Variation analysis of Swine influenza virus (SIV) H1N1 sequences in experimen...Álvaro L. Valiñas
Swine influenza is a highly contagious and widely distributed disease that generates important economic losses in the pig industry. Nowadays, one of the most extended strategy used to control Swine influenza viruses (SIVs) is the trivalent vaccine application, which formulation contains the most frequently circulating SIV subtypes H1N1, H1N2 and H3N2. These vaccines do not provide sterilizing immunity against the virus, potentially favoring viral evolutionary dynamics. To better understand the main mechanisms that shape viral evolution, in this work, the SIV intra-host diversity was analyzed in samples collected from both, vaccinated and non-vaccinated animals challenged with H1N1 influenza A virus. In the present study 276 single nucleotide variants were found within 28 whole SIV genomes obtained by next generation sequencing. Differences in nucleotide variants between groups were established and the impact of each substitution found was hypothesized according to previous literature. Substitutions were allocated along all influenza genetic segments, while the most relevant non-synonymous substitutions were allocated in the NS1 protein on samples collected only from vaccinated animals. These substitutions could affect both, mRNA viral translation and pathogenesis. Moreover, new viral variants were found in both vaccinated and non-vaccinated pigs, showing relevant substitutions in the HA, NA and NP proteins that may be contributing to evasion of host immune system, virulence and host adaptation. Overall, results of the present study suggest that SIV is continuously evolving despite vaccine application, therefore new substitutions may increase viral fitness under field conditions.
Variation analysis of Swine influenza virus (SIV) H1N1 sequences in experimen...Álvaro L. Valiñas
Swine influenza is a highly contagious and widely distributed disease that generates important economic losses in the pig industry. Nowadays, one of the most extended strategy used to control Swine influenza viruses (SIVs) is the trivalent vaccine application, which formulation contains the most frequently circulating SIV subtypes H1N1, H1N2 and H3N2. These vaccines do not provide sterilizing immunity against the virus, potentially favoring viral evolutionary dynamics. To better understand the main mechanisms that shape viral evolution, in this work, the SIV intra-host diversity was analyzed in samples collected from both, vaccinated and non-vaccinated animals challenged with H1N1 influenza A virus. In the present study 276 single nucleotide variants were found within 28 whole SIV genomes obtained by next generation sequencing. Differences in nucleotide variants between groups were established and the impact of each substitution found was hypothesized according to previous literature. Substitutions were allocated along all influenza genetic segments, while the most relevant non-synonymous substitutions were allocated in the NS1 protein on samples collected only from vaccinated animals. These substitutions could affect both, mRNA viral translation and pathogenesis. Moreover, new viral variants were found in both vaccinated and non-vaccinated pigs, showing relevant substitutions in the HA, NA and NP proteins that may be contributing to evasion of host immune system, virulence and host adaptation. Overall, results of the present study suggest that SIV is continuously evolving despite vaccine application, therefore new substitutions may increase viral fitness under field conditions.
Identification of SNP markers for resistance to Salmonella and IBDV in indige...ILRI
Poster prepared by Psifidi, G. Banos, O. Matika, Tadelle Dessie, R. Christley, P. Wigley, J.M. Bettridge, O. Hanotte, Takele Taye Desta and P. Kaiser for the Annual Meeting of the Society of Veterinary Epidemiology and Preventive Medicine, Madrid, Spain, 20-22 March 2013.
Variation analysis of Swine influenza virus (SIV) H1N1 sequences in experimen...Álvaro L. Valiñas
Swine influenza is a highly contagious and widely distributed disease that generates important economic losses in the pig industry. Nowadays, one of the most extended strategy used to control Swine influenza viruses (SIVs) is the trivalent vaccine application, which formulation contains the most frequently circulating SIV subtypes H1N1, H1N2 and H3N2. These vaccines do not provide sterilizing immunity against the virus, potentially favoring viral evolutionary dynamics. To better understand the main mechanisms that shape viral evolution, in this work, the SIV intra-host diversity was analyzed in samples collected from both, vaccinated and non-vaccinated animals challenged with H1N1 influenza A virus. In the present study 276 single nucleotide variants were found within 28 whole SIV genomes obtained by next generation sequencing. Differences in nucleotide variants between groups were established and the impact of each substitution found was hypothesized according to previous literature. Substitutions were allocated along all influenza genetic segments, while the most relevant non-synonymous substitutions were allocated in the NS1 protein on samples collected only from vaccinated animals. These substitutions could affect both, mRNA viral translation and pathogenesis. Moreover, new viral variants were found in both vaccinated and non-vaccinated pigs, showing relevant substitutions in the HA, NA and NP proteins that may be contributing to evasion of host immune system, virulence and host adaptation. Overall, results of the present study suggest that SIV is continuously evolving despite vaccine application, therefore new substitutions may increase viral fitness under field conditions.
Variation analysis of Swine influenza virus (SIV) H1N1 sequences in experimen...Álvaro L. Valiñas
Swine influenza is a highly contagious and widely distributed disease that generates important economic losses in the pig industry. Nowadays, one of the most extended strategy used to control Swine influenza viruses (SIVs) is the trivalent vaccine application, which formulation contains the most frequently circulating SIV subtypes H1N1, H1N2 and H3N2. These vaccines do not provide sterilizing immunity against the virus, potentially favoring viral evolutionary dynamics. To better understand the main mechanisms that shape viral evolution, in this work, the SIV intra-host diversity was analyzed in samples collected from both, vaccinated and non-vaccinated animals challenged with H1N1 influenza A virus. In the present study 276 single nucleotide variants were found within 28 whole SIV genomes obtained by next generation sequencing. Differences in nucleotide variants between groups were established and the impact of each substitution found was hypothesized according to previous literature. Substitutions were allocated along all influenza genetic segments, while the most relevant non-synonymous substitutions were allocated in the NS1 protein on samples collected only from vaccinated animals. These substitutions could affect both, mRNA viral translation and pathogenesis. Moreover, new viral variants were found in both vaccinated and non-vaccinated pigs, showing relevant substitutions in the HA, NA and NP proteins that may be contributing to evasion of host immune system, virulence and host adaptation. Overall, results of the present study suggest that SIV is continuously evolving despite vaccine application, therefore new substitutions may increase viral fitness under field conditions.
Identification of SNP markers for resistance to Salmonella and IBDV in indige...ILRI
Poster prepared by Psifidi, G. Banos, O. Matika, Tadelle Dessie, R. Christley, P. Wigley, J.M. Bettridge, O. Hanotte, Takele Taye Desta and P. Kaiser for the Annual Meeting of the Society of Veterinary Epidemiology and Preventive Medicine, Madrid, Spain, 20-22 March 2013.
Prevalence and molecular characterisation of Eimeria species in Ethiopian vil...ILRI
Poster prepared by L. Luu , J. Bettridge, R. Christley, K. Melese, D. Blake, Tadelle Dessie, P. Wigley, Takele Taye Desta, O. Hanotte, P. Kaiser, Zelalem Gutu Terfa, M. Collins and S. Lynch for the Annual Meeting of the Society of Veterinary Epidemiology and Preventive Medicine, Madrid, Spain, 20-22 March 2013.
Background
Influenza A viruses are medically significant pathogens responsible for higher mortality and morbidity throughout the world. Swine influenza is known to be caused by influenza A subtypes H1N1, H1N2, and H3N2, which are highly contagious, and belongs to the family Orthomyxoviridae. Efficient and accurate diagnosis of influenza A in individuals is critical for monitoring of a constantly evolving pandemic. A rapid result is important, because timely treatment can reduce disease severity and duration. Rapid antigen tests were among the first-line diagnostic tools for the detection of pandemic H1N1 (2009) virus infection during the initial outbreak. Current study focuses on the significant approach of the usage of molecular method utilizing real-time PCR for the detection of type A influenza virus (H1N1 subtype) in humans.
Methods
A total of 2000 mixed nasal/throat swab specimens collected in commercial viral transport from Apollo hospitals, Hyderabad were submitted to Institute of Preventive Medicine for molecular testing by reverse transcriptase polymerase chain reaction (RT-PCR) from 2009 to 2015 from its affiliated primary care clinics.
Results
Among the 2000 samples collected, 700 samples were positive for Human Inf A, swine Inf A, and Swine Inf H1 (fourth table in the article). One thousand two hundred samples were negative for Human Inf A, swine Inf A, and Swine Inf H1, and 100 samples were positive for Influenza A only.
Conclusion
The molecular testing of H1N1 patients helped the clinicians in timely diagnosis and treatment of these patients during the pandemic surveillance. The RT-PCR test has higher sensitivity and specificity; hence it is considered to be the best tool to use during the pandemic surveillance, as compared to the any other commercial antigen-based tests, which show a variable performance, with the sensitivities of tests from different manufacturers ranging from 9 to 77%.
Transmission of foot-and-mouth disease from persistently infected carrier cat...EuFMD
The 2018 Open Session of the EuFMD Standing Technical Committee was held in Borgo Egnazia - Italy, 29-31 October 2018 . The session theme was on global vaccine security
The European Commission for the Control of Foot-and-Mouth Disease (EuFMD), one of FAO’s oldest Commissions, came into being on the 12th June 1954, with the pledge of the sixth founding member state to the principles of a coordinated and common action against Foot-and-mouth Disease.
Respiratory pathogens in an intensive poultry farm in Debre Zeit, EthiopiaILRI
Poster prepared by S. Hutton, J. Bettridge, T. Habte, R. Christley , E. Sambo and K. Ganapathy for the Annual Meeting of the Society of Veterinary Epidemiology and Preventive Medicine, Madrid, Spain, 20-22 March 2013.
Modern Disease Trends in Correlation to Glyphosate Application: a 20-Year Per...Amen Clinics
Compilation of graphs from the review paper: Glyphosate, pathways to modern disease II: Celiac sprue and gluten intolerance, 2013 - By: Anthony Samsel and Stephanie Seneff. Slide #4 graph (autism) courtesy of Nancy Swanson.
SMBE Satellite Meeting on Pathogen Evolution and TransmissionJennifer Gardy
My slides from the SMBE meeting held February 2016 in Shiga Kogen, Japan - a quick overview of some lessons learned about evolution in a TB outbreak investigation.
Talk at Doherty Institute Advances in Microbial Genomics for Public Health and Clinical Microbiology symposium.
Salmonella genomics for epidemiology and emerging threats.
Ebola virus surveillance in pigs presenting for slaughter in UgandaILRI
Poster by Christine Atherstone, Silvia Alonso, Delia Grace, Michael Ward, Navneet Dhand and Siobhan Mor presented at the 4th International One Health Congress and 6th Biennial Congress of the International Association for Ecology and Health (One Health EcoHealth 2016), Melbourne, Australia, 3–7 December 2016.
Dr. Paulo Arruda - Continuing Diagnostic Investigation–Novel SapelovirusJohn Blue
Continuing Diagnostic Investigation–Novel Sapelovirus - Dr. Paulo Arruda, from the 2016 Allen D. Leman Swine Conference, September 17-20, 2016, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2016-leman-swine-conference-material
Prevalence and molecular characterisation of Eimeria species in Ethiopian vil...ILRI
Poster prepared by L. Luu , J. Bettridge, R. Christley, K. Melese, D. Blake, Tadelle Dessie, P. Wigley, Takele Taye Desta, O. Hanotte, P. Kaiser, Zelalem Gutu Terfa, M. Collins and S. Lynch for the Annual Meeting of the Society of Veterinary Epidemiology and Preventive Medicine, Madrid, Spain, 20-22 March 2013.
Background
Influenza A viruses are medically significant pathogens responsible for higher mortality and morbidity throughout the world. Swine influenza is known to be caused by influenza A subtypes H1N1, H1N2, and H3N2, which are highly contagious, and belongs to the family Orthomyxoviridae. Efficient and accurate diagnosis of influenza A in individuals is critical for monitoring of a constantly evolving pandemic. A rapid result is important, because timely treatment can reduce disease severity and duration. Rapid antigen tests were among the first-line diagnostic tools for the detection of pandemic H1N1 (2009) virus infection during the initial outbreak. Current study focuses on the significant approach of the usage of molecular method utilizing real-time PCR for the detection of type A influenza virus (H1N1 subtype) in humans.
Methods
A total of 2000 mixed nasal/throat swab specimens collected in commercial viral transport from Apollo hospitals, Hyderabad were submitted to Institute of Preventive Medicine for molecular testing by reverse transcriptase polymerase chain reaction (RT-PCR) from 2009 to 2015 from its affiliated primary care clinics.
Results
Among the 2000 samples collected, 700 samples were positive for Human Inf A, swine Inf A, and Swine Inf H1 (fourth table in the article). One thousand two hundred samples were negative for Human Inf A, swine Inf A, and Swine Inf H1, and 100 samples were positive for Influenza A only.
Conclusion
The molecular testing of H1N1 patients helped the clinicians in timely diagnosis and treatment of these patients during the pandemic surveillance. The RT-PCR test has higher sensitivity and specificity; hence it is considered to be the best tool to use during the pandemic surveillance, as compared to the any other commercial antigen-based tests, which show a variable performance, with the sensitivities of tests from different manufacturers ranging from 9 to 77%.
Transmission of foot-and-mouth disease from persistently infected carrier cat...EuFMD
The 2018 Open Session of the EuFMD Standing Technical Committee was held in Borgo Egnazia - Italy, 29-31 October 2018 . The session theme was on global vaccine security
The European Commission for the Control of Foot-and-Mouth Disease (EuFMD), one of FAO’s oldest Commissions, came into being on the 12th June 1954, with the pledge of the sixth founding member state to the principles of a coordinated and common action against Foot-and-mouth Disease.
Respiratory pathogens in an intensive poultry farm in Debre Zeit, EthiopiaILRI
Poster prepared by S. Hutton, J. Bettridge, T. Habte, R. Christley , E. Sambo and K. Ganapathy for the Annual Meeting of the Society of Veterinary Epidemiology and Preventive Medicine, Madrid, Spain, 20-22 March 2013.
Modern Disease Trends in Correlation to Glyphosate Application: a 20-Year Per...Amen Clinics
Compilation of graphs from the review paper: Glyphosate, pathways to modern disease II: Celiac sprue and gluten intolerance, 2013 - By: Anthony Samsel and Stephanie Seneff. Slide #4 graph (autism) courtesy of Nancy Swanson.
SMBE Satellite Meeting on Pathogen Evolution and TransmissionJennifer Gardy
My slides from the SMBE meeting held February 2016 in Shiga Kogen, Japan - a quick overview of some lessons learned about evolution in a TB outbreak investigation.
Talk at Doherty Institute Advances in Microbial Genomics for Public Health and Clinical Microbiology symposium.
Salmonella genomics for epidemiology and emerging threats.
Ebola virus surveillance in pigs presenting for slaughter in UgandaILRI
Poster by Christine Atherstone, Silvia Alonso, Delia Grace, Michael Ward, Navneet Dhand and Siobhan Mor presented at the 4th International One Health Congress and 6th Biennial Congress of the International Association for Ecology and Health (One Health EcoHealth 2016), Melbourne, Australia, 3–7 December 2016.
Dr. Paulo Arruda - Continuing Diagnostic Investigation–Novel SapelovirusJohn Blue
Continuing Diagnostic Investigation–Novel Sapelovirus - Dr. Paulo Arruda, from the 2016 Allen D. Leman Swine Conference, September 17-20, 2016, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2016-leman-swine-conference-material
Kidney pain.org-umUMOD, Translational Nephrology! Contender for Top 10 of 201...StevanSimendic79
Genome-wide association scientific studies (GWAS) are women population based collaborative studies seeking it is partially patterns that would reveal common complex phenotypes.
Identification of a Novel Mutation (p.G328W) in the NR5A1 Gene in a Boy with ...CrimsonPublishersGJEM
The gene NR5A1 (nuclear receptor subfamily 5 group A member 1, OMIM +184757) encodes for the Steroidogenic factor1 (SF1), a key regulator of the adrenal/gonadal development and function. Disorders/Differences of Sex Development (DSD) are defined as conditions where the chromosomal/anatomical, phenotypic sex is atypical. Heterozygous mutations of NR5A1 gene are associated, in 46, XY DSD patients, with a wide phenotypic spectrum of the external genitalia, with or without adrenal failure. Here we report a 46, XY newborn carrying a novel heterozygous NR5A1 mutation that presents with ambiguous genitalia without adrenal failure.
1. TCF7L2 overexpression and Type 2
Diabetes:
Dissecting the function of Tcf7l2 as a
regulator of glucose metabolism
Kathleen Bailey, PhD
Department of Human Genetics
The University of Chicago
2. Genome-Wide Association Studies (GWAS) attempt to uncover the
biology behind complex diseases using a case-control study design
G allele found more
often in cases so may
contribute to disease
risk
3. More than 2,000 GWAS have been published identifying over
15,000 SNPs associated with different traits
NHGRI-EBI GWAS Catalog, www.ebi.ac.uk/gwas
published GWAS at
p<5x10-8 through
May 2014
= GWAS locus
4. NHGRI-EBI GWAS Catalog, www.ebi.ac.uk/gwas
published GWAS at
p<5x10-8 through
May 2014
= GWAS locus
Majority of variants associated with complex disease reside
within non-coding regions of the genome making it less clear
how these variants contribute to disease risk
More than 2,000 GWAS have been published identifying over
15,000 SNPs associated with different traits
5. GWAS for Type 2 diabetes (T2D) risk variants identified non-
coding variation in TCF7L2 as the strongest genetic
determinant of T2D risk
Voight et al. Nature Genetics 2010
TCF7L2
6. The diabetes-associated region within the TCF7L2 locus
encompasses an interval of high linkage disequilibrium
TCF7L2
T2D-associated variation is non-coding and perhaps plays a
regulatory role in TCF7L2 expression
*
Savic et al. Genome Research 2011
7. The majority of TCF7L2 enhancer activity is within sequences
spanning the T2D-associated region
Endogenous RP11-139K1RP11-466I19
LacZ
ATG
100kb
TCF7L2
RP11-466I19
RP11-139K1
*
LacZβ
Savic et al. Genome Research 2011
How does regulatory variation contribute to disease risk?
8. Gene XE E E E
Spatial, temporal, and quantitative control of gene expression
Gene X is expressed in
these four tissues driven
by these four enhancers
9. Gene XE E E E
Spatial, temporal, and quantitative control of gene expression
A mutation in one
enhancer can change
expression in one tissue,
in this case,
overexpression
10. Gene XE E E E
Spatial, temporal, and quantitative control of gene expression
However, a mutation can
also cause
underexpression in one
particular tissue
11. TCF7L2
*
Altered TCF7L2
Expression
Type 2 Diabetes
Susceptibility
Global overexpression Global underexpression
Glucose intolerance?
Does altered expression of TCF7L2 lead to T2D susceptibility
and in which direction does a change in expression lead to
glucose intolerance?
13. Beta cells
Hypothalamus
Liver
Adipocytes
Global overexpression
Tcf7l2E E E E
Goal of this study: Isolate the contribution of overexpression in each
tissue to determine in which tissue does overexpression cause
glucose intolerance
Given the modular action of enhancers, it is likely that Tcf7l2 is
overexpressed in a subset of these tissues leading to increased
risk of T2D