A unifying study of phenotypic and molecular genetic variability in natural populations of Anadenanthera colubrina var. cebil from Yungas and Paranaense biogeographic provinces in Argentina

Anadenanthera colubrina var. cebil is a native tree species in the South American subtropical forests that is discontinuously distributed. Thirteen quantitative traits and eight nuclear microsatellite loci were examined in individuals from two biogeographic provinces of Argentina in order to determine the number and composition of genetically distinguishable groups of individuals and explore possible spatial patterns of thephenotypic and genetic variability. Means of reproductive traits were higher in the Yungas than in the Paranaense biogeographic province whereas five out of eight non-reproductive quantitative traits showed higher mean values in the latter. Variance coefficients were moderate, and Analyses of Variance resulted in significant differences between and within provinces. Three clusters were defined based on spatial model for cluster membership for quantitative traits. One cluster grouped the individuals from the Paranaense biogeographic province whereas the individuals from the Yungas biogeographic province grouped regarding its population of origin. Parameters of molecular genetic variability showed higher values in the Yungas than in the Paranaense biogeographic province. Observed heterozygosity was lower than expected heterozygosity in both biogeographic provinces indicating an excess of homozygosity. The homozygosity test by Watterson and the exact test by Slatkin suggested diversifying selection for locus Ac41.1. Bayesian clustering spatial model for microsatellites loci data were performed for both all loci and all loci excluding locus Ac41.1. In both analyses two clusters were inferred. AMOVAs revealed similar results for all genotypes and for all genotypes defined excluding locus Ac41.1. Most of the total variance is attributable to genetic variation within clusters. The presence of homogeneous clusters was detected for both the phenotypic and molecular genetic variability. Two Bayesian clustering analyses were performed according to molecular genetic data, and two clusters were inferred. Individuals were assigned to their provinces of origin. Genetic molecular variation was higher in the populations of the Yungas biogeographic province which translates in highly qualified populations for conservation. Populations from the Paranaense biogeographic province showed the highest mean value of number of seeds per fruit making them valuable as well with regard to the exploitation of management strategies as a means to recover the impacted areas where these populations are located.Fil: García, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Prinz, Kathleen. Universität Göttingen; Alemania. Universitat Jena; AlemaniaFil: Barrandeguy, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Miretti, Marcos Mateo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Finkeldey, Reiner. Universitat Jena; Alemani

Modelling the impact of antibody-dependent enhancement on disease severity of Zika virus and dengue virus sequential and co-infection

Human infections with viruses of the genus Flavivirus, including dengue virus (DENV) and Zika virus (ZIKV), are of increasing global importance. Owing to antibody-dependent enhancement (ADE), secondary infection with one Flavivirus following primary infection with another Flavivirus can result in a significantly larger peak viral load with a much higher risk of severe disease. Although several mathematical models have been developed to quantify the virus dynamics in the primary and secondary infections of DENV, little progress has been made regarding secondary infection of DENV after a primary infection of ZIKV, or DENV-ZIKV co-infection. Here, we address this critical gap by developing compartmental models of virus dynamics. We first fitted the models to published data on dengue viral loads of the primary and secondary infections with the observation that the primary infection reaches its peak much more gradually than the secondary infection. We then quantitatively show that ADE is the key factor determining a sharp increase/decrease of viral load near the peak time in the secondary infection. In comparison, our simulations of DENV and ZIKV co-infection (simultaneous rather than sequential) show that ADE has very limited influence on the peak DENV viral load. This indicates pre-existing immunity to ZIKV is the determinant of a high level of ADE effect. Our numerical simulations show that (i) in the absence of ADE effect, a subsequent co-infection is beneficial to the second virus; and (ii) if ADE is feasible, then a subsequent co-infection can induce greater damage to the host with a higher peak viral load and a much earlier peak time for the second virus, and for the second peak for the first virus.Fil: Tang, Biao. University of York; Reino Unido. University of Toronto; CanadáFil: Xiao, Yanni. Xi'an Jiaotong University; ChinaFil: Sander, Beate. University of Toronto; CanadáFil: Kulkarni, Manisha A.. University of Ottawa; CanadáFil: Wu, Jianhong. University of York; Reino UnidoFil: Miretti, Marcos Mateo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; Argentin

Assessing ZIKV transmission dynamics and mitigation strategies : a multidisciplinary approach

The project took place in three Latin American countries that have different epidemiological and ecological settings of Zika virus transmission: Colombia, Argentina and Ecuador; with the objective of characterizing the ecological transmission dynamics of Zika virus (ZIKV) and designing integrated intervention approaches. The report provides country-specific information regarding project implementation. The multi-country regression analysis identified several factors associated with an increased density of adult female Aedes mosquitoes, which represent important risk factors for arboviral disease transmission that can be considered in the design of disease prevention and control strategies. The report includes analysis and outputs from the project

Evaluation of the presence of HLB in Rutaceae in nature reserves in Misiones, Argentina

The disease Huanglongbing (HLB) is currently the most serious threat for Argentina’s Citrus industry. Early diagnosis of affected tissues requires conventional molecular methods, polymerase chain reaction (PCR) or quantitative real time PCR (qPCR), due to the inability to grow any of the bacteria involved in the disease etiology: Candidatus Liberibacter asiaticus (CLas), africanus (CLaf), and americanus (CLam). Because HLB is incipient in Argentina eradication of all infected plants is recommended, however the presence of HLB in wild plants cannot be ruled out or has not been locally studied.EEA Bella VistaFil: Gochez, Alberto Martín. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bella Vista; ArgentinaFil: Aranda, M. Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bella Vista; ArgentinaFil: Velozo, Lucía. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bella Vista; ArgentinaFil: Buemo, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Genética Aplicada; ArgentinaFil: Rodríguez, Manuela. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales; ArgentinaFil: Agostini, Juan Pedro. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Montecarlo; ArgentinaFil: Talavera, Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Genética Aplicada; ArgentinaFil: Alayon Luaces, Paula. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias; ArgentinaFil: Gaiad, Emilio. Universidad Nacional del Nordeste. Facultad de Ciencias Agrarias; ArgentinaFil: Argüelles, Carina F. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Genética Aplicada; ArgentinaFil: Miretti, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Grupo de Investigación en Genética Aplicada; Argentin

Arbovirus vectors of epidemiological concern in the Americas: A scoping review of entomological studies on Zika, dengue and chikungunya virus vectors

Background Three arthropod-borne viruses (arboviruses) causing human disease have been the focus of a large number of studies in the Americas since 2013 due to their global spread and epidemiological impacts: Zika, dengue, and chikungunya viruses. A large proportion of infections by these viruses are asymptomatic. However, all three viruses are associated with moderate to severe health consequences in a small proportion of cases. Two mosquito species, Aedes aegypti and Aedes albopictus, are among the world´s most prominent arboviral vectors, and are known vectors for all three viruses in the Americas. Objectives This review summarizes the state of the entomological literature surrounding the mosquito vectors of Zika, dengue and chikungunya viruses and factors affecting virus transmission. The rationale of the review was to identify and characterize entomological studies that have been conducted in the Americas since the introduction of chikungunya virus in 2013, encompassing a period of arbovirus co-circulation, and guide future research based on identified knowledge gaps. Methods The preliminary search for this review was conducted on PubMed (National Library of Health, Bethesda, MD, United States). The search included the terms ´zika´ OR ´dengue´ OR ´chikungunya´ AND ´vector´ OR ´Aedes aegypti´ OR ´Aedes albopictus´. The search was conducted on March 1st of 2018, and included all studies since January 1st of 2013. Results A total of 96 studies were included in the scoping review after initial screening and subsequent exclusion of out-of-scope studies, secondary data publications, and studies unavailable in English language. Key findings We observed a steady increase in number of publications, from 2013 to 2018, with half of all studies published from January 2017 to March 2018. Interestingly, information on Zika virus vector species composition was abundant, but sparse on Zika virus transmission dynamics. Few studies examined natural infection rates of Zika virus, vertical transmission, or co-infection with other viruses. This is in contrast to the wealth of research available on natural infection and co-infection for dengue and chikungunya viruses, although vertical transmission research was sparse for all three viruses.Fil: Jones, Reilly. University of Toronto; CanadáFil: Kulkarni, Manisha A.. University of Ottawa; CanadáFil: Davidson, Thomas M.V.. University of Toronto; CanadáFil: Sander, Beate. Public Health Ontario; CanadáFil: González, Camila. Universidad de Los Andes; VenezuelaFil: Wu, Jianhong. York University ; CanadáFil: Miretti, Marcos Mateo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Posadas; ArgentinaFil: Espinel, Mauricio. Universidad Laica Elroy Alfaro de Manabí; EcuadorFil: Cevallos Viteri, Varsovia Enid. Instituto Nacional de Salud Pública; EcuadorFil: Cevallos, Varsovia. Instituto Nacional de Salud Pública; EcuadorFil: Talbot, Benoit. University of Ottawa; Canad

Genetic diversity of the Brazilian Creole cattle Pe-duro assessed by microsatellites and mitochondrial DNA

The objective of this study was to describe the genetic diversity and structure of the largest Pe-duro population by assessing variation at ten autosomal microsatellite (STR) loci and mitochondrial DNA (mtDNA) sequences. The mean expected heterozygosity was 0.755, the mean observed heterozygosity was 0.600 and significant inbreeding coefficient (Fis) and deviations from the Hardy-Weinberg equilibrium in most of analyzed loci demonstrate the impact of inbreeding and homozygosis on this population. A more in-depth genetic analysis could be achieved by expanding the STR list. The analysis of mtDNA provided evidence of ancestral African taurine haplotypes in Pe-duro and excluded maternal Zebuine introgression. In this report, the main Pe-duro population is genetically portrayed by sampling approximately 40% of it. As this herd represents the core of the Pe-duro conservation program, these findings are of outstanding value for the management and preservation of this Brazilian 'native' cattle breed.National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development - CNPqFoundation to Support Education, Research and Care of the Hospital of the Medical School of Ribeirao Preto, Universidade de Sao Paulo - FAEPAFoundation to Support Education, Research and Care of the Hospital of the Medical School of Ribeirao Preto, Universidade de Sao Paulo FAEP

Genetic Analysis of Completely Sequenced Disease-Associated MHC Haplotypes Identifies Shuffling of Segments in Recent Human History

The major histocompatibility complex (MHC) is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorphic regions of the human genome such as the MHC are, however, somewhat refractory to some whole-genome analysis methods. To address this issue, we are employing a bacterial artificial chromosome (BAC) cloning strategy to sequence entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3-DQ2) and compare it with the MHC reference haplotype and with a second haplotype, COX (HLA-A1-B8-Cw7-DR3-DQ2), that shares the same HLA-DRB1, -DQA1, and -DQB1 alleles. We have defined the complete gene, splice variant, and sequence variation contents of all three haplotypes, comprising over 259 annotated loci and over 20,000 single nucleotide polymorphisms (SNPs). Certain coding sequences vary significantly between different haplotypes, making them candidates for functional and disease-association studies. Analysis of the two DR3 haplotypes allowed delineation of the shared sequence between two HLA class II–related haplotypes differing in disease associations and the identification of at least one of the sites that mediated the original recombination event. The levels of variation across the MHC were similar to those seen for other HLA-disparate haplotypes, except for a 158-kb segment that contained the HLA-DRB1, -DQA1, and -DQB1 genes and showed very limited polymorphism compatible with identity-by-descent and relatively recent common ancestry (<3,400 generations). These results indicate that the differential disease associations of these two DR3 haplotypes are due to sequence variation outside this central 158-kb segment, and that shuffling of ancestral blocks via recombination is a potential mechanism whereby certain DR–DQ allelic combinations, which presumably have favoured immunological functions, can spread across haplotypes and populations

Variation analysis and gene annotation of eight MHC haplotypes: The MHC Haplotype Project

The human major histocompatibility complex (MHC) is contained within about 4 Mb on the short arm of chromosome 6 and is recognised as the most variable region in the human genome. The primary aim of the MHC Haplotype Project was to provide a comprehensively annotated reference sequence of a single, human leukocyte antigen-homozygous MHC haplotype and to use it as a basis against which variations could be assessed from seven other similarly homozygous cell lines, representative of the most common MHC haplotypes in the European population. Comparison of the haplotype sequences, including four haplotypes not previously analysed, resulted in the identification of >44,000 variations, both substitutions and indels (insertions and deletions), which have been submitted to the dbSNP database. The gene annotation uncovered haplotype-specific differences and confirmed the presence of more than 300 loci, including over 160 protein-coding genes. Combined analysis of the variation and annotation datasets revealed 122 gene loci with coding substitutions of which 97 were non-synonymous. The haplotype (A3-B7-DR15; PGF cell line) designated as the new MHC reference sequence, has been incorporated into the human genome assembly (NCBI35 and subsequent builds), and constitutes the largest single-haplotype sequence of the human genome to date. The extensive variation and annotation data derived from the analysis of seven further haplotypes have been made publicly available and provide a framework and resource for future association studies of all MHC-associated diseases and transplant medicine

Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC) and its application for DNA methylation analysis

Background: The major histocompatibility complex (MHC) is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome.Methods: To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP), methylated DNA immunoprecipitation (MeDIP), array comparative genomic hybridization (aCGH) and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls.Results: Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs). Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation.Conclusion: A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics

Immunogenomics: Molecular hide and seek

<p>Abstract</p> <p>Similar to other classical science disciplines, immunology has been embracing novel technologies and approaches giving rise to specialised sub-disciplines such as immunogenetics and, more recently, immunogenomics, which, in many ways, is the genome-wide application of immunogenetic approaches. Here, recent progress in the understanding of the immune sub-genome will be reviewed, and the ways in which immunogenomic datasets consisting of genetic and epigenetic variation, linkage disequilibrium and recombination can be harnessed for disease association and evolutionary studies will be discussed. The discussion will focus on data available for the major histocompatibility complex and the leukocyte receptor complex, the two most polymorphic regions of the human immune sub-genome.</p