. A highly unusual and unprecedented result was the observation that 5,269 out of 6,664 nominated genes (~80%) in the shRNA screens were exclusive to the pooled format, raising concerns as to the merits of pooled screens which qualify hits based on relative depletions, possibly due to multiple integrations per cell, data deconvolution or inaccuracies in intracellular processing causing off-target effects. Without golden standards in place, we would encourage the community to pay more attention to RNAi screening data analysis practices, bearing in mind that it is combinatorial in nature and one active siRNA duplex or shRNA hairpin per gene does not suffice credible hit nomination. Finally, we also would like to caution interpretation of pooled shRNA screening outcomes. PMID:23848309

  17. Identification and characterization of two chitin synthase genes in African malaria mosquito, Anopheles gambiae.

    PubMed

    Zhang, Xin; Zhang, Jianzhen; Park, Yoonseong; Zhu, Kun Yan

    2012-09-01

    Chitin synthase (CHS) represents an attractive target site for combating insect pests as insect growth and development are strictly dependent on precisely tuned chitin biosynthesis and this pathway is absent in humans and other vertebrates. Current knowledge on CHS in insects, especially their structures, functions, and regulations is still very limited. We report the identification and characterization of two chitin synthase genes, AgCHS1 and AgCHS2, in African malaria mosquito, Anopheles gambiae. AgCHS1 and AgCHS2 were predicted to encode proteins of 1,578 and 1,586 amino acid residues, respectively. Their deduced amino acid sequences show high similarities to other insect chitin synthases. Transcriptional analysis indicated that AgCHS1 was expressed in egg, larval, pupal and adult stages whereas AgCHS2 appeared to be expressed at relatively low levels, particularly during the larval stages as examined by reverse transcription (RT)-PCR and real-time quantitative PCR. Relatively high expression was detected in the carcass followed by the foregut and hindgut for AgCHS1, and the foregut (cardia included) followed by the midgut for AgCHS2. Fluorescence in situ hybridization (FISH) and immunohistochemical analysis revealed new information including the localization of the two enzymes in the ommatidia of the compound eyes, and AgCHS2 in the thoracic and abdominal inter-segmental regions of pupal integument. PMID:22683441

  18. Evolutionary systematics in African gerbilline rodents of the genus Gerbilliscus: inference from mitochondrial genes.

    PubMed

    Colangelo, Paolo; Granjon, Laurent; Taylor, Peter J; Corti, Marco

    2007-03-01

    Gerbilliscus has recently been proposed as an endemic African rodent genus distinct from the Asian Tatera. A molecular phylogeny of the genus, including nine species from southern, western and eastern Africa, is presented here based on the analysis of the cytochrome b and 16S mitochondrial genes. With an adequate taxonomic sampling over a wide geographic range, we here provide a clear picture of the phylogenetic relationships between species and species groups in this genus. Three distinct clades were resolved, corresponding to major geographical subdivisions: an eastern clade that possibly diverged first, then a southern and a western clades which appeared later. We suggest two possible hypotheses concerning the dispersal of the genus across Africa, considering also the patterns of karyotypic variation. Finally, we discuss the taxonomic status of G. gambianus and the relationships between Gerbillurus and Gerbilliscus, as previous studies have suggested that the former should be included in the latter. Our data seem to support the synonymy of the two taxa and suggest that Gerbillurus and Gerbilliscus lineages diverged from a common ancestor appeared in eastern Africa. PMID:17113792

  19. African Swine Fever Virus Multigene Family 360 and 530 Genes Are Novel Macrophage Host Range Determinants

    PubMed Central

    Zsak, L.; Lu, Z.; Burrage, T. G.; Neilan, J. G.; Kutish, G. F.; Moore, D. M.; Rock, D. L.

    2001-01-01

    Pathogenic African swine fever virus (ASFV) isolates primarily target cells of the mononuclear-phagocytic system in infected swine and replicate efficiently in primary macrophage cell cultures in vitro. ASFVs can, however, be adapted to grow in monkey cell lines. Characterization of two cell culture-adapted viruses, MS16 and BA71V, revealed that neither virus replicated in macrophage cell cultures. Cell viability experiments and ultrastructural analysis showed that infection with these viruses resulted in early macrophage cell death, which occurred prior to viral progeny production. Genomic cosmid clones from pathogenic ASFV isolate E70 were used in marker rescue experiments to identify sequences capable of restoring MS16 and BA71V growth in macrophage cell cultures. A cosmid clone representing a 38-kbp region at the left terminus of the genome completely restored the growth of both viruses. In subsequent fine-mapping experiments, an 11-kbp subclone from this region was sufficient for complete rescue of BA71V growth. Sequence analysis indicated that both MS16 and BA71V had significant deletions in the region containing members of multigene family 360 (MGF 360) and MGF530. Deletion of this same region from highly pathogenic ASFV isolate Pr4 significantly reduced viral growth in macrophage cell cultures. These findings indicate that ASFV MGF360 and MGF530 genes perform an essential macrophage host range function(s) that involves promotion of infected-cell survival. PMID:11238833

  20. African swine fever virus multigene family 360 and 530 genes are novel macrophage host range determinants.

    PubMed

    Zsak, L; Lu, Z; Burrage, T G; Neilan, J G; Kutish, G F; Moore, D M; Rock, D L

    2001-04-01

    Pathogenic African swine fever virus (ASFV) isolates primarily target cells of the mononuclear-phagocytic system in infected swine and replicate efficiently in primary macrophage cell cultures in vitro. ASFVs can, however, be adapted to grow in monkey cell lines. Characterization of two cell culture-adapted viruses, MS16 and BA71V, revealed that neither virus replicated in macrophage cell cultures. Cell viability experiments and ultrastructural analysis showed that infection with these viruses resulted in early macrophage cell death, which occurred prior to viral progeny production. Genomic cosmid clones from pathogenic ASFV isolate E70 were used in marker rescue experiments to identify sequences capable of restoring MS16 and BA71V growth in macrophage cell cultures. A cosmid clone representing a 38-kbp region at the left terminus of the genome completely restored the growth of both viruses. In subsequent fine-mapping experiments, an 11-kbp subclone from this region was sufficient for complete rescue of BA71V growth. Sequence analysis indicated that both MS16 and BA71V had significant deletions in the region containing members of multigene family 360 (MGF 360) and MGF530. Deletion of this same region from highly pathogenic ASFV isolate Pr4 significantly reduced viral growth in macrophage cell cultures. These findings indicate that ASFV MGF360 and MGF530 genes perform an essential macrophage host range function(s) that involves promotion of infected-cell survival. PMID:11238833

  1. Detecting Sex-Biased Gene Flow in African-Americans through the Analysis of Intra- and Inter-Population Variation at Mitochondrial DNA and Y- Chromosome Microsatellites

    PubMed Central

    Battaggia, C; Anagnostou, P; Bosch, I; Brisighelli, F; Destro-Bisol, G; Capocasa, M

    2012-01-01

    This study reports on variations at the mitochondrial DNA (mtDNA) hypervariable region 1 (HVR-1) and at seven Y-chromosome microsatellites in an African-American population sample from Chicago, IL, USA. Our results support the hypothesis that the population studied had undergone a European male-biased gene flow. We show that comparisons of intra-and inter-population diversity parameters between African-Americans, Europeans and Africans may help detect sex-biased gene flow, providing a complement to quantitative methods to estimate genetic admixture. PMID:24052726

  2. PSPHL and breast cancer in African American women: causative gene or population stratification?

    PubMed Central

    2014-01-01

    Background Phophoserine phosphatase-like (PSPHL) is expressed at significantly higher levels in breast tumors from African American women (AAW) compared to Caucasian women (CW). How overexpression of PSPHL contributes to outcome disparities is unclear, thus, molecular mechanisms driving expression differences between populations were evaluated. Results PCR was used to detect deletion of 30-Kb of chromosome 7p11 including the first three exons of PSPHL using genomic DNA from AAW (199 with invasive breast cancer, 360 controls) and CW (invasive breast cancer =589, 364 controls). Gene expression levels were evaluated by qRT-PCR using RNA isolated from tumor tissue and blood. Data were analyzed using chi-square analysis and Mann–Whitney U-tests; P < 0.05 was used to define significance. Gene expression levels correlated with deletion status: patients homozygous for the deletion had no detectable expression of PSPHL, while heterozygous had expression levels 2.1-fold lower than those homozygous for retention of PSPHL. Homozygous deletion of PSPHL was detected in 61% of CW compared to 6% of AAW with invasive breast cancer (P < 0.0001); genotype frequencies did not differ significantly between AAW with and without breast cancer (P = 0.211). Conclusions Thus, deletion of 7p11, which prevents expression of PSPHL, is significantly higher in CW compared to AAW, suggesting that this 30-kb deletion and subsequent disruption of PSPHL may be a derived trait in Caucasians. The similar frequency of the deletion allele in AAW with and without invasive breast cancer suggests that this difference represent population stratification, and does not contribute to cancer disparities. PMID:24650299

  3. Complement factor H gene associations with end-stage kidney disease in African Americans

    PubMed Central

    Bonomo, Jason A.; Palmer, Nicholette D.; Hicks, Pamela J.; Lea, Janice P.; Okusa, Mark D.; Langefeld, Carl D.; Bowden, Donald W.; Freedman, Barry I.

    2014-01-01

    Background Mutations in the complement factor H gene (CFH) region associate with renal-limited mesangial proliferative forms of glomerulonephritis including IgA nephropathy (IgAN), dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). Lack of kidney biopsies could lead to under diagnosis of CFH-associated end-stage kidney disease (ESKD) in African Americans (AAs), with incorrect attribution to other causes. A prior genome-wide association study in AAs with non-diabetic ESKD implicated an intronic CFH single nucleotide polymorphism (SNP). Methods Thirteen CFH SNPs (8 exonic, 2 synonymous, 2 3′UTR, and the previously associated intronic variant rs379489) were tested for association with common forms of non-diabetic and type 2 diabetes-associated (T2D) ESKD in 3770 AAs (1705 with non-diabetic ESKD, 1305 with T2D-ESKD, 760 controls). Most cases lacked kidney biopsies; those with known IgAN, DDD or C3GN were excluded. Results Adjusting for age, gender, ancestry and apolipoprotein L1 gene risk variants, single SNP analyses detected 6 CFH SNPs (5 exonic and the intronic variant) as significantly associated with non-diabetic ESKD (P = 0.002–0.01), three of these SNPs were also associated with T2D-ESKD. Weighted CFH locus-wide Sequence Kernel Association Testing (SKAT) in non-diabetic ESKD (P = 0.00053) and T2D-ESKD (P = 0.047) confirmed significant evidence of association. Conclusions CFH was associated with commonly reported etiologies of ESKD in the AA population. These results suggest that a subset of cases with ESKD clinically ascribed to the effects of hypertension or glomerulosclerosis actually have CFH-related forms of mesangial proliferative glomerulonephritis. Genetic testing may prove useful to identify the causes of renal-limited kidney disease in patients with ESKD who lack renal biopsies. PMID:24586071

  4. Mining a database of single amplified genomes from Red Sea brine pool extremophiles—improving reliability of gene function prediction using a profile and pattern matching algorithm (PPMA)

    PubMed Central

    Grötzinger, Stefan W.; Alam, Intikhab; Ba Alawi, Wail; Bajic, Vladimir B.; Stingl, Ulrich; Eppinger, Jörg

    2014-01-01

    Reliable functional annotation of genomic data is the key-step in the discovery of novel enzymes. Intrinsic sequencing data quality problems of single amplified genomes (SAGs) and poor homology of novel extremophile's genomes pose significant challenges for the attribution of functions to the coding sequences identified. The anoxic deep-sea brine pools of the Red Sea are a promising source of novel enzymes with unique evolutionary adaptation. Sequencing data from Red Sea brine pool cultures and SAGs are annotated and stored in the Integrated Data Warehouse of Microbial Genomes (INDIGO) data warehouse. Low sequence homology of annotated genes (no similarity for 35% of these genes) may translate into false positives when searching for specific functions. The Profile and Pattern Matching (PPM) strategy described here was developed to eliminate false positive annotations of enzyme function before progressing to labor-intensive hyper-saline gene expression and characterization. It utilizes InterPro-derived Gene Ontology (GO)-terms (which represent enzyme function profiles) and annotated relevant PROSITE IDs (which are linked to an amino acid consensus pattern). The PPM algorithm was tested on 15 protein families, which were selected based on scientific and commercial potential. An initial list of 2577 enzyme commission (E.C.) numbers was translated into 171 GO-terms and 49 consensus patterns. A subset of INDIGO-sequences consisting of 58 SAGs from six different taxons of bacteria and archaea were selected from six different brine pool environments. Those SAGs code for 74,516 genes, which were independently scanned for the GO-terms (profile filter) and PROSITE IDs (pattern filter). Following stringent reliability filtering, the non-redundant hits (106 profile hits and 147 pattern hits) are classified as reliable, if at least two relevant descriptors (GO-terms and/or consensus patterns) are present. Scripts for annotation, as well as for the PPM algorithm, are available

  5. Genome-Wide Local Ancestry Approach Identifies Genes and Variants Associated with Chemotherapeutic Susceptibility in African Americans

    PubMed Central

    Wheeler, Heather E.; Gorsic, Lidija K.; Welsh, Marleen; Stark, Amy L.; Gamazon, Eric R.; Cox, Nancy J.; Dolan, M. Eileen

    2011-01-01

    Chemotherapeutic agents are used in the treatment of many cancers, yet variable resistance and toxicities among individuals limit successful outcomes. Several studies have indicated outcome differences associated with ancestry among patients with various cancer types. Using both traditional SNP-based and newly developed gene-based genome-wide approaches, we investigated the genetics of chemotherapeutic susceptibility in lymphoblastoid cell lines derived from 83 African Americans, a population for which there is a disparity in the number of genome-wide studies performed. To account for population structure in this admixed population, we incorporated local ancestry information into our association model. We tested over 2 million SNPs and identified 325, 176, 240, and 190 SNPs that were suggestively associated with cytarabine-, 5′-deoxyfluorouridine (5′-DFUR)-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10−4). Importantly, some of these variants are found only in populations of African descent. We also show that cisplatin-susceptibility SNPs are enriched for carboplatin-susceptibility SNPs. Using a gene-based genome-wide association approach, we identified 26, 11, 20, and 41 suggestive candidate genes for association with cytarabine-, 5′-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10−3). Fourteen of these genes showed evidence of association with their respective chemotherapeutic phenotypes in the Yoruba from Ibadan, Nigeria (p<0.05), including TP53I11, COPS5 and GAS8, which are known to be involved in tumorigenesis. Although our results require further study, we have identified variants and genes associated with chemotherapeutic susceptibility in African Americans by using an approach that incorporates local ancestry information. PMID:21755009

  6. Appetite regulation genes are associated with body mass index in black South African adolescents: a genetic association study

    PubMed Central

    Crowther, Nigel J; van der Merwe, Lize; Pitamber, Punita; Norris, Shane A; Ramsay, Michèle

    2012-01-01

    Background Obesity is a complex trait with both environmental and genetic contributors. Genome-wide association studies have identified several variants that are robustly associated with obesity and body mass index (BMI), many of which are found within genes involved in appetite regulation. Currently, genetic association data for obesity are lacking in Africans—a single genome-wide association study and a few replication studies have been published in West Africa, but none have been performed in a South African population. Objective To assess the association of candidate loci with BMI in black South Africans. The authors focused on single nucleotide polymorphisms (SNPs) in the FTO, LEP, LEPR, MC4R, NPY2R and POMC genes. Design A genetic association study. Participants 990 randomly selected individuals from the larger Birth to Twenty cohort (a longitudinal birth cohort study of health and development in Africans). Measures The authors genotyped 44 SNPs within the six candidate genes that included known BMI-associated SNPs and tagSNPs based on linkage disequilibrium in an African population for FTO, LEP and NPY2R. To assess population substructure, the authors included 18 ancestry informative markers. Weight, height, sex, sex-specific pubertal stage and exact age collected during adolescence (13 years) were used to identify loci that predispose to obesity early in life. Results Sex, sex-specific pubertal stage and exact age together explain 14.3% of the variation in log(BMI) at age 13. After adjustment for these factors, four SNPs were individually significantly associated with BMI: FTO rs17817449 (p=0.022), LEP rs10954174 (p=0.0004), LEP rs6966536 (p=0.012) and MC4R rs17782313 (p=0.045). Together the four SNPs account for 2.1% of the variation in log(BMI). Each risk allele was associated with an estimated average increase of 2.5% in BMI. Conclusions The study highlighted SNPs in FTO and MC4R as potential genetic markers of obesity risk in South Africans. The

  7. Associations Between a Dopamine D4 Receptor Gene, Alcohol Use, and Sexual Behaviors among Female Adolescent African Americans

    PubMed Central

    Sales, Jessica M.; Smearman, Erica; Brown, Jennifer L.; Brody, Gene H.; Philibert, Robert A.; Rose, Eve; DiClemente, Ralph J.

    2016-01-01

    Adolescent African-American females are disproportionately impacted by HIV, thus there is a clear need to understand factors associated with increased HIV-risk behaviors among this vulnerable population. We sought to explore the association between a dopamine D4 receptor gene (DRD4), a genetic marker associated with natural variations in rewarding behaviors, and self-reported alcohol-use and sexual risk-behaviors, while controlling for other known correlates of risk-taking such as impulsivity, sensation seeking, and peer norms among a group of high-risk African American female adolescents to evaluate whether this biological factor enhances our understanding of patterns of risk in this vulnerable group. PMID:27087792

  8. Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans.

    PubMed

    Chang, Jeffrey S; Wrensch, Margaret R; Hansen, Helen M; Sison, Jennette D; Aldrich, Melinda C; Quesenberry, Charles P; Seldin, Michael F; Kelsey, Karl T; Kittles, Rick A; Silva, Gabriel; Wiencke, John K

    2008-11-01

    Few studies on the association between nucleotide excision repair (NER) variants and lung cancer risk have included Latinos and African Americans. We examine variants in 6 NER genes (ERCC2, ERCC4, ERCC5, LIG1, RAD23B and XPC) in association with primary lung cancer risk among 113 Latino and 255 African American subjects newly diagnosed with primary lung cancer from 1998 to 2003 in the San Francisco Bay Area and 579 healthy controls (299 Latinos and 280 African Americans). Individual single nucleotide polymorphism and haplotype analyses, multifactor dimensionality reduction (MDR) and principal components analysis (PCA) were performed to assess the association between 6 genes in the NER pathway and lung cancer risk. Among Latinos, ERCC2 haplotype CGA (rs238406, rs11878644, rs6966) was associated with reduced lung cancer risk [odds ratio (OR) of 0.65 and 95% confidence interval (CI): 0.44-0.97], especially among nonsmokers (OR = 0.29; 95% CI: 0.12-0.67). From MDR analysis, in Latinos, smoking and 3 SNPs (ERCC2 rs171140, ERCC5 rs17655 and LIG1 rs20581) together had a prediction accuracy of 67.4% (p = 0.001) for lung cancer. Among African Americans, His/His genotype of ERCC5 His1104Asp (rs17655) was associated with increased lung cancer risk (OR = 1.78; 95% CI: 1.09-2.91), and LIG1 haplotype GGGAA (rs20581, rs156641, rs3730931, rs20579 and rs439132) was associated with reduced lung cancer risk (OR = 0.61; 95% CI: 0.42-0.88). Our study suggests different elements of the NER pathway may be important in the different ethnic groups resulting either from different linkage relationship, genetic backgrounds and/or exposure histories. PMID:18709642

  9. Exonic rearrangements in the known Parkinson's disease-causing genes are a rare cause of the disease in South African patients.

    PubMed

    van der Merwe, Celia; Carr, Jonathan; Glanzmann, Brigitte; Bardien, Soraya

    2016-04-21

    Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. To date, a number of PD-causing genes have been found, including SNCA, LRRK2, VPS35, PARK2, PINK1, DJ-1, ATP13A2, and most recently CHCHD2. Mutations in these genes range from point mutations to larger exonic rearrangements including deletions and duplications. This study aimed to detect possible copy number variation (CNV) in the known PD-causing genes in a cohort of South African patients with PD. Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed on a total of 210 South African PD patients, and possible CNVs were verified using quantitative real time PCR. No homozygous or compound heterozygous exon rearrangements in the genes analysed were found in the patient group. A heterozygous PARK2 exon 4 deletion was found in a sporadic patient with an age at onset of 51 years. Sanger sequencing did not reveal any additional mutations in PARK2 in this patient. Combining our results with that of previous studies in a South African cohort, the frequency of exonic rearrangements in the known PD-causing genes is only 1.8% (8/439 patients). In conclusion, CNV in the known PD-causing genes are a rare cause of PD in a South African cohort, and there may be as yet unknown genetic causes of PD that are specific to patients of African ethnicity. PMID:27001088

  10. Five linkage regions each harbor multiple type 2 diabetes genes in the African American subset of the GENNID Study.

    PubMed

    Hasstedt, Sandra J; Highland, Heather M; Elbein, Steven C; Hanis, Craig L; Das, Swapan K

    2013-06-01

    We previously localized type 2 diabetes (T2D)-susceptibility genes to five chromosomal regions through a genome-wide linkage scan of T2D and age of diagnosis (AOD) in the African American subset of the GENNID sample. To follow up these findings, we repeated the linkage and association analysis using genotypes on an additional 9203 fine-mapping single nucleotide polymorphisms (SNPs) selected to tag genes under the linkage peaks. In each of the five regions, we confirmed linkage and inferred the presence of ≥2 susceptibility genes. The evidence of multiple susceptibility genes consisted of: (1) multiple linkage peaks in four of the five regions; and (2) association of T2D and AOD with SNPs within ≥2 genes in every region. The associated genes included 3 previously reported to associate with T2D or related traits (GRB10, NEDD4L, LIPG) and 24 novel candidate genes, including genes in lipid metabolism (ACOXL) and cell-cell and cell-matrix adhesion (MAGI2, CLDN4, CTNNA2). PMID:23552671

  11. Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort Suggests Population-Specific Associations of Rare Variants in MUC2.

    PubMed

    Visschedijk, Marijn C; Alberts, Rudi; Mucha, Soren; Deelen, Patrick; de Jong, Dirk J; Pierik, Marieke; Spekhorst, Lieke M; Imhann, Floris; van der Meulen-de Jong, Andrea E; van der Woude, C Janneke; van Bodegraven, Adriaan A; Oldenburg, Bas; Löwenberg, Mark; Dijkstra, Gerard; Ellinghaus, David; Schreiber, Stefan; Wijmenga, Cisca; Rivas, Manuel A; Franke, Andre; van Diemen, Cleo C; Weersma, Rinse K

    2016-01-01

    Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC. PMID:27490946

  12. Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort Suggests Population-Specific Associations of Rare Variants in MUC2

    PubMed Central

    Visschedijk, Marijn C.; Alberts, Rudi; Mucha, Soren; Deelen, Patrick; de Jong, Dirk J.; Pierik, Marieke; Spekhorst, Lieke M.; Imhann, Floris; van der Meulen-de Jong, Andrea E.; van der Woude, C. Janneke; van Bodegraven, Adriaan A.; Oldenburg, Bas; Löwenberg, Mark; Dijkstra, Gerard; Ellinghaus, David; Schreiber, Stefan; Wijmenga, Cisca; Rivas, Manuel A.; Franke, Andre

    2016-01-01

    Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC. PMID:27490946

  13. Growth and development of the ovary and small follicle pool from mid fetal life to pre-puberty in the African elephant (Loxodonta africana)

    PubMed Central

    2012-01-01

    Background Follicle numbers and developing ovarian morphology, particularly with reference to the presence of interstitial tissue, are intimately linked within the ovary of the African elephant during the period spanning mid-gestation to puberty. These have not been previously quantified in any studies. The collection of 7 sets of elephant fetal ovaries between 11.2 and 20.2 months of gestation, and 29 pairs of prepubertal calf ovaries between 2 months and 9 years of age during routine management off-takes of complete family groups in private conservancies in Zimbabwe provided an opportunity for a detailed study of this period. Results The changing morphology of the ovary is described as the presumptive cortex and medulla components of the fetal ovary settled into their adult form. Interstitial tissue dominated the ovary in late fetal life and these cells stained strongly for 3β–hydroxysteroid dehydrogenase. This staining continued postnatally through to 4.5 years of age suggesting continued secretion of progestagens by the ovary during this period. The considerable growth of antral follicles peaked at 28% of ovarian volume at around 16.7 months of fetal age. The numbers of small follicles (primordial, early primary and true primary), counted in the cortex using stereological protocols, revealed fewer small follicles in the ovaries of animals aged 0 to 4.5 years of age than during either late fetal life or prepubertal life. Conclusions The small follicle populations of the late-fetal and prepubertal ovaries of the African elephant were described along with the changing morphology of these organs. The changes noted represent a series of events that have been recorded only in the elephant and the giraffe species to date. The expansion of the interstitial tissue of the fetal ovary and its continued presence in early post natal life may well contribute to the control of follicle development in these early years. Further research is required to determine

  14. Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies.

    PubMed

    Fish, Maryam; Shaboodien, Gasnat; Kraus, Sarah; Sliwa, Karen; Seidman, Christine E; Burke, Michael A; Crotti, Lia; Schwartz, Peter J; Mayosi, Bongani M

    2016-01-01

    Cardiomyopathy is an important cause of heart failure in Sub-Saharan Africa, accounting for up to 30% of adult heart failure hospitalisations. This high prevalence poses a challenge in societies without access to resources and interventions essential for disease management. Over 80 genes have been implicated as a cause of cardiomyopathy. Mutations in the phospholamban (PLN) gene are associated with dilated cardiomyopathy (DCM) and severe heart failure. In Africa, the prevalence of PLN mutations in cardiomyopathy patients is unknown. Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing. We detected the previously reported PLN c.25C > T (p.R9C) mutation in a South African family with severe autosomal dominant DCM. Haplotype analysis revealed that this mutation occurred against a different haplotype background to that of the original North American family and was therefore unlikely to have been inherited from a common ancestor. No other mutations in PLN were detected (mutation prevalence = 0.2%). We conclude that PLN is a rare cause of cardiomyopathy in African patients. The PLN p.R9C mutation is not well-tolerated, emphasising the importance of this gene in cardiac function. PMID:26917049

  15. Genetic variants in one-carbon metabolism genes and breast cancer risk in European American and African American women.

    PubMed

    Gong, Zhihong; Yao, Song; Zirpoli, Gary; David Cheng, Ting-Yuan; Roberts, Michelle; Khoury, Thaer; Ciupak, Gregory; Davis, Warren; Pawlish, Karen; Jandorf, Lina; Bovbjerg, Dana H; Bandera, Elisa V; Ambrosone, Christine B

    2015-08-01

    Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis, repair and DNA methylation. The impact of single nucleotide polymorphisms (SNPs) in folate-metabolizing enzymes has been investigated in risk of breast cancer among European or Asian populations, but not among women of African ancestry. We conducted a comprehensive analysis of SNPs in eleven genes involved in one-carbon metabolism and risk of breast cancer in 1,275 European-American (EA) and 1,299 African-American (AA) women who participated in the Women's Circle of Health Study. Allele frequencies varied significantly between EA and AA populations. A number of these SNPs, specifically in genes including MTR, MTRR, SHMT1, TYMS and SLC19A1, were associated with overall breast cancer risk, as well as risk by estrogen receptor (ER) status, in either EA or AA women. Associations appeared to be modified by dietary folate intake. Although single-SNP associations were not statistically significant after correcting for multiple comparisons, polygenetic score analyses revealed significant associations with breast cancer risk. Per unit increase of the risk score was associated with a modest 19 to 50% increase in risk of breast cancer overall, ER positive or ER negative cancer (all p < 0.0005) in EAs or AAs. In summary, our data suggest that one-carbon metabolizing gene polymorphisms could play a role in breast cancer and that may differ between EA and AA women. PMID:25598430

  16. Mutation analysis of the phospholamban gene in 315 South Africans with dilated, hypertrophic, peripartum and arrhythmogenic right ventricular cardiomyopathies

    PubMed Central

    Fish, Maryam; Shaboodien, Gasnat; Kraus, Sarah; Sliwa, Karen; Seidman, Christine E.; Burke, Michael A.; Crotti, Lia; Schwartz, Peter J.; Mayosi, Bongani M.

    2016-01-01

    Cardiomyopathy is an important cause of heart failure in Sub-Saharan Africa, accounting for up to 30% of adult heart failure hospitalisations. This high prevalence poses a challenge in societies without access to resources and interventions essential for disease management. Over 80 genes have been implicated as a cause of cardiomyopathy. Mutations in the phospholamban (PLN) gene are associated with dilated cardiomyopathy (DCM) and severe heart failure. In Africa, the prevalence of PLN mutations in cardiomyopathy patients is unknown. Our aim was to screen 315 patients with arrhythmogenic right ventricular cardiomyopathy (n = 111), DCM (n = 95), hypertrophic cardiomyopathy (n = 40) and peripartum cardiomyopathy (n = 69) for disease-causing PLN mutations by high resolution melt analysis and DNA sequencing. We detected the previously reported PLN c.25C > T (p.R9C) mutation in a South African family with severe autosomal dominant DCM. Haplotype analysis revealed that this mutation occurred against a different haplotype background to that of the original North American family and was therefore unlikely to have been inherited from a common ancestor. No other mutations in PLN were detected (mutation prevalence = 0.2%). We conclude that PLN is a rare cause of cardiomyopathy in African patients. The PLN p.R9C mutation is not well-tolerated, emphasising the importance of this gene in cardiac function. PMID:26917049

  17. A Genome-wide study of blood pressure in African Americans accounting for gene-smoking interaction

    PubMed Central

    Taylor, Jacquelyn Y.; Schwander, Karen; Kardia, Sharon L. R.; Arnett, Donna; Liang, Jingjing; Hunt, Steven C.; Rao, D.C.; Sun, Yan V.

    2016-01-01

    Cigarette smoking has been shown to be a health hazard. In addition to being considered a negative lifestyle behavior, studies have shown that cigarette smoking has been linked to genetic underpinnings of hypertension. Because African Americans have the highest incidence and prevalence of hypertension, we examined the joint effect of genetics and cigarette smoking on health among this understudied population. The sample included African Americans from the genome wide association studies of HyperGEN (N = 1083, discovery sample) and GENOA (N = 1427, replication sample), both part of the FBPP. Results suggested that 2 SNPs located on chromosomes 14 (NEDD8; rs11158609; raw p = 9.80 × 10−9, genomic control-adjusted p = 2.09 × 10−7) and 17 (TTYH2; rs8078051; raw p = 6.28 × 10−8, genomic control-adjusted p = 9.65 × 10−7) were associated with SBP including the genetic interaction with cigarette smoking. These two SNPs were not associated with SBP in a main genetic effect only model. This study advances knowledge in the area of main and joint effects of genetics and cigarette smoking on hypertension among African Americans and offers a model to the reader for assessing these risks. More research is required to determine how these genes play a role in expression of hypertension. PMID:26752167

  18. A pooling-based genome-wide analysis identifies new potential candidate genes for atopy in the European Community Respiratory Health Survey (ECRHS)

    PubMed Central

    2009-01-01

    Background Asthma and atopy are complex phenotypes with shared genetic component. In this study we attempt to identify genes related to these traits performing a two-stage DNA pooling genome-wide analysis in order to reduce costs. First, we assessed all markers in a subset of subjects using DNA pooling, and in a second stage we evaluated the most promising markers at an individual level. Methods For the genome-wide analysis, we constructed DNA pools from 75 subjects with atopy and asthma, 75 subjects with atopy and without asthma and 75 control subjects without atopy or asthma. In a second stage, the most promising regions surrounding significant markers after correction for false discovery rate were replicated with individual genotyping of samples included in the pools and an additional set of 429 atopic subjects and 222 controls from the same study centres. Results Homo sapiens protein kinase-like protein SgK493 (SGK493) was found to be associated with atopy. To lesser extent mitogen-activated protein kinase 5 (MAP3K5), collagen type XVIII alpha 1 (COL18A1) and collagen type XXIX alpha 1 (COL29A1) were also found to be associated with atopy. Functional evidences points out a role for MAP3K5, COL18A1 and COL29A1 but the function of SGK493 is unknown. Conclusion In this analysis we have identified new candidate regions related to atopy and suggest SGK493 as an atopy locus, although these results need further replication. PMID:19961619

  19. Determining the optimal number of individual samples to pool for quantification of average herd levels of antimicrobial resistance genes in Danish pig herds using high-throughput qPCR.

    PubMed

    Clasen, Julie; Mellerup, Anders; Olsen, John Elmerdahl; Angen, Øystein; Folkesson, Anders; Halasa, Tariq; Toft, Nils; Birkegård, Anna Camilla

    2016-06-30

    The primary objective of this study was to determine the minimum number of individual fecal samples to pool together in order to obtain a representative sample for herd level quantification of antimicrobial resistance (AMR) genes in a Danish pig herd, using a novel high-throughput qPCR assay. The secondary objective was to assess the agreement between different methods of sample pooling. Quantification of AMR was achieved using a high-throughput qPCR method to quantify the levels of seven AMR genes (ermB, ermF, sulI, sulII, tet(M), tet(O) and tet(W)). A large variation in the levels of AMR genes was found between individual samples. As the number of samples in a pool increased, a decrease in sample variation was observed. It was concluded that the optimal pooling size is five samples, as an almost steady state in the variation was observed when pooling this number of samples. Good agreement between different pooling methods was found and the least time-consuming method of pooling, by transferring feces from each individual sample to a tube using a 10μl inoculation loop and adding 3.5ml of PBS, approximating a 10% solution, can therefore be used in future studies. PMID:27259826

  20. An African swine fever virus virulence-associated gene NL-S with similarity to the herpes simplex virus ICP34.5 gene.

    PubMed Central

    Zsak, L; Lu, Z; Kutish, G F; Neilan, J G; Rock, D L

    1996-01-01

    We described previously an African swine fever virus (ASFV) open reading frame, 23-NL, in the African isolate Malawi Lil 20/1 whose product shared significant similarity in a carboxyl-terminal domain with those of a mouse myeloid differentiation primary response gene, MyD116, and the herpes simplex virus neurovirulence-associated gene, ICP34.5 (M. D. Sussman, Z. Lu, G. Kutish, C. L. Afonso, P. Roberts, and D. L. Rock, J. Virol. 66:5586-5589, 1992). The similarity of 23-NL to these genes suggested that this gene may function in some aspect of ASFV virulence and/or host range. Sequence analysis of additional pathogenic viral isolates demonstrates that this gene is highly conserved among diverse ASFV isolates and that the gene product exists in either a long (184 amino acids as in 23-NL) or a short form (70 to 72 amino acids in other examined ASFV isolates). The short form of the gene, NL-S, encodes the complete highly conserved, hydrophilic, carboxyl-terminal domain of 56 amino acids common to 23-NL, MyD116, and ICP34.5. Recombinant NL-S gene deletion mutants and their revertants were constructed from the pathogenic ASFV isolate E70 and an E70 monkey cell culture-adapted virus, MS44, to study gene function. Although deletion of NL-S did not affect viral growth in primary swine macrophages or Vero cell cultures in vitro, the null mutant, E70/43, exhibited a marked reduction in pig virulence. In contrast to revertant or parental E70 where mortality was 100%, all E70/43-infected animals survived infection. With the exception of a transient fever response, E70/43-infected animals remained clinically normal and exhibited a 1,000-fold reduction in both mean and maximum viremia titers. All convalescent E70/43-infected animals survived infection when challenged with parental E70 at 30 days postinfection. These data indicate that the highly conserved NL-S gene of ASFV, while nonessential for growth in swine macrophages in vitro, is a significant viral virulence factor and may

  1. An African swine fever virus virulence-associated gene NL-S with similarity to the herpes simplex virus ICP34.5 gene.

    PubMed

    Zsak, L; Lu, Z; Kutish, G F; Neilan, J G; Rock, D L

    1996-12-01

    We described previously an African swine fever virus (ASFV) open reading frame, 23-NL, in the African isolate Malawi Lil 20/1 whose product shared significant similarity in a carboxyl-terminal domain with those of a mouse myeloid differentiation primary response gene, MyD116, and the herpes simplex virus neurovirulence-associated gene, ICP34.5 (M. D. Sussman, Z. Lu, G. Kutish, C. L. Afonso, P. Roberts, and D. L. Rock, J. Virol. 66:5586-5589, 1992). The similarity of 23-NL to these genes suggested that this gene may function in some aspect of ASFV virulence and/or host range. Sequence analysis of additional pathogenic viral isolates demonstrates that this gene is highly conserved among diverse ASFV isolates and that the gene product exists in either a long (184 amino acids as in 23-NL) or a short form (70 to 72 amino acids in other examined ASFV isolates). The short form of the gene, NL-S, encodes the complete highly conserved, hydrophilic, carboxyl-terminal domain of 56 amino acids common to 23-NL, MyD116, and ICP34.5. Recombinant NL-S gene deletion mutants and their revertants were constructed from the pathogenic ASFV isolate E70 and an E70 monkey cell culture-adapted virus, MS44, to study gene function. Although deletion of NL-S did not affect viral growth in primary swine macrophages or Vero cell cultures in vitro, the null mutant, E70/43, exhibited a marked reduction in pig virulence. In contrast to revertant or parental E70 where mortality was 100%, all E70/43-infected animals survived infection. With the exception of a transient fever response, E70/43-infected animals remained clinically normal and exhibited a 1,000-fold reduction in both mean and maximum viremia titers. All convalescent E70/43-infected animals survived infection when challenged with parental E70 at 30 days postinfection. These data indicate that the highly conserved NL-S gene of ASFV, while nonessential for growth in swine macrophages in vitro, is a significant viral virulence factor and may

  2. Phylogeny and biogeography of African Murinae based on mitochondrial and nuclear gene sequences, with a new tribal classification of the subfamily

    PubMed Central

    2008-01-01

    Background Within the subfamily Murinae, African murines represent 25% of species biodiversity, making this group ideal for detailed studies of the patterns and timing of diversification of the African endemic fauna and its relationships with Asia. Here we report the results of phylogenetic analyses of the endemic African murines through a broad sampling of murine diversity from all their distribution area, based on the mitochondrial cytochrome b gene and the two nuclear gene fragments (IRBP exon 1 and GHR). Results A combined analysis of one mitochondrial and two nuclear gene sequences consistently identified and robustly supported ten primary lineages within Murinae. We propose to formalize a new tribal arrangement within the Murinae that reflects this phylogeny. The diverse African murine assemblage includes members of five of the ten tribes and clearly derives from multiple faunal exchanges between Africa and Eurasia. Molecular dating analyses using a relaxed Bayesian molecular clock put the first colonization of Africa around 11 Mya, which is consistent with the fossil record. The main period of African murine diversification occurred later following disruption of the migration route between Africa and Asia about 7–9 Mya. A second period of interchange, dating to around 5–6.5 Mya, saw the arrival in Africa of Mus (leading to the speciose endemic Nannomys), and explains the appearance of several distinctive African lineages in the late Miocene and Pliocene fossil record of Eurasia. Conclusion Our molecular survey of Murinae, which includes the most complete sampling so far of African taxa, indicates that there were at least four separate radiations within the African region, as well as several phases of dispersal between Asia and Africa during the last 12 My. We also reconstruct the phylogenetic structure of the Murinae, and propose a new classification at tribal level for this traditionally problematic group. PMID:18616808

  3. An African swine fever virus gene with similarity to the proto-oncogene bcl-2 and the Epstein-Barr virus gene BHRF1.

    PubMed

    Neilan, J G; Lu, Z; Afonso, C L; Kutish, G F; Sussman, M D; Rock, D L

    1993-07-01

    An open reading frame, LMW5-HL, in the African swine fever virus genome displays a high degree of similarity to the proto-oncogene bcl-2 and, to a lesser degree, the Epstein-Barr virus gene BHRF1. A highly conserved central region is found in all three proteins. LMW5-HL encodes a protein of 18 kDa that is present in infected porcine macrophages at both early and late times postinfection. The similarity of LMW5-HL to bcl-2 and BHRF1 suggests a role for it in cell maintenance during productive or persistent viral infection. PMID:8389936

  4. An African swine fever virus gene with similarity to the proto-oncogene bcl-2 and the Epstein-Barr virus gene BHRF1.

    PubMed Central

    Neilan, J G; Lu, Z; Afonso, C L; Kutish, G F; Sussman, M D; Rock, D L

    1993-01-01

    An open reading frame, LMW5-HL, in the African swine fever virus genome displays a high degree of similarity to the proto-oncogene bcl-2 and, to a lesser degree, the Epstein-Barr virus gene BHRF1. A highly conserved central region is found in all three proteins. LMW5-HL encodes a protein of 18 kDa that is present in infected porcine macrophages at both early and late times postinfection. The similarity of LMW5-HL to bcl-2 and BHRF1 suggests a role for it in cell maintenance during productive or persistent viral infection. Images PMID:8389936

  5. Sequence evaluation of four pooled-tissue normalized bovine cDNA libraries and construction of a gene index for cattle.

    PubMed

    Smith, T P; Grosse, W M; Freking, B A; Roberts, A J; Stone, R T; Casas, E; Wray, J E; White, J; Cho, J; Fahrenkrug, S C; Bennett, G L; Heaton, M P; Laegreid, W W; Rohrer, G A; Chitko-McKown, C G; Pertea, G; Holt, I; Karamycheva, S; Liang, F; Quackenbush, J; Keele, J W

    2001-04-01

    An essential component of functional genomics studies is the sequence of DNA expressed in tissues of interest. To provide a resource of bovine-specific expressed sequence data and facilitate this powerful approach in cattle research, four normalized cDNA libraries were produced and arrayed for high-throughput sequencing. The libraries were made with RNA pooled from multiple tissues to increase efficiency of normalization and maximize the number of independent genes for which sequence data were obtained. Target tissues included those with highest likelihood to have impact on production parameters of animal health, growth, reproductive efficiency, and carcass merit. Success of normalization and inter- and intralibrary redundancy were assessed by collecting 6000-23,000 sequences from each of the libraries (68,520 total sequences deposited in GenBank). Sequence comparison and assembly of these sequences was performed in combination with 56,500 other bovine EST sequences present in the GenBank dbEST database to construct a cattle Gene Index (available from The Institute for Genomic Research at http://www.tigr.org/tdb/tgi.shtml). The 124,381 bovine ESTs present in GenBank at the time of the analysis form 16,740 assemblies that are listed and annotated on the Web site. Analysis of individual library sequence data indicates that the pooled-tissue approach was highly effective in preparing libraries for efficient deep sequencing. PMID:11282978

  6. Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett’s Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium

    PubMed Central

    Levine, David; Chow, Wong-Ho; Bernstein, Leslie; Casson, Alan G.; Risch, Harvey A.; Shaheen, Nicholas J.; Bird, Nigel C.; Reid, Brian J.; Corley, Douglas A.; Hardie, Laura J.; Wu, Anna H.; Fitzgerald, Rebecca C.; Pharoah, Paul; Caldas, Carlos; Romero, Yvonne; Vaughan, Thomas L.; MacGregor, Stuart; Whiteman, David; Westberg, Lars; Nyren, Olof; Lagergren, Jesper

    2015-01-01

    Background The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett’s oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. Methods This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Results Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Conclusion Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed. PMID:26406593

  7. African swine fever virus multigene family 360 genes affect virus replication and generalization of infection in Ornithodoros porcinus ticks.

    PubMed

    Burrage, T G; Lu, Z; Neilan, J G; Rock, D L; Zsak, L

    2004-03-01

    Recently, we reported that African swine fever virus (ASFV) multigene family (MGF) 360 and 530 genes are significant swine macrophage host range determinants that function by promoting infected-cell survival. To examine the function of these genes in ASFV's arthropod host, Ornithodoros porcinus porcinus, an MGF360/530 gene deletion mutant (Pr4Delta35) was constructed from an ASFV isolate of tick origin, Pr4. Pr4Delta35 exhibited a significant growth defect in ticks. The deletion of six MGF360 and two MGF530 genes from Pr4 markedly reduced viral replication in infected ticks 100- to 1,000-fold. To define the minimal set of MGF360/530 genes required for tick host range, additional gene deletion mutants lacking individual or multiple MGF genes were constructed. The deletion mutant Pr4Delta3-C2, which lacked three MGF360 genes (3HL, 3Il, and 3LL), exhibited reduced viral growth in ticks. Pr4Delta3-C2 virus titers in ticks were significantly reduced 100- to 1,000-fold compared to control values at various times postinfection. In contrast to the parental virus, with which high levels of virus replication were observed in the tissues of infected adults, Pr4Delta3-C2 replication was not detected in the midgut, hemolymph, salivary gland, coxal gland, or reproductive organs at 15 weeks postinfection. These data indicate that ASFV MGF360 genes are significant tick host range determinants and that they are required for efficient virus replication and generalization of infection. The impaired virus replication of Pr4Delta3-C2 in the tick midgut likely accounts for the absence of the generalized infection that is necessary for the natural transmission of virus from ticks to pigs. PMID:14963141

  8. African Swine Fever Virus Multigene Family 360 Genes Affect Virus Replication and Generalization of Infection in Ornithodoros porcinus Ticks

    PubMed Central

    Burrage, T. G.; Lu, Z.; Neilan, J. G.; Rock, D. L.; Zsak, L.

    2004-01-01

    Recently, we reported that African swine fever virus (ASFV) multigene family (MGF) 360 and 530 genes are significant swine macrophage host range determinants that function by promoting infected-cell survival. To examine the function of these genes in ASFV's arthropod host, Ornithodoros porcinus porcinus, an MGF360/530 gene deletion mutant (Pr4Δ35) was constructed from an ASFV isolate of tick origin, Pr4. Pr4Δ35 exhibited a significant growth defect in ticks. The deletion of six MGF360 and two MGF530 genes from Pr4 markedly reduced viral replication in infected ticks 100- to 1,000-fold. To define the minimal set of MGF360/530 genes required for tick host range, additional gene deletion mutants lacking individual or multiple MGF genes were constructed. The deletion mutant Pr4Δ3-C2, which lacked three MGF360 genes (3HL, 3Il, and 3LL), exhibited reduced viral growth in ticks. Pr4Δ3-C2 virus titers in ticks were significantly reduced 100- to 1,000-fold compared to control values at various times postinfection. In contrast to the parental virus, with which high levels of virus replication were observed in the tissues of infected adults, Pr4Δ3-C2 replication was not detected in the midgut, hemolymph, salivary gland, coxal gland, or reproductive organs at 15 weeks postinfection. These data indicate that ASFV MGF360 genes are significant tick host range determinants and that they are required for efficient virus replication and generalization of infection. The impaired virus replication of Pr4Δ3-C2 in the tick midgut likely accounts for the absence of the generalized infection that is necessary for the natural transmission of virus from ticks to pigs. PMID:14963141

  9. Gene expression profiling of breast cancer survivability by pooled cDNA microarray analysis using logistic regression, artificial neural networks and decision trees

    PubMed Central

    2013-01-01

    Background Microarray technology can acquire information about thousands of genes simultaneously. We analyzed published breast cancer microarray databases to predict five-year recurrence and compared the performance of three data mining algorithms of artificial neural networks (ANN), decision trees (DT) and logistic regression (LR) and two composite models of DT-ANN and DT-LR. The collection of microarray datasets from the Gene Expression Omnibus, four breast cancer datasets were pooled for predicting five-year breast cancer relapse. After data compilation, 757 subjects, 5 clinical variables and 13,452 genetic variables were aggregated. The bootstrap method, Mann–Whitney U test and 20-fold cross-validation were performed to investigate candidate genes with 100 most-significant p-values. The predictive powers of DT, LR and ANN models were assessed using accuracy and the area under ROC curve. The associated genes were evaluated using Cox regression. Results The DT models exhibited the lowest predictive power and the poorest extrapolation when applied to the test samples. The ANN models displayed the best predictive power and showed the best extrapolation. The 21 most-associated genes, as determined by integration of each model, were analyzed using Cox regression with a 3.53-fold (95% CI: 2.24-5.58) increased risk of breast cancer five-year recurrence… Conclusions The 21 selected genes can predict breast cancer recurrence. Among these genes, CCNB1, PLK1 and TOP2A are in the cell cycle G2/M DNA damage checkpoint pathway. Oncologists can offer the genetic information for patients when understanding the gene expression profiles on breast cancer recurrence. PMID:23506640

  10. Cryptic diversity and gene flow among three African agricultural pests: Ceratitis rosa, Ceratitis fasciventris and Ceratitis anonae (Diptera, Tephritidae).

    PubMed

    Virgilio, M; Delatte, H; Quilici, S; Backeljau, T; De Meyer, M

    2013-05-01

    The 'Ceratitis FAR complex' is a species complex of African fruit flies (Diptera, Tephritidae) including the major agricultural pest Ceratitis rosa and the morphologically similar Ceratitis fasciventris and Ceratitis anonae. To resolve their intra- and interspecific genetic relationships and to estimate gene flow within this complex, we surveyed allelic variation at 16 microsatellite loci in 27 African populations of the three morphospecies. Interpopulation genetic distances and individual Bayesian assignments distinguished five genotypic clusters: two involving C. rosa (R1, R2; that may occur in sympatry), two involving C. fasciventris (F1, F2; with parapatric distributions) and one involving C. anonae (A). Intra- and interspecific patterns of genetic differentiation were not hierarchically structured and genetic differentiation between conspecific clusters (F1-F2 and R1-R2) was higher or comparable with differentiation between heterospecific clusters (e.g. F1-A or R2-A). In some cases, gene flow estimates among morphospecies or among heterospecific genotypic clusters were significantly different from zero, showing the lack of reproductive isolation. Genetic differentiation between genotypic clusters was partly supported by morphological differences observed a posteriori in male secondary sexual characters. These results suggest important revisions to current models of ecological niche requirements and invasion risk of the major agricultural pest C. rosa and provide a basis for a taxonomic re-interpretation of the FAR complex. PMID:23506441

  11. Gene polymorphisms and gene scores linked to low serum carotenoid status and their associations with metabolic disturbance and depressive symptoms in African-American adults

    PubMed Central

    Beydoun, May A.; Nalls, Michael A.; Canas, J. Atilio; Evans, Michele K.; Zonderman, Alan B.

    2016-01-01

    Gene polymorphisms provide means to obtain unconfounded associations between carotenoids and various health outcomes. We tested whether gene polymophorisms and gene scores linked to serum carotenoid status are related to metabolic disturbance and depressive symptoms in African-American adults residing in Baltimore city, MD, using cross-sectional data from the Healthy Aging in Neighborhood of Diversity Across the Lifespan (HANDLS) study (Age range:30–64y, N=873–994). We examined 24 single nucleotide polymorphisms of various gene loci that were previously shown to be associated with low serum carotenoid status (SNPlcar). Genetic risk scores (5 low specific-carotenoid risk scores (LSCRS: α-carotene, β-carotene, lutein+zeaxanthin, β-cryptoxanthin, lycopene) and 1 low total-carotenoid risk score (LTCRS: total carotenoids)) were created. SNPlcar, LSCRS and LTCRS were entered as predictors for a number of health outcomes. Those included obesity, National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III metabolic syndrome (MetS) and its components, elevated homeostatic model assessment, Insulin Resistance (HOMA-IR), C-reactive protein (CRP), hyperuricemia and elevated depressive symptoms (EDS, Center for Epidemiologic Studies-Depression (CES-D) score≥16). Among key findings, SNPlcar were not associated with the main outcomes after correction for multiple testing. However, an inverse association was found between LTCRS and HDL-C dyslipidemia. Specifically, the α-carotene and β-cryptoxanthin LSCRS were associated with lower odds of HDL-C dyslipidemia. However, the β-cryptoxanthin LSCRS was linked to a higher odds of EDS, with a linear dose-response relationship. In sum, gene risk scores linked to low serum carotenoids had mixed effects on HDL-C dyslipidemia and EDS. Further studies using larger African-American samples are needed. PMID:25201307

  12. Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

    PubMed Central

    Fox, Ervin R.; Young, J. Hunter; Li, Yali; Dreisbach, Albert W.; Keating, Brendan J.; Musani, Solomon K.; Liu, Kiang; Morrison, Alanna C.; Ganesh, Santhi; Kutlar, Abdullah; Ramachandran, Vasan S.; Polak, Josef F.; Fabsitz, Richard R.; Dries, Daniel L.; Farlow, Deborah N.; Redline, Susan; Adeyemo, Adebowale; Hirschorn, Joel N.; Sun, Yan V.; Wyatt, Sharon B.; Penman, Alan D.; Palmas, Walter; Rotter, Jerome I.; Townsend, Raymond R.; Doumatey, Ayo P.; Tayo, Bamidele O.; Mosley, Thomas H.; Lyon, Helen N.; Kang, Sun J.; Rotimi, Charles N.; Cooper, Richard S.; Franceschini, Nora; Curb, J. David; Martin, Lisa W.; Eaton, Charles B.; Kardia, Sharon L.R.; Taylor, Herman A.; Caulfield, Mark J.; Ehret, Georg B.; Johnson, Toby; Chakravarti, Aravinda; Zhu, Xiaofeng; Levy, Daniel; Munroe, Patricia B.; Rice, Kenneth M.; Bochud, Murielle; Johnson, Andrew D.; Chasman, Daniel I.; Smith, Albert V.; Tobin, Martin D.; Verwoert, Germaine C.; Hwang, Shih-Jen; Pihur, Vasyl; Vollenweider, Peter; O'Reilly, Paul F.; Amin, Najaf; Bragg-Gresham, Jennifer L.; Teumer, Alexander; Glazer, Nicole L.; Launer, Lenore; Zhao, Jing Hua; Aulchenko, Yurii; Heath, Simon; Sõber, Siim; Parsa, Afshin; Luan, Jian'an; Arora, Pankaj; Dehghan, Abbas; Zhang, Feng; Lucas, Gavin; Hicks, Andrew A.; Jackson, Anne U.; Peden, John F.; Tanaka, Toshiko; Wild, Sarah H.; Rudan, Igor; Igl, Wilmar; Milaneschi, Yuri; Parker, Alex N.; Fava, Cristiano; Chambers, John C.; Kumari, Meena; JinGo, Min; van der Harst, Pim; Kao, Wen Hong Linda; Sjögren, Marketa; Vinay, D.G.; Alexander, Myriam; Tabara, Yasuharu; Shaw-Hawkins, Sue; Whincup, Peter H.; Liu, Yongmei; Shi, Gang; Kuusisto, Johanna; Seielstad, Mark; Sim, Xueling; Nguyen, Khanh-Dung Hoang; Lehtimäki, Terho; Matullo, Giuseppe; Wu, Ying; Gaunt, Tom R.; Charlotte Onland-Moret, N.; Cooper, Matthew N.; Platou, Carl G.P.; Org, Elin; Hardy, Rebecca; Dahgam, Santosh; Palmen, Jutta; Vitart, Veronique; Braund, Peter S.; Kuznetsova, Tatiana; Uiterwaal, Cuno S.P.M.; Campbell, Harry; Ludwig, Barbara; Tomaszewski, Maciej; Tzoulaki, Ioanna; Palmer, Nicholette D.; Aspelund, Thor; Garcia, Melissa; Chang, Yen-Pei C.; O'Connell, Jeffrey R.; Steinle, Nanette I.; Grobbee, Diederick E.; Arking, Dan E.; Hernandez, Dena; Najjar, Samer; McArdle, Wendy L.; Hadley, David; Brown, Morris J.; Connell, John M.; Hingorani, Aroon D.; Day, Ian N.M.; Lawlor, Debbie A.; Beilby, John P.; Lawrence, Robert W.; Clarke, Robert; Collins, Rory; Hopewell, Jemma C.; Ongen, Halit; Bis, Joshua C.; Kähönen, Mika; Viikari, Jorma; Adair, Linda S.; Lee, Nanette R.; Chen, Ming-Huei; Olden, Matthias; Pattaro, Cristian; Hoffman Bolton, Judith A.; Köttgen, Anna; Bergmann, Sven; Mooser, Vincent; Chaturvedi, Nish; Frayling, Timothy M.; Islam, Muhammad; Jafar, Tazeen H.; Erdmann, Jeanette; Kulkarni, Smita R.; Bornstein, Stefan R.; Grässler, Jürgen; Groop, Leif; Voight, Benjamin F.; Kettunen, Johannes; Howard, Philip; Taylor, Andrew; Guarrera, Simonetta; Ricceri, Fulvio; Emilsson, Valur; Plump, Andrew; Barroso, Inês; Khaw, Kay-Tee; Weder, Alan B.; Hunt, Steven C.; Bergman, Richard N.; Collins, Francis S.; Bonnycastle, Lori L.; Scott, Laura J.; Stringham, Heather M.; Peltonen, Leena; Perola, Markus; Vartiainen, Erkki; Brand, Stefan-Martin; Staessen, Jan A.; Wang, Thomas J.; Burton, Paul R.; SolerArtigas, Maria; Dong, Yanbin; Snieder, Harold; Wang, Xiaoling; Zhu, Haidong; Lohman, Kurt K.; Rudock, Megan E.; Heckbert, Susan R.; Smith, Nicholas L.; Wiggins, Kerri L.; Shriner, Daniel; Veldre, Gudrun; Viigimaa, Margus; Kinra, Sanjay; Prabhakaran, Dorairajan; Tripathy, Vikal; Langefeld, Carl D.; Rosengren, Annika; Thelle, Dag S.; MariaCorsi, Anna; Singleton, Andrew; Forrester, Terrence; Hilton, Gina; McKenzie, Colin A.; Salako, Tunde; Iwai, Naoharu; Kita, Yoshikuni; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ueshima, Hirotsugu; Umemura, Satoshi; Eyheramendy, Susana; Meitinger, Thomas; Wichmann, H.-Erich; Cho, Yoon Shin; Kim, Hyung-Lae; Lee, Jong-Young; Scott, James; Sehmi, Joban S.; Zhang, Weihua; Hedblad, Bo; Nilsson, Peter; Smith, George Davey; Wong, Andrew; Narisu, Narisu; Stančáková, Alena; Raffel, Leslie J.; Yao, Jie; Kathiresan, Sekar; O'Donnell, Chris; Schwartz, Steven M.; Arfan Ikram, M.; Longstreth, Will T.; Seshadri, Sudha; Shrine, Nick R.G.; Wain, Louise V.; Morken, Mario A.; Swift, Amy J.; Laitinen, Jaana; Prokopenko, Inga; Zitting, Paavo; Cooper, Jackie A.; Humphries, Steve E.; Danesh, John; Rasheed, Asif; Goel, Anuj; Hamsten, Anders; Watkins, Hugh; Bakker, Stephan J.L.; van Gilst, Wiek H.; Janipalli, Charles S.; Radha Mani, K.; Yajnik, Chittaranjan S.; Hofman, Albert; Mattace-Raso, Francesco U.S.; Oostra, Ben A.; Demirkan, Ayse; Isaacs, Aaron; Rivadeneira, Fernando; Lakatta, Edward G.; Orru, Marco; Scuteri, Angelo; Ala-Korpela, Mika; Kangas, Antti J.; Lyytikäinen, Leo-Pekka; Soininen, Pasi; Tukiainen, Taru; Würz, Peter; Twee-Hee Ong, Rick; Dörr, Marcus; Kroemer, Heyo K.; Völker, Uwe; Völzke, Henry; Galan, Pilar; Hercberg, Serge; Lathrop, Mark; Zelenika, Diana; Deloukas, Panos; Mangino, Massimo; Spector, Tim D.; Zhai, Guangju; Meschia, James F.; Nalls, Michael A.; Sharma, Pankaj; Terzic, Janos; Kranthi Kumar, M.J.; Denniff, Matthew; Zukowska-Szczechowska, Ewa; Wagenknecht, Lynne E.; Fowkes, Gerald R.; Charchar, Fadi J.; Schwarz, Peter E.H.; Hayward, Caroline; Guo, Xiuqing; Bots, Michiel L.; Brand, Eva; Samani, Nilesh J.; Polasek, Ozren; Talmud, Philippa J.; Nyberg, Fredrik; Kuh, Diana; Laan, Maris; Hveem, Kristian; Palmer, Lyle J.; van der Schouw, Yvonne T.; Casas, Juan P.; Mohlke, Karen L.; Vineis, Paolo; Raitakari, Olli; Wong, Tien Y.; Shyong Tai, E.; Laakso, Markku; Rao, Dabeeru C.; Harris, Tamara B.; Morris, Richard W.; Dominiczak, Anna F.; Kivimaki, Mika; Marmot, Michael G.; Miki, Tetsuro; Saleheen, Danish; Chandak, Giriraj R.; Coresh, Josef; Navis, Gerjan; Salomaa, Veikko; Han, Bok-Ghee; Kooner, Jaspal S.; Melander, Olle; Ridker, Paul M.; Bandinelli, Stefania; Gyllensten, Ulf B.; Wright, Alan F.; Wilson, James F.; Ferrucci, Luigi; Farrall, Martin; Tuomilehto, Jaakko; Pramstaller, Peter P.; Elosua, Roberto; Soranzo, Nicole; Sijbrands, Eric J.G.; Altshuler, David; Loos, Ruth J.F.; Shuldiner, Alan R.; Gieger, Christian; Meneton, Pierre; Uitterlinden, Andre G.; Wareham, Nicholas J.; Gudnason, Vilmundur; Rettig, Rainer; Uda, Manuela; Strachan, David P.; Witteman, Jacqueline C.M.; Hartikainen, Anna-Liisa; Beckmann, Jacques S.; Boerwinkle, Eric; Boehnke, Michael; Larson, Martin G.; Järvelin, Marjo-Riitta; Psaty, Bruce M.; Abecasis, Gonçalo R.; Elliott, Paul; van Duijn , Cornelia M.; Newton-Cheh, Christopher

    2011-01-01

    The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. PMID:21378095

  13. Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

    PubMed

    Fox, Ervin R; Young, J Hunter; Li, Yali; Dreisbach, Albert W; Keating, Brendan J; Musani, Solomon K; Liu, Kiang; Morrison, Alanna C; Ganesh, Santhi; Kutlar, Abdullah; Ramachandran, Vasan S; Polak, Josef F; Fabsitz, Richard R; Dries, Daniel L; Farlow, Deborah N; Redline, Susan; Adeyemo, Adebowale; Hirschorn, Joel N; Sun, Yan V; Wyatt, Sharon B; Penman, Alan D; Palmas, Walter; Rotter, Jerome I; Townsend, Raymond R; Doumatey, Ayo P; Tayo, Bamidele O; Mosley, Thomas H; Lyon, Helen N; Kang, Sun J; Rotimi, Charles N; Cooper, Richard S; Franceschini, Nora; Curb, J David; Martin, Lisa W; Eaton, Charles B; Kardia, Sharon L R; Taylor, Herman A; Caulfield, Mark J; Ehret, Georg B; Johnson, Toby; Chakravarti, Aravinda; Zhu, Xiaofeng; Levy, Daniel

    2011-06-01

    The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. PMID:21378095

  14. Prevalence of common vitamin D receptor gene polymorphisms in HIV-infected and uninfected South Africans

    PubMed Central

    McNamara, Lynne; Takuva, Simbarashe; Chirwa, Tobias; MacPhail, Patrick

    2016-01-01

    Background: Host genetic factors may a play role in susceptibility to infection. Vitamin-D is an immunomodulator that may play a role in HIV infection. Vitamin-D action is mediated by the vitamin-D receptor. We establish prevalence of ApaI, BsmI, FokI and TaqI polymorphisms (VDRPs) amongst a black southern African HIV+ve population and investigate polymorphic differences between HIV+ve and -ve people. Methods: Seventy-nine sex and age-group matched HIV+ve patients of African origin initiating antiretroviral therapy (ART) and 79 HIV-ve participants, also of African origin, were recruited from a public sector HIV testing and treatment clinic and investigated for the 4 polymorphisms. The genotype frequencies were compared, odds ratios and 95% confidence intervals of the association of HIV status and each genotype were calculated. Both dominant, co-dominant, recessive and allele models were tested. Results: We found no evidence of difference in distribution and association between HIV infection and the genotypes of the BsmI, FokI and TaqI VDR polymorphisms. The genotype distributions were consistent with Hardy-Weinberg equilibrium for these genotypes. The ApaI genotype showed differences in distribution by HIV status in the dominant and co-dominant models. However this finding is cautiously stated as the ApaI genotype violated the Hardy-Weinberg equilibrium and frequency of the minor variant was unexpectedly low in this population. Conclusion: We do not show convincing differences in distribution of the VDR genotypes among HIV+ve and HIV-ve black southern African persons. Future studies need to be replicated in larger study populations as understanding polymorphic differences and similarities may offer insights into the different susceptibility and progression of HIV in southern African populations. PMID:27186331

  15. Vitamin D Receptor Gene Expression and Function in a South African Population: Ethnicity, Vitamin D and FokI

    PubMed Central

    O′Neill, Vanessa; Asani, Furaha Florence; Jeffery, Tamsyn Jacki; Saccone, Donovan Sean; Bornman, Liza

    2013-01-01

    Polymorphisms of the vitamin D receptor gene (VDR) have been associated inconsistently with various diseases, across populations of diverse origin. The T(f) allele of the functional SNP FokI, in exon 2 of VDR, results in a longer vitamin D receptor protein (VDR) isoform, proposed to be less active. Genetic association of VDR with disease is likely confounded by ethnicity and environmental factors such as plasma 25(OH)D3 status. We hypothesized that VDR expression, VDR level and transactivation of target genes, CAMP and CYP24A1, depend on vitamin D, ethnicity and FokI genotype. Healthy volunteers participated in the study (African, n = 40 and White, n = 20). Plasma 25(OH)D3 levels were quantified by LC-MS and monocytes cultured, with or without 1,25(OH)2D3. Gene expression and protein level was quantified using qRT-PCR and flow cytometry, respectively. Mean plasma 25(OH)D3 status was normal and not significantly different between ethnicities. Neither 25(OH)D3 status nor 1,25(OH)2D3 supplementation significantly influenced expression or level of VDR. Africans had significantly higher mean VDR protein levels (P<0.050), nonetheless transactivated less CAMP expression than Whites. Genotyping the FokI polymorphism by pyrosequencing together with HapMap data, showed a significantly higher (P<0.050) frequency of the CC genotype in Africans than in Whites. FokI genotype, however, did not influence VDR expression or VDR level, but influenced overall transactivation of CAMP and 1,25(OH)2D3-elicited CYP24A1 induction; the latter, interacting with ethnicity. In conclusion, differential VDR expression relates to ethnicity, rather than 25(OH)D3 status and FokI genotype. Instead, VDR transactivation of CAMP is influenced by FokI genotype and, together with ethnicity, influence 1,25(OH)2D3-elicited CYP24A1 expression. Thus, the expression and role of VDR to transactivate target genes is determined not only by genetics, but also by ethnicity and environment involving complex

  16. A BIR motif containing gene of African swine fever virus, 4CL, is nonessential for growth in vitro and viral virulence.

    PubMed

    Neilan, J G; Lu, Z; Kutish, G F; Zsak, L; Burrage, T G; Borca, M V; Carrillo, C; Rock, D L

    1997-04-14

    An African swine fever virus (ASFV) gene with similarity to viral and cellular inhibitor of apoptosis genes (iap) has been described in the African isolate Malawi Lil-20/1 (ORF 4CL) and a cell-culture-adapted European virus, BA71V (ORF A224L). The similarity of the ASFV gene to genes involved in inhibiting cellular apoptosis suggested the gene may regulate apoptosis in ASFV-infected cells and thus may function in ASFV virulence and/or host range. Sequence analysis of additional African and European pathogenic isolates demonstrates that this gene is highly conserved among both pig and tick ASFV isolates and that its similarity to iap genes is limited to the presence of a single IAP repeat motif (BIR motif) in the ASFV gene. To study gene function, a 4CL gene deletion mutant, delta 4CL, was constructed from the pathogenic Malawi Lil-20/1 isolate. Growth characteristics of delta 4CL in swine macrophage cell cultures were indistinguishable from those of parental virus. Infected macrophage survival time and the induction and magnitude of apoptosis in virus-infected macrophages were comparable for cells infected with either delta 4CL or parental virus. In infected swine, delta 4CL exhibited an unaltered Malawi Lil-20/1 virulence phenotype. These data indicate that, although highly conserved among ASFV isolates, the 4CL gene is nonessential for growth in macrophage cell cultures in vitro and for pig virulence. Additionally, despite its limited similarity to JAP genes, 4CL exhibits no anti-apoptotic function in infected macrophage cell cultures. The high degree of gene conservation among ASFV isolates, together with the apparent lack of function in the swine host, suggests 4CL may be a host range gene involved in aspects of infection in the arthropod host, ticks of the genus Ornithodoros. PMID:9143281

  17. Discovery of a Dicer-Independent, Cell-Type Dependent Alternate Targeting Sequence Generator: Implications in Gene Silencing & Pooled RNAi Screens

    PubMed Central

    Bhinder, Bhavneet; Shum, David; Li, Mu; Ibáñez, Glorymar; Vlassov, Alexander V.; Magdaleno, Susan; Djaballah, Hakim

    2014-01-01

    There is an acceptance that plasmid-based delivery of interfering RNA always generates the intended targeting sequences in cells, making it as specific as its synthetic counterpart. However, recent studies have reported on cellular inefficiencies of the former, especially in light of emerging gene discordance at inter-screen level and across formats. Focusing primarily on the TRC plasmid-based shRNA hairpins, we reasoned that alleged specificities were perhaps compromised due to altered processing; resulting in a multitude of random interfering sequences. For this purpose, we opted to study the processing of hairpin TRCN#40273 targeting CTTN; which showed activity in a miRNA-21 gain-of-function shRNA screen, but inactive when used as an siRNA duplex. Using a previously described walk-through method, we identified 36 theoretical cleavage variants resulting in 78 potential siRNA duplexes targeting 53 genes. We synthesized and tested all of them. Surprisingly, six duplexes targeting ASH1L, DROSHA, GNG7, PRKCH, THEM4, and WDR92 scored as active. QRT-PCR analysis on hairpin transduced reporter cells confirmed knockdown of all six genes, besides CTTN; revealing a surprising 7 gene-signature perturbation by this one single hairpin. We expanded our qRT-PCR studies to 26 additional cell lines and observed unique knockdown profiles associated with each cell line tested; even for those lacking functional DICER1 gene suggesting no obvious dependence on dicer for shRNA hairpin processing; contrary to published models. Taken together, we report on a novel dicer independent, cell-type dependent mechanism for non-specific RNAi gene silencing we coin Alternate Targeting Sequence Generator (ATSG). In summary, ATSG adds another dimension to the already complex interpretation of RNAi screening data, and provides for the first time strong evidence in support of arrayed screening, and questions the scientific merits of performing pooled RNAi screens, where deconvolution of up to genome

  18. HTR1B, ADIPOR1, PPARGC1A, and CYP19A1 and Obesity in a Cohort of Caucasians and African Americans: An Evaluation of Gene-Environment Interactions and Candidate Genes

    PubMed Central

    Edwards, Todd L.; Velez Edwards, Digna R.; Villegas, Raquel; Cohen, Sarah S.; Buchowski, Maciej S.; Fowke, Jay H.; Schlundt, David; Long, Ji Rong; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou; Hargreaves, Margaret K.; Jeffrey, Smith; Williams, Scott M.; Signorello, Lisa B.; Blot, William J.; Matthews, Charles E.

    2012-01-01

    The World Health Organization estimates that the number of obese and overweight adults has increased to 1.6 billion, with concomitant increases in comorbidity. While genetic factors for obesity have been extensively studied in Caucasians, fewer studies have investigated genetic determinants of body mass index (BMI; weight (kg)/height (m)2) in African Americans. A total of 38 genes and 1,086 single nucleotide polymorphisms (SNPs) in African Americans (n = 1,173) and 897 SNPs in Caucasians (n = 1,165) were examined in the Southern Community Cohort Study (2002–2009) for associations with BMI and gene × environment interactions. A statistically significant association with BMI survived correction for multiple testing at rs4140535 (β = −0.04, 95% confidence interval: −0.06, −0.02; P = 5.76 × 10−5) in African Americans but not in Caucasians. Gene-environment interactions were observed with cigarette smoking and a SNP in ADIPOR1 in African Americans, as well as between a different SNP in ADIPOR1 and physical activity in Caucasians. A SNP in PPARGC1A interacted with alcohol consumption in African Americans, and a different SNP in PPARGC1A was nominally associated in Caucasians. A SNP in CYP19A1 interacted with dietary energy intake in African Americans, and another SNP in CYP191A had an independent association with BMI in Caucasians. PMID:22106445

  19. Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans

    PubMed Central

    David, Sean P.; Wang, Ange; Kapphahn, Kristopher; Hedlin, Haley; Desai, Manisha; Henderson, Michael; Yang, Lingyao; Walsh, Kyle M.; Schwartz, Ann G.; Wiencke, John K.; Spitz, Margaret R.; Wenzlaff, Angela S.; Wrensch, Margaret R.; Eaton, Charles B.; Furberg, Helena; Mark Brown, W.; Goldstein, Benjamin A.; Assimes, Themistocles; Tang, Hua; Kooperberg, Charles L.; Quesenberry, Charles P.; Tindle, Hilary; Patel, Manali I.; Amos, Christopher I.; Bergen, Andrew W.; Swan, Gary E.; Stefanick, Marcia L.

    2016-01-01

    Background Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene–environment interactions is not well understood. Methods We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case–control study of African-American females and males (1078 lung cancer cases and 822 controls). Findings Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10− 5). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = − 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans. Interpretation These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers. PMID:26981579

  20. Sex-biased gene flow in African Americans but not in American Caucasians.

    PubMed

    Gonçalves, V F; Prosdocimi, F; Santos, L S; Ortega, J M; Pena, S D J

    2007-01-01

    We have previously shown evidence of strong sex-biased genetic blending in the founding and ongoing history of the Brazilian population, with the African and Amerindian contribution being highest from maternal lineages (as measured by mitochondrial DNA) and the European contribution foremost from paternal lineages (estimated from Y-chromosome haplogroups). The same phenomenon has been observed in several other Latin American countries, suggesting that it might constitute a universal characteristic of the Iberian colonization of the Americas. However, it has also recently been detected in the Black population of the United States. We thus wondered if the same could be observed in American Caucasians. To answer that question, we retrieved 1387 hypervariable I Caucasian mitochondrial DNA sequences from the FBI population database and established their haplogroups and continental geographical sources. In sharp contrast with the situation of the Caucasian population of Latin American countries, only 3.1% of the American Caucasian sequences had African and/or Amerindian origin. To explain this discrepancy we propose that the finding of elevated genomic contributions from European males and Amerindian or African females depends not only on the occurrence of directional mating, but also on the "racial" categorization of the children born from these relations. In this respect, social practices in Latin America and in the United States diverge considerably; in the former socially significant "races" are normally designated according to physical appearance, while in the latter descent appears to be the most important factor. PMID:17573655

  1. Saturation of an Intra-Gene Pool Linkage Map: Towards a Unified Consensus Linkage Map for Fine Mapping and Synteny Analysis in Common Bean

    PubMed Central

    Galeano, Carlos H.; Fernandez, Andrea C.; Franco-Herrera, Natalia; Cichy, Karen A.; McClean, Phillip E.; Vanderleyden, Jos; Blair, Matthew W.

    2011-01-01

    Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364×G19833 (DG) and BAT93×JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning. PMID:22174773

  2. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model.

    PubMed

    Jennis, Matthew; Kung, Che-Pei; Basu, Subhasree; Budina-Kolomets, Anna; Leu, Julia I-Ju; Khaku, Sakina; Scott, Jeremy P; Cai, Kathy Q; Campbell, Michelle R; Porter, Devin K; Wang, Xuting; Bell, Douglas A; Li, Xiaoxian; Garlick, David S; Liu, Qin; Hollstein, Monica; George, Donna L; Murphy, Maureen E

    2016-04-15

    A nonsynonymous single-nucleotide polymorphism at codon 47 inTP53exists in African-descent populations (P47S, rs1800371; referred to here as S47). Here we report that, in human cell lines and a mouse model, the S47 variant exhibits a modest decrease in apoptosis in response to most genotoxic stresses compared with wild-type p53 but exhibits a significant defect in cell death induced by cisplatin. We show that, compared with wild-type p53, S47 has nearly indistinguishable transcriptional function but shows impaired ability to transactivate a subset of p53 target genes, including two involved in metabolism:Gls2(glutaminase 2) andSco2 We also show that human and mouse cells expressing the S47 variant are markedly resistant to cell death by agents that induce ferroptosis (iron-mediated nonapoptotic cell death). We show that mice expressing S47 in homozygous or heterozygous form are susceptible to spontaneous cancers of diverse histological types. Our data suggest that the S47 variant may contribute to increased cancer risk in individuals of African descent, and our findings highlight the need to assess the contribution of this variant to cancer risk in these populations. These data also confirm the potential relevance of metabolism and ferroptosis to tumor suppression by p53. PMID:27034505

  3. ABCC5 transporter is a novel type 2 diabetes susceptibility gene in European and African American populations.

    PubMed

    Direk, Kenan; Lau, Winston; Small, Kerrin S; Maniatis, Nikolas; Andrew, Toby

    2014-09-01

    Numerous functional studies have implicated PARL in relation to type 2 diabetes (T2D). We hypothesised that conflicting human association studies may be due to neighbouring causal variants being in linkage disequilibrium (LD) with PARL. We conducted a comprehensive candidate gene study of the extended LD genomic region that includes PARL and transporter ABCC5 using three data sets (two European and one African American), in relation to healthy glycaemic variation, visceral fat accumulation and T2D disease. We observed no evidence for previously reported T2D association with Val262Leu or PARL using array and fine-map genomic and expression data. By contrast, we observed strong evidence of T2D association with ABCC5 (intron 26) for European and African American samples (P = 3E-07) and with ABCC5 adipose expression in Europeans [odds ratio (OR) = 3.8, P = 2E-04]. The genomic location estimate for the ABCC5 functional variant, associated with all phenotypes and expression data (P = 1E-11), was identical for all samples (at Chr3q 185,136 kb B36), indicating that the risk variant is an expression quantitative trait locus (eQTL) with increased expression conferring risk of disease. That the association with T2D is observed in populations of disparate ancestry suggests the variant is a ubiquitous risk factor for T2D. PMID:25117150

  4. The Ep152R ORF of African Swine Fever Virus strain Georgia encodes for an essential gene that interacts with host protein BAG6

    Technology Transfer Automated Retrieval System (TEKTRAN)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The viral genome encodes for more than 150 genes, and only a select few have been studied in some detail. Here we rep...

  5. Androgen Metabolism Gene Polymorphisms, Associations with Prostate Cancer Risk and Pathological Characteristics: A Comparative Analysis between South African and Senegalese Men

    PubMed Central

    Fernandez, Pedro; Zeigler-Johnson, Charnita M.; Spangler, Elaine; van der Merwe, André; Jalloh, Mohamed; Gueye, Serigne M.; Rebbeck, Timothy R.

    2012-01-01

    Prostate cancer is the most common cancer in men in developed countries and the leading cause of mortality in males in less developed countries. African ethnicity is one of the major risk factors for developing prostate cancer. Pathways involved in androgen metabolism have been implicated in the etiology of the disease. Analyses of clinical data and CYP3A4, CYP3A5, and SRD5A2 genotypes were performed in South African White (120 cases; 134 controls), Mixed Ancestry (207 cases; 167 controls), and Black (25 cases; 20 controls) men, as well as in Senegalese men (86 cases; 300 controls). Senegalese men were diagnosed earlier with prostate cancer and had higher median PSA levels compared to South African men. Metastasis occurred more frequently in Senegalese men. Gene polymorphism frequencies differed significantly between South African and Senegalese men. The CYP3A4 rs2740574 polymorphism was associated with prostate cancer risk and tumor aggressiveness in South African men, after correction for population stratification, and the SRD5A2 rs523349 CG genotype was inversely associated with high-stage disease in Senegalese men. These data suggest that variants previously associated with prostate cancer in other populations may also affect prostate cancer risk in African men. PMID:23091730

  6. Deletion of a CD2-Like Gene, 8-DR, from African Swine Fever Virus Affects Viral Infection in Domestic Swine

    PubMed Central

    Borca, M. V.; Carrillo, C.; Zsak, L.; Laegreid, W. W.; Kutish, G. F.; Neilan, J. G.; Burrage, T. G.; Rock, D. L.

    1998-01-01

    An African swine fever virus (ASFV) gene with similarity to the T-lymphocyte surface antigen CD2 has been found in the pathogenic African isolate Malawi Lil-20/1 (open reading frame [ORF] 8-DR) and a cell culture-adapted European virus, BA71V (ORF EP402R) and has been shown to be responsible for the hemadsorption phenomenon observed for ASFV-infected cells. The structural and functional similarities of the ASFV gene product to CD2, a cellular protein involved in cell-cell adhesion and T-cell-mediated immune responses, suggested a possible role for this gene in tissue tropism and/or immune evasion in the swine host. In this study, we constructed an ASFV 8-DR gene deletion mutant (Δ8-DR) and its revertant (8-DR.R) from the Malawi Lil-20/1 isolate to examine gene function in vivo. In vitro, Δ8-DR, 8-DR.R, and the parental virus exhibited indistinguishable growth characteristics on primary porcine macrophage cell cultures. In vivo, 8-DR had no obvious effect on viral virulence in domestic pigs; disease onset, disease course, and mortality were similar for the mutant Δ8-DR, its revertant 8-DR.R, and the parental virus. Altered viral infection was, however, observed for pigs infected with Δ8-DR. A delay in spread to and/or replication of Δ8-DR in the draining lymph node, a delay in generalization of infection, and a 100- to 1,000-fold reduction in virus titers in lymphoid tissue and bone marrow were observed. Onset of viremia for Δ8-DR-infected animals was significantly delayed (by 2 to 5 days), and mean viremia titers were reduced approximately 10,000-fold at 5 days postinfection and 30- to 100-fold at later times; moreover, unlike in 8-DR.R-infected animals, the viremia was no longer predominantly erythrocyte associated but rather was equally distributed among erythrocyte, leukocyte, and plasma fractions. Mitogen-dependent lymphocyte proliferation of swine peripheral blood mononuclear cells in vitro was reduced by 90 to 95% following infection with 8-DR.R but

  7. Deletion of a CD2-like gene, 8-DR, from African swine fever virus affects viral infection in domestic swine.

    PubMed

    Borca, M V; Carrillo, C; Zsak, L; Laegreid, W W; Kutish, G F; Neilan, J G; Burrage, T G; Rock, D L

    1998-04-01

    An African swine fever virus (ASFV) gene with similarity to the T-lymphocyte surface antigen CD2 has been found in the pathogenic African isolate Malawi Lil-20/1 (open reading frame [ORF] 8-DR) and a cell culture-adapted European virus, BA71V (ORF EP402R) and has been shown to be responsible for the hemadsorption phenomenon observed for ASFV-infected cells. The structural and functional similarities of the ASFV gene product to CD2, a cellular protein involved in cell-cell adhesion and T-cell-mediated immune responses, suggested a possible role for this gene in tissue tropism and/or immune evasion in the swine host. In this study, we constructed an ASFV 8-DR gene deletion mutant (delta8-DR) and its revertant (8-DR.R) from the Malawi Lil-20/1 isolate to examine gene function in vivo. In vitro, delta8-DR, 8-DR.R, and the parental virus exhibited indistinguishable growth characteristics on primary porcine macrophage cell cultures. In vivo, 8-DR had no obvious effect on viral virulence in domestic pigs; disease onset, disease course, and mortality were similar for the mutant delta8-DR, its revertant 8-DR.R, and the parental virus. Altered viral infection was, however, observed for pigs infected with delta8-DR. A delay in spread to and/or replication of delta8-DR in the draining lymph node, a delay in generalization of infection, and a 100- to 1,000-fold reduction in virus titers in lymphoid tissue and bone marrow were observed. Onset of viremia for delta8-DR-infected animals was significantly delayed (by 2 to 5 days), and mean viremia titers were reduced approximately 10,000-fold at 5 days postinfection and 30- to 100-fold at later times; moreover, unlike in 8-DR.R-infected animals, the viremia was no longer predominantly erythrocyte associated but rather was equally distributed among erythrocyte, leukocyte, and plasma fractions. Mitogen-dependent lymphocyte proliferation of swine peripheral blood mononuclear cells in vitro was reduced by 90 to 95% following infection

  8. Genetic diversity of the black gram [Vigna mungo (L.) Hepper] gene pool as revealed by SSR markers

    PubMed Central

    Kaewwongwal, Anochar; Kongjaimun, Alisa; Somta, Prakit; Chankaew, Sompong; Yimram, Tarikar; Srinives, Peerasak

    2015-01-01

    In this study, 520 cultivated and 14 wild accessions of black gram (Vigna mungo (L.) Hepper) were assessed for diversity using 22 SSR markers. Totally, 199 alleles were detected with a mean of 9.05 alleles per locus. Wild black gram showed higher gene diversity than cultivated black gram. Gene diversity of cultivated accessions among regions was comparable, while allelic richness of South Asia was higher than that of other regions. 78.67% of the wild gene diversity presented in cultivated accessions, indicating that the domestication bottleneck effect in black gram is relatively low. Genetic distance analysis revealed that cultivated black gram was more closely related to wild black gram from South Asia than that from Southeast Asia. STRUCTURE, principal coordinate and neighbor-joining analyses consistently revealed that 534 black gram accessions were grouped into three major subpopulations. The analyses also revealed that cultivated black gram from South Asia was genetically distinct from that from West Asia. Comparison by SSR analysis with other closely related Vigna species, including mungbean, azuki bean, and rice bean, revealed that level of gene diversity of black gram is comparable to that of mungbean and rice bean but lower than that of azuki bean. PMID:26069442

  9. Regulatory variant in FZD6 gene contributes to nonsyndromic cleft lip and palate in an African-American family.

    PubMed

    Cvjetkovic, Nevena; Maili, Lorena; Weymouth, Katelyn S; Hashmi, S Shahrukh; Mulliken, John B; Topczewski, Jacek; Letra, Ariadne; Yuan, Qiuping; Blanton, Susan H; Swindell, Eric C; Hecht, Jacqueline T

    2015-09-01

    Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect affecting 135,000 newborns worldwide each year. While a multifactorial etiology has been suggested as the cause, despite decades of research, the genetic underpinnings of NSCLP remain largely unexplained. In our previous genome-wide linkage study of a large NSCLP African-American family, we identified a candidate locus at 8q21.3-24.12 (LOD = 2.98). This region contained four genes, Frizzled-6 (FZD6), Matrilin-2 (MATN2), Odd-skipped related 2 (OSR2) and Solute Carrier Family 25, Member 32 (SLC25A32). FZD6 was located under the maximum linkage peak. In this study, we sequenced the coding and noncoding regions of these genes in two affected family members, and identified a rare variant in intron 1 of FZD6 (rs138557689; c.-153 + 432A>C). The variant C allele segregated with NSCLP in this family, through affected and unaffected individuals, and was found in one other NSCLP African-American family. Functional assays showed that this allele creates an allele-specific protein-binding site and decreases promoter activity. We also observed that loss and gain of fzd6 in zebrafish contributes to craniofacial anomalies. FZD6 regulates the WNT signaling pathway, which is involved in craniofacial development, including midfacial formation and upper labial fusion. We hypothesize, therefore, that alteration in FZD6 expression contributes to NSCLP in this family by perturbing the WNT signaling pathway. PMID:26436110

  10. Regulatory variant in FZD6 gene contributes to nonsyndromic cleft lip and palate in an African-American family

    PubMed Central

    Cvjetkovic, Nevena; Maili, Lorena; Weymouth, Katelyn S; Hashmi, S Shahrukh; Mulliken, John B; Topczewski, Jacek; Letra, Ariadne; Yuan, Qiuping; Blanton, Susan H; Swindell, Eric C; Hecht, Jacqueline T

    2015-01-01

    Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect affecting 135,000 newborns worldwide each year. While a multifactorial etiology has been suggested as the cause, despite decades of research, the genetic underpinnings of NSCLP remain largely unexplained. In our previous genome-wide linkage study of a large NSCLP African-American family, we identified a candidate locus at 8q21.3-24.12 (LOD = 2.98). This region contained four genes, Frizzled-6 (FZD6), Matrilin-2 (MATN2), Odd-skipped related 2 (OSR2) and Solute Carrier Family 25, Member 32 (SLC25A32). FZD6 was located under the maximum linkage peak. In this study, we sequenced the coding and noncoding regions of these genes in two affected family members, and identified a rare variant in intron 1 of FZD6 (rs138557689; c.-153 + 432A>C). The variant C allele segregated with NSCLP in this family, through affected and unaffected individuals, and was found in one other NSCLP African-American family. Functional assays showed that this allele creates an allele-specific protein-binding site and decreases promoter activity. We also observed that loss and gain of fzd6 in zebrafish contributes to craniofacial anomalies. FZD6 regulates the WNT signaling pathway, which is involved in craniofacial development, including midfacial formation and upper labial fusion. We hypothesize, therefore, that alteration in FZD6 expression contributes to NSCLP in this family by perturbing the WNT signaling pathway. PMID:26436110

  11. The B chromosomes of the African cichlid fish Haplochromis obliquidens harbour 18S rRNA gene copies

    PubMed Central

    2010-01-01

    Background Diverse plant and animal species have B chromosomes, also known as accessory, extra or supernumerary chromosomes. Despite being widely distributed among different taxa, the genomic nature and genetic behavior of B chromosomes are still poorly understood. Results In this study we describe the occurrence of B chromosomes in the African cichlid fish Haplochromis obliquidens. One or two large B chromosome(s) occurring in 39.6% of the analyzed individuals (both male and female) were identified. To better characterize the karyotype and assess the nature of the B chromosomes, fluorescence in situ hybridization (FISH) was performed using probes for telomeric DNA repeats, 18S and 5S rRNA genes, SATA centromeric satellites, and bacterial artificial chromosomes (BACs) enriched in repeated DNA sequences. The B chromosomes are enriched in repeated DNAs, especially non-active 18S rRNA gene-like sequences. Conclusion Our results suggest that the B chromosome could have originated from rDNA bearing subtelo/acrocentric A chromosomes through formation of an isochromosome, or by accumulation of repeated DNAs and rRNA gene-like sequences in a small proto-B chromosome derived from the A complement. PMID:20051104

  12. Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus.

    PubMed

    Sanford, B; Holinka, L G; O'Donnell, V; Krug, P W; Carlson, J; Alfano, M; Carrillo, C; Wu, Ping; Lowe, Andre; Risatti, G R; Gladue, D P; Borca, M V

    2016-02-01

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically deleting virus genes involved in virulence, including the thymidine kinase (TK) gene. TK has been shown to be involved in the virulence of several viruses, including ASFV. Here we report the construction of a recombinant virus (ASFV-G/V-ΔTK) obtained by deleting the TK gene in a virulent strain of ASFV Georgia adapted to replicate in Vero cells (ASFV-G/VP30). ASFV-G/P-ΔTK demonstrated decreased replication both in primary swine macrophage cell cultures and in Vero cells compared with ASFV-G/VP30. In vivo, intramuscular administration of up to 10(6) TCID50 of ASFV-G/V-ΔTK does not result in ASF disease. However, these animals are not protected when challenged with the virulent parental Georgia strain. PMID:26656424

  13. Sensitivity of African swine fever virus to type I interferon is linked to genes within multigene families 360 and 505.

    PubMed

    Golding, Josephine P; Goatley, Lynnette; Goodbourn, Steve; Dixon, Linda K; Taylor, Geraldine; Netherton, Christopher L

    2016-06-01

    African swine fever virus (ASFV) causes a lethal haemorrhagic disease of pigs. There are conflicting reports on the role of interferon in ASFV infection. We therefore analysed the interaction of ASFV with porcine interferon, in vivo and in vitro. Virulent ASFV induced biologically active IFN in the circulation of pigs from day 3-post infection, whereas low virulent OUR T88/3, which lacks genes from multigene family (MGF) 360 and MGF505, did not. Infection of porcine leucocytes enriched for dendritic cells, with ASFV, in vitro, induced high levels of interferon, suggesting a potential source of interferon in animals undergoing acute ASF. Replication of OUR T88/3, but not virulent viruses, was reduced in interferon pretreated macrophages and a recombinant virus lacking similar genes to those absent in OUR T88/3 was also inhibited. These findings suggest that as well as inhibiting the induction of interferon, MGF360 and MGF505 genes also enable ASFV to overcome the antiviral state. PMID:27043071

  14. Sensitivity of African swine fever virus to type I interferon is linked to genes within multigene families 360 and 505

    PubMed Central

    Golding, Josephine P.; Goatley, Lynnette; Goodbourn, Steve; Dixon, Linda K.; Taylor, Geraldine; Netherton, Christopher L.

    2016-01-01

    African swine fever virus (ASFV) causes a lethal haemorrhagic disease of pigs. There are conflicting reports on the role of interferon in ASFV infection. We therefore analysed the interaction of ASFV with porcine interferon, in vivo and in vitro. Virulent ASFV induced biologically active IFN in the circulation of pigs from day 3-post infection, whereas low virulent OUR T88/3, which lacks genes from multigene family (MGF) 360 and MGF505, did not. Infection of porcine leucocytes enriched for dendritic cells, with ASFV, in vitro, induced high levels of interferon, suggesting a potential source of interferon in animals undergoing acute ASF. Replication of OUR T88/3, but not virulent viruses, was reduced in interferon pretreated macrophages and a recombinant virus lacking similar genes to those absent in OUR T88/3 was also inhibited. These findings suggest that as well as inhibiting the induction of interferon, MGF360 and MGF505 genes also enable ASFV to overcome the antiviral state. PMID:27043071

  15. Tyrosinase-positive oculocutaneous albinism in Southern African blacks: P gene-associated haplotypes suggest a major mutation in the 5{prime} region of the gene

    SciTech Connect

    Ramsay, M.; Stevens, G.; Beukering, J. van

    1994-09-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) occurs with a prevalence of 1 in 3900 among Southern African (SA) blacks. The major contributors to morbidity and mortality are skin cancer and decreased visual acuity. Two distinct phenotypes occur, namely individuals with ephelides (darkly pigmented patches) and those without. There is complete concordance with regard to ephelus status among siblings. The disorder is linked to markers on chromosome 15q11.2-q12, and no obligatory cross-overs were observed with polymophic markers at the human homolog, P, of the mouse pink eyed dilute gene, p. Contrary to what has been shown for Caucasoid ty-pos OCA, this condition shows locus homogeneity among SA blacks. The P gene is an excellent candidate for ty-pos OCA and mutations in this gene will confirm its role in causing the common form of albinism in SA. Numerous P gene mutations have been described in other populations. In an attempt to detect mutations, the P gene cDNA was used to search for structural rearrangements or polymorphisms. Six polymorphisms (plR10/Scal, 912/Xbal, 912/HincII, 912/TaqI, 1412/TaqI [two systems] and 1412/HindIII) were detected with subclones of the P cDNA and haplotypes were determined in each family. None were clearly associated with an albinism-related rearrangement. However, strong linkage disequilibrium was observed with alleles at loci toward the 5{prime} region of the gene ({triangle}=0.65, 0.57 and 0.80 for the three polymorphisms detected with the 912 subclone), suggesting a major ty-pos OCA mutation in this region. Haplotype analysis provides evidence for a major mutation associated with the same haplotype in individuals with ephelides (8/12 OCA chromosomes) and those without ephelides (24:30). The presence of other ty-pos OCA associated haplotypes indicates several other less common mutations.

  16. No significant impact of IFN-γ pathway gene variants on tuberculosis susceptibility in a West African population.

    PubMed

    Meyer, Christian G; Intemann, Christopher D; Förster, Birgit; Owusu-Dabo, Ellis; Franke, Andre; Horstmann, Rolf D; Thye, Thorsten

    2016-05-01

    The concept of interferon-γ (IFN-γ) having a central role in cell-mediated immune defence to Mycobacterium tuberculosis has long been proposed. Observations made through early candidate gene studies of constituents of the IFN-γ pathway have identified moderately associated variants associated with resistance or susceptibility to tuberculosis (TB). By analysing 20 major genes whose proteins contribute to IFN-γ signalling we have assessed a large fraction of the variability in genes that might contribute to susceptibility to TB. Genetic variants were identified by sequencing the promoter regions and all exons of IFNG, IFNGR1, IFNGR2, IRF1, IL12A, IL12B, IL12RB1, IL12RB2, IL23A, IL23R, IL27, EBI3, IL27RA, IL6ST, SOCS1, STAT1, STAT4, JAK2, TYK2 and TBX21 in 69 DNA samples from Ghana. In addition, we screened all exons of IFNGR1 in a Ghanaian study group comprising 1999 TB cases and 2589 controls by high-resolution melting point analysis. The fine-mapping approach allows for a detailed screening of all variants, common and rare. Statistical comparisons of cases and controls, however, did not yield significant results after correction for multiple testing with any of the 246 variants selected for genotyping in this investigation. Gene-wise haplotype tests and analysis of rare variants did not reveal any significant association with susceptibility to TB in our investigation as well. Although this analysis was applied on a plausible set of IFN-γ pathway genes in the largest African TB cohort available so far, the lack of significant results challenges the view that genetic marker of the IFN-γ pathway have an important impact on susceptibility to TB. PMID:26242990

  17. Expression and Sequence Evolution of Aromatase cyp19a1 and Other Sexual Development Genes in East African Cichlid Fishes

    PubMed Central

    Böhne, Astrid; Heule, Corina; Boileau, Nicolas; Salzburger, Walter

    2013-01-01

    Sex determination mechanisms are highly variable across teleost fishes and sexual development is often plastic. Nevertheless, downstream factors establishing the two sexes are presumably conserved. Here, we study sequence evolution and gene expression of core genes of sexual development in a prime model system in evolutionary biology, the East African cichlid fishes. Using the available five cichlid genomes, we test for signs of positive selection in 28 genes including duplicates from the teleost whole-genome duplication, and examine the expression of these candidate genes in three cichlid species. We then focus on a particularly striking case, the A- and B-copies of the aromatase cyp19a1, and detect different evolutionary trajectories: cyp19a1A evolved under strong positive selection, whereas cyp19a1B remained conserved at the protein level, yet is subject to regulatory changes at its transcription start sites. Importantly, we find shifts in gene expression in both copies. Cyp19a1 is considered the most conserved ovary-factor in vertebrates, and in all teleosts investigated so far, cyp19a1A and cyp19a1B are expressed in ovaries and the brain, respectively. This is not the case in cichlids, where we find new expression patterns in two derived lineages: the A-copy gained a novel testis-function in the Ectodine lineage, whereas the B-copy is overexpressed in the testis of the speciest-richest cichlid group, the Haplochromini. This suggests that even key factors of sexual development, including the sex steroid pathway, are not conserved in fish, supporting the idea that flexibility in sexual determination and differentiation may be a driving force of speciation. PMID:23883521

  18. Rapid genome-wide evolution in Brassica rapa populations following drought revealed by sequencing of ancestral and descendant gene pools.

    PubMed

    Franks, Steven J; Kane, Nolan C; O'Hara, Niamh B; Tittes, Silas; Rest, Joshua S

    2016-08-01

    There is increasing evidence that evolution can occur rapidly in response to selection. Recent advances in sequencing suggest the possibility of documenting genetic changes as they occur in populations, thus uncovering the genetic basis of evolution, particularly if samples are available from both before and after selection. Here, we had a unique opportunity to directly assess genetic changes in natural populations following an evolutionary response to a fluctuation in climate. We analysed genome-wide differences between ancestors and descendants of natural populations of Brassica rapa plants from two locations that rapidly evolved changes in multiple phenotypic traits, including flowering time, following a multiyear late-season drought in California. These ancestor-descendant comparisons revealed evolutionary shifts in allele frequencies in many genes. Some genes showing evolutionary shifts have functions related to drought stress and flowering time, consistent with an adaptive response to selection. Loci differentiated between ancestors and descendants (FST outliers) were generally different from those showing signatures of selection based on site frequency spectrum analysis (Tajima's D), indicating that the loci that evolved in response to the recent drought and those under historical selection were generally distinct. Very few genes showed similar evolutionary responses between two geographically distinct populations, suggesting independent genetic trajectories of evolution yielding parallel phenotypic changes. The results show that selection can result in rapid genome-wide evolutionary shifts in allele frequencies in natural populations, and highlight the usefulness of combining resurrection experiments in natural populations with genomics for studying the genetic basis of adaptive evolution. PMID:27072809

  19. Gene-based analysis of the fibroblast growth factor receptor signaling pathway in relation to breast cancer in African American women: the AMBER consortium.

    PubMed

    Ruiz-Narváez, Edward A; Haddad, Stephen A; Lunetta, Kathryn L; Yao, Song; Bensen, Jeannette T; Sucheston-Campbell, Lara E; Hong, Chi-Chen; Haiman, Christopher A; Olshan, Andrew F; Ambrosone, Christine B; Palmer, Julie R

    2016-01-01

    We conducted gene-based analysis in 26 genes in the FGFR signaling pathway to identify genes carrying genetic variation affecting risk of breast cancer and the specific estrogen receptor (ER) subtypes. Tagging single-nucleotide polymorphisms (SNPs) for each gene were selected and genotyped on a customized Illumina Exome Array. Imputation was carried out using 1000 Genomes haplotypes. The analysis included 3237 SNPs in 3663 breast cancer cases (including 1983 ER-positive, and 1098 ER-negative) and 4687 controls from the African American Breast Cancer Epidemiology and Risk consortium, a collaborative project of four large studies of breast cancer in African American women (Carolina Breast Cancer Study, Black Women's Health Study, Women's Circle of Health Study, and Multiethnic Cohort). We used a multi-locus adaptive joint (AdaJoint) test to determine the association of each gene in the FGFR signaling pathway with overall breast cancer and ER subtypes. The FGF1 gene was significantly associated with risk of ER-negative breast cancer (P = 0.001). The FGFR2 gene was associated with risk of overall breast cancer (P = 0.002) and ER-positive breast cancer (P = 0.002). The FGF1 gene affects risk of ER-negative breast cancer in African American women. We confirmed the association of the FGFR2 gene with risk of overall and ER-positive breast cancer. These results highlight the importance of the FGFR signaling pathway in the pathogenesis of breast cancer, and suggest that different genes in the same pathway may be associated with different ER breast cancer subtypes. PMID:26743380

  20. Harnessing microbial gene pools to remediate persistent organic pollutants using genetically modified plants--a viable technology?

    PubMed

    Rylott, Elizabeth L; Johnston, Emily J; Bruce, Neil C

    2015-11-01

    It has been 14 years since the international community came together to legislate the Stockholm Convention on Persistent Organic Pollutants (POPs), restricting the production and use of specific chemicals that were found to be environmentally stable, often bioaccumulating, with long-term toxic effects. Efforts are continuing to remove these pollutants from the environment. While incineration and chemical treatment can be successful, these methods require the removal of tonnes of soil, at high cost, and are damaging to soil structure and microbial communities. The engineering of plants for in situ POP remediation has had highly promising results, and could be a more environmentally-friendly alternative. This review discusses the characterization of POP-degrading bacterial pathways, and how the genes responsible have been harnessed using genetic modification (GM) to introduce these same abilities into plants. Recent advances in multi-gene cloning, genome editing technologies and expression in monocot species are accelerating progress with remediation-applicable species. Examples include plants developed to degrade 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), trichloroethylene (TCE), and polychlorinated biphenyls (PCBs). However, the costs and timescales needed to gain regulatory approval, along with continued public opposition, are considerable. The benefits and challenges in this rapidly developing and promising field are discussed. PMID:26283045

  1. MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

    PubMed Central

    Tagliabue, E; Fargnoli, M C; Gandini, S; Maisonneuve, P; Liu, F; Kayser, M; Nijsten, T; Han, J; Kumar, R; Gruis, N A; Ferrucci, L; Branicki, W; Dwyer, T; Blizzard, L; Helsing, P; Autier, P; García-Borrón, J C; Kanetsky, P A; Landi, M T; Little, J; Newton-Bishop, J; Sera, F; Raimondi, S

    2015-01-01

    Background: The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics. Methods: Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses. Results: Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair. Conclusions: Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype. PMID:26103569

  2. Gene-Specific DNA Methylation Association with Serum Levels of C-Reactive Protein in African Americans

    PubMed Central

    Sun, Yan V.; Lazarus, Alicia; Smith, Jennifer A.; Chuang, Yu-Hsuan; Zhao, Wei; Turner, Stephen T.; Kardia, Sharon L. R.

    2013-01-01

    A more thorough understanding of the differences in DNA methylation (DNAm) profiles in populations may hold promise for identifying molecular mechanisms through which genetic and environmental factors jointly contribute to human diseases. Inflammation is a key molecular mechanism underlying several chronic diseases including cardiovascular disease, and it affects DNAm profile on both global and locus-specific levels. To understand the impact of inflammation on the DNAm of the human genome, we investigated DNAm profiles of peripheral blood leukocytes from 966 African American participants in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. By testing the association of DNAm sites on CpG islands of over 14,000 genes with C-reactive protein (CRP), an inflammatory biomarker of cardiovascular disease, we identified 257 DNAm sites in 240 genes significantly associated with serum levels of CRP adjusted for age, sex, body mass index and smoking status, and corrected for multiple testing. Of the significantly associated DNAm sites, 80.5% were hypomethylated with higher CRP levels. The most significant Gene Ontology terms enriched in the genes associated with the CRP levels were immune system process, immune response, defense response, response to stimulus, and response to stress, which are all linked to the functions of leukocytes. While the CRP-associated DNAm may be cell-type specific, understanding the DNAm association with CRP in peripheral blood leukocytes of multi-ethnic populations can assist in unveiling the molecular mechanism of how the process of inflammation affects the risks of developing common disease through epigenetic modifications. PMID:23977389

  3. Admixture Aberration Analysis: Application to Mapping in Admixed Population Using Pooled DNA

    NASA Astrophysics Data System (ADS)

    Bercovici, Sivan; Geiger, Dan

    Admixture mapping is a gene mapping approach used for the identification of genomic regions harboring disease susceptibility genes in the case of recently admixed populations such as African Americans. We present a novel method for admixture mapping, called admixture aberration analysis (AAA), that uses a DNA pool of affected admixed individuals. We demonstrate through simulations that AAA is a powerful and economical mapping method under a range of scenarios, capturing complex human diseases such as hypertension and end stage kidney disease. The method has a low false-positive rate and is robust to deviation from model assumptions. Finally, we apply AAA on 600 prostate cancer-affected African Americans, replicating a known risk locus. Simulation results indicate that the method can yield over 96% reduction in genotyping. Our method is implemented as a Java program called AAAmap and is freely available.

  4. [First North African observation of Leber congenital amaurosis secondary to CEP290 gene mutation].

    PubMed

    Aboussair, N; Berahou, A; Perrault, I; Elalaoui, S Chafai; Megzari, A; Rozet, J M; Kaplan, J; Sefiani, A

    2010-02-01

    Leber congenital amaurosis (LCA) is a the earliest and most severe form of retinal dystrophy responsible for congenital blindness. LCA has genetic heterogeneity and the study of this disease is elucidating the genetics and molecular interactions involved in the development of the retina. To date, 11 LCA genes have been mapped, ten of which have been identified. The CEP290 gene has been shown to account for Joubert and Senior-Loken syndromes and to be a frequent cause of nonsyndromic LCA. We report here the first Arab patient, born to consanguineous parents, with Leber congenital amaurosis attributable to mutation of the CEP290 gene. PMID:20056295

  5. Shallow gene pools in the high intertidal: extreme loss of genetic diversity in viviparous sea stars (Parvulastra).

    PubMed

    Keever, Carson C; Puritz, Jonathan B; Addison, Jason A; Byrne, Maria; Grosberg, Richard K; Toonen, Robert J; Hart, Michael W

    2013-10-23

    We document an extreme example of reproductive trait evolution that affects population genetic structure in sister species of Parvulastra cushion stars from Australia. Self-fertilization by hermaphroditic adults and brood protection of benthic larvae causes strong inbreeding and range-wide genetic poverty. Most samples were fixed for a single allele at nearly all nuclear loci; heterozygotes were extremely rare (0.18%); mitochondrial DNA sequences were more variable, but few populations shared haplotypes in common. Isolation-with-migration models suggest that these patterns are caused by population bottlenecks (relative to ancestral population size) and low gene flow. Loss of genetic diversity and low potential for dispersal between high-intertidal habitats may have dire consequences for extinction risk and potential for future adaptive evolution in response to climate and other selective agents. PMID:23925835

  6. Gene-environment interactions between JAZF1 and occupational and household lead exposure in prostate cancer among African American men

    PubMed Central

    Neslund-Dudas, Christine; Levin, Albert M.; Beebe-Dimmer, Jennifer L.; Bock, Cathryn H.; Nock, Nora L.; Rundle, Andrew; Jankowski, Michelle; Krajenta, Richard; Dou, Q. Ping; Mitra, Bharati; Tang, Deliang; Rebbeck, Timothy R.; Rybicki, Benjamin A.

    2014-01-01

    Purpose A single nucleotide polymorphism, rs10486567, in JAZF1 has consistently been associated with increased risk of prostate cancer. The physical interaction of zinc finger proteins, such as JAZF1, with heavy metals may play a role in carcinogenesis. This study assessed potential gene-environment statistical interactions (GxE) between rs10486567 and heavy metals in prostate cancer. Methods In a case-only study of 228 African American prostate cancer cases, GxE between rs10486567 and sources of cadmium (Cd) and lead (Pb) were assessed. Unconditional logistic regression was used to estimate interaction odds ratios and GEE was used for models containing nested data. Case-control validation of IORs was performed, using 82 controls frequency matched to cases on age-race. Results Among cases, a potential GxE interaction was observed between rs10486567 CC genotype and living in a Census tract with a high proportion of housing built before 1950, a proxy for household Pb exposure, when compared to CT or TT carriers (OR 1.81; 95% CI 1.04-3.16; p=0.036). A stronger GxE interaction was observed when both housing and occupational Pb exposure were taken into account (OR 2.62; 95% CI 1.03-6.68; p=0.04). Case-control stratified analyses showed the odds of being a CC carrier was higher in cases compared to controls among men living in areas with older housing (OR 2.03; CI 0.99-4.19; p=0.05) or having high occupational Pb exposure (OR 2.50; CI 1.01-6.18; p=0.05). Conclusions In African American men, the association between JAZF1 rs10486567 and prostate cancer may be modified by exposure to heavy metals such as Pb. PMID:24801046

  7. Confirmation of the potential usefulness of two human beta globin pseudogene markers to estimate gene flows to and from sub-Saharan Africans.

    PubMed

    Ciminelli, Bianca Maria; Pompei, Fiorenza; Relucenti, Michela; Lum, J Koji; Simporé, Jacques; Spedini, Gabriella; Martínez-Labarga, Cristina; Pardo, Miguel G

    2002-04-01

    Two polymorphic sites, -107 and -100 with respect to the "cap" site of the human beta globin pseudogene, recently discovered in our laboratory, turned out to have an ethnically complementary distribution. The first site is polymorphic in Europeans, North Africans, Indians (Hindu), and Oriental Asians, and monomorphic in sub-Saharan Africans. Conversely, the second site is polymorphic in sub-Saharan African populations and monomorphic in the aforementioned populations. Here we report the gene frequencies of these two polymorphic sites in nine additional populations (Egyptians, Spaniards, Japanese, Chinese, Filipinos, Vietnamese, Africans from Togo and from Benin, and Pygmies), confirming their ethnospecificity and, through the analysis of these two markers in Oromo and Amhara of Ethiopia (two mixed populations), their usefulness in genetic admixture studies. Moreover, we studied another marker polymorphic in sub-Saharan African populations only, a TaqI restriction fragment length polymorphism located in the same region as the present markers, demonstrating the absence of linkage disequilibrium between it and the -100 site, so that we can exclude that the information they provide is redundant. PMID:12030652

  8. Mitochondrial gene content, arrangement and composition compared in African and Asian schistosomes.

    PubMed

    Le, T H; Humair, P F; Blair, D; Agatsuma, T; Littlewood, D T; McManus, D P

    2001-09-28

    Complete sequences were obtained for the coding portions of the mitochondrial (mt) genomes of Schistosoma mansoni (NMRI strain, Puerto Rico; 14 415 bp), S. japonicum (Anhui strain, China; 14 085 bp) and S. mekongi (Khong Island, Laos; 14 072 bp). Each comprises 36 genes: 12 protein-encoding genes (cox1-3, nad1-6, nad4L, atp6 and cob); two ribosomal RNAs, rrnL (large subunit rRNA or 16S) and rrnS (small subunit rRNA or 12S); as well as 22 transfer RNA (tRNA) genes. The atp8 gene is absent. A large segment (9.6 kb) of the coding region (comprising 14 tRNAs, eight complete and two incomplete protein-encoding genes) for S. malayensis (Baling, Malaysian Peninsula) was also obtained. Each genome also possesses a long non-coding region that is divided into two parts (a small and a large non-coding region, the latter not fully sequenced in any species) by one or more tRNAs. The protein-encoding genes are similar in size, composition and codon usage in all species except for cox1 in S. mansoni (609 aa) and cox2 in S. mekongi (219 aa), both of which are longer than homologues in other species. An unexpected finding in all the Schistosoma species was the presence of a leucine zipper motif in the nad4L gene. The gene order in S. mansoni is strikingly different from that seen in the S. japonicum group and other flatworms. There is a high level of identity (87-94% at both the nucleotide and amino acid levels) for all protein-encoding genes of S. mekongi and S. malayensis. The identity between genes of these two species and those of S. japonicum is less (56-83% for amino acids and 73-79% for nucleotides). The identity between the genes of S. mansoni and the Asian schistosomes is far less (33-66% for amino acids and 54-68% for nucleotides), an observation consistent with the known phylogenetic distance between S. mansoni and the other species. PMID:11551632

  9. Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection.

    PubMed

    Hsieh, PingHsun; Veeramah, Krishna R; Lachance, Joseph; Tishkoff, Sarah A; Wall, Jeffrey D; Hammer, Michael F; Gutenkunst, Ryan N

    2016-03-01

    African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged from other anatomically modern humans, and they likely experienced strong selective pressures due to their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. To account for the complex demographic history of these populations that includes both isolation and gene flow, we fit models using the joint allele frequency spectrum and validated them using independent approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers and Pygmies, 90,000 or 150,000 yr ago. We also find that bidirectional asymmetric gene flow is statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as previously suggested. We then applied complementary statistics to scan the genome for evidence of selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this bias, we assigned P-values for candidates using whole-genome simulations incorporating demography and variation in both recombination and mutation rates. We found that genes and gene sets involved in muscle development, bone synthesis, immunity, reproduction, cell signaling and development, and energy metabolism are likely to be targets of positive natural selection in Western African Pygmies or their recent ancestors. PMID:26888263

  10. Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

    PubMed Central

    Hsieh, PingHsun; Veeramah, Krishna R.; Lachance, Joseph; Tishkoff, Sarah A.; Wall, Jeffrey D.; Hammer, Michael F.; Gutenkunst, Ryan N.

    2016-01-01

    African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged from other anatomically modern humans, and they likely experienced strong selective pressures due to their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. To account for the complex demographic history of these populations that includes both isolation and gene flow, we fit models using the joint allele frequency spectrum and validated them using independent approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers and Pygmies, 90,000 or 150,000 yr ago. We also find that bidirectional asymmetric gene flow is statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as previously suggested. We then applied complementary statistics to scan the genome for evidence of selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this bias, we assigned P-values for candidates using whole-genome simulations incorporating demography and variation in both recombination and mutation rates. We found that genes and gene sets involved in muscle development, bone synthesis, immunity, reproduction, cell signaling and development, and energy metabolism are likely to be targets of positive natural selection in Western African Pygmies or their recent ancestors. PMID:26888263

  11. Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy in African Americans.

    PubMed

    Leak, T S; Perlegas, P S; Smith, S G; Keene, K L; Hicks, P J; Langefeld, C D; Mychaleckyj, J C; Rich, S S; Kirk, J K; Freedman, B I; Bowden, D W; Sale, M M

    2009-03-01

    Variants in the engulfment and cell motility 1 (ELMO1) gene are associated with nephropathy due to type 2 diabetes mellitus (T2DM) in a Japanese cohort. We comprehensively evaluated this gene in African American (AA) T2DM patients with end-stage renal disease (ESRD). Three hundred and nine HapMap tagging SNPs and 9 reportedly associated SNPs were genotyped in 577 AA T2DM-ESRD patients and 596 AA non-diabetic controls, plus 43 non-diabetic European American controls and 45 Yoruba Nigerian samples for admixture adjustment. Replication analyses were conducted in 558 AA with T2DM-ESRD and 564 controls without diabetes. Extension analyses included 328 AA with T2DM lacking nephropathy and 326 with non-diabetic ESRD. The original and replication analyses confirmed association with four SNPs in intron 13 (permutation p-values for combined analyses = 0.001-0.003), one in intron 1 (P = 0.004) and one in intron 5 (P = 0.002) with T2DM-associated ESRD. In a subsequent combined analysis of all 1,135 T2DM-ESRD cases and 1,160 controls, an additional 7 intron 13 SNPs produced evidence of association (P = 3.5 x 10(-5)- P = 0.05). No associations were seen with these SNPs in those with T2DM lacking nephropathy or with ESRD due to non-diabetic causes. Variants in intron 13 of the ELMO1 gene appear to confer risk for diabetic nephropathy in AA. PMID:19183347

  12. Evidence for Non-neutral Evolution in a Sodium Channel Gene in African Weakly Electric Fish (Campylomormyrus, Mormyridae).

    PubMed

    Paul, Christiane; Kirschbaum, Frank; Mamonekene, Victor; Tiedemann, Ralph

    2016-08-01

    Voltage-gated sodium channels, Nav1, play a crucial role in the generation and propagation of action potentials and substantially contribute to the shape of their rising phase. The electric organ discharge (EOD) of African weakly electric fish (Mormyroidea) is the sum of action potentials fired from all electrocytes of the electric organ at the same time and hence voltage-gated sodium channels are one factor-together with the electrocyte's morphology and innervation pattern-that determines the properties of these EODs. Due to the fish-specific genome duplication, teleost fish possess eight copies of sodium channel genes (SCN), which encode for Nav1 channels. In mormyroids, SCN4aa is solely expressed in the electrocytes of the adult electric organ. In this study, we compared entire SCN4aa sequences of six species of the genus Campylomormyrus and identified nonsynonymous substitutions among them. SCN4aa in Campylomormyrus exhibits a much higher evolutionary rate compared to its paralog SCN4ab, whose expression is not restricted to the electric organ. We also found evidence for strong positive selection on the SCN4aa gene within Mormyridae and along the lineage ancestral to the Mormyridae. We have identified sites at which all nonelectric teleosts are monomorphic in their amino acid, but mormyrids have different amino acids. Our findings confirm the crucial role of SCN4aa in EOD evolution among mormyrid weakly electric fish. The inferred positive selection within Mormyridae makes this gene a prime candidate for further investigation of the divergent evolution of pulse-type EODs among closely related species. PMID:27481396

  13. Child maltreatment, impulsivity, and antisocial behavior in African American children: Moderation effects from a cumulative dopaminergic gene index.

    PubMed

    Thibodeau, Eric L; Cicchetti, Dante; Rogosch, Fred A

    2015-11-01

    A model examining the effects of an increasing number of maltreatment subtypes experienced on antisocial behavior, as mediated by impulsivity and moderated by a polygenic index of dopaminergic genotypes, was investigated. An African American sample of children (N = 1,012, M age = 10.07) with and without maltreatment histories participated. Indicators of aggression, delinquency, and disruptive peer behavior were obtained from peer- and counselor-rated measures to form a latent variable of antisocial behavior; impulsivity was assessed by counselor report. Five genotypes in four dopaminergic genes (dopamine receptors D4, D2, known as DRD4, DRD2; dopamine active transporter 1, known as DAT1; and catechol-O-methyltransferase, known as COMT) conferring heightened environmental sensitivity were combined into one polygenic index. Using structural equation modeling, a first-stage, moderated-mediation model was evaluated. Age and sex were entered as covariates, both as main effects and in interaction with maltreatment and the gene index. The model had excellent fit: χ2 (32, N = 1,012) = 86.51, p < .001; comparative fit index = 0.982, Tucker-Lewis index = 0.977, root mean square error of approximation = 0.041, and standardized root mean square residual = 0.022. The effect of maltreatment subtypes on antisocial behavior was partially mediated by impulsivity (β = 0.173, p < .001), and these relations were moderated by the number of differentiating dopaminergic genotypes. Specifically, a significant Gene × Environment interaction (β = 0.016, p = .013) indicated that the relation between maltreatment and impulsivity was stronger as children evinced more differentiating genotypes, thereby strengthening the mediational effect of impulsivity on antisocial behavior. These findings elucidate the manner by which maltreated children develop early signs of antisocial behavior, and the genetic mechanisms involved in greater vulnerability for maladaptation in impulse control within the

  14. Recombination between viral DNA and the transgenic coat protein gene of African cassava mosaic geminivirus.

    PubMed

    Frischmuth, T; Stanley, J

    1998-05-01

    Nicotiana benthamiana was transformed with three different constructs (pCRA1, pCRA2 and pJC1) containing the coat protein coding sequence of African cassava mosaic virus (ACMV). Transformed plants were inoculated with a coat protein deletion mutant of ACMV that induces mild systemic symptoms in control plants. Several inoculated plants of transgenic lines CRA1/3, CRA1/4, CRA2/1 and CRA2/2 developed severe systemic symptoms typical of ACMV. DNA analysis revealed that, in these plants, recombination had occurred between the mutant viral DNA and the integrated construct DNA, resulting in the production of recombinant virus progeny with 'wild-type' characteristics. No reversion of mutant to 'wild-type' virus was observed in pJC1-transformed plants. Recombinant virus from several transgenic plants was analysed by PCR and parts of DNA A of virus progeny were cloned. Sequence analysis revealed that only a few nucleotides were changed from the published sequence. PMID:9603342

  15. Allele mining in the gene pool of wild Solanum species for homologues of late blight resistance gene RB/Rpi-blb1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Solanum bulbocastanum comprising a CC-NBS-LRR gene RB/Rpi-blb1 confers broad-spectrum resistance to Phytophthora infestans and is currently employed in potato breeding for durable late blight (LB) resistance. Genomes of several Solanum species were reported to contain RB homologues with confirmed b...

  16. Epidemiology, ecology and gene pool of influenza A virus in Egypt: Will Egypt be the epicentre of the next influenza pandemic?

    PubMed Central

    Abdelwhab, EM; Abdel-Moneim, Ahmed S

    2015-01-01

    Outside Asia, Egypt is considered to be an influenza H5N1 epicentre and presents a far greater pandemic risk than other countries. The long-term endemicity of H5N1 and the recent emergence of H9N2 in poultry call attention to the need for unravelling the epidemiology, ecology and highly diverse gene pool of influenza A virus (IAV) in Egypt which is the aim of this review. Isolation of a considerable number of IAV subtypes from several avian and mammalian hosts was described. Co-infections of poultry with H5N1 and H9N2 and subclinical infections of pigs and humans with H1N1 and H5N1 may raise the potential for the reassortment of these viruses. Moreover, the adjustment of IAV genomes, particularly H5N1, to optimize their evolution toward efficient transmission in human is progressing in Egypt. Understanding the present situation of influenza viruses in Egypt will help in the control of the disease and can potentially prevent a possible pandemic. PMID:25635701

  17. Arachidonate 5-lipoxygenase gene variants affect response to fish oil supplementation by healthy African Americans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To determine the effects of arachidonate 5-lipoxygenase gene (ALOX5) variants on plasma lipid and lipoprotein concentrations and changes in response to fish oil supplementation. We hypothesized that Sp1 variants in the ALOX5 promoter, which have previously been associated with cardiovascu...

  18. Swimming Pool Safety

    MedlinePlus

    ... insist that the following rules are followed: Keep toys away from the pool when the pool is ... after each use. No tricycles or other riding toys at poolside. No electrical appliances near the pool. ...

  19. Expression of heat shock protein-coding genes associated with anhydrobiosis in an African chironomid Polypedilum vanderplanki

    PubMed Central

    Gusev, Oleg; Cornette, Richard

    2010-01-01

    In order to survive in extreme environments, organisms need to develop special adaptations both on physiological and molecular levels. The sleeping chironomid Polypedilum vanderplanki, inhabiting temporary water pools in semi-arid regions of Africa, is the only insect to have evolutionarily acquired the ability to withstand prolonged complete desiccation at larval stage, entering a state called anhydrobiosis. Even after years in a dry state, larvae are able to revive within a short period of time, completely restoring metabolism. Because of the possible involvement of stress proteins in the preservation of biomolecules during the anhydrobiosis of the sleeping chironomid, we have analyzed the expression of genes encoding six heat shock proteins (Pv-hsp90, Pv-hsp70, Pv-hsc70, Pv-hsp60, Pv-hsp20, and Pv-p23) and one heat shock factor (Pv-hsf1) in dehydrating, rehydrating, and heat-shocked larvae. All examined genes were significantly up-regulated in the larvae upon dehydration and several patterns of expression were detected. Gene transcript of Pv-hsf1 was up-regulated within 8 h of desiccation, followed by large shock proteins expression reaching peak at 24–48 h of desiccation. Heat-shock-responsive Pv-hsp70 and Pv-hsp60 showed a two-peak expression: in dehydrating and rehydrating larvae. Both small alpha-crystallin heat shock proteins (sHSP) transcripts were accumulated in the desiccated larvae, but showed different expression profiles. Both sHSP-coding genes were found to be heat-inducible, and Pv-hsp20 was up-regulated in the larvae at the early stage of desiccation. In contrast, expression of the second transcript, corresponding to Pv-p23, was limited to the late stages of desiccation, suggesting possible involvement of this protein in the glass-state formation in anhydrobiotic larvae. We discuss possible roles of proteins encoded by these stress genes during the different stages of anhydrobiosis in P. vanderplanki. Electronic supplementary material The

  20. Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants

    PubMed Central

    Deo, R.; Nalls, M.A.; Avery, C.L.; Smith, J.G.; Evans, D.S.; Keller, M.F.; Butler, A.M.; Buxbaum, S.G.; Li, G.; Quibrera, P. Miguel; Smith, E.N.; Tanaka, T.; Akylbekova, E.L.; Alonso, A.; Arking, D.E.; Benjamin, E.J.; Berenson, G.S.; Bis, J.C.; Chen, L.Y.; Chen, W.; Cummings, S.R.; Ellinor, P.T.; Evans, M.K.; Ferrucci, L.; Fox, E.R.; Heckbert, S.R.; Heiss, G.; Hsueh, W.C.; Kerr, K.F.; Limacher, M.C.; Liu, Y.; Lubitz, S.A.; Magnani, J.W.; Mehra, R.; Marcus, G.M.; Murray, S.S.; Newman, A.B.; Njajou, O.; North, K.E.; Paltoo, D.N.; Psaty, B.M.; Redline, S.S.; Reiner, A.P.; Robinson, J.G.; Rotter, J.I.; Samdarshi, T.E.; Schnabel, R.B.; Schork, N.J.; Singleton, A.B.; Siscovick, D.; Soliman, E.Z.; Sotoodehnia, N.; Srinivasan, S.R.; Taylor, H.A.; Trevisan, M.; Zhang, Z.; Zonderman, A.B.; Newton-Cheh, C.; Whitsel, E.A.

    2013-01-01

    BACKGROUND Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE To identify novel genetic variants associated with resting heart rate in African Americans. METHODS Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P ≤ 2.5 × 10−8). RESULTS Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98 × 10−15). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin. PMID:23183192

  1. Localization of the gene causing keratolytic winter erythema to chromosome 8p22-p23, and evidence for a founder effect in South African Afrikaans-speakers.

    PubMed Central

    Starfield, M; Hennies, H C; Jung, M; Jenkins, T; Wienker, T; Hull, P; Spurdle, A; Küster, W; Ramsay, M; Reis, A

    1997-01-01

    Keratolytic winter erythema (KWE), also known as "Oudtshoorn skin disease," or "erythrokeratolysis hiemalis," is an autosomal dominant skin disorder of unknown etiology characterized by a cyclical erythema, hyperkeratosis, and recurrent and intermittent peeling of the palms and soles, particularly during winter. Initially KWE was believed to be unique to South Africa, but recently a large pedigree of German origin has been identified. The disorder occurs with a prevalence of 1/7,000 in the South African Afrikaans-speaking Caucasoid population, and this high frequency has been attributed to founder effect. After a number of candidate regions were excluded from linkage to KWE in both the German family and several South African families, a genomewide analysis was embarked on. Linkage to the microsatellite marker D8S550 on chromosome 8p22-p23 was initially observed, with a maximum LOD score (Z(max)) of 9.2 at a maximum recombination fraction (theta(max)) of .0 in the German family. Linkage was also demonstrated in five of the larger South African families, with Z(max) = 7.4 at theta(max) = .02. When haplotypes were constructed, 11 of 14 South African KWE families had the complete "ancestral" haplotype, and 3 demonstrated conservation of parts of this haplotype, supporting the hypothesis of founder effect. The chromosome segregating with the disease in the German family demonstrated a different haplotype, suggesting that these chromosomes do not have a common origin. Recombination events place the KWE gene in a 6-cM interval between D8S550 and D8S552. If it is assumed that there was a single South African founder, a proposed ancestral recombinant suggests that the gene is most likely in a 1-cM interval between D8S550 and D8S265. PMID:9311742

  2. Immune gene expression profiling of PBMC isolated from horses vaccinated with attenuated African horsesickness virus serotype 4.

    PubMed

    Pretorius, A; Faber, F E; van Kleef, M

    2016-02-01

    Development of African horsesickness (AHS) subunit vaccines will have to include a rational approach that uses knowledge of how the virus interacts with the host immune system. The global in vivo immune response induced by attenuated AHSV serotype 4 in horses was characterised using transcriptome sequencing. PBMC were collected with 24h intervals for four days after inoculation and four days after a second boost, 21 days later. Transcriptome data were normalised to the day 0 naïve transcriptome and up- or down-regulated immune genes identified using the CLC workbench. Peak expression was observed 24h after each inoculation. Innate immunity was up-regulated after both inoculations and was characterised by type-1 interferon activation via the RIG-1/MDA5 pathway and the up-regulation of complement cascade components. After the second boost an adaptive immune response could be identified that included the production of cytokines indicative of T helper (Th)1, Th2 and Th17 responses. PMID:26382058

  3. Natural alleles of a proteasome α2 subunit gene contribute to thermotolerance and adaptation of African rice.

    PubMed

    Li, Xin-Min; Chao, Dai-Yin; Wu, Yuan; Huang, Xuehui; Chen, Ke; Cui, Long-Gang; Su, Lei; Ye, Wang-Wei; Chen, Hao; Chen, Hua-Chang; Dong, Nai-Qian; Guo, Tao; Shi, Min; Feng, Qi; Zhang, Peng; Han, Bin; Shan, Jun-Xiang; Gao, Ji-Ping; Lin, Hong-Xuan

    2015-07-01

    Global warming threatens many aspects of human life, for example, by reducing crop yields. Breeding heat-tolerant crops using genes conferring thermotolerance is a fundamental way to help deal with this challenge. Here we identify a major quantitative trait locus (QTL) for thermotolerance in African rice (Oryza glaberrima), Thermo-tolerance 1 (TT1), which encodes an α2 subunit of the 26S proteasome involved in the degradation of ubiquitinated proteins. Ubiquitylome analysis indicated that OgTT1 protects cells from heat stress through more efficient elimination of cytotoxic denatured proteins and more effective maintenance of heat-response processes than achieved with OsTT1. Variation in TT1 has been selected for on the basis of climatic temperature and has had an important role in local adaptation during rice evolution. In addition, we found that overexpression of OgTT1 was associated with markedly enhanced thermotolerance in rice, Arabidopsis and Festuca elata. This discovery may lead to an increase in crop security in the face of the ongoing threat of global warming. PMID:25985140

  4. Toll-like receptor 3 gene polymorphisms in South African Blacks with type 1 diabetes.

    PubMed

    Pirie, F J; Pegoraro, R; Motala, A A; Rauff, S; Rom, L; Govender, T; Esterhuizen, T M

    2005-08-01

    Type 1 diabetes is the consequence of exposure of genetically susceptible individuals to specific environmental precipitants. The innate immune system provides the initial response to exogenous antigen and links with the adaptive immune system. The aim of this study was to assess the role of polymorphisms occurring in the cytoplasmic region of toll-like receptor (TLR) 3 gene and immediate 5' sequence, in subjects of Zulu descent with type 1 diabetes in KwaZulu-Natal, South Africa. Seventy-nine subjects with type 1 diabetes and 74 healthy normal glucose tolerant gender-matched control subjects were studied. Parts of exon 4 and exon 3/intron 3 of the TLR3 gene were studied by polymerase chain reaction, direct sequencing and restriction enzyme digestion with Bts 1. Of the nine polymorphisms studied, a significant association with type 1 diabetes was found for the major allele in the 2593 C/T polymorphism and for the minor alleles in the 2642 C/A and 2690 A/G polymorphisms, which were found to be in complete linkage disequilibrium. Correction of the P-values for the number of alleles studied, however, rendered the results no longer significant. These results suggest that polymorphisms in the TLR3 gene, which is part of the innate immune system, may be associated with type 1 diabetes in this population. PMID:16029432

  5. Genetic variants in anti-Mullerian hormone and anti-Mullerian hormone receptor genes and breast cancer risk in Caucasians and African Americans.

    PubMed

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2014-01-01

    Anti-Mullerian hormone (AMH) regulates ovarian folliculogenesis by signaling via its receptors, and elevated serum AMH levels are associated with an increased risk of breast cancer. No previous studies have examined the effects of genetic variants in AMH-related genes on breast cancer risk. We evaluated the associations of 62 single nucleotide polymorphisms (SNPs) in AMH and its receptor genes, including AMH type 1 receptor (ACVR1) and AMH type 2 receptor (AMHR2), with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 62 SNPs evaluated, two showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratios (ORs) (95% confidence interval (95% CI)) of those two SNPs (ACVR1 rs12694937[C] and ACVR1 rs2883605[T]) for the risk of breast cancer among Caucasian women were 2.33 (1.20-4.52) and 0.68 (0.47-0.98), respectively. The age-adjusted additive ORs (95% CI) of those two SNPs (ACVR1 rs1146031[G] and AMHR2 functional SNP rs2002555[G]) for the risk of breast cancer among African American women were 0.63 (0.44-0.92) and 1.67 (1.10-2.53), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in AMH-related genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:25379134

  6. Genetic variants in anti-Mullerian hormone and anti-Mullerian hormone receptor genes and breast cancer risk in Caucasians and African Americans

    PubMed Central

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2014-01-01

    Anti-Mullerian hormone (AMH) regulates ovarian folliculogenesis by signaling via its receptors, and elevated serum AMH levels are associated with an increased risk of breast cancer. No previous studies have examined the effects of genetic variants in AMH-related genes on breast cancer risk. We evaluated the associations of 62 single nucleotide polymorphisms (SNPs) in AMH and its receptor genes, including AMH type 1 receptor (ACVR1) and AMH type 2 receptor (AMHR2), with the risk of breast cancer in the Women’s Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 62 SNPs evaluated, two showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratios (ORs) (95% confidence interval (95% CI)) of those two SNPs (ACVR1 rs12694937[C] and ACVR1 rs2883605[T]) for the risk of breast cancer among Caucasian women were 2.33 (1.20-4.52) and 0.68 (0.47-0.98), respectively. The age-adjusted additive ORs (95% CI) of those two SNPs (ACVR1 rs1146031[G] and AMHR2 functional SNP rs2002555[G]) for the risk of breast cancer among African American women were 0.63 (0.44-0.92) and 1.67 (1.10-2.53), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in AMH-related genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:25379134

  7. The African swine fever virus thymidine kinase gene is required for efficient replication in swine macrophages and for virulence in swine.

    PubMed

    Moore, D M; Zsak, L; Neilan, J G; Lu, Z; Rock, D L

    1998-12-01

    African swine fever virus (ASFV) replicates in the cytoplasm of infected cells and contains genes encoding a number of enzymes needed for DNA synthesis, including a thymidine kinase (TK) gene. Recombinant TK gene deletion viruses were produced by using two highly pathogenic isolates of ASFV through homologous recombination with an ASFV p72 promoter-beta-glucuronidase indicator cassette (p72GUS) flanked by ASFV sequences targeting the TK region. Attempts to isolate double-crossover TK gene deletion mutants on swine macrophages failed, suggesting a growth deficiency of TK- ASFV on macrophages. Two pathogenic ASFV isolates, ASFV Malawi and ASFV Haiti, partially adapted to Vero cells, were used successfully to construct TK deletion viruses on Vero cells. The selected viruses grew well on Vero cells, but both mutants exhibited a growth defect on swine macrophages at low multiplicities of infection (MOI), yielding 0.1 to 1.0% of wild-type levels. At high MOI, the macrophage growth defect was not apparent. The Malawi TK deletion mutant showed reduced virulence for swine, producing transient fevers, lower viremia titers, and reduced mortality. In contrast, 100% mortality was observed for swine inoculated with the TK+ revertant virus. Swine surviving TK- ASFV infection remained free of clinical signs of African swine fever following subsequent challenge with the parental pathogenic ASFV. The data indicate that the TK gene of ASFV is important for growth in swine macrophages in vitro and is a virus virulence factor in swine. PMID:9811782

  8. The African Swine Fever Virus Thymidine Kinase Gene Is Required for Efficient Replication in Swine Macrophages and for Virulence in Swine

    PubMed Central

    Moore, D. M.; Zsak, L.; Neilan, J. G.; Lu, Z.; Rock, D. L.

    1998-01-01

    African swine fever virus (ASFV) replicates in the cytoplasm of infected cells and contains genes encoding a number of enzymes needed for DNA synthesis, including a thymidine kinase (TK) gene. Recombinant TK gene deletion viruses were produced by using two highly pathogenic isolates of ASFV through homologous recombination with an ASFV p72 promoter–β-glucuronidase indicator cassette (p72GUS) flanked by ASFV sequences targeting the TK region. Attempts to isolate double-crossover TK gene deletion mutants on swine macrophages failed, suggesting a growth deficiency of TK− ASFV on macrophages. Two pathogenic ASFV isolates, ASFV Malawi and ASFV Haiti, partially adapted to Vero cells, were used successfully to construct TK deletion viruses on Vero cells. The selected viruses grew well on Vero cells, but both mutants exhibited a growth defect on swine macrophages at low multiplicities of infection (MOI), yielding 0.1 to 1.0% of wild-type levels. At high MOI, the macrophage growth defect was not apparent. The Malawi TK deletion mutant showed reduced virulence for swine, producing transient fevers, lower viremia titers, and reduced mortality. In contrast, 100% mortality was observed for swine inoculated with the TK+ revertant virus. Swine surviving TK− ASFV infection remained free of clinical signs of African swine fever following subsequent challenge with the parental pathogenic ASFV. The data indicate that the TK gene of ASFV is important for growth in swine macrophages in vitro and is a virus virulence factor in swine. PMID:9811782

  9. CD1A, D and E gene polymorphisms in a North African population from Morocco.

    PubMed

    Aureli, Anna; Oumhani, Khadija; Del Beato, Tiziana; El Aouad, Rajae; Piancatelli, Daniela

    2016-07-01

    CD1 molecules are specialized in capturing and presenting lipids and glycolipids to distinct subsets of T and NKT cells. Glycolipid presentation could play a significant role in the immune response against microbial infections. There are five closely linked CD1 genes in humans, named CD1A, B, C, D, and E, which all show a limited polymorphism. In this study, exon 2 polymorphisms of CD1A, CD1D and CD1E were investigated and allele, genotype and haplotype frequencies of these loci were reported in a Moroccan population. A comparison with allele, genotype and haplotype frequencies observed in other geographic areas was also performed. Results confirmed the presence of ethnic differences in CD1 polymorphism, mainly in CD1D (in this population two additional CD1D variant alleles, CD1D(∗)03 and CD1D(∗)04, were described) and E genes. These data could be useful to evaluate a possible pathogenetic role of CD1 in diseases. Increasing the knowledge in this field may offer possibilities for the development of new immunotherapeutic approaches. PMID:27156638

  10. Leptin (ob gene) of the South African clawed frog Xenopus laevis

    PubMed Central

    Crespi, Erica J.; Denver, Robert J.

    2006-01-01

    Leptin, the protein product of the obese (ob) gene, is a type-I cytokine hormone secreted by fat that is integral to food intake regulation and influences almost every physiological system in juvenile and adult mammals. Since the identification of leptin in the mouse in 1994, biologists have searched for orthologous genes in other species with limited success. In this article, we report the identification and functional characterization of leptin and leptin receptor (LR) in Xenopus. Despite low amino acid sequence similarity to mammalian leptins (≈35%) the frog protein has a nearly identical predicted tertiary structure and can activate the frog and mouse LRs in vitro. We showed that recombinant frog leptin (rxLeptin) is a potent anorexigen in frogs, as it is in mammals, but this response does not develop until midprometamorphosis. However, during early prometamorphosis, exogenous rxLeptin induced growth and development of the hind limb, where LR mRNA is expressed. The rxLeptin also stimulated cell proliferation in cultured hind limbs from early prometamorphic tadpoles, as measured by [3H]thymidine uptake. These findings are evidence that leptin can influence limb growth and differentiation during early development. Furthermore, the isolation and characterization of leptin and its receptor in a nonamniote provides an essential foundation for elucidating the structural and functional evolution of this important hormone. PMID:16782821

  11. REDUCED GLUTEAL EXPRESSION OF ADIPOGENIC AND LIPOGENIC GENES IN BLACK SOUTH AFRICAN WOMEN IS ASSOCIATED WITH OBESITY-RELATED INSULIN RESISTANCE

    PubMed Central

    Goedecke, Julia H.; Evans, Juliet; Keswell, Dheshnie; Stimson, Roland H.; Livingstone, Dawn E.W.; Hayes, Philip; Adams, Kevin; Dave, Joel A.; Victor, Hendriena; Levitt, Naomi S.; Lambert, Estelle V.; Walker, Brian R.; Seckl, Jonathan R.; Olsson, Tommy; Kahn, Steven E.

    2014-01-01

    Context Black South African women are less insulin sensitive than their white counterparts, despite less central and greater peripheral fat deposition. We hypothesized that this paradox may be explained, in part, by differences in the adipogenic capacity of subcutaneous adipose tissue (SAT). Objective To measure adipogenic and lipogenic gene expression in abdominal and gluteal SAT depots, and determine their relationships with insulin sensitivity (SI) in South African women. Design Cross-sectional. Participants 14 normal-weight (BMI <25 kg/m2) black, 13 normal-weight white, 14 obese (BMI >30 kg/m2) black and 13 obese white premenopausal South African women. Main outcomes SI (frequently sampled intravenous glucose tolerance test) in relation to expression of adipogenic and lipogenic genes in abdominal and gluteal SAT depots. Results With increasing BMI, black women had less visceral fat (P=0.03) and more abdominal (P=0.017) and gynoid (P=0.041) SAT but had lower SI (P<0.01) than white women. The expression of adipogenic and lipogenic genes was proportionately lower with obesity in black, but not white women in the gluteal and deep SAT depots (P<0.05 for ethnicity x BMI effect). In black women only, the expression of these genes correlated positively with SI (all P<0.05), independently of age and fat mass. Conclusions Obese black women have reduced SAT expression of adipogenic and lipogenic genes compared to white women, which associates with reduced SI. These findings suggest that obesity in black women impairs SAT adipogenesis and storage, potentially leading to insulin resistance and increased risk of type 2 diabetes. PMID:21956425

  12. Reconciling Differences in Pool-GWAS Between Populations: A Case Study of Female Abdominal Pigmentation in Drosophila melanogaster

    PubMed Central

    Endler, Lukas; Betancourt, Andrea J.; Nolte, Viola; Schlötterer, Christian

    2016-01-01

    The degree of concordance between populations in the genetic architecture of a given trait is an important issue in medical and evolutionary genetics. Here, we address this problem, using a replicated pooled genome-wide association study approach (Pool-GWAS) to compare the genetic basis of variation in abdominal pigmentation in female European and South African Drosophila melanogaster. We find that, in both the European and the South African flies, variants near the tan and bric-à-brac 1 (bab1) genes are most strongly associated with pigmentation. However, the relative contribution of these loci differs: in the European populations, tan outranks bab1, while the converse is true for the South African flies. Using simulations, we show that this result can be explained parsimoniously, without invoking different causal variants between the populations, by a combination of frequency differences between the two populations and dominance for the causal alleles at the bab1 locus. Our results demonstrate the power of cost-effective, replicated Pool-GWAS to shed light on differences in the genetic architecture of a given trait between populations. PMID:26715669

  13. An African swine fever virus gene with homology to DNA ligases.

    PubMed Central

    Hammond, J M; Kerr, S M; Smith, G L; Dixon, L K

    1992-01-01

    Sequence analysis of the SalI g region of the genome of a virulent isolate of ASFV (Malawi Lil 20/1) has revealed an open reading frame with the potential to encode a 48 kilodalton (kD) polypeptide which has significant homology with eukaryotic and prokaryotic DNA ligases. This ASFV encoded gene also contains the putative active site region of DNA ligases including the lysine residue which is necessary for enzyme-adenylate adduct formation, but lacks the C-terminal basic region conserved in other eukaryotic DNA ligases. A novel [32P]-labelled potential DNA ligase-adenylate adduct of M(r) 45 kD was observed upon incubation of ASFV infected cell cytoplasmic extracts with alpha-[32P]-ATP and subsequent analysis of products by SDS/PAGE. These data together suggest that ASFV encodes its own DNA ligase. Images PMID:1614852

  14. Dopamine Receptor Gene D4 Polymorphisms and Early Sexual Onset: Gender and Environmental Moderation in a Sample of African American Youth

    PubMed Central

    Kogan, Steven M.; Lei, Man-Kit; Beach, Steven R. H.; Brody, Gene H.; Windle, Michael; Lee, Sunbok; MacKillop, James; Chen, Yi-fu

    2014-01-01

    Purpose Early sexual onset and its consequences disproportionately affect African American youth, particularly male youth. The dopamine receptor D4 gene, DRD4, has been linked to sexual activity and other forms of appetitive behavior, particularly for male youth and in combination with environmental factors [gene × environment (G × E) effects]. The differential susceptibility perspective suggests that DRD4 may exert this effect by amplifying the effects of both positive and negative environments. We hypothesized that DRD4 status would amplify the influence of both positive and negative neighborhood environments on early sexual onset among male, but not female, African Americans. Methods Hypotheses were tested with self-report, biospecimen, and census data from 5 prospective studies of male and female African American youth in rural Georgia communities, N = 1677. Early sexual onset was defined as intercourse before age 14. Results No significant G × E findings emerged for female youth. Male youth with a DRD4-long allele were more likely than those with 2 DRD4-short alleles to report early sexual onset in negative community environments and not to report early onset in positive community environments. Conclusions Dopaminergic regulation of adolescent sexual behaviors may operate differently by gender. DRD4 operated as an environmental amplification, rather than a vulnerability, factor. PMID:24742759

  15. Non-equilibrium estimates of gene flow inferred from nuclear genealogies suggest that Iberian and North African wall lizards (Podarcis spp.) are an assemblage of incipient species

    PubMed Central

    2008-01-01

    Background The study of recently-diverged species offers significant challenges both in the definition of evolutionary entities and in the estimation of gene flow among them. Iberian and North African wall lizards (Podarcis) constitute a cryptic species complex for which previous assessments of mitochondrial DNA (mtDNA) and allozyme variation are concordant in describing the existence of several highly differentiated evolutionary units. However, these studies report important differences suggesting the occurrence of gene flow among forms. Here we study sequence variation in two nuclear introns, β-fibint7 and 6-Pgdint7, to further investigate overall evolutionary dynamics and test hypotheses related to species delimitation within this complex. Results Both nuclear gene genealogies fail to define species as monophyletic. To discriminate between the effects of incomplete lineage sorting and gene flow in setting this pattern, we estimated migration rates among species using both FST-based estimators of gene flow, which assume migration-drift equilibrium, and a coalescent approach based on a model of divergence with gene flow. Equilibrium estimates of gene flow suggest widespread introgression between species, but coalescent estimates describe virtually zero admixture between most (but not all) species pairs. This suggests that although gene flow among forms may have occurred the main cause for species polyphyly is incomplete lineage sorting, implying that most forms have been isolated since their divergence. This observation is therefore in accordance with previous reports of strong differentiation based on mtDNA and allozyme data. Conclusion These results corroborate most forms of Iberian and North African Podarcis as differentiated, although incipient, species, supporting a gradual view of speciation, according to which species may persist as distinct despite some permeability to genetic exchange and without having clearly definable genetic boundaries. Additionally

  16. Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study.

    PubMed

    Ng, Maggie C Y; Saxena, Richa; Li, Jiang; Palmer, Nicholette D; Dimitrov, Latchezar; Xu, Jianzhao; Rasmussen-Torvik, Laura J; Zmuda, Joseph M; Siscovick, David S; Patel, Sanjay R; Crook, Errol D; Sims, Mario; Chen, Yii-Der I; Bertoni, Alain G; Li, Mingyao; Grant, Struan F A; Dupuis, Josée; Meigs, James B; Psaty, Bruce M; Pankow, James S; Langefeld, Carl D; Freedman, Barry I; Rotter, Jerome I; Wilson, James G; Bowden, Donald W

    2013-03-01

    Type 2 diabetes (T2D) disproportionally affects African Americans (AfA) but, to date, genetic variants identified from genome-wide association studies (GWAS) are primarily from European and Asian populations. We examined the single nucleotide polymorphism (SNP) and locus transferability of 40 reported T2D loci in six AfA GWAS consisting of 2,806 T2D case subjects with or without end-stage renal disease and 4,265 control subjects from the Candidate Gene Association Resource Plus Study. Our results revealed that seven index SNPs at the TCF7L2, KLF14, KCNQ1, ADCY5, CDKAL1, JAZF1, and GCKR loci were significantly associated with T2D (P < 0.05). The strongest association was observed at TCF7L2 rs7903146 (odds ratio [OR] 1.30; P = 6.86 × 10⁻⁸). Locus-wide analysis demonstrated significant associations (P(emp) < 0.05) at regional best SNPs in the TCF7L2, KLF14, and HMGA2 loci as well as suggestive signals in KCNQ1 after correction for the effective number of SNPs at each locus. Of these loci, the regional best SNPs were in differential linkage disequilibrium (LD) with the index and adjacent SNPs. Our findings suggest that some loci discovered in prior reports affect T2D susceptibility in AfA with similar effect sizes. The reduced and differential LD pattern in AfA compared with European and Asian populations may facilitate fine mapping of causal variants at loci shared across populations. PMID:23193183

  17. A conserved African swine fever virus right variable region gene, l11L, is non-essential for growth in vitro and virulence in domestic swine.

    PubMed

    Kleiboeker, S B; Kutish, G F; Neilan, J G; Lu, Z; Zsak, L; Rock, D L

    1998-05-01

    The right variable region of the African swine fever virus (ASFV) genome is known to contain genes with functions involving virus virulence and host range in swine. A novel open reading frame, ORF l11L, which was absent in the non-pathogenic, cell culture-adapted European isolate BA71V, was identified in the pathogenic African isolate Malawi Lil-20/1. The location of l11L in the right variable region, together with its absence in BA71V, suggested that l11L may have a function in virus virulence and/or host range. Here, we show that the l11L gene is highly conserved among pathogenic African, European and Caribbean ASFV field isolates and that it exists either in a short form, encoding a protein of 77-78 amino acids (9.1 kDa) or in a longer form of 93-94 amino acids (11.1 kDa). The presence of two predicted membrane-spanning segments suggests that l11L is an integral membrane protein. RT-PCR analysis demonstrated that l11L mRNA is expressed late in the virus replication cycle. A recombinant l11L gene deletion mutant, deltal11L, was constructed from the ASFV isolate Malawi Lil-20/1 to examine gene function. Deletion of l11L did not affect virus replication in swine macrophage cell cultures nor virulence in domestic pigs, indicating that l11L is non-essential for growth in vitro and for virus virulence in domestic swine. PMID:9603334

  18. Regulation of the activities of African cassava mosaic virus promoters by the AC1, AC2, and AC3 gene products.

    PubMed

    Haley, A; Zhan, X; Richardson, K; Head, K; Morris, B

    1992-06-01

    DNA fragments comprising each of the promoter regions from the geminivirus African cassava mosaic virus (ACMV) were cloned into the pUC18-based vector, pG1, producing transcriptional fusions with the beta-glucuronidase gene (GUS) and nopaline synthase terminator sequence. The relative activity of each promoter construct was analyzed by a GUS expression assay of extracts from Nicotiana clevelandii protoplasts coelectroporated with the GUS reporter constructs and constructs in which individual ACMV open reading frames (ORFs) were placed under control of a cauliflower mosaic virus 35 S promoter. Results suggest repression of the AC1 gene by its gene product, which is required for ACMV DNA synthesis. The promoter activity observed for the single promoter for the DNA A genes encoding functions of spread and the regulation of replication (AC2 and AC3 ORFs) was unaffected by coelectroporation with any of the ACMV ORF constructs. Promoters for the AV1 (coat protein) gene and the two DNA B genes (BV1 and BC1) were activated by electroporation of the AC2 ORF construct. To a lesser extent promoters for the AV1 and BV1 genes were activated with the AC3 ORF construct. The same pattern of promoter repression and activation was observed when transgenic N. benthamiana plants expressing the GUS reporter constructions were inoculated with ACMV DNA A. PMID:1585657

  19. Transcriptome sequencing reveals population differentiation in gene expression linked to functional traits and environmental gradients in the South African shrub Protea repens.

    PubMed

    Akman, Melis; Carlson, Jane E; Holsinger, Kent E; Latimer, Andrew M

    2016-04-01

    Understanding the environmental and genetic mechanisms underlying locally adaptive trait variation across the ranges of species is a major focus of evolutionary biology. Combining transcriptome sequencing with common garden experiments on populations spanning geographical and environmental gradients holds promise for identifying such mechanisms. The South African shrub Protea repens displays diverse phenotypes in the wild along drought and temperature gradients. We grew plants from seeds collected at 19 populations spanning this species' range, and sequenced the transcriptomes of these plants to reveal gene pathways associated with adaptive trait variation. We related expression in co-expressed gene networks to trait phenotypes measured in the common garden and to source population climate. We found that expression in gene networks correlated with source-population environment and with plant traits. In particular, the activity of gene networks enriched for growth related pathways correlated strongly with source site minimum winter temperature and with leaf size, stem diameter and height in the garden. Other gene networks with enrichments for photosynthesis related genes showed associations with precipitation. Our results strongly suggest that this species displays population-level differences in gene expression that have been shaped by source population site climate, and that are reflected in trait variation along environmental gradients. PMID:26618926

  20. Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry

    PubMed Central

    Tanaka, Toshiko; Towers, G. Wayne; Verhoef, Hans; Veenemans, Jacobien; Talsma, Elise F.; Harryvan, Jan; Boekschoten, Mark V.; Feskens, Edith J.; Melse-Boonstra, Alida

    2016-01-01

    Background Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. Methods We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. Results In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. Conclusions In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations. PMID:27332551

  1. The effects of genes implicated in cardiovascular disease on blood pressure response to treatment among treatment-naive hypertensive African Americans in the GenHAT study.

    PubMed

    Do, A N; Lynch, A I; Claas, S A; Boerwinkle, E; Davis, B R; Ford, C E; Eckfeldt, J H; Tiwari, H K; Arnett, D K; Irvin, M R

    2016-09-01

    African Americans have the highest prevalence of hypertension in the United States. Blood pressure (BP) control is important to reduce cardiovascular disease-related morbidity and mortality in this ethnic group. Genetic variants have been found to be associated with BP response to treatment. Previous pharmacogenetic studies of BP response to treatment in African Americans suffer limitations of small sample size as well as a limited number of candidate genes, and often focused on one antihypertensive treatment. Using 1131 African-American treatment-naive participants from the Genetics of Hypertension Associated Treatment Study, we examined whether variants in 35 candidate genes might modulate BP response to four different antihypertensive medications, including an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), and an a-adrenergic blocker (doxazosin) as compared with a thiazide diuretic (chlorthalidone) after 6 months of follow-up. Several suggestive gene by treatment interactions were identified. For example, among participants with two minor alleles of renin rs6681776, diastolic BP response was much improved on doxazosin compared with chlorthalidone (on average -9.49 mm Hg vs -1.70 mm Hg) (P=0.007). Although several suggestive loci were identified, none of the findings passed significance criteria after correction for multiple testing. Given the impact of hypertension and its sequelae in this population, this research highlights the potential for genetic factors to contribute to BP response to treatment. Continued concerted research efforts focused on genetics are needed to improve treatment response in this high-risk group. PMID:26791477

  2. Swimming pool cleaner poisoning

    MedlinePlus

    Swimming pool cleaner poisoning occurs when someone swallows this type of cleaner, touches it, or breathes in ... The harmful substances in swimming pool cleaner are: Bromine ... copper Chlorine Soda ash Sodium bicarbonate Various mild acids

  3. Swimming pool granuloma

    MedlinePlus

    A swimming pool granuloma is a long-term (chronic) skin infection. It is caused by the bacteria Mycobacterium marinum . ... A swimming pool granuloma occurs when water containing Mycobacterium marinum bacteria enters a break in the skin. Signs of ...

  4. The science of pooling

    SciTech Connect

    Gilbert, E.

    1995-10-01

    The pooling of data from radon studies is described. Pooling refers to the analysis of original data from several studies, not meta-analysis in which summary measures from published data are analyzed. A main objective for pooling is to reduce uncertainty and to obtain more precise estimates of risk than would be available from any single study.

  5. Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP.

    PubMed

    Grant, Struan F A; Li, Mingyao; Bradfield, Jonathan P; Kim, Cecilia E; Annaiah, Kiran; Santa, Erin; Glessner, Joseph T; Casalunovo, Tracy; Frackelton, Edward C; Otieno, F George; Shaner, Julie L; Smith, Ryan M; Imielinski, Marcin; Eckert, Andrew W; Chiavacci, Rosetta M; Berkowitz, Robert I; Hakonarson, Hakon

    2008-01-01

    Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2) = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08-1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49) and of 1.31 (95% CI 1.050-1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact. PMID:18335027

  6. Genome-wide search for susceptibility genes to type 2 diabetes in West Africans: potential role of C-peptide.

    PubMed

    Chen, Guanjie; Adeyemo, Adebowale; Zhou, Jie; Chen, Yuanxiu; Huang, Hanxia; Doumatey, Ayo; Lashley, Kerrie; Agyenim-Boateng, Kofi; Eghan, Benjamin A; Acheampong, Joseph; Fasanmade, Olufemi; Johnson, Thomas; Okafor, Godfrey; Oli, Johnnie; Amoah, Albert; Rotimi, Charles

    2007-12-01

    C-peptide is a substance that the pancreas releases into the circulation in equimolar amounts to insulin and has demonstrated important physiological effects which relate to the vascular field, in particular the microcirculation. For this analysis, we included 321 full and 36 half sibling pairs affected with type 2 diabetes (T2D) from West Africa. A genome-wide panel of 390 tri-nucleotide and tetra-nucleotide repeats with an average distance of 8.9 cM was performed on a total of 691 persons. Variance components based on multipoint linkage approach as implemented in SOLAR were performed for log C-peptide. Significant linkage evidences were observed on 10q23 at D10S2327 with a LOD score of 4.04 (nominal p-value=0.000008, empirical p-value=0.0004); and on 4p15 at D4S2632 with a LOD score of 3.48 (nominal p-value=0.000031, empirical p-value=0.0013). Other suggestive evidence of linkage were observed on 15q14 at D15S659 with a LOD score 2.41 (nominal p-value=0.000435, empirical p-value=0.0068), and on 18p11 near D18S976 with a LOD score 2.18 (nominal p-value=0.000771 and empirical p-value=0.0094). Interestingly, five positional candidate genes for diabetes and related complications are located in our linkage region (the pituitary adenylate cyclase activating polypeptide (PACAP in 18p11); the peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1 in 4p15); PTEN, PPP1R5, and IDE located in 10q23. In conclusion, we identified four major genetic loci (10q23, 4p15, 15q14, and 18p11) influencing C-peptide concentration in West Africans with T2D. PMID:17548123

  7. Effects of Lifestyle Modification on Telomerase Gene Expression in Hypertensive Patients: A Pilot Trial of Stress Reduction and Health Education Programs in African Americans

    PubMed Central

    Duraimani, Shanthi; Schneider, Robert H.; Randall, Otelio S.; Nidich, Sanford I.; Xu, Shichen; Ketete, Muluemebet; Rainforth, Maxwell A.; Gaylord-King, Carolyn; Salerno, John W.; Fagan, John

    2015-01-01

    Background African Americans suffer from disproportionately high rates of hypertension and cardiovascular disease. Psychosocial stress, lifestyle and telomere dysfunction contribute to the pathogenesis of hypertension and cardiovascular disease. This study evaluated effects of stress reduction and lifestyle modification on blood pressure, telomerase gene expression and lifestyle factors in African Americans. Methods Forty-eight African American men and women with stage I hypertension who participated in a larger randomized controlled trial volunteered for this substudy. These subjects participated in either stress reduction with the Transcendental Meditation technique and a basic health education course (SR) or an extensive health education program (EHE) for 16 weeks. Primary outcomes were telomerase gene expression (hTERT and hTR) and clinic blood pressure. Secondary outcomes included lifestyle-related factors. Data were analyzed for within-group and between-group changes. Results Both groups showed increases in the two measures of telomerase gene expression, hTR mRNA levels (SR: p< 0.001; EHE: p< 0.001) and hTERT mRNA levels (SR: p = 0.055; EHE: p< 0.002). However, no statistically significant between-group changes were observed. Both groups showed reductions in systolic BP. Adjusted changes were SR = -5.7 mm Hg, p< 0.01; EHE = -9.0 mm Hg, p < 0.001 with no statistically significant difference between group difference. There was a significant reduction in diastolic BP in the EHE group (-5.3 mm Hg, p< 0.001) but not in SR (-1.2 mm Hg, p = 0.42); the between-group difference was significant (p = 0.04). The EHE group showed a greater number of changes in lifestyle behaviors. Conclusion In this pilot trial, both stress reduction (Transcendental Meditation technique plus health education) and extensive health education groups demonstrated increased telomerase gene expression and reduced BP. The association between increased telomerase gene expression and reduced BP

  8. Loss of the gene for the alpha subunit of ATP synthase (ATP5A1) from the W chromosome in the African grey parrot (Psittacus erithacus).

    PubMed

    de Kloet, S R

    2001-08-01

    This study describes the results of an analysis using Southern blotting, the polymerase chain reaction, and sequencing which shows that the African grey parrot (Psittacus erithacus) lacks the W-chromosomal gene for the alpha subunit of mitochondrial ATP synthase (ATP5A1W). Additional evidence shows that in other psittacines a fragment of the ATP5A1W gene contains five times as many nonsynonymous nucleotide replacements as the homologous fragment of the Z gene. Therefore, whereas in these other psittacines the corresponding ATP5A1Z protein fragment is highly conserved and varies by only a few, moderately conservative amino acid substitutions, the homologous ATP5A1W fragments contain a considerable number of, sometimes highly nonconservative, amino acid replacements. In one of these species, the ringneck parakeet (Psittacula krameri), the ATP5A1W gene is present in an inactive form because of the presence of a nonsense codon. Other changes, possibly leading to an inactive ATP5A1W gene product, involve the substitution of arginine residues by cysteine in the ATP5A1W protein of the mitred conure (Aratinga mitrata) and the blue and gold macaw (Ara ararauna). The data suggest also that although the divergence of the psittacine ATP5A1W and ATP5A1Z genes preceded the origin of the psittacidae, this divergence occurred independently of a similar process in the myna (Gracula religiosa), the outgroup used in this study. PMID:11479684

  9. Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

    PubMed Central

    Keku, Temitope O.; Vidal, Adriana; Oliver, Shannon; Hoyo, Catherine; Hall, Ingrid J.; Omofoye, Seun; McDoom, Maya; Worley, Kendra; Galanko, Joseph; Sandler, Robert S.; Millikan, Robert

    2014-01-01

    Purpose Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)n repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. Methods Participants were African Americans (231cases, 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens, and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5′-exonuclease (Taqman) assay. The IGF-I (CA)n repeat was assayed by PCR, and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Results The IGF-I (CA)19 repeat was higher in White controls (50%) than African American controls (31%). Whites homozygous for the IGF-I (CA)19 repeat had a nearly two fold increase in risk of colon cancer (OR=1.77; 95%CI=1.15–2.73), but not African Americans (OR= 0.73, 95%CI 0.50–1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR= 0.49, 95%CI 0.28–0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p- trend < 0.05). Conclusions These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans. PMID:22565227

  10. Phylogenomic analysis of 11 complete African swine fever virus genome sequences

    SciTech Connect

    Villiers, Etienne P. de; Gallardo, Carmina; Arias, Marisa; Martin, Raquel

    2010-04-25

    Viral molecular epidemiology has traditionally analyzed variation in single genes. Whole genome phylogenetic analysis of 123 concatenated genes from 11 ASFV genomes, including E75, a newly sequenced virulent isolate from Spain, identified two clusters. One contained South African isolates from ticks and warthog, suggesting derivation from a sylvatic transmission cycle. The second contained isolates from West Africa and the Iberian Peninsula. Two isolates, from Kenya and Malawi, were outliers. Of the nine genomes within the clusters, seven were within p72 genotype 1. The 11 genomes sequenced comprised only 5 of the 22 p72 genotypes. Comparison of synonymous and non-synonymous mutations at the genome level identified 20 genes subject to selection pressure for diversification. A novel gene of the E75 virus evolved by the fusion of two genes within the 360 multicopy family. Comparative genomics reveals high diversity within a limited sample of the ASFV viral gene pool.

  11. Polymorphisms within the neuronal cadherin (CDH2) gene are associated with obsessive-compulsive disorder (OCD) in a South African cohort.

    PubMed

    McGregor, N W; Lochner, C; Stein, D J; Hemmings, S M J

    2016-02-01

    OCD is characterised by recurrent obsessions and compulsions that result in severe distress and increased risk for comorbidity. Recently published findings have indicated that the neuronal cadherin gene (CDH2) plays a role in the development of canine OCD, and led us to investigate the human ortholog, CDH2, in a human OCD cohort. Seven CDH2 polymorphisms were selected and genotyped in a South African Caucasian cohort of 234 OCD patients and 180 healthy controls using TaqMan assays. Polymorphisms were analysed in a single-locus and haplotypic context. Of the seven polymorphisms, two reached statistical significance for OCD under additive and codominant models of inheritance (rs1120154 and rs12605662). CDH2 SNP, rs1120154, C-allele carriers were found to be significantly associated with lower risk to develop OCD compared to TT-homozygotes (OR = 0.49; 95% CI: 0.32-0.75; p < 0.001), and rs12605662 G-allele carriers were significantly associated with reduced risk OCD compared to TT-homozygotes (OR = 0.46; 95% CI: 0.30-0.71; p < 0.001), Furthermore, a single haplotype was found to infer an increased risk for OCD diagnosis (*rs8087457-rs1148374: A-T). Polymorphisms within the CDH2 gene are associated with susceptibility to OCD in a South African cohort. PMID:26093892

  12. Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically de...

  13. Genetics Home Reference: African iron overload

    MedlinePlus

    ... of a genetic condition? Genetic and Rare Diseases Information Center Frequency African iron overload is common in rural areas of central and ... more about the gene associated with African iron overload SLC40A1 Related Information What is a gene? What is a gene ...

  14. IDDM2 and the polymorphism of the human tyrosine hydroxylase (hTH) gene in African Americans with type-1 diabetes.

    PubMed Central

    Berka, Noureddine; Nunlee-Bland, Gail; Erabhaoui, Elhajja; Belmamoun, Maher; Dunston, Georgia M.

    2004-01-01

    In this study, we investigate the polymorphic microsatellite repeat (TCAT)n, in the insulin gene region that has been associated with susceptibility to type-1 diabetes in some Caucasian populations. The microsatellite repeat polymorphism begins at base pair 1,170 in intron 1 of the hTH gene, which is located on the short arm of chromosome 11. This study is the first to investigate the association of this microsatellite repeat polymorphism in African-American type-1 diabetes patients and controls. The predicted amplified sequence was 254 bp. We found five alleles among African Americans in the Washington, DC area. The alleles were labeled K5 (244 bp), K4 (248 bp), K3 (252 bp), K2 (256 bp), and K1 (260 bp), and heterozygosity was greater than 0.75. The most frequent allele of the hTH microsatellite repeats was K5 (248 bp) with a frequency 0.62 in controls and 0.66 in type-1 diabetes patients, which did not differ significantly. Although the largest allele was more frequent in controls, the difference was not statistically significant. The five alleles of the hTH microsatellite generated 15 different genotypes. The most frequent genotype in controls and patients was K5/K4, whose frequencies were 0.19 and 0.17, respectively. No significant differences in genotype frequencies were found between type-1 diabetes patients and controls. This data shifts the focus from hTH to the VNTR at the insulin gene for IDDM2, the second major candidate gene for type-1 diabetes. PMID:15303408

  15. Identification of Susceptibility Genes for Peritoneal, Ovarian, and Deep Infiltrating Endometriosis Using a Pooled Sample-Based Genome-Wide Association Study

    PubMed Central

    Borghese, Bruno; Tost, Jörg; de Surville, Magalie; Busato, Florence; Letourneur, Frank; Mondon, Françoise; Vaiman, Daniel; Chapron, Charles

    2015-01-01

    Characterizing genetic contributions to endometriosis might help to shorten the time to diagnosis, especially in the most severe forms, but represents a challenge. Previous genome-wide association studies (GWAS) made no distinction between peritoneal endometriosis (SUP), endometrioma (OMA), and deep infiltrating endometriosis (DIE). We therefore conducted a pooled sample-based GWAS and distinguished histologically confirmed endometriosis subtypes. We performed an initial discovery step on 10-individual pools (two pools per condition). After quality control filtering, a Monte-Carlo simulation was used to rank the significant SNPs according to the ratio of allele frequencies and the coefficient of variation. Then, a replication step of individual genotyping was conducted in an independent cohort of 259 cases and 288 controls. Our approach was very stringent but probably missed a lot of information due to the Monte-Carlo simulation, which likely explained why we did not replicate results from “classic” GWAS. Four variants (rs227849, rs4703908, rs2479037, and rs966674) were significantly associated with an increased risk of OMA. Rs4703908, located close to ZNF366, provided a higher risk of OMA (OR = 2.22; 95% CI: 1.26–3.92) and DIE, especially with bowel involvement (OR = 2.09; 95% CI: 1.12–3.91). ZNF366, involved in estrogen metabolism and progression of breast cancer, is a new biologically plausible candidate for endometriosis. PMID:25722978

  16. African human mtDNA phylogeography at-a-glance.

    PubMed

    Rosa, Alexandra; Brehem, António

    2011-01-01

    The mitochondrial DNA (mtDNA) genetic system has long proven to be useful for studying the demographic history of our species, since their proposed Southeast/East African origin 200 kya. Despite the weak archaeological and anthropologic records, which render a difficult understanding of early intra- continental migrations, the phylogenetic L0-L1'6 split at about 140-160 kya is thought to represent also an early sub-structuring of small and isolated communities in South and East Africa. Regional variation accumulated over the following millennia, with L2 and L3 lineages arising in Central and East Africa 100-75 kya. Their sub-Saharan dispersal not later than 60 kya, largely overwhelmed the L0'1 distribution, nowadays limited to South African Khoisan and Central African Pygmies. Cyclic expansions and retractions of the equatorial forest between 40 kya and the "Last Glacial Aridity Maximum" were able to reduce the genetic diversity of modern humans. Surviving regional-specific lineages have emerged from the Sahelian refuge areas, repopulating the region and contributing to the overall West African genetic similarity. Particular L1- L3 lineages mirror the substantial population growth made possible by moister and warmer conditions of the Sahara's Wet Phase and the adoption of agriculture and iron smelting techniques. The diffusion of the farming expertise from a Central African source towards South Africa was mediated by the Bantu people 3 kya. The strong impact of their gene flow almost erased the pre-existent maternal pool. Non-L mtDNAs testify for Eurasian lineages that have enriched the African maternal pool at different timeframes: i) Near and Middle Eastern influences in Upper Palaeolithic, probably link to the spread of Afro-Asiatic languages; ii) particular lineages from West Eurasia around or after the glacial period; iii) post-glacial mtDNA signatures from the Franco-Cantabrian refugia, that have crossed the Strait of Gibraltar and iv) Eurasian lineages

  17. Cold pool dissipation

    NASA Astrophysics Data System (ADS)

    Grant, Leah D.; Heever, Susan C.

    2016-02-01

    The mechanisms by which sensible heat fluxes (SHFs) alter cold pool characteristics and dissipation rates are investigated in this study using idealized two-dimensional numerical simulations and an environment representative of daytime, dry, continental conditions. Simulations are performed with no SHFs, SHFs calculated using a bulk formula, and constant SHFs for model resolutions with horizontal (vertical) grid spacings ranging from 50 m (25 m) to 400 m (200 m). In the highest resolution simulations, turbulent entrainment of environmental air into the cold pool is an important mechanism for dissipation in the absence of SHFs. Including SHFs enhances cold pool dissipation rates, but the processes responsible for the enhanced dissipation differ depending on the SHF formulation. The bulk SHFs increase the near-surface cold pool temperatures, but their effects on the overall cold pool characteristics are small, while the constant SHFs influence the near-surface environmental stability and the turbulent entrainment rates into the cold pool. The changes to the entrainment rates are found to be the most significant of the SHF effects on cold pool dissipation. SHFs may also influence the timing of cold pool-induced convective initiation by altering the environmental stability and the cold pool intensity. As the model resolution is coarsened, cold pool dissipation is found to be less sensitive to SHFs. Furthermore, the coarser resolution simulations not only poorly but sometimes wrongly represent the SHF impacts on the cold pools. Recommendations are made regarding simulating the interaction of cold pools with convection and the land surface in cloud-resolving models.

  18. Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans.

    PubMed

    Man, Michael; Farmen, Mark; Dumaual, Carmen; Teng, Choo Hua; Moser, Brian; Irie, Shin; Noh, Gyu Jeong; Njau, Reuben; Close, Sandra; Wise, Stephen; Hockett, Richard

    2010-08-01

    The advent of high-throughput technologies has proven valuable in the assessment of genetic differences and their effects on drug activation, metabolism, disposition, and transport. However, most studies to date have focused on a small number of genes or few alleles, some of which are rare and therefore observed infrequently or lacked rigorous ethnic characterization, thus reducing the ability to extrapolate within and among populations. In this study, the authors comprehensively assessed the allele frequencies of 165 variants comprising 27 drug-metabolizing enzyme and transporter (DMET) genes from 2188 participants across 3 major ethnic populations: Caucasians, Africans, and East Asians. This sample size was sufficiently large to demonstrate genetic differences among these major ethnic groups while concomitantly confirming similarities among East Asian subpopulations (Korean, Han Chinese, and Japanese). A comprehensive presentation of allele and genotype frequencies is included in the online supplement, and 3 of the most widely studied cytochrome P450 (CYP) genes, CYP2D6, CYP2C19, and CYP2C9; 2 non-CYP enzymes, NAT1 and TMPT; and 2 transporter genes, SLCO1B1 and SLCO2B1, are presented herein according to ethnic classification. PMID:20173083

  19. The Ep152R ORF of African swine fever virus strain Georgia encodes for an essential gene that interacts with host protein BAG6.

    PubMed

    Borca, Manuel V; O'Donnell, Vivian; Holinka, Lauren G; Rai, Devendra K; Sanford, Brenton; Alfano, Marialexia; Carlson, Jolene; Azzinaro, Paul A; Alonso, Covadonga; Gladue, Douglas P

    2016-09-01

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The viral genome encodes for more than 150 genes, and only a select few of these genes have been studied in some detail. Here we report the characterization of open reading frame Ep152R that has a predicted complement control module/SCR domain. This domain is found in Vaccinia virus proteins that are involved in blocking the immune response during viral infection. A recombinant ASFV harboring a HA tagged version of the Ep152R protein was developed (ASFV-G-Ep152R-HA) and used to demonstrate that Ep152R is an early virus protein. Attempts to construct recombinant viruses having a deleted Ep152R gene were consistently unsuccessful indicating that Ep152R is an essential gene. Interestingly, analysis of host-protein interactions for Ep152R using a yeast two-hybrid screen, identified BAG6, a protein previously identified as being required for ASFV replication. Furthermore, fluorescent microscopy analysis confirms that Ep152R-BAG6 interaction actually occurs in cells infected with ASFV. PMID:27497620

  20. Contrasting patterns of gene flow between sister plant species in the understorey of African moist forests - the case of sympatric and parapatric Marantaceae species.

    PubMed

    Ley, A C; Hardy, O J

    2014-08-01

    Gene flow within and between species is a fundamental process shaping the evolutionary history of taxa. However, the extent of hybridization and reinforcement is little documented in the tropics. Here we explore the pattern of gene flow between three sister species from the herbaceous genus Marantochloa (Marantaceae), sympatrically distributed in the understorey of the African rainforest, using data from the chloroplast and nuclear genomes (DNA sequences and AFLP). We found highly contrasting patterns: while there was no evidence of gene flow between M. congensis and M. monophylla, species identity between M. monophylla and M. incertifolia was maintained despite considerable gene flow. We hypothesize that M. incertifolia originated from an ancient hybridization event between M. congensis and M. monophylla, considering the current absence of hybridization between the two assumed parent species, the rare presence of shared haplotypes between all three species and the high percentage of haplotypes shared by M. incertifolia with each of the two parent species. This example is contrasted with two parapatrically distributed species from the same family in the genus Haumania forming a hybrid zone restricted to the area of overlap. This work illustrates the diversity of speciation/introgression patterns that can potentially occur in the flora of tropical Africa. PMID:24792083

  1. Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.

    PubMed

    Sajuthi, Satria P; Sharma, Neeraj K; Chou, Jeff W; Palmer, Nicholette D; McWilliams, David R; Beal, John; Comeau, Mary E; Ma, Lijun; Calles-Escandon, Jorge; Demons, Jamehl; Rogers, Samantha; Cherry, Kristina; Menon, Lata; Kouba, Ethel; Davis, Donna; Burris, Marcie; Byerly, Sara J; Ng, Maggie C Y; Maruthur, Nisa M; Patel, Sanjay R; Bielak, Lawrence F; Lange, Leslie A; Guo, Xiuqing; Sale, Michèle M; Chan, Kei Hang K; Monda, Keri L; Chen, Gary K; Taylor, Kira; Palmer, Cameron; Edwards, Todd L; North, Kari E; Haiman, Christopher A; Bowden, Donald W; Freedman, Barry I; Langefeld, Carl D; Das, Swapan K

    2016-08-01

    Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes, were evaluated by mining GWAS datasets. eQTL analysis identified 1971 and 2078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2 were identified in both tissues. 62.1 % of top cis-eSNPs were within ±50 kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu ) and identified genetically regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes. PMID:27193597

  2. Nevoid basal cell carcinoma syndrome with medulloblastoma in an African-American boy: A rare case illustrating gene-environment interaction

    SciTech Connect

    Korczak, J.F.; Goldstein, A.M.; Kase, R.G.

    1997-03-31

    We present an 8-year-old African-American boy with medulloblastoma and nevoid basal cell carcinoma syndrome (NBCCS) who exhibited the radiosensitive response of basal cell carcinoma (BCC) formation in the area irradiated for medulloblastoma. Such a response is well-documented in Caucasian NBCCS patients with medulloblastoma. The propositus was diagnosed with medulloblastoma at the age of 2 years and underwent surgery, chemotherapy, and craniospinal irradiation. At the age of 6 years, he was diagnosed with NBCCS following his presentation with a large odontogenic keratocyst of the mandible, pits of the palms and soles and numerous BCCs in the area of the back and neck that had been irradiated previously for medulloblastoma. Examination of other relatives showed that the propositus mother also had NBCCS but was more mildly affected; in particular, she had no BCCs. This case illustrates complex gene-environment interaction, in that increased skin pigmentation in African-Americans is presumably protective against ultraviolet, but not ionizing, radiation. This case and other similar cases in the literature show the importance of considering NBCCS in the differential diagnosis of any patient who presents with a medulloblastoma, especially before the age of 5 years, and of examining other close relatives for signs of NBCCS to determine the patient`s at-risk status. Finally, for individuals who are radiosensitive, protocols that utilize chemotherapy in lieu of radiotherapy should be considered. 27 refs., 4 figs.

  3. Common and rare single nucleotide polymorphisms in the LDLR gene are present in a black South African population and associate with low-density lipoprotein cholesterol levels.

    PubMed

    van Zyl, Tertia; Jerling, Johann C; Conradie, Karin R; Feskens, Edith J M

    2014-02-01

    The LDL receptor has an essential role in regulating plasma LDL-C levels. Genetic variation in the LDLR gene can be associated with either lower or moderately raised plasma levels of LDL-C, or may cause familial hypercholesterolemia. The prevalence of single-nucleotide polymorphisms (SNPs) in the LDLR in the black South African population is not known and therefore, we aimed to determine the genotypic variation of the LDLR in the study population as well as to define the association of the different genotypes with plasma LDL-C levels. A random selection of 1860 apparently healthy black South African volunteers aged 35-60 years was made in a cross-sectional study. Novel SNPs were identified in a subset of 30 individuals by means of automated sequencing before screening the entire cohort by means of the Illumina VeraCode GoldenGate Genotyping Assay on a BeadXpress Reader system. Twenty-five SNPs were genotyped, two of which were novel. A very rare SNP, rs17249141, in the promoter region was significantly associated with lower levels of LDL-C. Four other SNPs (rs2738447, rs14158, rs2738465 and rs3180023) were significantly associated with increased levels of LDL-C. We can conclude that some of the various SNPs identified do indeed associate with LDL-C levels. PMID:24284361

  4. Lack of specific alleles for the bovine chemokine (C-X-C) receptor type 4 (CXCR4) gene in West African cattle questions its role as a candidate for trypanotolerance.

    PubMed

    Álvarez, Isabel; Pérez-Pardal, Lucía; Traoré, Amadou; Fernández, Iván; Goyache, Félix

    2016-08-01

    A panel of 81 Asian, African and European cattle (Bos taurus and B. indicus) was analysed for the whole sequence of the CXCR4 gene (3844bp), a strong candidate for cattle trypanotolerance. Thirty-one polymorphic sites identified gave 31 different haplotypes. Neutrality tests rejected the hypothesis of either positive or purifying selection. Bayesian phylogenetic tree showed differentiation of haplotypes into two clades gathering genetic variability predating domestication. Related with clades definition, linkage disequilibrium analyses suggested the existence of one only linkage block on the CXCR4 gene. Two tag SNPs identified on exon 2 captured 50% of variability. Whatever the analysis carried out, no clear separation between cattle groups was identified. Most haplotypes identified in West African taurine cattle were also found in European cattle and in Asian and West African zebu. West African taurine samples did not carry unique variants on the CXCR4 gene sequence. The current analysis failed in identifying a causal mutation on the CXCR4 gene underlying a previously reported QTL for cattle trypanotolerance on BTA2. PMID:27117936

  5. Evaluation of the BD GeneOhm Methicillin-Resistant Staphylococcus aureus (MRSA) Assay as a Method for Detection of MRSA Isolates, Using a Large Collection of European and North African Isolates

    PubMed Central

    Bes, Michele; Meugnier, Helene; Tigaud, Sylvestre; Etienne, Jérôme; Vandenesch, François; Laurent, Frédéric

    2014-01-01

    Using a large collection of European and North African methicillin-resistant Staphylococcus aureus (MRSA) isolates with a variety of genetic backgrounds and staphylococcal cassette chromosome mec (SCCmec) types, we evaluated the reliability of the BD GeneOhm MRSA assay. Results revealed high performance of this test for detecting MRSA strains provided from Europe and North Africa (98.3%). PMID:25274997

  6. 13 CFR 120.611 - Pools backing Pool Certificates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pools backing Pool Certificates. 120.611 Section 120.611 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Secondary Market Certificates § 120.611 Pools backing Pool Certificates. (a) Pool characteristics. As...

  7. Pooled genetic analysis reveals an association of SNPs of only a few genes with risk predisposition to ischemic stroke in a Chinese population.

    PubMed

    Zhang, Zhenchang; Su, Gang; Guo, Jia; Li, Jiong; Wu, Hua; Wang, Manxia; Xie, Xiaodong

    2015-03-01

    Up to date, series of studies on ischemic stroke had resulted in inconsistent conclusion. In this study, we aimed to evaluate which specific genes were associated with increased predisposition to stroke in a Chinese population. To identify the specific genes and polymorphisms associated with predisposition to ischemic stroke, we performed high throughput sequenom based next-generation sequencing from 743 patient with history of ischemic stroke. Variants SNPs in nNOS, renalase, MTHFR, CELSR1 and XYLB genes were found significantly associated with IS, thus suggesting involvement of these loci to IS in Chinese patients. Because of different locations on chromosomes, haplotype analyses were not feasible. Our results demonstrate the top level genes that are related to normal vascular physiology, viz. genes of nitric oxide synthesis, endothelial health and smooth muscle biology. Further validation studies are awaited. PMID:25855559

  8. Virulence Gene Pool Detected in Bovine Group C Streptococcus dysgalactiae subsp. dysgalactiae Isolates by Use of a Group A S. pyogenes Virulence Microarray ▿

    PubMed Central

    Rato, Márcia G.; Nerlich, Andreas; Bergmann, René; Bexiga, Ricardo; Nunes, Sandro F.; Vilela, Cristina L.; Santos-Sanches, Ilda; Chhatwal, Gursharan S.

    2011-01-01

    A custom-designed microarray containing 220 virulence genes of Streptococcus pyogenes (group A Streptococcus [GAS]) was used to test group C Streptococcus dysgalactiae subsp. dysgalactiae (GCS) field strains causing bovine mastitis and group C or group G Streptococcus dysgalactiae subsp. equisimilis (GCS/GGS) isolates from human infections, with the latter being used for comparative purposes, for the presence of virulence genes. All bovine and all human isolates carried a fraction of the 220 genes (23% and 39%, respectively). The virulence genes encoding streptolysin S, glyceraldehyde-3-phosphate dehydrogenase, the plasminogen-binding M-like protein PAM, and the collagen-like protein SclB were detected in the majority of both bovine and human isolates (94 to 100%). Virulence factors, usually carried by human beta-hemolytic streptococcal pathogens, such as streptokinase, laminin-binding protein, and the C5a peptidase precursor, were detected in all human isolates but not in bovine isolates. Additionally, GAS bacteriophage-associated virulence genes encoding superantigens, DNase, and/or streptodornase were detected in bovine isolates (72%) but not in the human isolates. Determinants located in non-bacteriophage-related mobile elements, such as the gene encoding R28, were detected in all bovine and human isolates. Several virulence genes, including genes of bacteriophage origin, were shown to be expressed by reverse transcriptase PCR (RT-PCR). Phylogenetic analysis of superantigen gene sequences revealed a high level (>98%) of identity among genes of bovine GCS, of the horse pathogen Streptococcus equi subsp. equi, and of the human pathogen GAS. Our findings indicate that alpha-hemolytic bovine GCS, an important mastitis pathogen and considered to be a nonhuman pathogen, carries important virulence factors responsible for virulence and pathogenesis in humans. PMID:21525223

  9. Protective potency of clove oil and its transcriptional down-regulation of Aeromonas sobria virulence genes in African catfish (Clarias gariepinus L.).

    PubMed

    Abd El-Hamid, M I; Abd El-Aziz, N K; Ali, H A

    2016-01-01

    Disease episodes of fish caused by Aeromonas species are moved to the top list of limiting problems worldwide. The present study was planned to verify the in vitro antibacterial activities as well as the in vivo potential values of clove oil and ciprofloxacin against Aeromonas sobria in African catfish (Clarias gariepinus). The in vitro phenotypic virulence activities and the successful amplification of aerolysin and hemolysin genes in the precisely identified A. sobria strain were predictive for its virulence. In the in vivo assay, virulence of A. sobria strain was fully demonstrated based on constituent mRNA expression profile of tested virulence genes and typical septicemia associated with high mortalities of infected fish. Apparent lower mortality rates were correlated well with both decrescent bacterial burden and significant down-regulated transcripts of representative genes in the treated groups with clove oil, followed by ciprofloxacin as a prophylactic use for 15 days (P < 0.0001); however, the essential oil apart from ciprofloxacin significantly enhanced different hematological parameters (P < 0.05). In addition, administration of antibiotic may be considered as a pronounced stress factor in the fish even when it used in the prophylactic dose. In conclusion, medicinal plants-derived essential oils provide a virtually safer alternative to chemotherapeutics on fish, consumers and ecosystems. PMID:27609474

  10. Functionality and Cell Anchorage Dependence of the African Swine Fever Virus Gene A179L, a Viral bcl-2 Homolog, in Insect Cells

    PubMed Central

    Brun, Alejandro; Rodríguez, Fernando; Escribano, José M.; Alonso, Covadonga

    1998-01-01

    The African swine fever virus gene A179L has been shown to be a functional member of the ced9/bcl-2 family of apoptosis inhibitors in mammalian cell lines. In this work we have expressed the A179L gene product (p21) under the control of the baculovirus polyhedrin promoter using a baculovirus system. Expression of the A179L gene neither altered the baculovirus replication phenotype nor delayed the shutoff of cellular protein synthesis, but it extended the survival of the infected insect cells to very late times postinfection. The increase in cell survival rates correlated with a marked apoptosis reduction after baculovirus infection. Interestingly, prevention of apoptosis was observed when recombinant baculovirus infections were carried out in monolayer cell cultures but not when cells were infected in suspension, suggesting a cell anchorage dependence for p21 function in insect cells. Cell survival was enhanced under optimal conditions of cell attachment and cell-to-cell contact as provided by extracellular matrix components or poly-d-lysine. Since it was observed that cytoskeleton organization varied depending on culture conditions of insect cells (grown in monolayer versus grown in suspension), these results suggested that A179L might regulate apoptosis in insect cells only when the cytoskeletal support of intracellular signaling is maintained upon cell adhesion. Thus, cell shape and cytoskeleton status might allow variations in intracellular transduction of signals related to cell survival in virus-infected cells. PMID:9811766

  11. Improving AFLP analysis of large-scale patterns of genetic variation--a case study with the Central African lianas Haumania spp (Marantaceae) showing interspecific gene flow.

    PubMed

    Ley, A C; Hardy, O J

    2013-04-01

    AFLP markers are often used to study patterns of population genetic variation and gene flow because they offer a good coverage of the nuclear genome, but the reliability of AFLP scoring is critical. To assess interspecific gene flow in two African rainforest liana species (Haumania danckelmaniana, H. liebrechtsiana) where previous evidence of chloroplast captures questioned the importance of hybridization and species boundaries, we developed new AFLP markers and a novel approach to select reliable bands from their degree of reproducibility. The latter is based on the estimation of the broad-sense heritability of AFLP phenotypes, an improvement over classical scoring error rates, which showed that the polymorphism of most AFLP bands was affected by a substantial nongenetic component. Therefore, using a quantitative genetics framework, we also modified an existing estimator of pairwise kinship coefficient between individuals correcting for the limited heritability of markers. Bayesian clustering confirms the recognition of the two Haumania species. Nevertheless, the decay of the relatedness between individuals of distinct species with geographic distance demonstrates that hybridization affects the nuclear genome. In conclusion, although we showed that AFLP markers might be substantially affected by nongenetic factors, their analysis using the new methods developed considerably advanced our understanding of the pattern of gene flow in our model species. PMID:23398575

  12. Genetic variants determining survival and fertility in an adverse African environment: a population-based large-scale candidate gene association study

    PubMed Central

    Koopman, Jacob J.E.; Pijpe, Jeroen; Böhringer, Stefan; van Bodegom, David; Eriksson, Ulrika K.; Sanchez-Faddeev, Hernando; Ziem, Juventus B.; Zwaan, Bas; Slagboom, P. Eline; de Knijff, Peter; Westendorp, Rudi G.J.

    2016-01-01

    Human survival probability and fertility decline strongly with age. These life history traits have been shaped by evolution. However, research has failed to uncover a consistent genetic determination of variation in survival and fertility. As an explanation, such genetic determinants have been selected in adverse environments, in which humans have lived during most of their history, but are almost exclusively studied in populations in modern affluent environments. Here, we present a large-scale candidate gene association study in a rural African population living in an adverse environment. In 4387 individuals, we studied 4052 SNPs in 148 genes that have previously been identified as possible determinants of survival or fertility in animals or humans. We studied their associations with survival comparing newborns, middle-age adults, and old individuals. In women, we assessed their associations with reported and observed numbers of children. We found no statistically significant associations of these SNPs with survival between the three age groups nor with women's reported and observed fertility. Population stratification was unlikely to explain these results. Apart from a lack of power, we hypothesise that genetic heterogeneity of complex phenotypes and gene-environment interactions prevent the identification of genetic variants explaining variation in survival and fertility in humans. PMID:27356285

  13. Differential endothelial cell gene expression by African Americans versus Caucasian Americans: a possible contribution to health disparity in vascular disease and cancer

    PubMed Central

    2011-01-01

    Background Health disparities and the high prevalence of cardiovascular disease continue to be perplexing worldwide health challenges. This study addresses the possibility that genetic differences affecting the biology of the vascular endothelium could be a factor contributing to the increased burden of cardiovascular disease and cancer among African Americans (AA) compared to Caucasian Americans (CA). Methods From self-identified, healthy, 20 to 29-year-old AA (n = 21) and CA (n = 17), we established cultures of blood outgrowth endothelial cells (BOEC) and applied microarray profiling. BOEC have never been exposed to in vivo influences, and their gene expression reflects culture conditions (meticulously controlled) and donor genetics. Significance Analysis of Microarray identified differential expression of single genes. Gene Set Enrichment Analysis examined expression of pre-determined gene sets that survey nine biological systems relevant to endothelial biology. Results At the highly stringent threshold of False Discovery Rate (FDR) = 0, 31 single genes were differentially expressed in AA. PSPH exhibited the greatest fold-change (AA > CA), but this was entirely accounted for by a homolog (PSPHL) hidden within the PSPH probe set. Among other significantly different genes were: for AA > CA, SOS1, AMFR, FGFR3; and for AA < CA, ARVCF, BIN3, EIF4B. Many more (221 transcripts for 204 genes) were differentially expressed at the less stringent threshold of FDR <.05. Using the biological systems approach, we identified shear response biology as being significantly different for AA versus CA, showing an apparent tonic increase of expression (AA > CA) for 46/157 genes within that system. Conclusions Many of the genes implicated here have substantial roles in endothelial biology. Shear stress response, a critical regulator of endothelial function and vascular homeostasis, may be different between AA and CA. These results potentially have direct implications for the role of

  14. Swimming pool. View of aisle between swimming pool and seating ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Swimming pool. View of aisle between swimming pool and seating area. Non-original spa pool is partially visible on right. - Jewish Community Center of San Francisco, 3200 California Street, San Francisco, San Francisco County, CA

  15. Comparative De Novo Transcriptome Analysis of Fertilized Ovules in Xanthoceras sorbifolium Uncovered a Pool of Genes Expressed Specifically or Preferentially in the Selfed Ovule That Are Potentially Involved in Late-Acting Self-Incompatibility

    PubMed Central

    Zhou, Qingyuan; Zheng, Yuanrun

    2015-01-01

    species. The availability of a pool of specifically or preferentially expressed genes from selfed ovules for X. sorbifolium will be a valuable resource for future genetic analyses of candidate genes involved in the LSI response. PMID:26485030

  16. Weld pool phenomena

    SciTech Connect

    David, S.A.; Vitek, J.M.; Zacharia, T.; DebRoy, T.

    1994-09-01

    During welding, the composition, structure and properties of the welded structure are affected by the interaction of the heat source with the metal. The interaction affects the fluid flow, heat transfer and mass transfer in the weld pool, and the solidification behavior of the weld metal. In recent years, there has been a growing recognition of the importance of the weld pool transport processes and the solid state transformation reactions in determining the composition, structure and properties of the welded structure. The relation between the weld pool transport processes and the composition and structure is reviewed. Recent applications of various solidification theories to welding are examined to understand the special problems of weld metal solidification. The discussion is focussed on the important problems and issues related to weld pool transport phenomena and solidification. Resolution of these problems would be an important step towards a science based control of composition, structure and properties of the weld metal.

  17. Vitamin D Pooling Project

    Cancer.gov

    The Vitamin D Pooling Project of Rarer Cancers brought together investigators from 10 cohorts to conduct a large prospective epidemiologic study of the association between vitamin D status and seven rarer cancers.

  18. Pools for the Handicapped.

    ERIC Educational Resources Information Center

    American School and University, 1979

    1979-01-01

    Three institutions in Ohio now stress hydrotherapy and water recreation as important parts of individual educational programs for the handicapped. Specially designed and adapted pools provide freedom of movement and ego building as well as physical education and recreation. (Author)

  19. Swimming pool granuloma

    MedlinePlus

    Aquarium granuloma; Fish tank granuloma ... Risks include exposure to swimming pools, salt water aquariums, or ocean fish. ... Wash hands and arms thoroughly after cleaning aquariums. Or, wear rubber gloves when cleaning.

  20. The 894T allele of endothelial nitric oxide synthase gene is related to left ventricular mass in African Americans with high-normal blood pressure.

    PubMed Central

    Lapu-Bula, Rigobert; Quarshie, Alexander; Lyn, Deborah; Oduwole, Adefisayo; Pack, Cheryl; Morgan, Jan; Nkemdiche, Sunday; Igho-Pemu, Priscilla; Onwuanyi, Anekwe; Li, Rongling; Ofili, Elizabeth

    2005-01-01

    BACKGROUND AND OBJECTIVES: The 894T allele in exon 7 of the endothelial nitric oxide synthase (eNOS) gene has been inconsistently associated with hypertension in different racial groups. Because high-normal blood pressure (BP) confers an increased risk for the development of hypertension and other cardiovascular disorders, including left ventricular hypertrophy (LVH), we tested the hypothesis that the allelic variation (894T) in the eNOS gene would directly correlate with alterations in LV mass (LVM) in individuals with high-normal BP. METHODS: Genotype distribution of G894T was compared between 20 African Americans (10 females/10 males) with high-normal BP (systolic BP of 130-139 and/or diastolic BP of 85-89 mmHg) and 64 counterparts (37 females/27 males) with normal BP (<130/85 mmHg). Echocardiographic LVM was calculated (Devereux formula) and indexed to body surface area to define the presence of LVH (LVMI >134/110 g/m2 for men/women). RESULTS: For the entire group, the 894T allelic frequencies (15, 48%) and G894T genotype distributions were consistent with the Hardy-Weinberg equilibrium expectations (estimated disequilibrium coefficient = 0.0118, P=0.40). LVMI was significantly higher in homozygous carriers (TT) of the rare 894T allele (n = 3 females/0 males) than in heterozygous GT (n = 13 females/7 males) and individuals bearing the GG (n=34 females/27 males) variant (124 +/- 70 vs. 82 +/- 24 and 82 +/- 19 g/m2, respectively, P < 0.05). The observed relationship between eNOS 894T allele and LVMI was restricted to individuals with high-normal BP (r = 0.94, P = 0.03) but not in those with normal BP (r = 0.39, P =0.64), by analysis of variance (ANOVA) after adjusting for age, gender, body mass index, smoking and systolic BP. CONCLUSION: These findings, not previously described, provide important preliminary evidence to suggest an increased susceptibility to LVH in African Americans who carry the 894T variant of the eNOS gene and have high-normal blood pressure

  1. Genetic moderation of child maltreatment effects on depression and internalizing symptoms by 5-HTTLPR, BDNF, NET, and CRHR1 genes in African-American children

    PubMed Central

    Cicchetti, Dante; Rogosch, Fred A.

    2014-01-01

    Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African-American children (N = 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report (Children’s Depression Inventory, CDI) and adult counselor-report (Teacher Report Form, TRF). DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: 5-HTTLPR, BDNF, NET, and CRHR1. ANCOVAs with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their GxE interactions. Maltreatment consistently was associated with higher CDI and TRF symptoms. Results for child self-report symptoms indicated a GxE interaction for BDNF and maltreatment. Additionally, BDNF and tri-allelic 5-HTTLPR interacted with child maltreatment in a GxGxE interaction. Analyses for counselor-report of child anxiety/depression symptoms on the TRF indicated moderation of child maltreatment effects by tri-allelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. NET was found to further moderate the GxE interaction of 5-HTTLPR and maltreatment status revealing a GxGxE interaction. This GxGxE was extended by consideration of variation in maltreatment subtype experiences. Finally, GxGxE effects were observed for the co-action of BDNF and the CRHR1 haplotype. The findings illustrate the variable influence of specific genotypes in GxE interactions based on variation in maltreatment experiences and the importance of a multi-genic approach for understanding influences on depression and internalizing symptoms among African-American children. PMID:25422957

  2. Transcriptional expression of Epstein-Barr virus genes and proto-oncogenes in north African nasopharyngeal carcinoma.

    PubMed

    Sbih-Lammali, F; Djennaoui, D; Belaoui, H; Bouguermouh, A; Decaussin, G; Ooka, T

    1996-05-01

    Cases of nasopharyngeal carcinoma (NPC) from North Africa show an unusual bimodal age distribution. As elsewhere, the tumor is closely associated with the presence of Epstein-Barr virus (EBV). The expression of EBV genes and c-onc genes was studied in biopsy specimens from tumors at different clinical stages from 11 young (10 to 30-year-old) and 11 adult (30 to 65-year-old) patients. It was found that the two age groups do not differ in their pattern of gene expression, that there is a tendency for later stage biopsies to express more viral and c-onc transcripts, and that samples expressing larger numbers of EBV genes also tend to express many different c-onc specificities. PMID:8732865

  3. The Lysobacter capsici AZ78 Genome Has a Gene Pool Enabling it to Interact Successfully with Phytopathogenic Microorganisms and Environmental Factors.

    PubMed

    Puopolo, Gerardo; Tomada, Selena; Sonego, Paolo; Moretto, Marco; Engelen, Kristof; Perazzolli, Michele; Pertot, Ilaria

    2016-01-01

    Lysobacter capsici AZ78 has considerable potential for biocontrol of phytopathogenic microorganisms. However, lack of information about genetic cues regarding its biological characteristics may slow down its exploitation as a biofungicide. In order to obtain a comprehensive overview of genetic features, the L. capsici AZ78 genome was sequenced, annotated and compared with the phylogenetically related pathogens Stenotrophomonas malthophilia K729a and Xanthomonas campestris pv. campestris ATCC 33913. Whole genome comparison, supported by functional analysis, indicated that L. capsici AZ78 has a larger number of genes responsible for interaction with phytopathogens and environmental stress than S. malthophilia K729a and X. c. pv. campestris ATCC 33913. Genes involved in the production of antibiotics, lytic enzymes and siderophores were specific for L. capsici AZ78, as well as genes involved in resistance to antibiotics, environmental stressors, fungicides and heavy metals. The L. capsici AZ78 genome did not encompass genes involved in infection of humans and plants included in the S. malthophilia K729a and X. c. pv. campestris ATCC 33913 genomes, respectively. The L. capsici AZ78 genome provides a genetic framework for detailed analysis of other L. capsici members and the development of novel biofungicides based on this bacterial strain. PMID:26903975

  4. The Lysobacter capsici AZ78 Genome Has a Gene Pool Enabling it to Interact Successfully with Phytopathogenic Microorganisms and Environmental Factors

    PubMed Central

    Puopolo, Gerardo; Tomada, Selena; Sonego, Paolo; Moretto, Marco; Engelen, Kristof; Perazzolli, Michele; Pertot, Ilaria

    2016-01-01

    Lysobacter capsici AZ78 has considerable potential for biocontrol of phytopathogenic microorganisms. However, lack of information about genetic cues regarding its biological characteristics may slow down its exploitation as a biofungicide. In order to obtain a comprehensive overview of genetic features, the L. capsici AZ78 genome was sequenced, annotated and compared with the phylogenetically related pathogens Stenotrophomonas malthophilia K729a and Xanthomonas campestris pv. campestris ATCC 33913. Whole genome comparison, supported by functional analysis, indicated that L. capsici AZ78 has a larger number of genes responsible for interaction with phytopathogens and environmental stress than S. malthophilia K729a and X. c. pv. campestris ATCC 33913. Genes involved in the production of antibiotics, lytic enzymes and siderophores were specific for L. capsici AZ78, as well as genes involved in resistance to antibiotics, environmental stressors, fungicides and heavy metals. The L. capsici AZ78 genome did not encompass genes involved in infection of humans and plants included in the S. malthophilia K729a and X. c. pv. campestris ATCC 33913 genomes, respectively. The L. capsici AZ78 genome provides a genetic framework for detailed analysis of other L. capsici members and the development of novel biofungicides based on this bacterial strain. PMID:26903975

  5. Sulfonamide and tetracycline resistance genes in total- and culturable-bacterial assemblages in South African aquatic environments.

    PubMed

    Suzuki, Satoru; Ogo, Mitsuko; Koike, Tatsuya; Takada, Hideshige; Newman, Brent

    2015-01-01

    Antibiotic resistant bacteria are ubiquitous in the natural environment. The introduction of effluent derived antibiotic resistance genes (ARGs) into aquatic environments is of concern in the spreading of genetic risk. This study showed the prevalence of sulfonamide and tetracycline resistance genes, sul1, sul2, sul3, and tet(M), in the total bacterial assemblage and colony forming bacterial assemblage in river and estuarine water and sewage treatment plants (STP) in South Africa. There was no correlation between antibiotic concentrations and ARGs, suggesting the targeted ARGs are spread in a wide area without connection to selection pressure. Among sul genes, sul1 and sul2 were major genes in the total (over 10(-2) copies/16S) and colony forming bacteria assemblages (∼10(-1) copies/16S). In urban waters, the sul3 gene was mostly not detectable in total and culturable assemblages, suggesting sul3 is not abundant. tet(M) was found in natural assemblages with 10(-3) copies/16S level in STP, but was not detected in colony forming bacteria, suggesting the non-culturable (yet-to-be cultured) bacterial community in urban surface waters and STP effluent possess the tet(M) gene. Sulfamethoxazole (SMX) resistant (SMX(r)) and oxytetracycline (OTC) resistant (OTC(r)) bacterial communities in urban waters possessed not only sul1 and sul2 but also sul3 and tet(M) genes. These genes are widely distributed in SMX(r) and OTC(r) bacteria. In conclusion, urban river and estuarine water and STP effluent in the Durban area were highly contaminated with ARGs, and the yet-to-be cultured bacterial community may act as a non-visible ARG reservoir in certain situations. PMID:26300864

  6. Sulfonamide and tetracycline resistance genes in total- and culturable-bacterial assemblages in South African aquatic environments

    PubMed Central

    Suzuki, Satoru; Ogo, Mitsuko; Koike, Tatsuya; Takada, Hideshige; Newman, Brent

    2015-01-01

    Antibiotic resistant bacteria are ubiquitous in the natural environment. The introduction of effluent derived antibiotic resistance genes (ARGs) into aquatic environments is of concern in the spreading of genetic risk. This study showed the prevalence of sulfonamide and tetracycline resistance genes, sul1, sul2, sul3, and tet(M), in the total bacterial assemblage and colony forming bacterial assemblage in river and estuarine water and sewage treatment plants (STP) in South Africa. There was no correlation between antibiotic concentrations and ARGs, suggesting the targeted ARGs are spread in a wide area without connection to selection pressure. Among sul genes, sul1 and sul2 were major genes in the total (over 10-2 copies/16S) and colony forming bacteria assemblages (∼10-1 copies/16S). In urban waters, the sul3 gene was mostly not detectable in total and culturable assemblages, suggesting sul3 is not abundant. tet(M) was found in natural assemblages with 10-3 copies/16S level in STP, but was not detected in colony forming bacteria, suggesting the non-culturable (yet-to-be cultured) bacterial community in urban surface waters and STP effluent possess the tet(M) gene. Sulfamethoxazole (SMX) resistant (SMXr) and oxytetracycline (OTC) resistant (OTCr) bacterial communities in urban waters possessed not only sul1 and sul2 but also sul3 and tet(M) genes. These genes are widely distributed in SMXr and OTCr bacteria. In conclusion, urban river and estuarine water and STP effluent in the Durban area were highly contaminated with ARGs, and the yet-to-be cultured bacterial community may act as a non-visible ARG reservoir in certain situations. PMID:26300864

  7. Association analysis of photoperiodic flowering time genes in west and central African sorghum [Sorghum bicolor (L.) Moench

    PubMed Central

    2012-01-01

    Background Photoperiod-sensitive flowering is a key adaptive trait for sorghum (Sorghum bicolor) in West and Central Africa. In this study we performed an association analysis to investigate the effect of polymorphisms within the genes putatively related to variation in flowering time on photoperiod-sensitive flowering in sorghum. For this purpose a genetically characterized panel of 219 sorghum accessions from West and Central Africa was evaluated for their photoperiod response index (PRI) based on two sowing dates under field conditions. Results Sorghum accessions used in our study were genotyped for single nucleotide polymorphisms (SNPs) in six genes putatively involved in the photoperiodic control of flowering time. Applying a mixed model approach and previously-determined population structure parameters to these candidate genes, we found significant associations between several SNPs with PRI for the genes CRYPTOCHROME 1 (CRY1-b1) and GIGANTEA (GI). Conclusions The negative values of Tajima's D, found for the genes of our study, suggested that purifying selection has acted on genes involved in photoperiodic control of flowering time in sorghum. The SNP markers of our study that showed significant associations with PRI can be used to create functional markers to serve as important tools for marker-assisted selection of photoperiod-sensitive cultivars in sorghum. PMID:22394582

  8. Differential gene expression in the liver of the African lungfish, Protopterus annectens, after 6 days of estivation in air.

    PubMed

    Loong, A M; Hiong, K C; Wong, W P; Chew, S F; Ip, Y K

    2012-02-01

    This study aimed to identify estivation-specific gene clusters through the determination of differential gene expressions in the liver of Protopterus annectens after 6 days of estivation in a mucus cocoon in air (normoxia) using suppression subtractive hybridization polymerase chain reaction. Our results demonstrated that 6 days of estivation in normoxia led to up-regulation of mRNA expressions of several genes related to urea synthesis, including carbamoyl phosphate synthetase (Cps), argininosuccinate synthetase and glutamine synthetase. They indicate that increased urea synthesis, despite being energy-intensive, is an important adaptive response of estivation. They also offer indirect support to the proposition that urea synthesis in this lungfish involved a Cps that uses glutamine as a substrate. In addition, up- or down-regulation of several gene clusters occurred in the liver of P. annectens after 6 days of estivation in normoxia. These estivation-specific genes were involved in the prevention of clot formation, activation of the lectin pathway for complement activation, conservation of minerals (e.g. iron and copper) and increased production of hemoglobin beta. Since there were up- and down-regulation of mRNA expressions of genes related to ribosomal proteins and translational elongation factors, there could be simultaneous increases in protein degradation and protein synthesis during the first 6 days (the induction phase) of estivation, confirming the importance of reconstruction of protein structures in preparation for the maintenance phase of estivation. PMID:21915614

  9. [Dose-Response Dependences for Frequency of RET/PTC Gene Rearrangements in Papillary Thyroid Carcinoma after Irradiation. Simple Pooling Analysis of Molecular Epidemiological Data].

    PubMed

    Koterov, A N; Ushenkova, L N; Biryukov, A P

    2016-01-01

    On the basis of all possible publications on the theme included in the previously formed base of sources on molecular epidemiology of RET/PTC rearrangements in thyroid papillary carcinoma a pooled analysis ("simple pooling data") on determination of the dose-effect dependences for RET/PTC frequency in radiogenic carcinomas of various irradiated groups was performed. (They are groups subjected to radiotherapeutic exposure, residents near the Chernobyl nuclear power plant (CNPP) and victims of nuclear bombing). The tendency to Pearson linear correlation (r = 0.746; p = 0.148) between the frequency of RET/PTC and the estimated dose on thyroid in the regions affected by the CNPP accident was revealed. But this tendency was recognized to be random owing to abnormally low values of the indicator for the most contaminated Gomel region. The method tentatively called "case-control" showed reliable differences in thyroid dose values for carcinomas with RET/PTC and without those. The versatility of changes was found: the lack of RET/PTC for radiotherapeutic impacts was associated with higher doses, whereas in case of the CNPP accident and for nuclear bombing victims it was the opposite. Probably, in the first case the "cellular cleaning" phenomenon after exposure to very high doses took place. Search of direct Pearson correlations between average/median thyroid doses on groups and RET/PTC frequency in carcinomas of these groups showed a high reliability for the dose-effect dependences- at the continuous dose scale (for RET/PTC in total and RET/PTC1 respectively: r = 0.830; p = 0.002 and r = 0.906; p = 0.0003); while there was no significant correlation received for RET/PTC3. When using the weighting least square regression analysis (proceeding from the number of carcinomas in samples), the specified regularities remained. Attempts to influence the strength of correlation by exception ofthe data of all the samples connected with the accident on the CNPP did not significantly

  10. African Swine Fever Virus Georgia Isolate Harboring Deletions of MGF360 and MGF505 Genes Is Attenuated in Swine and Confers Protection against Challenge with Virulent Parental Virus

    PubMed Central

    O'Donnell, Vivian; Holinka, Lauren G.; Gladue, Douglas P.; Sanford, Brenton; Krug, Peter W.; Lu, Xiqiang; Arzt, Jonathan; Reese, Bo; Carrillo, Consuelo; Risatti, Guillermo R.

    2015-01-01

    ABSTRACT African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The control of African swine fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines have been developed using genetically modified live attenuated ASFVs where viral genes involved in virus virulence were removed from the genome. Multigene family 360 (MGF360) and MGF505 represent a group of genes sharing partial sequence and structural identities that have been connected with ASFV host range specificity, blocking of the host innate response, and virus virulence. Here we report the construction of a recombinant virus (ASFV-G-ΔMGF) derived from the highly virulent ASFV Georgia 2007 isolate (ASFV-G) by specifically deleting six genes belonging to MGF360 or MGF505: MGF505-1R, MGF360-12L, MGF360-13L, MGF360-14L, MGF505-2R, and MGF505-3R. ASFV-G-ΔMGF replicates as efficiently in primary swine macrophage cell cultures as the parental virus. In vivo, ASFV-G-ΔMGF is completely attenuated in swine, since pigs inoculated intramuscularly (i.m.) with either 102 or 104 50% hemadsorbing doses (HAD50) remained healthy, without signs of the disease. Importantly, when these animals were subsequently exposed to highly virulent parental ASFV-G, no signs of the disease were observed, although a proportion of these animals harbored the challenge virus. This is the first report demonstrating the role of MGF genes acting as independent determinants of ASFV virulence. Additionally, ASFV-G-ΔMGF is the first experimental vaccine reported to induce protection in pigs challenged with highly virulent and epidemiologically relevant ASFV-G. IMPORTANCE The main problem for controlling ASF is the lack of vaccines. Studies focusing on understanding ASFV virulence led to the production of genetically modified recombinant viruses that, while attenuated, are able to confer

  11. Exploring the tertiary gene pool of bread wheat: sequence assembly and analysis of chromosome 5M(g) of Aegilops geniculata.

    PubMed

    Tiwari, Vijay K; Wang, Shichen; Danilova, Tatiana; Koo, Dal Hoe; Vrána, Jan; Kubaláková, Marie; Hribova, Eva; Rawat, Nidhi; Kalia, Bhanu; Singh, Narinder; Friebe, Bernd; Doležel, Jaroslav; Akhunov, Eduard; Poland, Jesse; Sabir, Jamal S M; Gill, Bikram S

    2015-11-01

    Next-generation sequencing (NGS) provides a powerful tool for the discovery of important genes and alleles in crop plants and their wild relatives. Despite great advances in NGS technologies, whole-genome shotgun sequencing is cost-prohibitive for species with complex genomes. An attractive option is to reduce genome complexity to a single chromosome prior to sequencing. This work describes a strategy for studying the genomes of distant wild relatives of wheat by isolating single chromosomes from addition or substitution lines, followed by chromosome sorting using flow cytometry and sequencing of chromosomal DNA by NGS technology. We flow-sorted chromosome 5M(g) from a wheat/Aegilops geniculata disomic substitution line [DS5M(g) (5D)] and sequenced it using an Illumina HiSeq 2000 system at approximately 50 × coverage. Paired-end sequences were assembled and used for structural and functional annotation. A total of 4236 genes were annotated on 5M(g) , in close agreement with the predicted number of genes on wheat chromosome 5D (4286). Single-gene FISH indicated no major chromosomal rearrangements between chromosomes 5M(g) and 5D. Comparing chromosome 5M(g) with model grass genomes identified synteny blocks in Brachypodium distachyon, rice (Oryza sativa), sorghum (Sorghum bicolor) and barley (Hordeum vulgare). Chromosome 5M(g) -specific SNPs and cytogenetic probe-based resources were developed and validated. Deletion bin-mapped and ordered 5M(g) SNP markers will be useful to track 5M-specific introgressions and translocations. This study provides a detailed sequence-based analysis of the composition of a chromosome from a distant wild relative of bread wheat, and opens up opportunities to develop genomic resources for wild germplasm to facilitate crop improvement. PMID:26408103

  12. Vernal Pool Lessons and Activities.

    ERIC Educational Resources Information Center

    Childs, Nancy; Colburn, Betsy

    This curriculum guide accompanies Certified: A Citizen's Step-by-Step Guide to Protecting Vernal Pools which is designed to train volunteers in the process of identifying vernal pool habitat so that as many of these pools as possible can be certified by the Massachusetts Natural Heritage and Endangered Species Program. Vernal pools are a kind of…

  13. Toll-like receptor gene variants and bacterial vaginosis among HIV-1 infected and uninfected African women.

    PubMed

    Mackelprang, R D; Scoville, C W; Cohen, C R; Ondondo, R O; Bigham, A W; Celum, C; Campbell, M S; Essex, M; Wald, A; Kiarie, J; Ronald, A; Gray, G; Lingappa, J R

    2015-01-01

    Bacterial vaginosis (BV) is a common vaginal syndrome associated with altered microflora that increases the risk of preterm delivery and acquisition of sexually transmitted diseases. The cause of BV is unknown although toll-like receptors (TLRs), that are central to innate immune responses, may be important. We evaluated associations between TLR SNPs and BV among HIV-1 infected and uninfected African women. Logistic regression was used to assess associations between SNPs (N=99) in TLRs 2-4, 7-9 and BV (as classified by Nugent's criteria). Among HIV-1 uninfected women, TLR7 rs5743737 and TLR7 rs1634323 were associated with a decreased risk of BV, whereas TLR7 rs179012 was associated with an increased risk. TLR2 SNP rs3804099 was associated with a decreased risk of BV among HIV-1 infected women. Our findings indicate that there may be differences in TLR association with BV among HIV-1 infected and HIV-1 uninfected women. PMID:25928881

  14. Variation of Gene Expression Associated with Colonisation of an Anthropized Environment: Comparison between African and European Populations of Drosophila simulans

    PubMed Central

    Wurmser, François; Mary-Huard, Tristan; Daudin, Jean-Jacques; Joly, Dominique; Montchamp-Moreau, Catherine

    2013-01-01

    The comparison of transcriptome profiles among populations is a powerful tool for investigating the role of gene expression change in adaptation to new environments. In this study, we use massively parallel sequencing of 3′ cDNAs obtained from large samples of adult males, to compare a population of Drosophila simulans from a natural reserve within its ancestral range (eastern Africa) with a derived population collected in the strongly anthropized Rhône valley (France). The goal was to scan for adaptation linked to the invasion of new environments by the species. Among 15,090 genes retained for the analysis, 794 were found to be differentially expressed between the two populations. We observed an increase in expression of reproduction-related genes in eastern Africa, and an even stronger increase in expression of Cytochrome P450, Glutathione transferase and Glucuronosyl transferase genes in the derived population. These three gene families are involved in detoxification processes, which suggests that pesticides are a major environmental pressure for the species in this area. The survey of the Cyp6g1 upstream region revealed the insertion of a transposable element, Juan, in the regulatory sequence that is almost fixed in the Rhône Valley, but barely present in Mayotte. This shows that Cyp6g1 has undergone parallel evolution in derived populations of D. simulans as previously shown for D. melanogaster. The increasing amount of data produced by comparative population genomics and transcriptomics should permit the identification of additional genes associated with functional divergence among those differentially expressed. PMID:24260296

  15. The African Pediatric Fellowship Program: Training in Africa for Africans.

    PubMed

    Wilmshurst, Jo M; Morrow, Brenda; du Preez, Avril; Githanga, David; Kennedy, Neil; Zar, Heather J

    2016-01-01

    Africa has a significant burden of childhood disease, with relatively few skilled health care professionals. The African Paediatric Fellowship Programme was developed by the Department of Pediatrics and Child Health at the University of Cape Town to provide relevant training for African child health professionals, by Africans, within Africa. Trainees identified by partner academic institutions spend 6 months to 2 years training in the Department of Pediatrics and allied disciplines. They then return to their home institution to build practice, training, research, and advocacy. From 2008 to 2015, 73 physicians have completed or are completing training in general pediatrics or a pediatric subspecialty. At 1 year posttraining, 98% to 100% are practicing back in their home institution. The impact of the returning fellows is evident from their practice interventions, research collaborations, and positions as stakeholders who can change health care policies. Thirty-three centers in 13 African countries are partners with the program, and the program template is now followed by other partner sites in Africa. Increasing and retaining the skills pool of African child health specialists is building a network of motivated, highly skilled clinicians who are equipped to advance child health in Africa. PMID:26659458

  16. African Universities Tackle the Continent's Agricultural Crisis

    ERIC Educational Resources Information Center

    Lindow, Megan

    2009-01-01

    Pests, population growth, and depleted soil have wreaked havoc on agriculture in Africa, so universities across the continent are rethinking how they teach the topic. Some African universities have been building their own networks and pooling their limited resources to train more agricultural scientists and improve their responsiveness to the…

  17. Hydrodynamic gene delivery of baboon trypanosome lytic factor eliminates both animal and human-infective African trypanosomes.

    PubMed

    Thomson, Russell; Molina-Portela, Pilar; Mott, Helen; Carrington, Mark; Raper, Jayne

    2009-11-17

    Several species of African trypanosomes cause fatal disease in livestock, but most cannot infect humans due to innate trypanosome lytic factors (TLFs). Human TLFs are pore forming high-density lipoprotein (HDL) particles that contain apolipoprotein L-I (apoL-I) the trypanolytic component, and haptoglobin-related protein (Hpr), which binds free hemoglobin (Hb) in blood and facilitates the uptake of TLF via a trypanosome haptoglobin-hemoglobin receptor. The human-infective Trypanosoma brucei rhodesiense escapes lysis by TLF by expression of serum resistance-associated (SRA) protein, which binds and neutralizes apoL-I. Unlike humans, baboons are not susceptible to infection by T. b. rhodesiense due to previously unidentified serum factors. Here, we show that baboons have a TLF complex that contains orthologs of Hpr and apoL-I and that full-length baboon apoL-I confers trypanolytic activity to mice and when expressed together with baboon Hpr and human apoA-I, provides protection against both animal infective and the human-infective T. brucei rhodesiense in vivo. We further define two critical lysines near the C terminus of baboon apoL-1 that are necessary and sufficient to prevent binding to SRA and thereby confer resistance to human-infective trypanosomes. These findings form the basis for the creation of TLF transgenic livestock that would be resistant to animal and human-infective trypanosomes, which would result in the reduction of disease and the zoonotic transmission of human infective trypanosomes. PMID:19858474

  18. Genome-wide patterns of population structure and admixture in West Africans and African Americans.

    PubMed

    Bryc, Katarzyna; Auton, Adam; Nelson, Matthew R; Oksenberg, Jorge R; Hauser, Stephen L; Williams, Scott; Froment, Alain; Bodo, Jean-Marie; Wambebe, Charles; Tishkoff, Sarah A; Bustamante, Carlos D

    2010-01-12

    Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans (n = 365) and individuals with ancestry from West Africa (n = 203 from 12 populations) and Europe (n = 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion. Among African Americans, analysis of genomic admixture by a principal component-based approach indicates that the median proportion of European ancestry is 18.5% (25th-75th percentiles: 11.6-27.7%), with very large variation among individuals. In the African-American sample as a whole, few autosomal regions showed exceptionally high or low mean African ancestry, but the X chromosome showed elevated levels of African ancestry, consistent with a sex-biased pattern of gene flow with an excess of European male and African female ancestry. We also find that genomic profiles of individual African Americans afford personalized ancestry reconstructions differentiating ancient vs. recent European and African ancestry. Finally, patterns of genetic similarity among inferred African segments of African-American genomes and genomes of contemporary African populations included in this study suggest African ancestry is most similar to non-Bantu Niger-Kordofanian-speaking populations, consistent with historical documents of the African Diaspora and trans-Atlantic slave trade. PMID:20080753

  19. Thread Pool Interface (TPI)

    2008-04-01

    Thread Pool Interface (TpI) provides a simple interface for running functions written in C or C++ in a thread-parallel mode. Application or library codes may need to perform operations thread-parallel on machines with multicore processors. the TPI library provides a simple mechanism for managing thread activation, deactivation, and thread-parallel execution of application-provided subprograms.

  20. The Future of Pooling.

    ERIC Educational Resources Information Center

    Young, Peter C.; Fone, Martin

    1997-01-01

    Discusses seven propositions underlying the strategies that insurance pools can, will, and must pursue: (1) risk management versus risk financing; (2) elimination of windfall advantages; (3) the maintenance of market-dominant status; (4) cost leadership; (5) client focus; (6) innovation and diversification; and (7) leadership challenges. A sidebar…

  1. Data Pool Description

    Atmospheric Science Data Center

    2016-04-29

    ... "Internet Options", "Advanced" tab, "Enable FTP folder view (outside of Internet Explorer)" under "Browsing"  • Use IE7 for FTP ... FTP mode is required to access the Data Pool from the command line as "ftp -p l5eil01.larc.nasa.gov" , where the system translates ...

  2. Prevalence and characterization of plasmid-mediated quinolone resistance genes in Aeromonas spp. isolated from South African freshwater fish.

    PubMed

    Chenia, Hafizah Yousuf

    2016-08-16

    An increasing incidence of multidrug-resistant Aeromonas spp., which are both fish and emerging opportunistic human pathogens, has been observed worldwide. Quinolone-resistant Aeromonas spp. isolates are increasingly being observed in clinical and environmental settings, and this has been attributed primarily to target gene alterations, efflux, and transferable quinolone resistance. Thirty-four Aeromonas spp., obtained from freshwater aquaculture systems, were screened for the presence of GyrA and ParC substitutions, efflux activity and the prevalence of plasmid-mediated quinolone resistance genes, qnr and aac-6'-Ib-cr. Although 44% of isolates were resistant to nalidixic acid, the majority were susceptible to ciprofloxacin and ofloxacin. The predominant GyrA substitution was Ser-83→Val among Aeromonas veronii isolates whilst Aeromonas hydrophila isolates displayed a Ser-83→Ile substitution, and Ser-80→Ile substitutions were observed in ParC. Minimum inhibitory concentrations of fluoro(quinolones) were determined in the presence and absence of the efflux pump inhibitor, phenylalanine-arginine β-naphthylamide (PAβN). Addition of PAβN had no effect on the levels of fluoro(quinolone) resistance observed for these isolates. Although no aac-6'-Ib-cr variant genes were identified, qnrB and qnrS were detected for 41% and 24% of isolates, respectively, by Southern hybridization and confirmed by PCR and sequencing. Quinolone resistance in these fish-associated Aeromonas isolates was related to mutations in the quinolone resistance determining regions of GyrA and ParC and presence of qnrB and qnrS. The presence of qnr alleles in Aeromonas spp. isolates may facilitate high-level fluoroquinolone resistance and potentially serve as reservoirs for the dissemination of qnr genes to other aquatic microbes. PMID:27180024

  3. Population genetic structure of the African elephant in Uganda based on variation at mitochondrial and nuclear loci: evidence for male-biased gene flow.

    PubMed

    Nyakaana, S; Arctander, P

    1999-07-01

    A drastic decline has occurred in the size of the Uganda elephant population in the last 40 years, exacerbated by two main factors; an increase in the size of the human population and poaching for ivory. One of the attendant consequences of such a decline is a reduction in the amount of genetic diversity in the surviving populations due to increased effects of random genetic drift. Information about the amount of genetic variation within and between the remaining populations is vital for their future conservation and management. The genetic structure of the African elephant in Uganda was examined using nucleotide variation of mitochondrial control region sequences and four nuclear microsatellite loci in 72 individuals from three localities. Eleven mitochondrial DNA (mtDNA) haplotypes were observed, nine of which were geographically localized. We found significant genetic differentiation between the three populations at the mitochondrial locus while three out of the four microsatellite loci differentiated KV and QE, one locus differentiated KV and MF and no loci differentiated MF and QE. Expected heterozygosity at the four loci varied between 0.51 and 0.84 while nucleotide diversity at the mitochondrial locus was 1.4%. Incongruent patterns of genetic variation within and between populations were revealed by the two genetic systems, and we have explained these in terms of the differences in the effective population sizes of the two genomes and male-biased gene flow between populations. PMID:10447852

  4. Four plant defensins from an indigenous South African Brassicaceae species display divergent activities against two test pathogens despite high sequence similarity in the encoding genes

    PubMed Central

    2011-01-01

    Background Plant defensins are an important component of the innate defence system of plants where they form protective antimicrobial barriers between tissue types of plant organs as well as around seeds. These peptides also have other activities that are important for agricultural applications as well as the medical sector. Amongst the numerous plant peptides isolated from a variety of plant species, a significant number of promising defensins have been isolated from Brassicaceae species. Here we report on the isolation and characterization of four defensins from Heliophila coronopifolia, a native South African Brassicaceae species. Results Four defensin genes (Hc-AFP1-4) were isolated with a homology based PCR strategy. Analysis of the deduced amino acid sequences showed that the peptides were 72% similar and grouped closest to defensins isolated from other Brassicaceae species. The Hc-AFP1 and 3 peptides shared high homology (94%) and formed a unique grouping in the Brassicaceae defensins, whereas Hc-AFP2 and 4 formed a second homology grouping with defensins from Arabidopsis and Raphanus. Homology modelling showed that the few amino acids that differed between the four peptides had an effect on the surface properties of the defensins, specifically in the alpha-helix and the loop connecting the second and third beta-strands. These areas are implicated in determining differential activities of defensins. Comparing the activities after recombinant production of the peptides, Hc-AFP2 and 4 had IC50 values of 5-20 μg ml-1 against two test pathogens, whereas Hc-AFP1 and 3 were less active. The activity against Botrytis cinerea was associated with membrane permeabilization, hyper-branching, biomass reduction and even lytic activity. In contrast, only Hc-AFP2 and 4 caused membrane permeabilization and severe hyper-branching against the wilting pathogen Fusarium solani, while Hc-AFP1 and 3 had a mild morphogenetic effect on the fungus, without any indication of

  5. Patterns of Mitochondrial Variation within and between African Malaria Vectors, Anopheles Gambiae and An. Arabiensis, Suggest Extensive Gene Flow

    PubMed Central

    Besansky, N. J.; Lehmann, T.; Fahey, G. T.; Fontenille, D.; Braack, LEO.; Hawley, W. A.; Collins, F. H.

    1997-01-01

    Anopheles gambiae and An. arabiensis are mosquito species responsible for most malaria transmission in sub-Saharan Africa. They are also closely related sibling species that share chromosomal and molecular polymorphisms as a consequence of incomplete lineage sorting or introgressive hybridization. To help resolve these processes, this study examined the partitioning of mtDNA sequence variation within and between species across Africa, from both population genetic and phylogeographic perspectives. Based on partial gene sequences from the cytochrome b, ND1 and ND5 genes, haplotype diversity was high but sequences were very closely related. Within species, little or no population subdivision was detected, and there was no evidence for isolation by distance. Between species, there were no fixed nucleotide differences, a high proportion of shared polymorphisms, and eight haplotypes in common over distances as great as 6000 km. Only one of 16 shared polymorphisms led to an amino acid difference, and there was no compelling evidence for nonneutral variation. Parsimony networks constructed of haplotypes from both species revealed no correspondence of haplotype with either geography or taxonomy. This trend of low intraspecific genetic divergence is consistent with evidence from allozyme and microsatellite data and is interpreted in terms of both extensive gene flow and recent range expansion from relatively large, stable populations. We argue that retention of ancestral polymorphisms is a plausible but insufficient explanation for low interspecific genetic divergence, and that extensive hybridization is a contributing factor. PMID:9409838

  6. The African buffalo parasite Theileria. sp. (buffalo) can infect and immortalize cattle leukocytes and encodes divergent orthologues of Theileria parva antigen genes.

    PubMed

    Bishop, R P; Hemmink, J D; Morrison, W I; Weir, W; Toye, P G; Sitt, T; Spooner, P R; Musoke, A J; Skilton, R A; Odongo, D O

    2015-12-01

    African Cape buffalo (Syncerus caffer) is the wildlife reservoir of multiple species within the apicomplexan protozoan genus Theileria, including Theileria parva which causes East coast fever in cattle. A parasite, which has not yet been formally named, known as Theileria sp. (buffalo) has been recognized as a potentially distinct species based on rDNA sequence, since 1993. We demonstrate using reverse line blot (RLB) and sequencing of 18S rDNA genes, that in an area where buffalo and cattle co-graze and there is a heavy tick challenge, T. sp. (buffalo) can frequently be isolated in culture from cattle leukocytes. We also show that T. sp. (buffalo), which is genetically very closely related to T. parva, according to 18s rDNA sequence, has a conserved orthologue of the polymorphic immunodominant molecule (PIM) that forms the basis of the diagnostic ELISA used for T. parva serological detection. Closely related orthologues of several CD8 T cell target antigen genes are also shared with T. parva. By contrast, orthologues of the T. parva p104 and the p67 sporozoite surface antigens could not be amplified by PCR from T. sp. (buffalo), using conserved primers designed from the corresponding T. parva sequences. Collectively the data re-emphasise doubts regarding the value of rDNA sequence data alone for defining apicomplexan species in the absence of additional data. 'Deep 454 pyrosequencing' of DNA from two Theileria sporozoite stabilates prepared from Rhipicephalus appendiculatus ticks fed on buffalo failed to detect T. sp. (buffalo). This strongly suggests that R. appendiculatus may not be a vector for T. sp. (buffalo). Collectively, the data provides further evidence that T. sp. (buffalo). is a distinct species from T. parva. PMID:26543804

  7. The African buffalo parasite Theileria. sp. (buffalo) can infect and immortalize cattle leukocytes and encodes divergent orthologues of Theileria parva antigen genes

    PubMed Central

    Bishop, R.P.; Hemmink, J.D.; Morrison, W.I.; Weir, W.; Toye, P.G.; Sitt, T.; Spooner, P.R.; Musoke, A.J.; Skilton, R.A.; Odongo, D.O.

    2015-01-01

    African Cape buffalo (Syncerus caffer) is the wildlife reservoir of multiple species within the apicomplexan protozoan genus Theileria, including Theileria parva which causes East coast fever in cattle. A parasite, which has not yet been formally named, known as Theileria sp. (buffalo) has been recognized as a potentially distinct species based on rDNA sequence, since 1993. We demonstrate using reverse line blot (RLB) and sequencing of 18S rDNA genes, that in an area where buffalo and cattle co-graze and there is a heavy tick challenge, T. sp. (buffalo) can frequently be isolated in culture from cattle leukocytes. We also show that T. sp. (buffalo), which is genetically very closely related to T. parva, according to 18s rDNA sequence, has a conserved orthologue of the polymorphic immunodominant molecule (PIM) that forms the basis of the diagnostic ELISA used for T. parva serological detection. Closely related orthologues of several CD8 T cell target antigen genes are also shared with T. parva. By contrast, orthologues of the T. parva p104 and the p67 sporozoite surface antigens could not be amplified by PCR from T. sp. (buffalo), using conserved primers designed from the corresponding T. parva sequences. Collectively the data re-emphasise doubts regarding the value of rDNA sequence data alone for defining apicomplexan species in the absence of additional data. ‘Deep 454 pyrosequencing’ of DNA from two Theileria sporozoite stabilates prepared from Rhipicephalus appendiculatus ticks fed on buffalo failed to detect T. sp. (buffalo). This strongly suggests that R. appendiculatus may not be a vector for T. sp. (buffalo). Collectively, the data provides further evidence that T. sp. (buffalo). is a distinct species from T. parva. PMID:26543804

  8. A prospective study of common variants in the CX3CR1 gene and risk of macular degeneration: pooled analysis from five long-term studies

    PubMed Central

    Schaumberg, Debra A.; Rose, Lynda; DeAngelis, Margaret M.; Semba, Richard D.; Hageman, Gregory S.; Chasman, Daniel I.

    2014-01-01

    Context The CX3CR1 gene is implicated as a candidate gene for age-related macular degeneration (AMD) through several lines of evidence. There is uncertainty, however, as to whether common genetic variants in CX3CR1 alter risk of AMD, since prior studies have been inconsistent and mostly limited to evaluation of two non-synonymous variants, T280M (rs3732378) and V249I (rs3732379). Objective We aimed to determine if common variants in CX3CR1 predict future risk of AMD. Design Prospective nested case-control study within five large study populations with long-term follow-up. Participants We measured genotypes for T280M, V249I and 13 other common single-nucleotide polymorphisms (SNPs) of the CX3CR1 gene among people who developed AMD (N=1110, including N=369 with neovascular AMD) and 2532 age- and sex-matched controls. Main outcome measures We determined the incidence rate ratios (RR) and 95% confidence intervals (CI) for incidence of AMD for each variant, and examined interactions with other AMD-associated variants and modifiable risk factors. Results In additive genetic models, we identified non-significant associations with AMD for T280M (RR=0.87, P=0.074) and three other SNPs, rs2853707 (RR=0.88, P=0.069), rs12636547 (RR=0.85, P=0.098), and rs1877563 (RR=0.84, P=0.056), one of which, rs2853707, is positioned in the CX3CR1 promoter region and was associated with neovascular AMD (RR=0.75, P=0.028). We observed that a recessive model was a better fit to the data for some SNPs, with associations between rs11715522 and AMD (RR=1.27, P=0.034), and between rs2669845 (RR=3.10, P=0.035), rs2853707 (RR=0.48, P=0.050) and rs9868689 (RR=0.31, P=0.017) and neovascular AMD. Moreover, in exploratory analyses we identified a number of possible interactions including between V249I and rs2669845 and dietary intake of omega-3 fatty acids (P=0.004, and P=0.009, respectively) for AMD; between rs2669845 and obesity (P=0.031) for neovascular AMD; between T280M and complement component 3

  9. The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids

    SciTech Connect

    Kedda, M.A.; Stevens, G.; Manga, P.; Viljoen, C.; Jenkins, T.; Ramsay, M. Univ. of Witwatersrand, Johannesburg )

    1994-06-01

    Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid [open quotes]ty-pos OCA[close quotes] individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and [open quotes]normal[close quotes] chromosomes. No haplotype showed statistically significant association with ty-pos OCA, and thus none could be used to predict the origins of the ty-pos OCA mutations. On the basis of the D15S12 results, there is evidence for multiple ty-pos OCA mutations in southern African negroids. 31 refs., 1 fig., 3 tabs.

  10. Polymorphism of the human factor H-related gene (FHR-1) and of factor H in a West African individual

    SciTech Connect

    Meyer, C.G.; Skerka, C.; Zipfel, P.F.

    1995-03-01

    The human factor H-related 1 (FHR-1) protein is structurally and immunogenically related to the regulatory complement protein factor H (FH). Polymorphism of the FHR-1 gene is indicated by the nucleotide differences as described by the five cDNA clones isolated so far. In order to further analyze this polymorphism we identified PCR-primers which allow the simultaneous amplification of FHR-1 and FH alleles in a single polymerase chain reaction (PCR). By DNA sequence analysis, two novel FHR-1 variants and one as yet unrecognized FH allele could be characterized in an individual from Benin, West Africa. 2 refs., 1 fig.

  11. Allergic to Pool Water

    PubMed Central

    2012-01-01

    To identify the allergy problem of a 36-year old swimming instructor, who experiences heavy itching and rashes whenever she comes in contact with pool water. Patch tests were performed with European standard series and materials from the work floor. A positive patch test to aluminum chloride and flocculant was observed. Occupational dermatitis is, based on a contact allergy to aluminum chloride in the flocculant. PMID:22993713

  12. Large Multiethnic Candidate Gene Study for C-Reactive Protein Levels: Identification of a Novel Association at CD36 in African Americans

    PubMed Central

    Ellis, Jaclyn; Lange, Ethan M.; Li, Jin; Dupuis, Josee; Baumert, Jens; Walston, Jeremy D.; Keating, Brendan J.; Durda, Peter; Fox, Ervin R.; Palmer, Cameron D.; Meng, Yan A.; Young, Taylor; Farlow, Deborah N.; Schnabel, Renate B.; Marzi, Carola S.; Larkin, Emma; Martin, Lisa W.; Bis, Joshua C.; Auer, Paul; Ramachandran, Vasan S.; Gabriel, Stacey B.; Willis, Monte S.; Pankow, James S.; Papanicolaou, George J.; Rotter, Jerome I.; Ballantyne, Christie M.; Gross, Myron D.; Lettre, Guillaume; Wilson, James G.; Peters, Ulrike; Koenig, Wolfgang; Tracy, Russell P.; Redline, Susan; Reiner, Alex P.; Benjamin, Emelia J.; Lange, Leslie A.

    2014-01-01

    C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multi-ethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women’s Health Initiative (WHI) and KORA studies. We observed array-wide significance (p<2.2×10−6) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p=2.0×10−6; CRP, p=4.2×10−71; APOE, p=1.6×10−6). The fourth significant locus, CD36 (p=1.6×10−6), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding (p=1.8×10−5) in an independent sample of 8041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance (p=1.5×10−10). In the race-combined meta-analyses, 13 loci reached significance, including ten (CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one (ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected (RPS6KB1, p=2.0×10−6; CD36, p=1.4×10−6). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent. PMID:24643644

  13. Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.

    PubMed

    Ellis, Jaclyn; Lange, Ethan M; Li, Jin; Dupuis, Josee; Baumert, Jens; Walston, Jeremy D; Keating, Brendan J; Durda, Peter; Fox, Ervin R; Palmer, Cameron D; Meng, Yan A; Young, Taylor; Farlow, Deborah N; Schnabel, Renate B; Marzi, Carola S; Larkin, Emma; Martin, Lisa W; Bis, Joshua C; Auer, Paul; Ramachandran, Vasan S; Gabriel, Stacey B; Willis, Monte S; Pankow, James S; Papanicolaou, George J; Rotter, Jerome I; Ballantyne, Christie M; Gross, Myron D; Lettre, Guillaume; Wilson, James G; Peters, Ulrike; Koenig, Wolfgang; Tracy, Russell P; Redline, Susan; Reiner, Alex P; Benjamin, Emelia J; Lange, Leslie A

    2014-08-01

    C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multiethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7,570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women's Health Initiative (WHI) and KORA studies. We observed array-wide significance (p < 2.2 × 10(-6)) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p = 2.0 × 10(-6); CRP, p = 4.2 × 10(-71); APOE, p = 1.6 × 10(-6)). The fourth significant locus, CD36 (p = 1.6 × 10(-6)), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding (p = 1.8 × 10(-5)) in an independent sample of 8,041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance (p = 1.5 × 10(-10)). In the race-combined meta-analyses, 13 loci reached significance, including ten (CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one (ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected (RPS6KB1, p = 2.0 × 10(-6); CD36, p = 1.4 × 10(-6)). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent. PMID:24643644

  14. Swimming Pools and Molluscum Contagiosum

    MedlinePlus

    ... Travelers' Health: Smallpox & Other Orthopoxvirus-Associated Infections Poxvirus Swimming Pools Recommend on Facebook Tweet Share Compartir The ... often ask if molluscum virus can spread in swimming pools. There is also concern that it can ...

  15. Fructan synthesis, accumulation and polymer traits. II. Fructan pools in populations of perennial ryegrass (Lolium perenne L.) with variation for water-soluble carbohydrate and candidate genes were not correlated with biosynthetic activity and demonstrated constraints to polymer chain extension

    PubMed Central

    Gallagher, Joe A.; Cairns, Andrew J.; Thomas, David; Timms-Taravella, Emma; Skøt, Kirsten; Charlton, Adam; Williams, Peter; Turner, Lesley B.

    2015-01-01

    Differences have been shown between ryegrass and fescue within the Festulolium subline introgression family for fructan synthesis, metabolism, and polymer-size traits. It is well-established that there is considerable variation for water-soluble carbohydrate and fructan content within perennial ryegrass. However there is much still to be discovered about the fructan polymer pool in this species, especially in regard to its composition and regulation. It is postulated that similar considerable variation for polymer traits may exist, providing useful polymers for biorefining applications. Seasonal effects on fructan content together with fructan synthesis and polymer-size traits have been examined in diverse perennial ryegrass material comprising contrasting plants from a perennial ryegrass F2 mapping family and from populations produced by three rounds of phenotypic selection. Relationships with copy number variation in candidate genes have been investigated. There was little evidence of any variation in fructan metabolism across this diverse germplasm under these conditions that resulted in substantial differences in the complement of fructan polymers present in leaf tissue at high water-soluble carbohydrate concentrations. The importance of fructan synthesis during fructan accumulation was unclear as fructan content and polymer characteristics in intact plants during the growing season did not reflect the capacity for de novo synthesis. However, the retention of fructan in environmental conditions favoring high sink/low source demand may be an important component of the high sugar trait and the roles of breakdown and turnover are discussed. PMID:26528321

  16. A genome-wide study of preferential amplification/hybridization in microarray-based pooled DNA experiments

    PubMed Central

    Yang, H.-C.; Liang, Y.-J.; Huang, M.-C.; Li, L.-H.; Lin, C.-H.; Wu, J.-Y.; Chen, Y.-T.; Fann, C.S.J.

    2006-01-01

    Microarray-based pooled DNA methods overcome the cost bottleneck of simultaneously genotyping more than 100 000 markers for numerous study individuals. The success of such methods relies on the proper adjustment of preferential amplification/hybridization to ensure accurate and reliable allele frequency estimation. We performed a hybridization-based genome-wide single nucleotide polymorphisms (SNPs) genotyping analysis to dissect preferential amplification/hybridization. The majority of SNPs had less than 2-fold signal amplification or suppression, and the lognormal distributions adequately modeled preferential amplification/hybridization across the human genome. Comparative analyses suggested that the distributions of preferential amplification/hybridization differed among genotypes and the GC content. Patterns among different ethnic populations were similar; nevertheless, there were striking differences for a small proportion of SNPs, and a slight ethnic heterogeneity was observed. To fulfill appropriate and gratuitous adjustments, databases of preferential amplification/hybridization for African Americans, Caucasians and Asians were constructed based on the Affymetrix GeneChip Human Mapping 100 K Set. The robustness of allele frequency estimation using this database was validated by a pooled DNA experiment. This study provides a genome-wide investigation of preferential amplification/hybridization and suggests guidance for the reliable use of the database. Our results constitute an objective foundation for theoretical development of preferential amplification/hybridization and provide important information for future pooled DNA analyses. PMID:16931491

  17. African Aesthetics

    ERIC Educational Resources Information Center

    Abiodun, Rowland

    2001-01-01

    No single traditional discipline can adequately supply answers to the many unresolved questions in African art history. Because of the aesthetic, cultural, historical, and, not infrequently, political biases, already built into the conception and development of Western art history, the discipline of art history as defined and practiced in the West…

  18. Discovery of Point Mutations in the Voltage-Gated Sodium Channel from African Aedes aegypti Populations: Potential Phylogenetic Reasons for Gene Introgression

    PubMed Central

    Muranami, Yuto; Kawashima, Emiko; Osei, Joseph H. N.; Sakyi, Kojo Yirenkyi; Dadzie, Samuel; de Souza, Dziedzom K.; Appawu, Maxwell; Ohta, Nobuo; Minakawa, Noboru

    2016-01-01

    Background Yellow fever is endemic in some countries in Africa, and Aedes aegpyti is one of the most important vectors implicated in the outbreak. The mapping of the nation-wide distribution and the detection of insecticide resistance of vector mosquitoes will provide the beneficial information for forecasting of dengue and yellow fever outbreaks and effective control measures. Methodology/Principal Findings High resistance to DDT was observed in all mosquito colonies collected in Ghana. The resistance and the possible existence of resistance or tolerance to permethrin were suspected in some colonies. High frequencies of point mutations at the voltage-gated sodium channel (F1534C) and one heterozygote of the other mutation (V1016I) were detected, and this is the first detection on the African continent. The frequency of F1534C allele and the ratio of F1534C homozygotes in Ae. aegypti aegypti (Aaa) were significantly higher than those in Ae. aegypti formosus (Aaf). We could detect the two types of introns between exon 20 and 21, and the F1534C mutations were strongly linked with one type of intron, which was commonly found in South East Asian and South and Central American countries, suggesting the possibility that this mutation was introduced from other continents or convergently selected after the introgression of Aaa genes from the above area. Conclusions/Significance The worldwide eradication programs in 1940s and 1950s might have caused high selection pressure on the mosquito populations and expanded the distribution of insecticide-resistant Ae. aegypti populations. Selection of the F1534C point mutation could be hypothesized to have taken place during this period. The selection of the resistant population of Ae. aegypti with the point mutation of F1534C, and the worldwide transportation of vector mosquitoes in accordance with human activity such as trading of used tires, might result in the widespread distribution of F1534C point mutation in tropical countries

  19. Rapid speciation, morphological evolution, and adaptation to extreme environments in South African sand lizards (Meroles) as revealed by mitochondrial gene sequences.

    PubMed

    Harris, D J; Arnold, E N; Thomas, R H

    1998-08-01

    Data derived from the morphology of the seven species of South African sand lizards, Meroles (Reptilia, Lacertidae), and their outgroups produce a robust estimate of phylogeny when a maximum parsimony approach is applied. The estimate is fully resolved with little character conflict and internal branches are relatively long. This analysis indicates that Meroles is a true clade that includes the aberrant lacertid long separated as Aporosaura anchietae. The tree is pectinate, its successive external branches representing species with increasing adaptation to desert conditions, especially aeolian sand habitats. This pattern, and the robustness of the tree, support a model of invasion of severe habitats in which successive rounds of speciation, displacement, and adaptation result in spread into extreme ecological situations. To test the robust morphological phylogeny and, indirectly, the model as well, DNA from mitochondrial 12S and 16S ribosomal genes was sequenced and analyzed by both maximum parsimony and maximum likelihood approaches. Trees produced were largely congruent with that derived from morphology, although different from ones resulting from protein electrophoresis. However, in contrast to the internal branches of the morphological tree, those of the DNA maximum likelihood tree are quite short. The DNA data provide some corroboration for the relationships within Meroles based on morphology and consequently for the model as well. The disparity in internal branch lengths between the maximum parsimony morphological and maximum likelihood DNA trees may well indicate that the multiple adaptations to desert conditions arising on the main lineage of Meroles evolved quite rapidly. In this study DNA thus not only corroborates the phylogeny but also provides evidence about another aspect of evolutionary history. PMID:9751916

  20. Differential Gene Expression in the Brain of the African Lungfish, Protopterus annectens, after Six Days or Six Months of Aestivation in Air

    PubMed Central

    Hiong, Kum C.; Ip, Yuen K.; Wong, Wai P.; Chew, Shit F.

    2013-01-01

    The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the brain of P. annectens during the induction (6 days) and maintenance (6 months) phases of aestivation as compared with the freshwater control using suppression subtractive hybridization. During the induction phase of aestivation, the mRNA expression of prolactin (prl) and growth hormone were up-regulated in the brain of P. annectens, which indicate for the first time the possible induction role of these two hormones in aestivation. Also, the up-regulation of mRNA expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein γ polypeptide and the down-regulation of phosphatidylethanolamine binding protein, suggest that there could be a reduction in biological and neuronal activities in the brain. The mRNA expression of cold inducible RNA-binding protein and glucose regulated protein 58 were also up-regulated in the brain, probably to enhance their cytoprotective effects. Furthermore, the down-regulation of prothymosin α expression suggests that there could be a suppression of transcription and cell proliferation in preparation for the maintenance phase. In general, the induction phase appeared to be characterized by reduction in glycolytic capacity and metabolic activity, suppression of protein synthesis and degradation, and an increase in defense against ammonia toxicity. In contrast, there was a down-regulation in the mRNA expression of prl in the brain of P. annectens during the maintenance phase of aestivation. In addition, there could be an increase in oxidative defense capacity, and up-regulation of transcription, translation, and glycolytic capacities in preparation for arousal. Overall, our results signify the importance of reconstruction of protein structures and regulation of energy expenditure during

  1. Differential gene expression in the brain of the African lungfish, Protopterus annectens, after six days or six months of aestivation in air.

    PubMed

    Hiong, Kum C; Ip, Yuen K; Wong, Wai P; Chew, Shit F

    2013-01-01

    The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the brain of P. annectens during the induction (6 days) and maintenance (6 months) phases of aestivation as compared with the freshwater control using suppression subtractive hybridization. During the induction phase of aestivation, the mRNA expression of prolactin (prl) and growth hormone were up-regulated in the brain of P. annectens, which indicate for the first time the possible induction role of these two hormones in aestivation. Also, the up-regulation of mRNA expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein γ polypeptide and the down-regulation of phosphatidylethanolamine binding protein, suggest that there could be a reduction in biological and neuronal activities in the brain. The mRNA expression of cold inducible RNA-binding protein and glucose regulated protein 58 were also up-regulated in the brain, probably to enhance their cytoprotective effects. Furthermore, the down-regulation of prothymosin α expression suggests that there could be a suppression of transcription and cell proliferation in preparation for the maintenance phase. In general, the induction phase appeared to be characterized by reduction in glycolytic capacity and metabolic activity, suppression of protein synthesis and degradation, and an increase in defense against ammonia toxicity. In contrast, there was a down-regulation in the mRNA expression of prl in the brain of P. annectens during the maintenance phase of aestivation. In addition, there could be an increase in oxidative defense capacity, and up-regulation of transcription, translation, and glycolytic capacities in preparation for arousal. Overall, our results signify the importance of reconstruction of protein structures and regulation of energy expenditure during

  2. Plasticity of the Reproductive Axis Caused by Social Status Change in an African Cichlid Fish: II. Testicular Gene Expression and Spermatogenesis

    PubMed Central

    Maruska, Karen P.; Fernald, Russell D.

    2011-01-01

    Reproduction in all vertebrates is controlled by the brain-pituitary-gonad (BPG) axis, which is regulated socially in males of the African cichlid fish Astatotilapia burtoni. Although social information influences GnRH1 neurons at the apex of the BPG axis, little is known about how the social environment and dominance affects the cellular and molecular composition of the testes to regulate reproductive capacity. We created an opportunity for reproductively suppressed males to ascend in status and then measured changes in gene expression and tissue morphology to discover how quickly the perception of this opportunity can influence the testes. Our results show rapid up-regulation of mRNA levels of FSH receptor and several steroid receptor subtypes in the testes during social ascent. In contrast, LH receptor was not elevated until 72 h after ascent, but this increase was coincident with elevated circulating androgens and early stages of spermatogenesis, suggesting a role in steroidogenesis. The spermatogenic potential of the testes, as measured by cellular composition, was also elevated before the overall increase in testes size. The presence of cysts at all stages of spermatogenesis, coupled with lower levels of gonadotropin and steroid receptors in subordinate males, suggests that the BPG axis and spermatogenesis are maintained at a subthreshold level in anticipation of the chance to gain a territory and become reproductively active. Our results show that the testis is stimulated extremely quickly after perception of social opportunity, presumably to allow suppressed males to rapidly achieve high reproductive success in a dynamic social environment. PMID:21084443

  3. Origin and speciation of haplochromine fishes in East African crater lakes investigated by the analysis of their mtDNA, Mhc genes, and SINEs.

    PubMed

    Sato, Akie; Takezaki, Naoko; Tichy, Herbert; Figueroa, Felipe; Mayer, Werner E; Klein, Jan

    2003-09-01

    The Western Branch of the East African Great Rift Valley is pocketed with craters of extinct or dormant volcanoes. Many of the craters are filled with water, and the lakes are inhabited by fishes. The objective of the present study was to determine the amount and nature of genetic variation in haplochromine fishes inhabiting two of these crater lakes, Lake Lutoto and Lake Nshere, and to use this information to infer the origin and history of the two populations. To this end, sequences of mitochondrial (mt) DNA control region, exon 2 of major histocompatibility complex (Mhc) class II B genes, and short interspersed elements (SINEs) were analyzed. The results indicate that the Lake Nshere and Lake Lutoto fishes originated from different but related large founding populations derived from the Kazinga Channel, which connects Lake Edward and Lake George. Some of the genetic polymorphism that existed in the ancestral populations was lost in the populations of the two lakes. The polymorphism that has been retained has persisted for some 50000 generations (years). During this time, new mutations arose and became fixed in each of the two populations in the mtDNA, giving rise to sets of diagnostic substitutions. Each population evolved in isolation after the colonization of the lakes less than 50000 years ago. There appears to be no population structure within the crater lake fishes, and their present effective population sizes are in the order of 104 to 105 individuals. Comparisons with the endemic haplochromine species of Lake Victoria reveal interesting parallels, as well as differences, which may help to understand the nature of the speciation process. PMID:12777512

  4. Secondary pool boiling effects

    NASA Astrophysics Data System (ADS)

    Kruse, C.; Tsubaki, A.; Zuhlke, C.; Anderson, T.; Alexander, D.; Gogos, G.; Ndao, S.

    2016-02-01

    A pool boiling phenomenon referred to as secondary boiling effects is discussed. Based on the experimental trends, a mechanism is proposed that identifies the parameters that lead to this phenomenon. Secondary boiling effects refer to a distinct decrease in the wall superheat temperature near the critical heat flux due to a significant increase in the heat transfer coefficient. Recent pool boiling heat transfer experiments using femtosecond laser processed Inconel, stainless steel, and copper multiscale surfaces consistently displayed secondary boiling effects, which were found to be a result of both temperature drop along the microstructures and nucleation characteristic length scales. The temperature drop is a function of microstructure height and thermal conductivity. An increased microstructure height and a decreased thermal conductivity result in a significant temperature drop along the microstructures. This temperature drop becomes more pronounced at higher heat fluxes and along with the right nucleation characteristic length scales results in a change of the boiling dynamics. Nucleation spreads from the bottom of the microstructure valleys to the top of the microstructures, resulting in a decreased surface superheat with an increasing heat flux. This decrease in the wall superheat at higher heat fluxes is reflected by a "hook back" of the traditional boiling curve and is thus referred to as secondary boiling effects. In addition, a boiling hysteresis during increasing and decreasing heat flux develops due to the secondary boiling effects. This hysteresis further validates the existence of secondary boiling effects.

  5. Vital fuelwood gene pool is in danger

    SciTech Connect

    Palmberg, C.; Pasca, T.M.

    1981-01-01

    A brief description is given an FAO/IBPGR (International Board for Plant Genetic Resources) project for the conservation and better utilization of genetic resources of arboreal species for the improvement of rural living; special emphasis is given to fuelwood species in dry areas.

  6. SCREENING CORIANDER GENE POOL FOR SPECIAL USES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coriander (Coriandrum sativum L.) is a member of the Apiaceae family with a wide diversity of uses. Its rapid life cycle allows it to fit into different growing seasons, making it possible to grow the crop under a wide range of conditions. Three subspecies and ten botanical varieties have been pro...

  7. Chromonoodles: Jump into the Gene Pool

    ERIC Educational Resources Information Center

    Farrar, Jennifer; Barnhart, Kelsi

    2011-01-01

    Chromosomes, alleles, chromatids, genotype, phenotype, mitosis, meiosis, fertilization--this vocabulary can be overwhelming, confusing, and difficult for students to tie together. However, since these terms are commonplace in the high school biology classroom, and are the basis for understanding both DNA and heredity, students must understand…

  8. The effects of genes implicated in cardiovascular disease on blood-pressure response to treatment among treatment-naïve hypertensive African Americans in the GenHAT study

    PubMed Central

    Do, Anh N; Lynch, Amy I; Claas, Steven A; Boerwinkle, Eric; Davis, Barry R; Ford, Charles E; Eckfeldt, John H; Tiwari, Hemant K; Arnett, Donna K; Irvin, Marguerite R

    2015-01-01

    African Americans have the highest prevalence of hypertension in the United States. Blood-pressure control is important to reduce cardiovascular disease (CVD)-related morbidity and mortality in this ethnic group. Genetic variants have been found to be associated with BP response to treatment. Previous pharmacogenetic studies of blood-pressure response to treatment in African Americans suffer limitations of small sample size as well as a limited number of candidate genes, and often focused on one antihypertensive treatment. Using 1,131 African-American treatment naïve participants from the Genetics of Hypertension Associated Treatment (GenHAT) Study, we examined whether variants in 35 candidate genes might modulate blood-pressure response to four different antihypertensive medications, including an angiotensin converting enzyme (ACE) inhibitor (lisinopril), a calcium channel blocker (amlodipine), and an α-adrenergic blocker (doxazosin) as compared to a thiazide diuretic (chlorthalidone) after 6 months of follow-up. Several suggestive gene by treatment interactions were identified. For example, among participants with two minor alleles of REN rs6681776, diastolic blood-pressure response was much improved on doxazosin compared to chlorthalidone (on average −9.49 mmHg vs. −1.70 mmHg) (P=0.007). Although several suggestive loci were identified, none of the findings passed significance criteria after correction for multiple testing. Given the impact of hypertension and its sequelae in this population, this research highlights the potential for genetic factors to contribute to blood-pressure response to treatment. Continued concerted research efforts focused on genetics are needed to improve treatment response in this high risk group. PMID:26791477

  9. Structural analysis of the 5 prime flanking region of the. beta. -globin gene in African sickle cell anemia patients: Further evidence for three origins of the sickle cell mutation in Africa

    SciTech Connect

    Chebloune, Y.; Pagnier, J.; Trabuchet, G.; Faure, C.; Verdier, G.; Labie, D.; Nigon, V. )

    1988-06-01

    Haplotype analysis of the {beta}-globin gene cluster shows two regions of DNA characterized by nonrandom association of restriction site polymorphisms. These regions are separated by a variable segment containing the repeated sequences (ATTTT){sub n} and (AT){sub x}T{sub y}, which might be involved in recombinational events. Studies of haplotypes linked to the sickle cell gene in Africa provide strong argument for three origins of the mutation: Benin, Senegal, and the Central African Republic. The structure of the variable segment in the three African populations was studied by S1 nuclease mapping of genomic DNA, which allows a comparison of several samples. A 1080-base-pair DNA segment was sequenced for one sample from each population. S1 nuclease mapping confirmed the homogeneity of each population with regard to both (ATTTT){sub n} and (AT){sub x}T{sub y} repeats. The authors found three additional structures for (AT){sub x}T{sub y} correlating with the geographic origin of the patients. Ten other nucleotide positions, 5{prime} and 3{prime} to the (AT){sub x}T{sub y} copies, were found to be variable when compared to homologous sequences from human and monkey DNAs. These results allow us to propose an evolutionary scheme for the polymorphisms in the 5{prime} flanking region of the {beta}-globin gene. The results strongly support the hypothesis of three origins for the sickle mutation in Africa.

  10. Absence of GJB2 gene mutations, the GJB6 deletion (GJB6-D13S1830) and four common mitochondrial mutations in nonsyndromic genetic hearing loss in a South African population

    PubMed Central

    Kabahuma, Rosemary I.; Ouyang, Xiaomei; Du, Li Lin; Yan, Denise; Hutchin, Tim; Ramsay, Michele; Penn, Claire; Liu, Xue-Zhong

    2015-01-01

    Objective The purpose of this study was to determine the prevalence of mutations in the GJB2 gene, the GJB6-D13S1830 deletion and the four common mitochondrial mutations (A1555G, A3243G, A7511C and A7445G) in a South African population. Methods Using single-strand conformation polymorphism and direct sequencing for screening GJB2 mutation; Multiplex PCR Amplification for GJB6-D13S1830 deletion and Restriction Fragment-Length Polymorphism (PCR-RFLP) analysis for the four common mtDNA mutations. We screened 182 hearing impaired students to determine the frequency of these mutations in the population. Results None of the reported disease causing mutations in GJB2 nor any novel pathogenic mutations in the coding region were detected, in contrast to the findings among Caucasians. The GJB6-D13S1830 deletion and the mitochondrial mutations were not observed in this group. Conclusion These results suggest that GJB2 may not be a significant deafness gene among sub-Saharan Africans, pointing to other unidentified genes as responsible for nonsyndromic hearing loss in these populations. PMID:21392827

  11. Examining the African American K-12 Public Superintendency from a Critical Race Theory Perspective: Counter-Stories about Hiring and Retention Practices

    ERIC Educational Resources Information Center

    Chalmers, Anthony Gene

    2012-01-01

    For the last decade, research has shown concern about the pool of African American candidates for the superintendency. Nationally, African American candidates make up two percent of superintendents and fourteen percent of the teaching force, the pool from which superintendents are traditionally chosen. Increasing demands to meet the needs of…

  12. Obesity and African Americans

    MedlinePlus

    ... Data > Minority Population Profiles > Black/African American > Obesity Obesity and African Americans African American women have the ... ss6304.pdf [PDF | 3.38MB] HEALTH IMPACT OF OBESITY More than 80 percent of people with type ...

  13. Ulk4 Regulates Neural Stem Cell Pool.

    PubMed

    Liu, Min; Guan, Zhenlong; Shen, Qin; Flinter, Frances; Domínguez, Laura; Ahn, Joo Wook; Collier, David A; O'Brien, Timothy; Shen, Sanbing

    2016-09-01

    The size of neural stem cell (NSC) pool at birth determines the starting point of adult neurogenesis. Aberrant neurogenesis is associated with major mental illness, in which ULK4 is proposed as a rare risk factor. Little is known about factors regulating the NSC pool, or function of the ULK4. Here, we showed that Ulk4(tm1a/tm1a) mice displayed a dramatically reduced NSC pool at birth. Ulk4 was expressed in a cell cycle-dependent manner and peaked in G2/M phases. Targeted disruption of the Ulk4 perturbed mid-neurogenesis and significantly reduced cerebral cortex in postnatal mice. Pathway analyses of dysregulated genes in Ulk4(tm1a/tm1a) mice revealed Ulk4 as a key regulator of cell cycle and NSC proliferation, partially through regulation of the Wnt signaling. In addition, we identified hemizygous deletion of ULK4 gene in 1.2/1,000 patients with pleiotropic symptoms including severe language delay and learning difficulties. ULK4, therefore, may significantly contribute to neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Stem Cells 2016;34:2318-2331. PMID:27300315

  14. Solar heater for swimming pools

    SciTech Connect

    Babcock, H.W.

    1984-12-04

    A solar heater for swimming pools is provided having one or more heating panels installable on a roof or the like and arranged to discharge into a pool equipped with an apron without need for disturbing or obstructing the apron. This is accomplished by the provision of an elevated bistable dumper adjacent the perimeter of the apron having a dispensing spout normally inclined upwardly but pivoting at intervals to discharge into the pool across the apron without obstructing it. Water to be heated is diverted from the pool filtering system to the solar heater via a pressure regulator and a solar responsive flow control.

  15. Synaptic vesicle pools: an update.

    PubMed

    Denker, Annette; Rizzoli, Silvio O

    2010-01-01

    During the last few decades synaptic vesicles have been assigned to a variety of functional and morphological classes or "pools". We have argued in the past (Rizzoli and Betz, 2005) that synaptic activity in several preparations is accounted for by the function of three vesicle pools: the readily releasable pool (docked at active zones and ready to go upon stimulation), the recycling pool (scattered throughout the nerve terminals and recycling upon moderate stimulation), and finally the reserve pool (occupying most of the vesicle clusters and only recycling upon strong stimulation). We discuss here the advancements in the vesicle pool field which took place in the ensuing years, focusing on the behavior of different pools under both strong stimulation and physiological activity. Several new findings have enhanced the three-pool model, with, for example, the disparity between recycling and reserve vesicles being underlined by the observation that the former are mobile, while the latter are "fixed". Finally, a number of altogether new concepts have also evolved such as the current controversy on the identity of the spontaneously recycling vesicle pool. PMID:21423521

  16. Gene May Explain Higher Rates of Some Cancers in Black People

    MedlinePlus

    ... News on: African American Health Cancer Genes and Gene Therapy Recent Health News Related MedlinePlus Health Topics African American Health Cancer Genes and Gene Therapy About MedlinePlus Site Map FAQs Contact Us Get ...

  17. Tidal Pools--Miniature Oceans

    ERIC Educational Resources Information Center

    Plake, Linda Perry

    1977-01-01

    A comprehensive discussion of the biological activity in tidal pools is provided. The importance of environmental factors such as oxygen supply, temperature, salinity, and light is detailed. Plants and animals that might be found in a tidal pool are identified and described. (BT)

  18. Synaptic Vesicle Pools: An Update

    PubMed Central

    Denker, Annette; Rizzoli, Silvio O.

    2010-01-01

    During the last few decades synaptic vesicles have been assigned to a variety of functional and morphological classes or “pools”. We have argued in the past (Rizzoli and Betz, 2005) that synaptic activity in several preparations is accounted for by the function of three vesicle pools: the readily releasable pool (docked at active zones and ready to go upon stimulation), the recycling pool (scattered throughout the nerve terminals and recycling upon moderate stimulation), and finally the reserve pool (occupying most of the vesicle clusters and only recycling upon strong stimulation). We discuss here the advancements in the vesicle pool field which took place in the ensuing years, focusing on the behavior of different pools under both strong stimulation and physiological activity. Several new findings have enhanced the three-pool model, with, for example, the disparity between recycling and reserve vesicles being underlined by the observation that the former are mobile, while the latter are “fixed”. Finally, a number of altogether new concepts have also evolved such as the current controversy on the identity of the spontaneously recycling vesicle pool. PMID:21423521

  19. The Genetic Diversity of the Nguni Breed of African Cattle (Bos spp.): Complete Mitochondrial Genomes of Haplogroup T1

    PubMed Central

    Horsburgh, K. Ann; Prost, Stefan; Gosling, Anna; Stanton, Jo-Ann; Rand, Christy; Matisoo-Smith, Elizabeth A.

    2013-01-01

    Domesticated cattle were commonplace in northern Africa by about 7,000 years ago. Archaeological evidence, however, suggests they were not established in southern Africa until much later, no earlier than 2,000 years ago. Genetic reconstructions have started to shed light on the movement of African cattle, but efforts have been frustrated by a lack of data south of Ethiopia and the nature of the mitochondrial haplogroup T1 which is almost fixed across the continent. We sequenced 35 complete mitochondrial genomes from a South African herd of Nguni cattle, a breed historically associated with Bantu speaking farmers who were among the first to bring cattle to southern Africa. As expected, all individuals in the study were found to be members of haplogroup T1. Only half of the sub-haplogroups of T1 (T1a-T1f) are represented in our sample and the overwhelming majority (94%) in this study belong to subhaplogroup T1b. A previous study of African cattle found frequencies of T1b of 27% in Egypt and 69% in Ethiopia. These results are consistent with serial multiple founder effects significantly shaping the gene pool as cattle were moved from north to south across the continent. Interestingly, these mitochondrial data give no indication that the impacts of the founder effects were ameliorated by gene flow from recently introduced Indian cattle breeds. PMID:23977187

  20. Africans in America.

    ERIC Educational Resources Information Center

    Hart, Ayanna; Spangler, Earl

    This book introduces African-American history and culture to children. The first Africans in America came from many different regions and cultures, but became united in this country by being black, African, and slaves. Once in America, Africans began a long struggle for freedom which still continues. Slavery, the Civil War, emancipation, and the…

  1. African Outreach Workshop 1974.

    ERIC Educational Resources Information Center

    Schmidt, Nancy J.

    This report discusses the 1974 African Outreach Workshop planned and coordinated by the African Studies Program at the University of Illinois at Urbana-Champaign. Its major aim was to assist teachers in developing curriculum units on African using materials available in their local community. A second aim was for the African Studies Program to…

  2. Association of primary open-angle glaucoma with mitochondrial variants and haplogroups common in African Americans

    PubMed Central

    Gudiseva, Harini V.; Trachtman, Benjamin; Bowman, Anita S.; Sagaser, Anna; Sankar, Prithvi; Miller-Ellis, Eydie; Lehman, Amanda; Addis, Victoria; O'Brien, Joan M.

    2016-01-01

    Purpose To estimate the population frequencies of all common mitochondrial variants and ancestral haplogroups among 1,999 subjects recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study, including 1,217 primary open-angle glaucoma (POAG) cases and 782 controls, and to identify ancestral subpopulations and mitochondrial mutations as potential risk factors for POAG susceptibility. Methods Subject classification by characteristic glaucomatous optic nerve findings and corresponding visual field defects, as defined by enrolling glaucoma specialists, stereo disc photography, phlebotomy, extraction of total DNA from peripheral blood or saliva, DNA quantification and normalization, PCR amplification of whole mitochondrial genomes, Ion Torrent deep semiconductor DNA sequencing on DNA pools (“Pool-seq”), Sanger sequencing of 3,479 individual mitochondrial DNAs, and bioinformatic analysis. Results The distribution of common African haplogroups within the POAAGG study population was broadly similar to prior surveys of African Americans. However, the POAG case population was found to be enriched in L1c2 haplogroups, which are defined in part by missense mutations m.6150G>A (Val83Ile, odds ratio [OR] 1.8, p=0.01), m.6253C>T (Met117Thr, rs200165736, OR 1.6, p=0.04), and m.6480G>A (Val193Ile, rs199476128, OR 4.6, p=0.04) in the cytochrome c oxidase subunit 1 (MT-CO1) gene and by a variant, m.2220A>G (OR 2.0, p=0.01), in MT-RNR2, which encodes the mitochondrial ribosomal 16s RNA gene. L2 haplogroups were predicted to be overrepresented in the POAG case population by Pool-seq, and the difference was confirmed to be significant with Sanger sequencing, that targeted the L2-associated variants m.2416T>C (rs28358580, OR 1.2, p=0.02) and m.2332C>T (OR 1.2, p=.02) in MT-RNR2. Another variant within MT-RNR2, m.3010G>A (rs3928306), previously implicated in sensitivity to the optic neuropathy-associated antibiotic linezolid, and arising on D4 and J1

  3. 13 CFR 120.1704 - Pool Loans eligible for Pooling.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., construction or renovation of an aquarium, zoo, golf course, or swimming pool; or (iv) To a business covered by... (“Other Gambling Industries”); golf courses—713910 (“Golf Courses and Country Clubs”); or aquariums...

  4. 13 CFR 120.1704 - Pool Loans eligible for Pooling.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., construction or renovation of an aquarium, zoo, golf course, or swimming pool; or (iv) To a business covered by... (“Other Gambling Industries”); golf courses—713910 (“Golf Courses and Country Clubs”); or aquariums...

  5. 13 CFR 120.1704 - Pool Loans eligible for Pooling.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., construction or renovation of an aquarium, zoo, golf course, or swimming pool; or (iv) To a business covered by... (“Other Gambling Industries”); golf courses—713910 (“Golf Courses and Country Clubs”); or aquariums...

  6. 13 CFR 120.1704 - Pool Loans eligible for Pooling.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., construction or renovation of an aquarium, zoo, golf course, or swimming pool; or (iv) To a business covered by... (“Other Gambling Industries”); golf courses—713910 (“Golf Courses and Country Clubs”); or aquariums...

  7. 13 CFR 120.1704 - Pool Loans eligible for Pooling.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., construction or renovation of an aquarium, zoo, golf course, or swimming pool; or (iv) To a business covered by... (“Other Gambling Industries”); golf courses—713910 (“Golf Courses and Country Clubs”); or aquariums...

  8. Pooling techniques for bioassay screening

    SciTech Connect

    Sun, L.C.; Baum, J.W.; Kaplan, E; Moorthy, A.R.

    1996-03-01

    Pooling techniques commonly are used to increase the throughput of samples used for screening purposes. While the advantages of such techniques are increased analytical efficiency and cost savings, the sensitivity of measurements decreases because it is inversely proportional to the number of samples in the pools. Consequently, uncertainties in estimates of dose and risk which are based on the results of pooled samples increase as the number of samples in the pools increases in all applications. However, sensitivities may not be seriously degraded, for example, in urinalysis, if the samples in the pools are of known time duration, or if the fraction of some attribute of the grab urine samples to that in a 24-hour composite is known (e.g., mass, specific gravity, creatinine, or volume, per 24-h interval). This paper presents square and cube pooling schemes that greatly increase throughput and can considerably reduce analytical costs (on a sample basis). The benefit-cost ratios for 5{times}5 square and 5{times}5{times}5 cube pooling schemes are 2.5 and 8.3, respectively. Three-dimensional and higher arrayed pooling schemes would result in even greater economies; however, significant improvements in analytical sensitivity are required to achieve these advantages. These are various other considerations for designing a pooling scheme, where the number of dimensions and of samples in the optimum array are influenced by: (1) the minimal detectable amount (MDA) of the analytical processes, (2) the screening dose-rate requirements, (3) the maximum masses or volumes of the composite samples that can be analyzed, (4) the information already available from results of composite analysis, and (5) the ability of an analytical system to guard against both false negative and false positive results. Many of these are beyond the scope of this paper but are being evaluated.

  9. Cellular ubiquitin pool dynamics and homeostasis

    PubMed Central

    Ryu, Kwon-Yul

    2014-01-01

    Ubiquitin (Ub) is a versatile signaling molecule that plays important roles in a variety of cellular processes. Cellular Ub pools, which are composed of free Ub and Ub conjugates, are in dynamic equilibrium inside cells. In particular, increasing evidence suggests that Ub homeostasis, or the maintenance of free Ub above certain threshold levels, is important for cellular function and survival under normal or stress conditions. Accurate determination of various Ub species, including levels of free Ub and specific Ub chain linkages, have become possible in biological specimens as a result of the introduction of the proteomic approach using mass spectrometry. This technology has facilitated research on dynamic properties of cellular Ub pools and has provided tools for in-depth investigation of Ub homeostasis. In this review, we have also discussed the consequences of the disruption of Ub pool dynamics and homeostasis via deletion of polyubiquitin genes or mutations of deubiquitinating enzymes. The common consequence was a reduced availability of free Ub and a significant impact on the function and viability of cells. These observations further indicate that the levels of free Ub are important determinants for cellular protection. [BMB Reports 2014; 47(9): 475-482] PMID:24924398

  10. Significant interactions between maternal PAH exposure and haplotypes in candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking African-American and Dominican mothers and newborns

    PubMed Central

    Tang, Deliang

    2014-01-01

    Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single-nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African-American (n = 132) and Dominican (n = 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in gene–environment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P. PMID:24177223

  11. Challenges to recruitment and retention of African Americans in the gene-environment trial of response to dietary interventions (GET READI) for heart health

    PubMed Central

    Kennedy, Betty M.; Harsha, David W.; Bookman, Ebony B.; Hill, Yolanda R.; Rankinen, Tuomo; Rodarte, Ruben Q.; Murla, Connie D.

    2011-01-01

    In this paper, challenges to recruiting African Americans specifically for a dietary feeding trial are examined, learning experiences gained and suggestions to overcome these challenges in future trials are discussed. A total of 333 individuals were randomized in the trial and 234 (167 sibling pairs and 67 parents/siblings) completed the dietary intervention and required DNA blood sampling for genetic analysis. The trial used multiple strategies for recruitment. Hand distributed letters and flyers through mass distribution at various churches resulted in the largest number (n = 153, 46%) of African Americans in the trial. Word of mouth accounted for the second largest number (n = 120, 36%) and included prior study participants. These two recruitment sources represented 82% (n = 273) of the total number of individuals randomized in GET READI. The remaining 18% (n = 60) consisted of a combination of sources including printed message on check stubs, newspaper articles, radio and TV appearances, screening events and presentations. Though challenging, the recruitment efforts for GET READI produced a significant number of African American participants despite the inability to complete the trial as planned because of low recruitment yields. Nevertheless, the recruitment process produced substantial numbers that successfully completed all study requirements. PMID:21865154

  12. Patent pools and diagnostic testing.

    PubMed

    Verbeure, Birgit; van Zimmeren, Esther; Matthijs, Gert; Van Overwalle, Geertrui

    2006-03-01

    There is increasing concern that overlapping patents in the field of genetics will create a costly and legally complex situation known as a patent thicket, which, along with the associated issues of accumulating royalty payments, can act as a disincentive for innovation. One potential means of preventing this is for the patent holders to enter into a so-called patent pool, such as those established in the electronics and telecommunications industries. Precedents for these also exist in the field of genetics, notably with the patents pertaining to the SARS genome. In this review, we initially address the patent pool concept in general and its application in genetics. Following this, we will explore patent pools in the diagnostic field in more detail, and examine some existing and novel examples of patent pools in genetics. PMID:16443296

  13. Ethiopian Mitochondrial DNA Heritage: Tracking Gene Flow Across and Around the Gate of Tears

    PubMed Central

    Kivisild, Toomas; Reidla, Maere; Metspalu, Ene; Rosa, Alexandra; Brehm, Antonio; Pennarun, Erwan; Parik, Jüri; Geberhiwot, Tarekegn; Usanga, Esien; Villems, Richard

    2004-01-01

    Approximately 10 miles separate the Horn of Africa from the Arabian Peninsula at Bab-el-Mandeb (the Gate of Tears). Both historic and archaeological evidence indicate tight cultural connections, over millennia, between these two regions. High-resolution phylogenetic analysis of 270 Ethiopian and 115 Yemeni mitochondrial DNAs was performed in a worldwide context, to explore gene flow across the Red and Arabian Seas. Nine distinct subclades, including three newly defined ones, were found to characterize entirely the variation of Ethiopian and Yemeni L3 lineages. Both Ethiopians and Yemenis contain an almost-equal proportion of Eurasian-specific M and N and African-specific lineages and therefore cluster together in a multidimensional scaling plot between Near Eastern and sub-Saharan African populations. Phylogeographic identification of potential founder haplotypes revealed that approximately one-half of haplogroup L0–L5 lineages in Yemenis have close or matching counterparts in southeastern Africans, compared with a minor share in Ethiopians. Newly defined clade L6, the most frequent haplogroup in Yemenis, showed no close matches among 3,000 African samples. These results highlight the complexity of Ethiopian and Yemeni genetic heritage and are consistent with the introduction of maternal lineages into the South Arabian gene pool from different source populations of East Africa. A high proportion of Ethiopian lineages, significantly more abundant in the northeast of that country, trace their western Eurasian origin in haplogroup N through assorted gene flow at different times and involving different source populations. PMID:15457403

  14. Pool impacts of Leidenfrost drop

    NASA Astrophysics Data System (ADS)

    Darbois Texier, Baptiste; Maquet, Laurent; Dorbolo, Stephane; Dehandschoewercker, Eline; Pan, Zhao; Truscott, Tadd

    2015-11-01

    This work concerns the impact of a droplet made of a volatile liquid (typically HFE) on a pool of an other liquid (typically silicone oil) which temperature is above the boiling point of the drop. Depending on the properties of the two liquids and the impacting conditions, four different regimes are observed. For low impacting speeds, the droplet bounces on the surface of the bath and finally levitates above it in a Leidenfrost state. Such a regime occurs as soon as the pool temperature exceeds the boiling point of the drop. This observation means that there is no threshold in temperature for a Leidenfrost effect on a liquid surface contrary to the case of a solid substrate. For intermediate impacting velocities, the pinch-off of the surface of the pool entraps the drop in the liquid bulk. The entrapped drop is separated from the pool by a layer of its own vapour in a similar way of antibulles. For increasing impacting speeds, the vapour layer between the drop and the pool does not hold during the pinch-off event. The contact of the drop with the hot liquid provokes a sudden and intense evaporation. At very large impacting speeds, the drop rapidely contacts the pool, spreads and finally induces a hemi-spherical cavity. In the end, these four different regimes are summarized in a Froud-Weber diagram which boundaries are discussed.

  15. Genetic structure of pastoral and farmer populations in the African Sahel.

    PubMed

    Černý, Viktor; Pereira, Luísa; Musilová, Eliška; Kujanová, Martina; Vašíková, Alžběta; Blasi, Paola; Garofalo, Luisa; Soares, Pedro; Diallo, Issa; Brdička, Radim; Novelletto, Andrea

    2011-09-01

    Traditional pastoralists survive in few places in the world. They can still be encountered in the African Sahel, where annual alternations of dry and wet seasons force them to continual mobility. Little is known about the genetic structure of these populations. We present here the population distribution of 312 hypervariable segment I mitochondrial DNA (mtDNA) and 364 Y-short tandem repeat haplotypes in both farmer and pastoralist groups from the Lake Chad Basin and the West African Sahel. We show that the majority of pastoral populations (represented in the African Sahel by the Fulani nomads) fail to show significant departure from neutrality for mtDNA as evidenced by Fu's Fs statistics and exhibit lower levels of intrapopulation diversity measures for mtDNA when contrasted with farmers. These differences were not observed for the Y chromosome. Furthermore, analyses of molecular variance and population distributions of the mtDNA haplotypes show more heterogeneity in the sedentary groups than in the pastoralists. On the other hand, pastoralists retain a signature of a wide phylogenetic distance contributing to their male gene pool, whereas in at least some of the farmer populations, a founder effect and/or drift might have led to the presence of a single major lineage. Interestingly, these observations are in contrast with those recorded in Central Asia, where similar comparisons of farmer and pastoral groups have recently been carried out. We can conclude that in Africa, there have been no substantial mating exchanges between the Fulani pastoralists coming to the Lake Chad Basin from the West African Sahel and their farmer neighbors. At the same time, we suggest that the emergence of pastoralism might be an earlier and/or a demographically more important event than the introduction of sedentary agriculture, at least in this part of Africa. PMID:21436121

  16. Introducing the Algerian Mitochondrial DNA and Y-Chromosome Profiles into the North African Landscape

    PubMed Central

    Bekada, Asmahan; Fregel, Rosa; Cabrera, Vicente M.; Larruga, José M.; Pestano, José; Benhamamouch, Soraya; González, Ana M.

    2013-01-01

    North Africa is considered a distinct geographic and ethnic entity within Africa. Although modern humans originated in this Continent, studies of mitochondrial DNA (mtDNA) and Y-chromosome genealogical markers provide evidence that the North African gene pool has been shaped by the back-migration of several Eurasian lineages in Paleolithic and Neolithic times. More recent influences from sub-Saharan Africa and Mediterranean Europe are also evident. The presence of East-West and North-South haplogroup frequency gradients strongly reinforces the genetic complexity of this region. However, this genetic scenario is beset with a notable gap, which is the lack of consistent information for Algeria, the largest country in the Maghreb. To fill this gap, we analyzed a sample of 240 unrelated subjects from a northwest Algeria cosmopolitan population using mtDNA sequences and Y-chromosome biallelic polymorphisms, focusing on the fine dissection of haplogroups E and R, which are the most prevalent in North Africa and Europe respectively. The Eurasian component in Algeria reached 80% for mtDNA and 90% for Y-chromosome. However, within them, the North African genetic component for mtDNA (U6 and M1; 20%) is significantly smaller than the paternal (E-M81 and E-V65; 70%). The unexpected presence of the European-derived Y-chromosome lineages R-M412, R-S116, R-U152 and R-M529 in Algeria and the rest of the Maghreb could be the counterparts of the mtDNA H1, H3 and V subgroups, pointing to direct maritime contacts between the European and North African sides of the western Mediterranean. Female influx of sub-Saharan Africans into Algeria (20%) is also significantly greater than the male (10%). In spite of these sexual asymmetries, the Algerian uniparental profiles faithfully correlate between each other and with the geography. PMID:23431392

  17. A Polymorphism in the Regulatory Region of the CC-Chemokine Receptor 5 Gene Influences Perinatal Transmission of Human Immunodeficiency Virus Type 1 to African-American Infants

    PubMed Central

    Kostrikis, Leondios G.; Neumann, Avidan U.; Thomson, Bruce; Korber, Bette T.; McHardy, Paul; Karanicolas, Rose; Deutsch, Lisa; Huang, Yaoxing; Lew, Judy F.; McIntosh, Kenneth; Pollack, Henry; Borkowsky, William; Spiegel, Hans M. L.; Palumbo, Paul; Oleske, James; Bardeguez, Arlene; Luzuriaga, Katherine; Sullivan, John; Wolinsky, Steven M.; Koup, Richard A.; Ho, David D.; Moore, John P.

    1999-01-01

    There are natural mutations in the coding and noncoding regions of the human immunodeficiency virus type 1 (HIV-1) CC-chemokine coreceptor 5 (CCR5) and in the related CCR2 protein (the CCR2-64I mutation). Individuals homozygous for the CCR5-Δ32 allele, which prevents CCR5 expression, strongly resist HIV-1 infection. Several genetic polymorphisms have been identified within the CCR5 5′ regulatory region, some of which influence the rate of disease progression in adult AIDS study cohorts. We genotyped 1,442 infants (1,235 uninfected and 207 HIV-1 infected) for five CCR5 and CCR2 polymorphisms: CCR5-59353-T/C, CCR5-59356-C/T CCR5-59402-A/G, CCR5-Δ32, and CCR2-64I. The clinical significance of each genotype was assessed by measuring whether it influenced the rate of perinatal HIV-1 transmission among 667 AZT-untreated mother-infant pairs (554 uninfected and 113 HIV-1 infected). We found that the mutant CCR5-59356-T allele is relatively common in African-Americans (20.6% allele frequency among 552 infants) and rare in Caucasians and Hispanics (3.4 and 5.6% of 174 and 458 infants, respectively; P < 0.001). There were 38 infants homozygous for CCR5-59356-T, of whom 35 were African-Americans. Among the African-American infants in the AZT-untreated group, there was a highly significant increase in HIV-1 transmission to infants with two mutant CCR5-59356-T alleles (47.6% of 21), compared to those with no or one mutant allele (13.4 to 14.1% of 187 and 71, respectively; P < 0.001). The increased relative risk was 5.9 (95% confidence interval, 2.3 to 15.3; P < 0.001). The frequency of the CCR5-59356-T mutation varies between population groups in the United States, a low frequency occurring in Caucasians and a higher frequency occurring in African-Americans. Homozygosity for CCR5-59356-T is strongly associated with an increased rate of perinatal HIV-1 transmission. PMID:10559343

  18. Development of a suspension microarray for the genotyping of African swine fever virus targeting the SNPs in the C-terminal end of the p72 gene region of the genome.

    PubMed

    Leblanc, N; Cortey, M; Fernandez Pinero, J; Gallardo, C; Masembe, C; Okurut, A R; Heath, L; van Heerden, J; Sánchez-Vizcaino, J M; Ståhl, K; Belák, S

    2013-08-01

    African swine fever virus (ASFV) causes one of the most dreaded transboundary animal diseases (TADs) in Suidae. African swine fever (ASF) often causes high rates of morbidity and mortality, which can reach 100% in domestic swine. To date, serological diagnosis has the drawback of not being able to differentiate variants of this virus. Previous studies have identified the 22 genotypes based on sequence variation in the C-terminal region of the p72 gene, which has become the standard for categorizing ASFVs. This article describes a genotyping assay developed using a segment of PCR-amplified genomic DNA of approximately 450 bp, which encompasses the C-terminal end of the p72 gene. Complementary paired DNA probes of 15 or 17 bp in length, which are identical except for a single nucleotide polymorphism (SNP) in the central position, were designed to either individually or in combination differentiate between the 22 genotypes. The assay was developed using xMAP technology; probes were covalently linked to microspheres, hybridized to PCR product, labelled with a reporter and read in the Luminex 200 analyzer. Characterization of the sample was performed by comparing fluorescence of the paired SNP probes, that is, the probe with higher fluorescence in a complementary pair identified the SNP that a particular sample possessed. In the final assay, a total of 52 probes were employed, 24 SNP pairs and 4 for general detection. One or more samples from each of the 22 genotypes were tested. The assay was able to detect and distinguish all 22 genotypes. This novel assay provides a powerful novel tool for the simultaneous rapid diagnosis and genotypic differentiation of ASF. PMID:22776009

  19. Black African Traditional Mathematics

    ERIC Educational Resources Information Center

    Zaslavsky, Claudia

    1970-01-01

    Discusses the traditional number systems and the origin of the number names used by several African peoples living south of the Sahara. Also included are limitations in African mathematical development, and possible topics for research. (RP)

  20. 47 CFR 13.215 - Question pools.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Question pools. 13.215 Section 13.215... Question pools. The question pool for each written examination element will be composed of questions acceptable to the FCC. Each question pool must contain at least five (5) times the number of...

  1. 47 CFR 13.215 - Question pools.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Question pools. 13.215 Section 13.215... Question pools. The question pool for each written examination element will be composed of questions acceptable to the FCC. Each question pool must contain at least five (5) times the number of...

  2. HYDROLOGY AND LANDSCAPE CONNECTIVITY OF VERNAL POOLS

    EPA Science Inventory

    Vernal pools are shaped by hydrologic processes which influence many aspects of pool function. The hydrologic budget of a pool can be summarized by a water balance equation that relates changes in the amount of water in the pool to precipitation, ground- and surface-water flows, ...

  3. 21 CFR 1250.89 - Swimming pools.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Swimming pools. 1250.89 Section 1250.89 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.89 Swimming pools. (a) Fill and draw swimming pools shall not be installed or used. (b) Swimming pools of the recirculation type shall...

  4. Swimming Pools. Managing School Facilities, Guide 2.

    ERIC Educational Resources Information Center

    Department for Education and Employment, London (England). Architects and Building Branch.

    This guide for schools with swimming pools offers advice concerning appropriate training for pool managers, the importance of water quality and testing, safety in the handling of chemicals, maintenance and cleaning requirements, pool security, and health concerns. The guide covers both indoor and outdoor pools, explains some technical terms,…

  5. The African Connection

    ERIC Educational Resources Information Center

    Oguntoyinbo, Lekan

    2012-01-01

    From student and faculty exchanges to joint research projects, U.S. universities maintain a broad spectrum of collaborative relationships with African universities. It's unclear how many U.S. colleges and universities have partnerships with African universities. The African Studies Association, an organization of scholars, doesn't keep that kind…

  6. In Vitro-Pooled shRNA Screening to Identify Determinants of Radiosensitivity.

    PubMed

    Ceroni, Alessandro; Higgins, Geoff S; Ebner, Daniel V

    2016-01-01

    Short hairpin RNA (shRNA)-pooled screening is a valuable and cost-effective tool for assaying the contribution of individual genes to cell viability and proliferation on a genomic scale. Here we describe the key considerations for the design and execution of a pooled shRNA screen to identify determinants of radiosensitivity. PMID:27581288

  7. Method of measuring a liquid pool volume

    DOEpatents

    Garcia, Gabe V.; Carlson, Nancy M.; Donaldson, Alan D.

    1991-01-01

    A method of measuring a molten metal liquid pool volume and in particular molten titanium liquid pools, including the steps of (a) generating an ultrasonic wave at the surface of the molten metal liquid pool, (b) shining a light on the surface of a molten metal liquid pool, (c) detecting a change in the frequency of light, (d) detecting an ultrasonic wave echo at the surface of the molten metal liquid pool, and (e) computing the volume of the molten metal liquid.

  8. T594M mutation of the epithelial sodium channel beta-subunit gene in pre-eclampsia and eclampsia in Black South African women.

    PubMed

    Pegoraro, R J; Roberts, C B; Rom, L; Moodley, J

    2004-09-01

    The possible role of the beta-subunit of the epithelial sodium channel T594M polymorphism in hypertensive disorders of pregnancy has not been examined. This study compared Black South African women with pre-eclampsia (n= 204), early onset pre-eclampsia (n= 67), eclampsia (n= 120) and gestational hypertension (n= 78) with 338 women from the same ethnic group who had full-term normotensive pregnancies, for the presence of the T594M polymorphism. The variant allele was detected in 1.7% to 3.8% of the various patient groups and in 3.6% of the control group reflecting no significant difference. These results suggest that the T594M polymorphism in the sodium channel beta-subunit is not associated with the pathogenesis of pre-eclampsia or gestational hypertension. PMID:15327619

  9. Differential gene expression in the liver of the African lungfish, Protopterus annectens, after 6 months of aestivation in air or 1 day of arousal from 6 months of aestivation.

    PubMed

    Hiong, Kum C; Ip, Yuen K; Wong, Wai P; Chew, Shit F

    2015-01-01

    The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the liver of P. annectens after 6 months (the maintenance phase) of aestivation as compared with the freshwater control, or after 1 day of arousal from 6 months aestivation as compared with 6 months of aestivation using suppression subtractive hybridization. During the maintenance phase of aestivation, the mRNA expression of argininosuccinate synthetase 1 and carbamoyl phosphate synthetase III were up-regulated, indicating an increase in the ornithine-urea cycle capacity to detoxify ammonia to urea. There was also an increase in the expression of betaine homocysteine-S-transferase 1 which could reduce and prevent the accumulation of hepatic homocysteine. On the other hand, the down-regulation of superoxide dismutase 1 expression could signify a decrease in ROS production during the maintenance phase of aestivation. In addition, the maintenance phase was marked by decreases in expressions of genes related to blood coagulation, complement fixation and iron and copper metabolism, which could be strategies used to prevent thrombosis and to conserve energy. Unlike the maintenance phase of aestivation, there were increases in expressions of genes related to nitrogen, carbohydrate and lipid metabolism and fatty acid transport after 1 day of arousal from 6 months aestivation. There were also up-regulation in expressions of genes that were involved in the electron transport system and ATP synthesis, indicating a greater demand for metabolic energy during arousal. Overall, our results signify the importance of sustaining a low rate of waste production and conservation of energy store during the maintenance phase, and the dependence on internal energy store for repair and structural modification during the arousal phase, of aestivation in the liver

  10. Differential Gene Expression in the Liver of the African Lungfish, Protopterus annectens, after 6 Months of Aestivation in Air or 1 Day of Arousal from 6 Months of Aestivation

    PubMed Central

    Hiong, Kum C.; Ip, Yuen K.; Wong, Wai P.; Chew, Shit F.

    2015-01-01

    The African lungfish, Protopterus annectens, can undergo aestivation during drought. Aestivation has three phases: induction, maintenance and arousal. The objective of this study was to examine the differential gene expression in the liver of P. annectens after 6 months (the maintenance phase) of aestivation as compared with the freshwater control, or after 1 day of arousal from 6 months aestivation as compared with 6 months of aestivation using suppression subtractive hybridization. During the maintenance phase of aestivation, the mRNA expression of argininosuccinate synthetase 1 and carbamoyl phosphate synthetase III were up-regulated, indicating an increase in the ornithine-urea cycle capacity to detoxify ammonia to urea. There was also an increase in the expression of betaine homocysteine-S-transferase 1 which could reduce and prevent the accumulation of hepatic homocysteine. On the other hand, the down-regulation of superoxide dismutase 1 expression could signify a decrease in ROS production during the maintenance phase of aestivation. In addition, the maintenance phase was marked by decreases in expressions of genes related to blood coagulation, complement fixation and iron and copper metabolism, which could be strategies used to prevent thrombosis and to conserve energy. Unlike the maintenance phase of aestivation, there were increases in expressions of genes related to nitrogen, carbohydrate and lipid metabolism and fatty acid transport after 1 day of arousal from 6 months aestivation. There were also up-regulation in expressions of genes that were involved in the electron transport system and ATP synthesis, indicating a greater demand for metabolic energy during arousal. Overall, our results signify the importance of sustaining a low rate of waste production and conservation of energy store during the maintenance phase, and the dependence on internal energy store for repair and structural modification during the arousal phase, of aestivation in the liver

  11. Flame spread across liquid pools

    NASA Technical Reports Server (NTRS)

    Ross, Howard; Miller, Fletcher; Schiller, David; Sirignano, William A.

    1993-01-01

    For flame spread over liquid fuel pools, the existing literature suggests three gravitational influences: (1) liquid phase buoyant convection, delaying ignition and assisting flame spread; (2) hydrostatic pressure variation, due to variation in the liquid pool height caused by thermocapillary-induced convection; and (3) gas-phase buoyant convection in the opposite direction to the liquid phase motion. No current model accounts for all three influences. In fact, prior to this work, there was no ability to determine whether ignition delay times and flame spread rates would be greater or lesser in low gravity. Flame spread over liquid fuel pools is most commonly characterized by the relationship of the initial pool temperature to the fuel's idealized flash point temperature, with four or five separate characteristic regimes having been identified. In the uniform spread regime, control has been attributed to: (1) gas-phase conduction and radiation; (2) gas-phase conduction only; (3) gas-phase convection and liquid conduction, and most recently (4) liquid convection ahead of the flame. Suggestions were made that the liquid convection was owed to both vuoyancy and thermocapillarity. Of special interest to this work is the determination of whether, and under what conditions, pulsating spread can and will occur in microgravity in the absence of buoyant flows in both phases. The approach we have taken to resolving the importance of buoyancy for these flames is: (1) normal gravity experiments and advanced diagnostics; (2) microgravity experiments; and (3) numerical modelling at arbitrary gravitational level.

  12. Monitoring pool-tail fines

    NASA Astrophysics Data System (ADS)

    Bunte, K.; Potyondy, J. P.; Abt, S. R.; Swingle, K. W.

    2010-12-01

    Fine sediment < 2 and < 6 mm deposited in pool-tail areas of mountain streams is often measured to monitor changes in the supply of fines (e.g., by dam removal, bank erosion, or watershed effects including fires and road building) or to assess the status and trend of aquatic ecosystems. Grid counts, pebble counts, and volumetric bedmaterial samples are typically used to quantify pool-tail fines. Grid-count results exhibit a high degree of variability not only among streams and among operators, but also among crews performing a nearly identical procedure (Roper et al. 2010). Variability is even larger when diverse methods are employed, each of which quantifies fines in a different way: grid counts visually count surface fines on small patches within the pool-tail area, pebble counts pick up and tally surface particles along (riffle) transects, and volumetric samples sieve out fines from small-scale bulk samples; and even when delimited to pool-tail areas, individual methods focus on different sampling locales. Two main questions were analyzed: 1) Do pool-tail fines exhibit patterns of spatial variability and are some grid count schemes more likely to provide accurate results than others. 2) How and why does the percentage of fines vary among grid counts, pebble counts, and volumetric samples. In a field study, grids were placed at 7 locales in two rows across the wetted width of 10 pool tails in a 14-m wide 3rd order coarse gravel-bed mountain stream with <4% sand and <8% < 6 mm. Several pebble count transects were placed across each pool-tail area, and three volumetric samples were collected in each of three pool tails. Pebble and grid counts both indicated a fining trend towards one or both banks, sometimes interrupted by a secondary peak of fines within the central half of the wetted width. Among the five sampling schemes tested, grid counts covering the wetted width with 7 locales produced the highest accuracy and the least variability among the pools of the

  13. Serum Total Bilirubin, not Cholelithiasis, is Influenced by UGT1A1 Polymorphism, Alpha Thalassemia and βs Haplotype: First Report on Comparison between Arab-Indian and African βs Genes

    PubMed Central

    Alkindi, Said Y.; Pathare, Anil; Al Zadjali, Shoaib; Panjwani, Vinodhkumar; Wasim, Fauzia; Khan, Hammad; Chopra, Pradeep; Krishnamoorthy, Rajagopal; Alkindi, Salam

    2015-01-01

    Background We explored the potential relationship between steady state serum bilirubin levels and the incidence of cholelithiasis in the context of UGT1A1 gene A(TA)nTAA promoter polymorphism in Omani sickle cell anemia (SCA) patients, homozygotes for African (Benin and Bantu) and Arab-Indian βS haplotypes, but sharing the same microgeographical environment and comparable life style factors. Methods 136 SCA patients were retrospectively studied in whom imaging data including abdominal CT scan, MRI or Ultrasonography were routinely available. Available data on the mean steady state hematological/biochemical parameters (n=136), βs haplotypes(n=136), α globin gene status (n=105) and UGT1A1 genotypes (n=133) were reviewed from the respective medical records. Results The mean serum total bilirubin level was significantly higher in the homozygous UGT1A1(AT)7 group as compared to UGT1A1(AT)6 group. Thus, not cholelithiasis but total serum bilirubin was influenced by UGT1A1 polymorphism in this SCA cohort. Conclusion As observed in other population groups, the UGT1A1 (AT)7 homozygosity was significantly associated with raised serum total bilirubin level, but the prevalence of gallstones in the Omani SCA patients was not associated with α thalassaemia, UGT1A1 polymorphism, or βs haplotypes. PMID:26543529

  14. Inferring parental genomic ancestries using pooled semi-Markov processes

    PubMed Central

    Zou, James Y.; Halperin, Eran; Burchard, Esteban; Sankararaman, Sriram

    2015-01-01

    Motivation: A basic problem of broad public and scientific interest is to use the DNA of an individual to infer the genomic ancestries of the parents. In particular, we are often interested in the fraction of each parent’s genome that comes from specific ancestries (e.g. European, African, Native American, etc). This has many applications ranging from understanding the inheritance of ancestry-related risks and traits to quantifying human assortative mating patterns. Results: We model the problem of parental genomic ancestry inference as a pooled semi-Markov process. We develop a general mathematical framework for pooled semi-Markov processes and construct efficient inference algorithms for these models. Applying our inference algorithm to genotype data from 231 Mexican trios and 258 Puerto Rican trios where we have the true genomic ancestry of each parent, we demonstrate that our method accurately infers parameters of the semi-Markov processes and parents’ genomic ancestries. We additionally validated the method on simulations. Our model of pooled semi-Markov process and inference algorithms may be of independent interest in other settings in genomics and machine learning. Contact: jazo@microsoft.com PMID:26072482

  15. Interactions between pool geometry and hydraulics

    USGS Publications Warehouse

    Thompson, D.M.; Nelson, J.M.; Wohl, E.E.

    1998-01-01

    An experimental and computational research approach was used to determine interactions between pool geometry and hydraulics. A 20-m-long, 1.8-m-wide flume was used to investigate the effect of four different geometric aspects of pool shape on flow velocity. Plywood sections were used to systematically alter constriction width, pool depth, pool length, and pool exit-slope gradient, each at two separate levels. Using the resulting 16 unique geometries with measured pool velocities in four-way factorial analyses produced an empirical assessment of the role of the four geometric aspects on the pool flow patterns and hence the stability of the pool. To complement the conclusions of these analyses, a two-dimensional computational flow model was used to investigate the relationships between pool geometry and flow patterns over a wider range of conditions. Both experimental and computational results show that constriction and depth effects dominate in the jet section of the pool and that pool length exhibits an increasing effect within the recirculating-eddy system. The pool exit slope appears to force flow reattachment. Pool length controls recirculating-eddy length and vena contracta strength. In turn, the vena contracta and recirculating eddy control velocities throughout the pool.

  16. Y chromosome lineages in men of west African descent.

    PubMed

    Torres, Jada Benn; Doura, Menahem B; Keita, Shomarka O Y; Kittles, Rick A

    2012-01-01

    The early African experience in the Americas is marked by the transatlantic slave trade from ∼1619 to 1850 and the rise of the plantation system. The origins of enslaved Africans were largely dependent on European preferences as well as the availability of potential laborers within Africa. Rice production was a key industry of many colonial South Carolina low country plantations. Accordingly, rice plantations owners within South Carolina often requested enslaved Africans from the so-called "Grain Coast" of western Africa (Senegal to Sierra Leone). Studies on the African origins of the enslaved within other regions of the Americas have been limited. To address the issue of origins of people of African descent within the Americas and understand more about the genetic heterogeneity present within Africa and the African Diaspora, we typed Y chromosome specific markers in 1,319 men consisting of 508 west and central Africans (from 12 populations), 188 Caribbeans (from 2 islands), 532 African Americans (AAs from Washington, DC and Columbia, SC), and 91 European Americans. Principal component and admixture analyses provide support for significant Grain Coast ancestry among African American men in South Carolina. AA men from DC and the Caribbean showed a closer affinity to populations from the Bight of Biafra. Furthermore, 30-40% of the paternal lineages in African descent populations in the Americas are of European ancestry. Diverse west African ancestries and sex-biased gene flow from EAs has contributed greatly to the genetic heterogeneity of African populations throughout the Americas and has significant implications for gene mapping efforts in these populations. PMID:22295064

  17. Y Chromosome Lineages in Men of West African Descent

    PubMed Central

    Keita, Shomarka O. Y.; Kittles, Rick A.

    2012-01-01

    The early African experience in the Americas is marked by the transatlantic slave trade from ∼1619 to 1850 and the rise of the plantation system. The origins of enslaved Africans were largely dependent on European preferences as well as the availability of potential laborers within Africa. Rice production was a key industry of many colonial South Carolina low country plantations. Accordingly, rice plantations owners within South Carolina often requested enslaved Africans from the so-called “Grain Coast” of western Africa (Senegal to Sierra Leone). Studies on the African origins of the enslaved within other regions of the Americas have been limited. To address the issue of origins of people of African descent within the Americas and understand more about the genetic heterogeneity present within Africa and the African Diaspora, we typed Y chromosome specific markers in 1,319 men consisting of 508 west and central Africans (from 12 populations), 188 Caribbeans (from 2 islands), 532 African Americans (AAs from Washington, DC and Columbia, SC), and 91 European Americans. Principal component and admixture analyses provide support for significant Grain Coast ancestry among African American men in South Carolina. AA men from DC and the Caribbean showed a closer affinity to populations from the Bight of Biafra. Furthermore, 30–40% of the paternal lineages in African descent populations in the Americas are of European ancestry. Diverse west African ancestries and sex-biased gene flow from EAs has contributed greatly to the genetic heterogeneity of African populations throughout the Americas and has significant implications for gene mapping efforts in these populations. PMID:22295064

  18. The genetic risk of acute seizures in African children with falciparum malaria

    PubMed Central

    Kariuki, Symon M; Rockett, Kirk; Clark, Taane G; Reyburn, Hugh; Agbenyega, Tsiri; Taylor, Terrie E; Birbeck, Gretchen L; Williams, Thomas N; Newton, Charles R J C

    2013-01-01

    Purpose It is unclear why some children with falciparum malaria develop acute seizures and what determines the phenotype of seizures. We sought to determine if polymorphisms of malaria candidate genes are associated with acute seizures. Methods Logistic regression was used to investigate genetic associations with malaria-associated seizures (MAS) and complex MAS (repetitive, prolonged, or focal seizures) in four MalariaGEN African sites, namely: Blantyre, Malawi; Kilifi, Kenya; Kumasi, Ghana; and Muheza, Tanzania. The analysis was repeated for five inheritance models (dominant, heterozygous, recessive, additive, and general) and adjusted for potential confounders and multiple testing. Key Findings Complex phenotypes of seizures constituted 71% of all admissions with MAS across the sites. MAS were strongly associated with cluster of differentiation-ligand-rs3092945 in females in Kilifi (p = 0.00068) and interleukin (IL)-17 receptor E-rs708567 in the pooled analysis across the sites (p = 0.00709). Complex MAS were strongly associated with epidermal growth factor module-containing mucin-like hormone receptor (EMR)1-rs373533 in Kumasi (p = 0.00033), but none in the pooled analysis. Focal MAS were strongly associated with IL-20 receptor A-rs1555498 in Muheza (p = 0.00016), but none in the pooled analysis. Prolonged MAS were strongly associated with complement receptor 1-rs17047660 in Kilifi (p = 0.00121) and glucose-6-phosphate dehydrogenase-rs1050828 in females in the pooled analysis (p = 0.00155). Repetitive MAS were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00003) and cystic fibrosis transmembrane conductance receptor-rs17140229 in the pooled analysis (p = 0.00543). MAS with coma/cerebral malaria were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00019) and IL10-rs3024500 in the pooled analysis across the sites (p = 0.00064). Significance We have identified a number of genetic associations that may explain the risk of seizures in >2,000 cases

  19. Identification of homogeneous and heterogeneous variables in pooled cohort studies.

    PubMed

    Cheng, Xin; Lu, Wenbin; Liu, Mengling

    2015-06-01

    Pooled analyses integrate data from multiple studies and achieve a larger sample size for enhanced statistical power. When heterogeneity exists in variables' effects on the outcome across studies, the simple pooling strategy fails to present a fair and complete picture of the effects of heterogeneous variables. Thus, it is important to investigate the homogeneous and heterogeneous structure of variables in pooled studies. In this article, we consider the pooled cohort studies with time-to-event outcomes and propose a penalized Cox partial likelihood approach with adaptively weighted composite penalties on variables' homogeneous and heterogeneous effects. We show that our method can characterize the variables as having heterogeneous, homogeneous, or null effects, and estimate non-zero effects. The results are readily extended to high-dimensional applications where the number of parameters is larger than the sample size. The proposed selection and estimation procedure can be implemented using the iterative shooting algorithm. We conduct extensive numerical studies to evaluate the performance of our proposed method and demonstrate it using a pooled analysis of gene expression in patients with ovarian cancer. PMID:25732747

  20. Effects of pool-fencing ordinances and other factors on childhood drowning in Los Angeles County, 1990-1995.

    PubMed Central

    Morgenstern, H; Bingham, T; Reza, A

    2000-01-01

    OBJECTIVES: This study estimated the effects of local pool-fencing ordinances and other factors on the rate of childhood drowning in Los Angeles County, California. METHODS: Stage 1 was a retrospective dynamic cohort study of all drownings among children younger than 10 years that occurred in residential swimming pools in Los Angeles County between 1990 and 1995. Stage 2 was a matched case-control study that compared pools in which childhood drownings occurred (cases) with randomly selected pools in which drownings did not occur (controls). RESULTS: The drowning rate was relatively high among toddlers (aged 1-4 years), boys, and African Americans and in areas with a high density of residential swimming pools. Pool-fencing ordinances were not associated with a reduced overall rate of childhood drowning. CONCLUSIONS: Local ordinances enacted in Los Angeles County before 1996 do not appear to have been effective in reducing the rate of childhood drowning in residential pools. Possible reasons for this ineffectiveness are insufficient building codes for isolating pools from homes, inadequate enforcement of the ordinances, and inadequate operation or maintenance of fencing equipment by pool owners. PMID:10754975

  1. Pool Safety: A Few Simple Rules.

    ERIC Educational Resources Information Center

    PTA Today, 1993

    1993-01-01

    Presents suggestions by the National Swimming Pool Safety Committee on how to keep children safe while swimming. Ideas include maintaining strict adult supervision, pool and spa barriers, and knowledge of cardiopulmonary resuscitation. (SM)

  2. Cold Pools in the Columbia Basin

    SciTech Connect

    Whiteman, Charles D.; Zhong, Shiyuan; Shaw, William J.; Hubbe, John M.; Bian, Xindi; Mittelstadt, J.

    2001-01-01

    Persistent midwinter cold air pools produce multi-day periods of cold, dreary weather in valleys and basins. Persistent stable stratification leads to the buildup of pollutants and moisture in the pool. Because the pool sometimes has temperatures below freezing while the air above is warmer, freezing precipitation often occurs with consequent effects on transportation and safety. Forecasting the buildup and breakdown of these cold pools is difficult because the physical mechanisms leading to their formation, maintenance, and destruction have received little study. This paper provides a succinct meteorological definition of a cold pool, develops a climatology of Columbia Basin cold pools, and analyzes remote and in situ temperature and wind sounding data for two winter cold pool episodes that were accompanied by fog and stratus, illustrating many of the physical mechanisms affecting cold pool evolution.

  3. Pool power control in remelting systems

    SciTech Connect

    Williamson, Rodney L.; Melgaard, David K.; Beaman, Joseph J.

    2011-12-13

    An apparatus for and method of controlling a remelting furnace comprising adjusting current supplied to an electrode based upon a predetermined pool power reference value and adjusting the electrode drive speed based upon the predetermined pool power reference value.

  4. CDC Study Finds Fecal Contamination in Pools

    MedlinePlus

    ... Communication (404) 639-3286 CDC study finds fecal contamination in pools A study of public pools done ... The E. coli is a marker for fecal contamination. Finding a high percentage of E. coli-positive ...

  5. African and non-African admixture components in African Americans and an African Caribbean population.

    PubMed

    Murray, Tanda; Beaty, Terri H; Mathias, Rasika A; Rafaels, Nicholas; Grant, Audrey Virginia; Faruque, Mezbah U; Watson, Harold R; Ruczinski, Ingo; Dunston, Georgia M; Barnes, Kathleen C

    2010-09-01

    Admixture is a potential source of confounding in genetic association studies, so it becomes important to detect and estimate admixture in a sample of unrelated individuals. Populations of African descent in the US and the Caribbean share similar historical backgrounds but the distributions of African admixture may differ. We selected 416 ancestry informative markers (AIMs) to estimate and compare admixture proportions using STRUCTURE in 906 unrelated African Americans (AAs) and 294 Barbadians (ACs) from a study of asthma. This analysis showed AAs on average were 72.5% African, 19.6% European and 8% Asian, while ACs were 77.4% African, 15.9% European, and 6.7% Asian which were significantly different. A principal components analysis based on these AIMs yielded one primary eigenvector that explained 54.04% of the variation and captured a gradient from West African to European admixture. This principal component was highly correlated with African vs. European ancestry as estimated by STRUCTURE (r(2)=0.992, r(2)=0.912, respectively). To investigate other African contributions to African American and Barbadian admixture, we performed PCA on approximately 14,000 (14k) genome-wide SNPs in AAs, ACs, Yorubans, Luhya and Maasai African groups, and estimated genetic distances (F(ST)). We found AAs and ACs were closest genetically (F(ST)=0.008), and both were closer to the Yorubans than the other East African populations. In our sample of individuals of African descent, approximately 400 well-defined AIMs were just as good for detecting substructure as approximately 14,000 random SNPs drawn from a genome-wide panel of markers. PMID:20717976

  6. The African superswell

    NASA Technical Reports Server (NTRS)

    Nyblade, Andrew A.; Robinson, Scott W.

    1994-01-01

    Maps of residual bathymetry in the ocean basins around the African continent reveal a broad bathymetric swell in the southeastern Atlantic Ocean with an amplitude of about 500 m. We propose that this region of anomalously shallow bathymetry, together with the contiguous eastern and southern African plateaus, form a superswell which we refer to as the African superswell. The origin of the African superswell is uncertain. However, rifting and volcanism in eastern Africa, as well as heat flow measurements in southern Africa and the southeastern Atlantic Ocean, suggest that the superswell may be attributed, at least in part, to heating of the lithosphere.

  7. Swimming pools soak up the sun

    SciTech Connect

    Cuoghi, D.; Hesse, P.; Schiller, T.

    1996-05-01

    Solar pool heaters survived the boom and bust solar years of the 1970s and 1980s. Today they are even popular and cost-effective in parts of the country where many people think solar is impractical. This article discusses the following topics: how solar pool heaters work; types of solar pool heater collectors; collector and pump sizing; collector siting and mounting; systems costs and economics; pool covers. 3 figs.

  8. 1968 Listing of Swimming Pool Equipment.

    ERIC Educational Resources Information Center

    National Sanitation Foundation, Ann Arbor, MI. Testing Lab.

    An up-to-date listing of swimming pool equipment including--(1) companies authorized to display the National Sanitation Foundation seal of approval, (2) equipment listed as meeting NSF swimming pool equipment standards relating to diatomite type filters, (3) equipment listed as meeting NSF swimming pool equipment standard relating to sand type…

  9. Apparatus for heating a swimming pool

    SciTech Connect

    Kremen, R.D.

    1983-09-06

    This disclosure relates to a solar heater apparatus for a swimming pool which incorporates a submersible suspendible black body sheet to serve as a device to absorb solar radiation and transfer the collected energy to the pool water so that the pool water can be efficiently heated.

  10. 7 CFR 1131.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1131.7 Section 1131.7 Agriculture... Handling Definitions § 1131.7 Pool plant. Pool Plant means a plant or unit of plants specified in paragraphs (a) through (e) of this section, but excluding a plant specified in paragraph (g) of this...

  11. 7 CFR 1001.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1001.7 Section 1001.7 Agriculture... Handling Definitions § 1001.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant described in paragraph (h)...

  12. 7 CFR 1126.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1126.7 Section 1126.7 Agriculture... Handling Definitions § 1126.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  13. 7 CFR 1005.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1005.7 Section 1005.7 Agriculture... Handling Definitions § 1005.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  14. 7 CFR 1007.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1007.7 Section 1007.7 Agriculture... Handling Definitions § 1007.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  15. 7 CFR 1001.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1001.7 Section 1001.7 Agriculture... Handling Definitions § 1001.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant described in paragraph (h)...

  16. 7 CFR 1030.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1030.7 Section 1030.7 Agriculture... Handling Definitions § 1030.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in paragraph (h)...

  17. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  18. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified...

  19. 7 CFR 1032.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1032.7 Section 1032.7 Agriculture... Handling Definitions § 1032.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (i) of...

  20. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (j) of...

  1. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  2. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (j) of...

  3. 7 CFR 1007.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1007.7 Section 1007.7 Agriculture... Handling Definitions § 1007.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  4. 7 CFR 1032.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1032.7 Section 1032.7 Agriculture... Handling Definitions § 1032.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (i) of...

  5. 7 CFR 1030.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1030.7 Section 1030.7 Agriculture... Handling Definitions § 1030.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in paragraph (h)...

  6. 7 CFR 1005.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1005.7 Section 1005.7 Agriculture... Handling Definitions § 1005.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  7. 7 CFR 1126.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1126.7 Section 1126.7 Agriculture... Handling Definitions § 1126.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  8. 7 CFR 1030.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1030.7 Section 1030.7 Agriculture... Handling Definitions § 1030.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in paragraph (h)...

  9. 7 CFR 1007.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1007.7 Section 1007.7 Agriculture... Handling Definitions § 1007.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  10. 7 CFR 1001.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1001.7 Section 1001.7 Agriculture... Handling Definitions § 1001.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant described in paragraph (h)...

  11. 7 CFR 1131.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1131.7 Section 1131.7 Agriculture... Handling Definitions § 1131.7 Pool plant. Pool Plant means a plant or unit of plants specified in paragraphs (a) through (e) of this section, but excluding a plant specified in paragraph (g) of this...

  12. 7 CFR 1001.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1001.7 Section 1001.7 Agriculture... Handling Definitions § 1001.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant described in paragraph (h)...

  13. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified...

  14. 7 CFR 1131.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1131.7 Section 1131.7 Agriculture... Handling Definitions § 1131.7 Pool plant. Pool Plant means a plant or unit of plants specified in paragraphs (a) through (e) of this section, but excluding a plant specified in paragraph (g) of this...

  15. 7 CFR 1030.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1030.7 Section 1030.7 Agriculture... Handling Definitions § 1030.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified in paragraph (h)...

  16. 7 CFR 1007.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1007.7 Section 1007.7 Agriculture... Handling Definitions § 1007.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  17. 7 CFR 1032.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1032.7 Section 1032.7 Agriculture... Handling Definitions § 1032.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (i) of...

  18. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  19. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  20. 7 CFR 1126.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1126.7 Section 1126.7 Agriculture... Handling Definitions § 1126.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  1. 7 CFR 1005.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1005.7 Section 1005.7 Agriculture... Handling Definitions § 1005.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  2. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 9 2012-01-01 2012-01-01 false Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (j) of...

  3. 7 CFR 1005.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1005.7 Section 1005.7 Agriculture... Handling Definitions § 1005.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  4. 7 CFR 1007.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1007.7 Section 1007.7 Agriculture... Handling Definitions § 1007.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  5. 7 CFR 1126.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1126.7 Section 1126.7 Agriculture... Handling Definitions § 1126.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  6. 7 CFR 1006.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1006.7 Section 1006.7 Agriculture... Handling Definitions § 1006.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  7. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified...

  8. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 9 2011-01-01 2011-01-01 false Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (j) of...

  9. 7 CFR 1005.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1005.7 Section 1005.7 Agriculture... Handling Definitions § 1005.7 Pool plant. Pool plant means a plant specified in paragraphs (a) through (d) of this section, a unit of plants as specified in paragraph (e) of this section, or a plant...

  10. 7 CFR 1032.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1032.7 Section 1032.7 Agriculture... Handling Definitions § 1032.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, or a plant specified in paragraph (i) of...

  11. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 9 2013-01-01 2013-01-01 false Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified...

  12. 7 CFR 1131.7 - Pool plant.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 9 2014-01-01 2013-01-01 true Pool plant. 1131.7 Section 1131.7 Agriculture... Handling Definitions § 1131.7 Pool plant. Pool Plant means a plant or unit of plants specified in paragraphs (a) through (e) of this section, but excluding a plant specified in paragraph (g) of this...

  13. 7 CFR 1033.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... its route distribution in this marketing area for 3 consecutive months or if the plant is required to... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1033.7 Section 1033.7 Agriculture... Handling Definitions § 1033.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants...

  14. 7 CFR 1030.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... its route distribution in this marketing area for 3 consecutive months or if the plant is required to... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1030.7 Section 1030.7 Agriculture... Handling Definitions § 1030.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants...

  15. 7 CFR 1131.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... its route distribution in this marketing area for 3 consecutive months or if the plant is required to... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1131.7 Section 1131.7 Agriculture... Handling Definitions § 1131.7 Pool plant. Pool Plant means a plant or unit of plants specified...

  16. 7 CFR 1001.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1001.7 Section 1001.7 Agriculture... Handling Definitions § 1001.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant described in paragraph (h)...

  17. 7 CFR 1124.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1124.7 Section 1124.7 Agriculture... Regulating Handling Definitions § 1124.7 Pool plant. Pool plant means a plant, unit of plants, or a system of plants as specified in paragraphs (a) through (f) of this section, but excluding a plant specified...

  18. 7 CFR 1032.7 - Pool plant.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... a majority of its route distribution in this marketing area for 3 consecutive months or if the plant... 7 Agriculture 9 2010-01-01 2009-01-01 true Pool plant. 1032.7 Section 1032.7 Agriculture... Handling Definitions § 1032.7 Pool plant. Pool plant means a plant, unit of plants, or system of plants...

  19. Serial analysis of gene expression (SAGE) in bovine trypanotolerance: preliminary results

    PubMed Central

    2003-01-01

    In Africa, trypanosomosis is a tsetse-transmitted disease which represents the most important constraint to livestock production. Several indigenous West African taurine (Bos taurus) breeds, such as the Longhorn (N'Dama) cattle are well known to control trypanosome infections. This genetic ability named "trypanotolerance" results from various biological mechanisms under multigenic control. The methodologies used so far have not succeeded in identifying the complete pool of genes involved in trypanotolerance. New post genomic biotechnologies such as transcriptome analyses are efficient in characterising the pool of genes involved in the expression of specific biological functions. We used the serial analysis of gene expression (SAGE) technique to construct, from Peripheral Blood Mononuclear Cells of an N'Dama cow, 2 total mRNA transcript libraries, at day 0 of a Trypanosoma congolense experimental infection and at day 10 post-infection, corresponding to the peak of parasitaemia. Bioinformatic comparisons in the bovine genomic databases allowed the identification of 187 up- and down- regulated genes, EST and unknown functional genes. Identification of the genes involved in trypanotolerance will allow to set up specific microarray sets for further metabolic and pharmacological studies and to design field marker-assisted selection by introgression programmes. PMID:12927079

  20. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    PubMed

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison M; Easton, Douglas F; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Fasching, Peter A; Haeberle, Lothar; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marmé, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Nielsen, Sune F; Nordestgaard, Børge G; González-Neira, Anna; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Dörk, Thilo; Bogdanova, Natalia V; Mannermaa, Arto; Hartikainen, Jaana M; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; García-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S; Pharoah, Paul D P; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry. PMID:26621531

  1. Patent pools: intellectual property rights and competition.

    PubMed

    Rodriguez, Victor

    2010-01-01

    Patent pools do not correct all problems associated with patent thickets. In this respect, patent pools might not stop the outsider problem from striking pools. Moreover, patent pools can be expensive to negotiate, can exclude patent holders with smaller numbers of patents or enable a group of major players to form a cartel that excludes new competitors. For all the above reasons, patent pools are subject to regulatory clearance because they could result in a monopoly. The aim of this article is to present the relationship between patents and competition in a broad context. PMID:20200607

  2. Patent Pools: Intellectual Property Rights and Competition

    PubMed Central

    Rodriguez, Victor

    2010-01-01

    Patent pools do not correct all problems associated with patent thickets. In this respect, patent pools might not stop the outsider problem from striking pools. Moreover, patent pools can be expensive to negotiate, can exclude patent holders with smaller numbers of patents or enable a group of major players to form a cartel that excludes new competitors. For all the above reasons, patent pools are subject to regulatory clearance because they could result in a monopoly. The aim of this article is to present the relationship between patents and competition in a broad context. PMID:20200607

  3. Method of measuring a liquid pool volume

    DOEpatents

    Garcia, G.V.; Carlson, N.M.; Donaldson, A.D.

    1991-03-19

    A method of measuring a molten metal liquid pool volume and in particular molten titanium liquid pools is disclosed, including the steps of (a) generating an ultrasonic wave at the surface of the molten metal liquid pool, (b) shining a light on the surface of a molten metal liquid pool, (c) detecting a change in the frequency of light, (d) detecting an ultrasonic wave echo at the surface of the molten metal liquid pool, and (e) computing the volume of the molten metal liquid. 3 figures.

  4. African swine fever virus Georgia isolate harboring deletions of 9GL and MGF360/505 genes is highly attenuated in swine but does not confer protection against parental virus challenge.

    PubMed

    O'Donnell, Vivian; Holinka, Lauren G; Sanford, Brenton; Krug, Peter W; Carlson, Jolene; Pacheco, Juan M; Reese, Bo; Risatti, Guillermo R; Gladue, Douglas P; Borca, Manuel V

    2016-08-01

    African swine fever virus (ASFV) produces a contagious disease of domestic pigs that results in severe economic consequences to the swine industry. Control of the disease has been hampered by the unavailability of vaccines. We recently reported the development of two experimental vaccine strains (ASFV-G-Δ9GL and ASFV-G-ΔMGF) based on the attenuation of the highly virulent and epidemiologically relevant Georgia2007 isolate. Deletion of the 9GL gene or six genes of the MGF360/505 group produced two attenuated ASFV strains which were able to confer protection to animals when challenged with the virulent parental virus. Both viruses, although efficient in inducing protection, present concerns regarding their safety. In an attempt to solve this problem we developed a novel virus strain, ASFV-G-Δ9GL/ΔMGF, based on the deletion of all genes deleted in ASFV-G-Δ9GL and ASFV-G-ΔMGF. ASFV-G-Δ9GL/ΔMGF is the first derivative of a highly virulent ASFV field strain subjected to a double round of recombination events seeking to sequentially delete specific genes. ASFV-G-Δ9GL/ΔMGF showed a decreased ability to replicate in primary swine macrophage cultures relative to that of ASFV-G and ASFV-G-ΔMGF but similar to that of ASFV-G-Δ9GL. ASFV-G-Δ9GL/ΔMGF was attenuated when intramuscularly inoculated into swine, even at doses as high as 10(6) HAD50. Animals infected with doses ranging from 10(2) to 10(6) HAD50 did not present detectable levels of virus in blood at any time post-infection and they did not develop detectable levels of anti-ASFV antibodies. Importantly, ASFV-G-Δ9GL/ΔMGF does not induce protection against challenge with the virulent parental ASFV-G isolate. Results presented here suggest caution towards approaches involving genomic manipulations when developing rationally designed ASFV vaccine strains. PMID:27182007

  5. Drowning in disinfection byproducts? Assessing swimming pool water.

    PubMed

    Zwiener, Christian; Richardson, Susan D; DeMarini, David M; De Marini, David M; Grummt, Tamara; Glauner, Thomas; Frimmel, Fritz H

    2007-01-15

    Disinfection is mandatory for swimming pools: public pools are usually disinfected by gaseous chlorine or sodium hypochlorite and cartridge filters; home pools typically use stabilized chlorine. These methods produce a variety of disinfection byproducts (DBPs), such as trihalomethanes (THMs), which are regulated carcinogenic DBPs in drinking water that have been detected in the blood and breath of swimmers and of nonswimmers at indoor pools. Also produced are halogenated acetic acids (HAAs) and haloketones, which irritate the eyes, skin, and mucous membranes; trichloramine, which is linked with swimming-pool-associated asthma; and halogenated derivatives of UV sun screens, some of which show endocrine effects. Precursors of DBPs include human body substances, chemicals used in cosmetics and sun screens, and natural organic matter. Analytical research has focused also on the identification of an additional portion of unknown DBPs using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS/MS with derivatization. Children swimmers have an increased risk of developing asthma and infections of the respiratory tract and ear. A 1.6-2.0-fold increased risk for bladder cancer has been associated with swimming or showering/bathing with chlorinated water. Bladder cancer risk from THM exposure (all routes combined) was greatest among those with the GSTT1-1 gene. This suggests a mechanism involving distribution of THMs to the bladder by dermal/inhalation exposure and activation there by GSTT1-1 to mutagens. DBPs may be reduced by engineering and behavioral means, such as applying new oxidation and filtration methods, reducing bromide and iodide in the source water, increasing air circulation in indoor pools, and assuring the cleanliness of swimmers. The positive health effects gained by swimming can be increased by reducing the potential adverse health risks. PMID:17310693

  6. 16 Extraordinary African Americans.

    ERIC Educational Resources Information Center

    Lobb, Nancy

    This collection for children tells the stories of 16 African Americans who helped make America what it is today. African Americans can take pride in the heritage of these contributors to society. Biographies are given for the following: (1) Sojourner Truth, preacher and abolitionist; (2) Frederick Douglass, abolitionist; (3) Harriet Tubman, leader…

  7. African Studies Computer Resources.

    ERIC Educational Resources Information Center

    Kuntz, Patricia S.

    African studies computer resources that are readily available in the United States with linkages to Africa are described, highlighting those most directly corresponding to African content. Africanists can use the following four fundamental computer systems: (1) Internet/Bitnet; (2) Fidonet; (3) Usenet; and (4) dial-up bulletin board services. The…

  8. African Literature as Celebration.

    ERIC Educational Resources Information Center

    Achebe, Chinua

    1989-01-01

    Describes the Igbo tradition of "Mbari," a communal creative enterprise that celebrates the world and the life lived in it through art. Contrasts the cooperative, social dimension of pre-colonial African culture with the exclusion and denial of European colonialism, and sees new African literature again celebrating human presence and dignity. (AF)

  9. Educating African American Males

    ERIC Educational Resources Information Center

    Bell, Edward E.

    2010-01-01

    Background: Schools across America spend money, invest in programs, and sponsor workshops, offer teacher incentives, raise accountability standards, and even evoke the name of Obama in efforts to raise the academic achievement of African American males. Incarceration and college retention rates point to a dismal plight for many African American…

  10. Africans Away from Home.

    ERIC Educational Resources Information Center

    Clarke, John Henrik

    Africans who were brought across the Atlantic as slaves never fully adjusted to slavery or accepted its inevitability. Resistance began on board the slave ships, where many jumped overboard or committed suicide. African slaves in South America led the first revolts against tyranny in the New World. The first slave revolt in the Caribbean occurred…

  11. Keeping African Masks Real

    ERIC Educational Resources Information Center

    Waddington, Susan

    2012-01-01

    Art is a good place to learn about our multicultural planet, and African masks are prized throughout the world as powerfully expressive artistic images. Unfortunately, multicultural education, especially for young children, can perpetuate stereotypes. Masks taken out of context lose their meaning and the term "African masks" suggests that there is…

  12. Transient pool boiling in microgravity

    NASA Technical Reports Server (NTRS)

    Ervin, J. S.; Merte, H., Jr.; Keller, R. B.; Kirk, K.

    1992-01-01

    Transient nucleate pool boiling experiments using R113 are conducted for short times in microgravity and in earth gravity with different heater surface orientations and subcoolings. The heating surface is a transparent gold film sputtered on a quartz substrate, which simultaneously provides surface temperature measurements and permits viewing of the boiling process from beneath. For the microgravity experiments, which have uniform initial temperatures and no fluid motion, the temperature distribution in the R 113 at the moment of boiling inception is known. High speed cameras with views both across and through the heating surface record the boiling spread across the heater surface, which is classified into six distinct categories.

  13. Polymorphisms in the carcinogen detoxification genes CYB5A and CYB5R3 and breast cancer risk in African American women

    PubMed Central

    Blanke, Kristina L.; Sacco, James C.; Millikan, Robert C.; Olshan, Andrew F.; Luo, Jingchun; Trepanier, Lauren A.

    2014-01-01

    Purpose Cytochrome b5 (encoded by CYB5A) and NADH cytochrome b5 reductase (encoded by CYB5R3) detoxify aromatic and heterocyclic amine mammary carcinogens found in cigarette smoke. We hypothesized that CYB5A and CYB5R3 polymorphisms would be associated with breast cancer risk in women. Methods We characterized the prevalence of 18 CYB5A and CYB5R3 variants in genomic DNA from African American (AfrAm) and Caucasian (Cauc) women from the Carolina Breast Cancer Study population (1946 cases and 1747 controls), and determined their associations with breast cancer risk, with effect modification by smoking. Results A CYB5R3 variant, I1M+6T (rs8190370) was significantly more common in breast cancer cases (MAF 0.0238) compared to controls (0.0169, P =0.039); this was attributable to a higher MAF in AfrAm cases (0.0611) compared to AfrAm controls (0.0441, P=0.046; adjusted OR 1.41, CI 0.98-2.04; P=0.062). When smoking was considered, I1M+6T was more strongly associated with breast cancer risk in AfrAm smokers (adjusted OR 2.10, 1.08-4.07; P=0.028) compared to never-smokers (OR=1.21; 0.77-1.88; P for interaction=0.176). I1M+6T and three additional CYB5R3 variants, -251T, I8-1676C, and *392C, as well as two CYB5A variants, 13G and I2-992T, were significantly more common in AfrAms compared to Caucs. Conclusions CYB5R3 I1M+6 C>T should be considered in future molecular epidemiologic studies of breast cancer risk in AfrAms. Further, variants in CYB5A and CYB5R3 should be considered in the evaluation of other tumors in AfrAms that are associated with aromatic and heterocyclic amine exposures, to include prostate, bladder, and colon cancers. PMID:25225034

  14. Diabetes in African Americans

    PubMed Central

    Marshall, M

    2005-01-01

    African Americans have a high risk for type 2 diabetes. Genetic traits, the prevalence of obesity, and insulin resistance all contribute to the risk of diabetes in the African American community. African Americans have a high rate of diabetic complications, because of poor glycaemic control and racial disparities in health care in the USA. African Americans with diabetes may have an atypical presentation that simulates type 1 diabetes, but then their subsequent clinical course is typical of type 2 diabetes. Culturally sensitive strategies, structured disease management protocols, and the assistance of nurses, diabetic educators, and other health care professionals are effective in improving the outcome of diabetes in the African American community. PMID:16344294

  15. African swine fever virus Georgia isolate harboring deletions of MGF360 and MGF505 genes is attenuated in swine and confers protection against challenge with the virulent parental virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The control of African Swine Fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines h...

  16. Deletion of African swine fever virus Georgia 2007 virulence-associated gene 9GL (B119L) leads to virus attenuation in swine at low doses while inducing an effective protection against homologous challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs that has significant economic consequences for swine breeding. The control of African Swine Fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines...

  17. African bees to control African elephants

    NASA Astrophysics Data System (ADS)

    Vollrath, Fritz; Douglas-Hamilton, Iain

    2002-11-01

    Numbers of elephants have declined in Africa and Asia over the past 30 years while numbers of humans have increased, both substantially. Friction between these two keystone species is reaching levels which are worryingly high from an ecological as well as a political viewpoint. Ways and means must be found to keep the two apart, at least in areas sensitive to each species' survival. The aggressive African bee might be one such method. Here we demonstrate that African bees deter elephants from damaging the vegetation and trees which house their hives. We argue that bees can be employed profitably to protect not only selected trees, but also selected areas, from elephant damage.

  18. Radioisotope Power System Pool Concept

    NASA Technical Reports Server (NTRS)

    Rusick, Jeffrey J.; Bolotin, Gary S.

    2015-01-01

    Advanced Radioisotope Power Systems (RPS) for NASA deep space science missions have historically used static thermoelectric-based designs because they are highly reliable, and their radioisotope heat sources can be passively cooled throughout the mission life cycle. Recently, a significant effort to develop a dynamic RPS, the Advanced Stirling Radioisotope Generator (ASRG), was conducted by NASA and the Department of Energy, because Stirling based designs offer energy conversion efficiencies four times higher than heritage thermoelectric designs; and the efficiency would proportionately reduce the amount of radioisotope fuel needed for the same power output. However, the long term reliability of a Stirling based design is a concern compared to thermoelectric designs, because for certain Stirling system architectures the radioisotope heat sources must be actively cooled via the dynamic operation of Stirling converters throughout the mission life cycle. To address this reliability concern, a new dynamic Stirling cycle RPS architecture is proposed called the RPS Pool Concept.

  19. OBS FOMAR POOL: Gibraltar and ALERTES-RIM experiments.

    NASA Astrophysics Data System (ADS)

    Pazos, Antonio; Martín Davila, Jose; Buforn, Elisa; Cabieces, Roberto; Santos, Jose; Sandoval, Nicolas; Roca, Antoni; Dahm, Torsten

    2016-04-01

    The Eurasian-African plate boundary crosses the called "Ibero-Maghrebian" region from the San Vicente Cape (SW Portugal) to Tunisia including the south Iberia, Alboran Sea, and northern of Morocco and Algeria. The low convergence rate at this plate boundary produces a continuous moderate seismic activity of low magnitude and shallow depth, where the occurrence of large earthquakes is separated by long time intervals, even with associated tsunamis, like the 1755 Lisbon earthquake. In this region, there are also intermediate and very deep earthquakes. Due to the fact that part of the seismic activity is located at marine areas, and also because of the poor geographic azimuthal coverage at some zones provided by the land stations (specially in the SW of the San Vicente Cape area), Royal Spanish Navy Observatory (ROA) acquired three "LOSTERN" broad band (CMG-40T sensors) OBS, manufactured by KUM (Kiel, Germany), and, more recently (2014), the Complutense University of Madrid (UCM) acquired another three with Trillium 120 sensors. All of them conform the OBS FOMAR pool. Since January to November 2014, the FOMAR pool has been deployed along the Gibraltar strait (Gibraltar experiment), in collaboration with SECEGSA (Spanish society to study the fix communication through the Gibraltar Strait), to study the local microseismicity in the Gibraltar strait area. Also, since September 2015, the FOMAR pool has been deployed for 8 months in SW of the San Vicente Cape with an hexagonal array configuration as a part of ALERTES-RIM project. In this work the some preliminary results of the Gibraltar strait and ALERTES-RIM OBS experiment are shown.

  20. Black versus Black: The Relationship among African, African American, and African Caribbean Persons.

    ERIC Educational Resources Information Center

    Jackson, Jennifer V.; Cothran, Mary E.

    2003-01-01

    Surveyed people of African descent regarding relationships among African, African-American, and African-Caribbean persons, focusing on contact and friendship, travel to countries of the diaspora, cross-cultural communication, thoughts and stereotypes, and education. Most respondents had contacts with the other groups, but groups had preconceived…

  1. Selective DNA pooling for determination of linkage between a molecular marker and a quantitative trait locus

    SciTech Connect

    Darvasi, A.; Soller, M.

    1994-12-01

    Selective genotyping is a method to reduce costs in marker-quantitative trait locus (QTL) linkage determination by genotyping only those individuals with extreme, and hence most informative, quantitative trait values. The DNA pooling strategy (termed: {open_quotes}selective DNA pooling{close_quotes}) takes this one step further by pooling DNA from the selected individuals at each of the two phenotypic extremes, and basing the test for linkage on marker allele frequencies as estimated from the pooled samples only. This can reduce genotyping costs of marker-QTL linkage determination by up to two orders of magnitude. Theoretical analysis of selective DNA pooling shows that for experiments involving backcross, F{sub 2} and half-sib designs, the power of selective DNA pooling for detecting genes with large effect can be the same as that obtained by individual selective genotyping. Power for detecting genes with small effect, however, was found to decrease strongly with increase in the technical error of estimating allele frequencies in the pooled samples. The effect of technical error, however, can be markedly reduced by replication of technical procedures. It is also shown that a proportion selected of 0.1 at each tail will be appropriate for a wide range of experimental conditions. 25 refs., 3 figs., 3 tabs.

  2. Selective DNA Pooling for Determination of Linkage between a Molecular Marker and a Quantitative Trait Locus

    PubMed Central

    Darvasi, A.; Soller, M.

    1994-01-01

    Selective genotyping is a method to reduce costs in marker-quantitative trait locus (QTL) linkage determination by genotyping only those individuals with extreme, and hence most informative, quantitative trait values. The DNA pooling strategy (termed: ``selective DNA pooling'') takes this one step further by pooling DNA from the selected individuals at each of the two phenotypic extremes, and basing the test for linkage on marker allele frequencies as estimated from the pooled samples only. This can reduce genotyping costs of marker-QTL linkage determination by up to two orders of magnitude. Theoretical analysis of selective DNA pooling shows that for experiments involving backcross, F(2) and half-sib designs, the power of selective DNA pooling for detecting genes with large effect, can be the same as that obtained by individual selective genotyping. Power for detecting genes with small effect, however, was found to decrease strongly with increase in the technical error of estimating allele frequencies in the pooled samples. The effect of technical error, however, can be markedly reduced by replication of technical procedures. It is also shown that a proportion selected of 0.1 at each tail will be appropriate for a wide range of experimental conditions. PMID:7896115

  3. Microbiological Analysis in Three Diverse Natural Geothermal Bathing Pools in Iceland

    PubMed Central

    Thorolfsdottir, Berglind Osk Th.; Marteinsson, Viggo Thor

    2013-01-01

    Natural thermal bathing pools contain geothermal water that is very popular to bathe in but the water is not sterilized, irradiated or treated in any way. Increasing tourism in Iceland will lead to increasing numbers of bath guests, which can in turn affect the microbial flora in the pools and therefore user safety. Today, there is no legislation that applies to natural geothermal pools in Iceland, as the water is not used for consumption and the pools are not defined as public swimming pools. In this study, we conducted a microbiological analysis on three popular but different natural pools in Iceland, located at Lýsuhóll, Hveravellir and Landmannalaugar. Total bacterial counts were performed by flow cytometry, and with plate count at 22 °C, 37 °C and 50 °C. The presence of viable coliforms, Enterococcus spp. and pseudomonads were investigated by growth experiments on selective media. All samples were screened for noroviruses by real time PCR. The results indicate higher fecal contamination in the geothermal pools where the geothermal water flow was low and bathing guest count was high during the day. The number of cultivated Pseudomonas spp. was high (13,000–40,000 cfu/100 mL) in the natural pools, and several strains were isolated and classified as opportunistic pathogens. Norovirus was not detected in the three pools. DNA was extracted from one-liter samples in each pool and analyzed by partial 16S rRNA gene sequencing. Microbial diversity analysis revealed different microbial communities between the pools and they were primarily composed of alpha-, beta- and gammaproteobacteria. PMID:23493033

  4. Astronomy for African development

    NASA Astrophysics Data System (ADS)

    Govender, Kevindran

    2011-06-01

    In recent years there have been a number of efforts across Africa to develop the field of astronomy as well as to reap benefit from astronomy for African people. This presentation will discuss the case of the SALT (Southern African Large Telescope) Collateral Benefits Programme (SCBP) which was set up to ensure societal benefit from astronomy. With African society as the target, the SCBP has embarked on various projects from school level education to public understanding of science to socio-economic development, the latter mainly being felt in the rural communities surrounding the South African Astronomical Observatory (home to SALT). A development plan for ``Astronomy in Africa'' will also be discussed. This plan has been drawn up with input from all over Africa and themed ``Astronomy for Education''. The Africa case stands as a good example for the IYA cornerstone project ``Developing Astronomy Globally'' which focuses on developing regions.

  5. African American Suicide

    MedlinePlus

    ... accounted for 83.8% of Caucasian elderly suicides. • Firearms were the predominant method of suicide among African ... per 100,000 annually. Source: Centers for Disease Control and Prevention. National Vital Statistics System. Mortality Data. ...

  6. The role of convectively-generated cold pools on model biases in the Sahara

    NASA Astrophysics Data System (ADS)

    Garcia-Carreras, Luis; Marsham, John H.; Parker, Douglas J.; Bain, Caroline L.; Milton, Sean; Saci, Azzedine; Salah-Ferroudj, Mohammed; Ouchene, Bouziane; Washington, Richard

    2013-04-01

    Radiosonde data from Fennec supersite-1 (Bordj Badji Mokhtar, Algeria) have been used to confront for the first time global model behaviour in the remote Sahara with regular in-situ profile observations. Convectively-generated cold pools are produced by the evaporation of precipitation and can propagate over large distances, particularly at night. These are an important component of mesoscale convective systems, which produce the majority of rainfall in the Sahel, and have been observed to ventilate the Sahara. Cold pools are, however, very poorly captured by parameterisations of convection. We assess how cold pool outflows from moist convection contribute to model biases in the Sahara and evaluate the impact of data assimilation on model analyses. The Saharan heat low is too warm and dry in the forecast and cold pools are shown to contribute to the majority of the mean bias. Although the model does not represent dust and cold pools are an important dust uplift mechanism, the sign of the errors is inconsistent with radiative impacts of dust. These biases can therefore be directly attributed to the missing advective cooling from cold pools. Cold pools cause 29% of the observed meridional humidity flux, but this contribution is absent both in the forecast and analysis, thus affecting the large-scale water cycle of the West African monsoon/Saharan heat low system. Assimilation of the radiosonde data reduces these errors, but significant temperature and meridional humidity-flux biases remain at night, when cold pools are most frequent and intense. This implies that significant errors remain in the analysis, and that these biases have a diurnal cycle which will in turn affect the diurnal cycle in the model. The model biases are consistent with the larger-scale heat-low biases in the operational Unified Model. Furthermore, model analyses show significant differences in the Sahara, hampering efforts to evaluate model performance in such a data-sparse region. These issues

  7. 21 CFR 1250.89 - Swimming pools.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... types of salt water pools shall be so operated that complete circulation and replacement of the water in... equipped so as to provide complete circulation, replacement, and filtration of the water in the pool every six hours or less. Suitable means of chlorination and, if necessary, other treatment of the...

  8. LinguisticBelief and PoolEvidence

    SciTech Connect

    DARBY, JOHN

    2008-03-11

    LinguisticBelief allows the creation and analysis of combinations of linguistic variables with epistemic uncertainty for decision making. The model is solved using approximate reasoning to implement the belief/plausibility measure of uncertainty for combinations of variables expressed as purely linguistic fuzzy sets. PoolEvidence pools evidence for linguistic variables from many experts for input into LinguisticBelief.

  9. 47 CFR 97.523 - Question pools.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Question pools. 97.523 Section 97.523 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.523 Question pools. All VECs must cooperate in maintaining...

  10. 47 CFR 97.523 - Question pools.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 false Question pools. 97.523 Section 97.523 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.523 Question pools. All VECs must cooperate in maintaining...

  11. 47 CFR 97.523 - Question pools.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Question pools. 97.523 Section 97.523 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.523 Question pools. All VECs must cooperate in maintaining...

  12. 47 CFR 97.523 - Question pools.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Question pools. 97.523 Section 97.523 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.523 Question pools. All VECs must cooperate in maintaining...

  13. 47 CFR 97.523 - Question pools.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Question pools. 97.523 Section 97.523 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Qualifying Examination Systems § 97.523 Question pools. All VECs must cooperate in maintaining...

  14. The Chemistry of Swimming Pool Maintenance

    ERIC Educational Resources Information Center

    Salter, Carl; Langhus, David L.

    2007-01-01

    The study of chemistry involved in the maintenance of a swimming pool provides a lot of chemical education to the students, including the demonstration of the importance of pH in water chemistry. The various chemical aspects hidden in the maintenance of the pool are being described.

  15. 10 CFR 36.33 - Irradiator pools.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... purification system designed to be capable of maintaining the water during normal operation at a conductivity..., irradiator pools must either: (1) Have a water-tight stainless steel liner or a liner metallurgically... water level that could allow water to drain out of the pool. Pipes that have intakes more than 0.5...

  16. 10 CFR 36.33 - Irradiator pools.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... purification system designed to be capable of maintaining the water during normal operation at a conductivity..., irradiator pools must either: (1) Have a water-tight stainless steel liner or a liner metallurgically... water level that could allow water to drain out of the pool. Pipes that have intakes more than 0.5...

  17. Camera Would Monitor Weld-Pool Contours

    NASA Technical Reports Server (NTRS)

    Gordon, Stephen S.; Gutow, David A.

    1990-01-01

    Weld pool illuminated and viewed coaxially along welding torch. Proposed monitoring subsystem for arc welder provides image in which horizontal portions of surface of weld pool highlighted. Monitoring and analyzing subsystems integrated into overall control system of robotic welder. Control system sets welding parameters to adapt to changing conditions, maintaining surface contour giving desired pattern of reflections.

  18. 10 CFR 36.33 - Irradiator pools.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Irradiator pools. 36.33 Section 36.33 Energy NUCLEAR....02 millisievert (2 millirems) per hour. ... issued after July 1, 1993, irradiator pools must have no outlets more than 0.5 meter below the normal...

  19. 21 CFR 1250.89 - Swimming pools.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... types of salt water pools shall be so operated that complete circulation and replacement of the water in... equipped so as to provide complete circulation, replacement, and filtration of the water in the pool every six hours or less. Suitable means of chlorination and, if necessary, other treatment of the...

  20. 21 CFR 1250.89 - Swimming pools.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... equipped so as to provide complete circulation, replacement, and filtration of the water in the pool every six hours or less. Suitable means of chlorination and, if necessary, other treatment of the water... types of salt water pools shall be so operated that complete circulation and replacement of the water...

  1. 21 CFR 1250.89 - Swimming pools.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... equipped so as to provide complete circulation, replacement, and filtration of the water in the pool every six hours or less. Suitable means of chlorination and, if necessary, other treatment of the water... types of salt water pools shall be so operated that complete circulation and replacement of the water...

  2. A Training Program for Swimming Pool Operators.

    ERIC Educational Resources Information Center

    Pope, James R., Jr.; Mihalik, Brian J.

    1985-01-01

    In the United States today, there is a dramatic shortage of qualified public swimming pool operators. This article describes a training program initiated in South Carolina to serve the needs of everyone responsible for and involved in the safe operation and management of a public swimming pool. (MT)

  3. African Swine Fever Virus Georgia 2007 with a Deletion of Virulence-Associated Gene 9GL (B119L), when Administered at Low Doses, Leads to Virus Attenuation in Swine and Induces an Effective Protection against Homologous Challenge

    PubMed Central

    O'Donnell, Vivian; Holinka, Lauren G.; Krug, Peter W.; Gladue, Douglas P.; Carlson, Jolene; Sanford, Brenton; Alfano, Marialexia; Kramer, Edward; Lu, Zhiqiang; Arzt, Jonathan; Reese, Bo; Carrillo, Consuelo; Risatti, Guillermo R.

    2015-01-01

    ABSTRACT African swine fever virus (ASFV) is the etiological agent of an often lethal disease of domestic pigs. Disease control strategies have been hampered by the unavailability of vaccines against ASFV. Since its introduction in the Republic of Georgia, a highly virulent virus, ASFV Georgia 2007 (ASFV-G), has caused an epizootic that spread rapidly into Eastern European countries. Currently no vaccines are available or under development to control ASFV-G. In the past, genetically modified ASFVs harboring deletions of virulence-associated genes have proven attenuated in swine, inducing protective immunity against challenge with homologous parental viruses. Deletion of the gene 9GL (open reading frame [ORF] B119L) in highly virulent ASFV Malawi-Lil-20/1 produced an attenuated phenotype even when administered to pigs at 106 50% hemadsorption doses (HAD50). Here we report the construction of a genetically modified ASFV-G strain (ASFV-G-Δ9GLv) harboring a deletion of the 9GL (B119L) gene. Like Malawi-Lil-20/1-Δ9GL, ASFV-G-Δ9GL showed limited replication in primary swine macrophages. However, intramuscular inoculation of swine with 104 HAD50 of ASFV-G-Δ9GL produced a virulent phenotype that, unlike Malawi-Lil-20/1-Δ9GL, induced a lethal disease in swine like parental ASFV-G. Interestingly, lower doses (102 to 103 HAD50) of ASFV-G-Δ9GL did not induce a virulent phenotype in swine and when challenged protected pigs against disease. A dose of 102 HAD50 of ASFV-G-Δ9GLv conferred partial protection when pigs were challenged at either 21 or 28 days postinfection (dpi). An ASFV-G-Δ9GL HAD50 of 103 conferred partial and complete protection at 21 and 28 dpi, respectively. The information provided here adds to our recent report on the first attempts toward experimental vaccines against ASFV-G. IMPORTANCE The main problem for controlling ASF is the lack of vaccines. Studies on ASFV virulence lead to the production of genetically modified attenuated viruses that induce

  4. Molecular identification of potential pathogens in water and air of a hospital therapy pool

    PubMed Central

    Angenent, Largus T.; Kelley, Scott T.; Amand, Allison St.; Pace, Norman R.; Hernandez, Mark T.

    2005-01-01

    Indoor warm-water therapy pool workers in a Midwestern regional hospital were diagnosed with non-tuberculosis pulmonary hypersensitive pneumonitis and Mycobacterium avium infections. In response, we conducted a multiseason survey of microorganisms present in this therapy pool water, in biofilms associated with the pool containment walls, and in air immediately above the pool. The survey used culture, microscopy, and culture-independent molecular phylogenetic analyses. Although outfitted with a state-of-the-art UV-peroxide disinfection system, the numbers of bacteria in the therapy pool water were relatively high compared with the potable water used to fill the pool. Regardless of the source, direct microscopic counts of microbes were routinely ≈1,000 times greater than conventional plate counts. Analysis of clone libraries of small subunit rRNA genes from environmental DNA provided phylogenetic diversity estimates of the microorganisms collected in and above the pool. A survey of >1,300 rRNA genes yielded a total of 628 unique sequences, the most common of which was nearly identical to that of M. avium strains. The high proportion of clones with different Mycobacterium spp. rRNA genes suggested that such organisms comprised a significant fraction of microbes in the pool water (to >30%) and preferentially partition into aerosols (to >80%) relative to other waterborne bacteria present. The results of the study strongly validate aerosol partitioning as a mechanism for disease transfer in these environments. The results also show that culture protocols currently used by public health facilities and agencies are seriously inadequate for the detection and enumeration of potential pathogens. PMID:15769858

  5. Population affinities of African Colombians to Sub-Saharan Africans based on dental morphology.

    PubMed

    Delgado-Burbano, M E

    2007-01-01

    The Atlantic slave trade moved more than 13 million Africans to American lands between the 15th and 19th centuries. Previous historical, linguistic, and social-cultural studies suggested a Western-Central Bantu African origin for the Colombian slaves; however, their precise provenance remains unclear. The present study investigates the variation of the epigenetic dental traits in the deciduous and permanent dentition and phenotypic affinities of a contemporary Afro-Colombian community (n=178) in an attempt to identify their possible African ancestors. The results of a multivariate analysis of principal components show that Afro-descendents from Guapi have strong phenotypic relationships with several Bantu-speakers groups of Western and Western-Central Africa (Sub-Saharan region), specifically from Gabon, Congo, Pygmies, Nigeria, Cameroon, Togo and Benin. In concordance with recent mtDNA studies, this research suggests a distant but important relationship between Afro-Colombians and Eastern and South-Eastern African populations. This analysis also shows a marked dental divergence with North African samples. The dental information is not very different from the cultural, linguistic and historic data; however, it is more in agreement with studies based on molecular variation. In addition, this study reveals that African-Americans from North America, Central America-Caribbean and South America have high biological variation essentially identical to their several Sub-Saharan sources. Although a microevolutionary model, based on differential rates of gene flow with Native American and European-American groups and little selective pressures influence, better explains the phenotypic variation observed, more African-American dental samples must be analyzed from a regional perspective. PMID:17675007

  6. Antigenic variation in African trypanosomes

    PubMed Central

    Horn, David

    2014-01-01

    Studies on Variant Surface Glycoproteins (VSGs) and antigenic variation in the African trypanosome, Trypanosoma brucei, have yielded a remarkable range of novel and important insights. The features first identified in T. brucei extend from unique to conserved-among-trypanosomatids to conserved-among-eukaryotes. Consequently, much of what we now know about trypanosomatid biology and much of the technology available has its origin in studies related to VSGs. T. brucei is now probably the most advanced early branched eukaryote in terms of experimental tractability and can be approached as a pathogen, as a model for studies on fundamental processes, as a model for studies on eukaryotic evolution or often all of the above. In terms of antigenic variation itself, substantial progress has been made in understanding the expression and switching of the VSG coat, while outstanding questions continue to stimulate innovative new approaches. There are large numbers of VSG genes in the genome but only one is expressed at a time, always immediately adjacent to a telomere. DNA repair processes allow a new VSG to be copied into the single transcribed locus. A coordinated transcriptional switch can also allow a new VSG gene to be activated without any detectable change in the DNA sequence, thereby maintaining singular expression, also known as allelic exclusion. I review the story behind VSGs; the genes, their expression and switching, their central role in T. brucei virulence, the discoveries that emerged along the way and the persistent questions relating to allelic exclusion in particular. PMID:24859277

  7. Apparatus for draining lower drywell pool water into suppresion pool in boiling water reactor

    DOEpatents

    Gluntz, Douglas M.

    1996-01-01

    An apparatus which mitigates temperature stratification in the suppression pool water caused by hot water drained into the suppression pool from the lower drywell pool. The outlet of a spillover hole formed in the inner bounding wall of the suppression pool is connected to and in flow communication with one end of piping. The inlet end of the piping is above the water level in the suppression pool. The piping is routed down the vertical downcomer duct and through a hole formed in the thin wall separating the downcomer duct from the suppression pool water. The piping discharge end preferably has an elevation at or near the bottom of the suppression pool and has a location in the horizontal plane which is removed from the point where the piping first emerges on the suppression pool side of the inner bounding wall of the suppression pool. This enables water at the surface of the lower drywell pool to flow into and be discharged at the bottom of the suppression pool.

  8. African-Americans and Alzheimer's

    MedlinePlus

    ... Share Plus on Google Plus African-Americans and Alzheimer's alz.org | IHaveAlz Introduction 10 Warning Signs Brain ... African-Americans are at a higher risk for Alzheimer's disease. Many Americans dismiss the warning signs of ...

  9. 10 CFR 36.63 - Pool water purity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Pool water purity. 36.63 Section 36.63 Energy NUCLEAR... § 36.63 Pool water purity. (a) Pool water purification system must be run sufficiently to maintain the conductivity of the pool water below 20 microsiemens per centimeter under normal circumstances. If pool...

  10. 10 CFR 36.63 - Pool water purity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Pool water purity. 36.63 Section 36.63 Energy NUCLEAR... § 36.63 Pool water purity. (a) Pool water purification system must be run sufficiently to maintain the conductivity of the pool water below 20 microsiemens per centimeter under normal circumstances. If pool...

  11. 10 CFR 36.63 - Pool water purity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Pool water purity. 36.63 Section 36.63 Energy NUCLEAR... § 36.63 Pool water purity. (a) Pool water purification system must be run sufficiently to maintain the conductivity of the pool water below 20 microsiemens per centimeter under normal circumstances. If pool...

  12. 13 CFR 120.1709 - Transfers of Pool Certificates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Establishment of SBA Secondary Market Guarantee Program for First Lien Position 504 Loan Pools § 120.1709... transfer. The Pool Investor must supply the following information in the letter: (1) Pool number; (2) Pool Certificate number; (3) Name of purchaser of Pool Certificate; (4) Address and tax identification number...

  13. Swimming Pools. A Guide to Their Planning, Design and Operation.

    ERIC Educational Resources Information Center

    Gabrielsen, M. Alexander, Ed.

    Information is presented regarding all phases of swimming pool development and operation from earliest planning considerations to final programing. This comprehensive book covers--(1) the steps involved in planning a pool, (2) designing the pool, (3) water circulation, filtration, and treatment, (4) community pools, school and agency pools, and…

  14. Pool-Riffle Formation in Mountain Streams

    NASA Astrophysics Data System (ADS)

    Chartrand, S. M.; Hassan, M. A.

    2014-12-01

    Pool-riffle formation in low-sinuosity mountain streams is thought to occur through at least two different mechanisms: (1) a transient flow obstruction converges flow, drives pool development and results in an upstream and downstream riffle, (2) variations in channel or valley width set up converging and expanding zones of flow, which leads to pool and riffle development, respectively. These two mechanisms require a width gradient which is not always present, or obviously so along all pool-riffle channel reaches. We propose a third formative mechanism to account for nearly uniform channel width profiles which depends on a spatially discrete and strong change in the bed surface grain size distribution that is characterized as coarse and perhaps better sorted than prevailing conditions. We are testing each of these formative mechanisms plus a no forcing alternative with physical experimentation and numerical modeling. We will present initial observations and findings from our work, focused on addressing the following three questions: (a) does each formative mechanism result in pool-riffle pair development? (b) if a pool-riffle pair forms, are the associated perturbations to the flow and sediment transport fields sufficient for development of additional pool-riffle pairs? and (c) are resultant morphologies comparable in terms of geometries?

  15. Pool-riffle Maintenance in Mountain Streams

    NASA Astrophysics Data System (ADS)

    Chartrand, S. M.

    2015-12-01

    Pool-riffles are maintained through a combination of at least several mechanisms that operate and interact over a range of temporal and spatial scales. Velocity or shear reversal is subsumed within several of these mechanisms, however a growing body of work suggests that (1) flow convergence into pools, (2) structuring of riffle crest sediments, and (3) local feedbacks between flood stage bedform evolution and hydrodynamics may be disproportionately important. We additionally propose that temporal and spatial patterns of sediment sorting across pool-riffles may also provide some level of bedform maintenance. A comprehensive understanding of these maintenance mechanisms is needed. We will report results of several flume experiments for autogenic pool-riffles. The experiments examined pool-riffle maintenance processes under variable flood and sediment supply conditions. A focus of our work is to characterize spatial and temporal patterns of pool-riffle sediment sorting, and to examine this in relation to temporal patterns of bedform evolution. The experiments represent a 5:1 scale-model of a prototype reach of a pool-riffle stream located within the University of British Columbia Malcolm Knapp Research Forest, Maple Ridge, BC.

  16. Genotyping common and rare variation using overlapping pool sequencing

    PubMed Central

    2011-01-01

    Background Recent advances in sequencing technologies set the stage for large, population based studies, in which the ANA or RNA of thousands of individuals will be sequenced. Currently, however, such studies are still infeasible using a straightforward sequencing approach; as a result, recently a few multiplexing schemes have been suggested, in which a small number of ANA pools are sequenced, and the results are then deconvoluted using compressed sensing or similar approaches. These methods, however, are limited to the detection of rare variants. Results In this paper we provide a new algorithm for the deconvolution of DNA pools multiplexing schemes. The presented algorithm utilizes a likelihood model and linear programming. The approach allows for the addition of external data, particularly imputation data, resulting in a flexible environment that is suitable for different applications. Conclusions Particularly, we demonstrate that both low and high allele frequency SNPs can be accurately genotyped when the DNA pooling scheme is performed in conjunction with microarray genotyping and imputation. Additionally, we demonstrate the use of our framework for the detection of cancer fusion genes from RNA sequences. PMID:21989232

  17. Transthyretin isoleucine-122 mutation in African and American blacks.

    PubMed

    Afolabi, I; Hamidi Asl, K; Nakamura, M; Jacobs, P; Hendrie, H; Benson, M D

    2000-06-01

    The gene frequency of the transthyretin (TTR) mutation (Val122Ile) was studied in African and African-American populations. The African populations analyzed included the Zulu and Xhosa of South Africa, and Yorubas from the city of Ibadan, Nigeria. The African-American population included patients at the Veterans Affairs (VA) Medical Center, Indianapolis, and newborns from a local hospital in Indianapolis. The Val122Ile TTR mutation was identified in 1 of 55 Zulu, 0 of 34 Xhosa, 0 of 9 Nigerian subjects, 5 of 51 Veteran patients, and 3 of 103 newborns. Assuming the 2.91% prevalence in newborns to be the norm, there is a significant increased prevalence in the VA patient population. PMID:10842715

  18. Airways disorders and the swimming pool.

    PubMed

    Bougault, Valérie; Boulet, Louis-Philippe

    2013-08-01

    Concerns have been expressed about the possible detrimental effects of chlorine derivatives in indoor swimming pool environments. Indeed, a controversy has arisen regarding the possibility that chlorine commonly used worldwide as a disinfectant favors the development of asthma and allergic diseases. The effects of swimming in indoor chlorinated pools on the airways in recreational and elite swimmers are presented. Recent studies on the influence of swimming on airway inflammation and remodeling in competitive swimmers, and the phenotypic characteristics of asthma in this population are reviewed. Preventative measures that could potentially reduce the untoward effects of pool environment on airways of swimmers are discussed. PMID:23830132

  19. The Struggles over African Languages

    ERIC Educational Resources Information Center

    Maseko, Pam; Vale, Peter

    2016-01-01

    In this interview, African Language expert Pam Maseko speaks of her own background and her first encounter with culture outside of her mother tongue, isiXhosa. A statistical breakdown of South African languages is provided as background. She discusses Western (originally missionary) codification of African languages and suggests that this approach…

  20. Psychological Misdiagnosis of African Americans.

    ERIC Educational Resources Information Center

    Garretson, Deborah J.

    1993-01-01

    Reviews historical and current problems with making accurate psychological diagnoses of African Americans. Suggests that misdiagnosis is strongly related to pathologization of African-American culture itself. Explores diagnostic process, stereotypes of African-American psychopathology, cultural differences in values and life stressors, and…