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1. Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQβ1

Author

Valencia, Ana, Vergara, Candelaria, Thio, Chloe L, Vince, Nicolas, Douillard, Venceslas, Grifoni, Alba, Cox, Andrea L, Johnson, Eric O, Kral, Alex H, Goedert, James J, Mangia, Alessandra, Piazzolla, Valeria, Mehta, Shruti H, Kirk, Gregory D, Kim, Arthur Y, Lauer, Georg M, Chung, Raymond T, Price, Jennifer C, Khakoo, Salim I, Alric, Laurent, Cramp, Matthew E, Donfield, Sharyne M, Edlin, Brian R, Busch, Michael P, Alexander, Graeme, Rosen, Hugo R, Murphy, Edward L, Wojcik, Genevieve L, Carrington, Mary, Gourraud, Pierre-Antoine, Sette, Alessandro, Thomas, David L, and Duggal, Priya

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Immunology, Genetics, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Infectious Diseases, Hepatitis, Hepatitis - C, Liver Disease, Emerging Infectious Diseases, Prevention, Good Health and Well Being, Acute Disease, Alleles, Amino Acid Substitution, Black People, Female, Gene Expression, Genome-Wide Association Study, Genotype, HLA-DQ beta-Chains, Hepacivirus, Hepatitis C, Host-Pathogen Interactions, Humans, Leucine, Male, Polymorphism, Single Nucleotide, Proline, Protein Isoforms, Remission, Spontaneous, White People, GWAS, HCV clearance, HLA imputation, HLA-DQβ1, MHC, fine-mapping, hepatitis C virus, host genetics, infection, trans-ancestral, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQβ1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQβ1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQβ1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQβ1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQβ1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

Published
2022

2. Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum

Author

Bin, Lianghua, Malley, Claire, Taylor, Patricia, Boorgula, Meher Preethi, Chavan, Sameer, Daya, Michelle, Mathias, Malaika, Shankar, Gautam, Rafaels, Nicholas, Vergara, Candelaria, Potee, Joseph, Campbell, Monica, Hanifin, Jon M, Simpson, Eric, Schneider, Lynda C, Gallo, Richard L, Hata, Tissa, Paller, Amy S, De Benedetto, Anna, Beck, Lisa A, Ong, Peck Y, Guttman‐Yassky, Emma, Richers, Brittany, Baraghoshi, David, Ruczinski, Ingo, Barnes, Kathleen C, Leung, Donald YM, and Mathias, Rasika A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Biotechnology, Sexually Transmitted Infections, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Skin, Dermatitis, Atopic, Glutathione Transferase, Herpesvirus 1, Human, Humans, Kaposi Varicelliform Eruption, Mutation, Nucleotide Transport Proteins, Whole Genome Sequencing, atopic dermatitis, eczema herpeticum, genetics, herpes simplex virus, SIDT2, whole genome sequencing, SIDT2, Immunology, Allergy
Abstract

BackgroundEczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+).MethodsWhole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH-) and 237 non-atopic control (NA) subjects. Variants were annotated, and a gene-based approach (SKAT-O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation.ResultsEight genes were identified in the comparison of recurrent ADEH+to ADEH-and NA subjects: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. Silencing SIDT2 and RBBP8NL in normal human primary keratinocytes (NHPKs) led to significantly increased HSV-1 replication. SIDT2-silenced NHPKs had decreased gene expression of IFNk and IL1b in response to HSV-1 infection. RBBP8NL-silenced NHPKs had decreased gene expression of IFNk, but increased IL1b. Additionally, silencing SIDT2 and RBBP8NL also inhibited gene expression of keratinocyte differentiation markers keratin 10 (KRT10) and loricrin (LOR).ConclusionSIDT2 and RBBP8NL participate in keratinocyte's response to HSV-1 infection. SIDT2 and RBBP8NL also regulate expression of keratinocyte differentiation genes of KRT10 and LOR.

Published
2021

3. A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus

Author

Vergara, Candelaria, Valencia, Ana, Thio, Chloe L, Goedert, James J, Mangia, Alessandra, Piazzolla, Valeria, Johnson, Eric, Kral, Alex H, O’Brien, Thomas R, Mehta, Shruti H, Kirk, Gregory D, Kim, Arthur Y, Lauer, Georg M, Chung, Raymond T, Cox, Andrea L, Peters, Marion G, Khakoo, Salim I, Alric, Laurent, Cramp, Matthew E, Donfield, Sharyne M, Edlin, Brian R, Busch, Michael P, Alexander, Graeme, Rosen, Hugo R, Murphy, Edward L, Wojcik, Genevieve L, Taub, Margaret A, Thomas, David L, and Duggal, Priya

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Human Genome, Vaccine Related, Hepatitis, Liver Disease, Women's Health, Emerging Infectious Diseases, Prevention, Infectious Diseases, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Biotechnology, Immunization, Hepatitis - C, Aetiology, 2.1 Biological and endogenous factors, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, Female, Genome-Wide Association Study, Hepacivirus, Hepatitis C, Humans, Male, Polymorphism, Single Nucleotide, Ribosomal Proteins, Septins, Sex Factors, Viral Load, HCV, GWAS, Sex, X chromosome, ARL5B, Septin 6, Host-genetics, infection, immune, Medical and Health Sciences, Microbiology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundSpontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors.MethodsTo identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group.ResultsA male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor.ConclusionsThese novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

Published
2021

4. Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection

Author

Vergara, Candelaria, Duggal, Priya, Thio, Chloe L, Valencia, Ana, O’Brien, Thomas R, Latanich, Rachel, Timp, Winston, Johnson, Eric O, Kral, Alex H, Mangia, Alessandra, Goedert, James J, Piazzola, Valeria, Mehta, Shruti H, Kirk, Gregory D, Peters, Marion G, Donfield, Sharyne M, Edlin, Brian R, Busch, Michael P, Alexander, Graeme, Murphy, Edward L, Kim, Arthur Y, Lauer, Georg M, Chung, Raymond T, Cramp, Matthew E, Cox, Andrea L, Khakoo, Salim I, Rosen, Hugo R, Alric, Laurent, Wheelan, Sarah J, Wojcik, Genevieve L, Thomas, David L, and Taub, Margaret A

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Emerging Infectious Diseases, Infectious Diseases, Chronic Liver Disease and Cirrhosis, Hepatitis, Digestive Diseases, Liver Disease, Hepatitis - C, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Black People, Haplotypes, Hepatitis C, Humans, Interferons, Phenotype, Polymorphism, Single Nucleotide, White People, Immunology
Abstract

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P

Published
2020

6. Author Correction: Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Author

Daya, Michelle, Rafaels, Nicholas, Brunetti, Tonya M, Chavan, Sameer, Levin, Albert M, Shetty, Aniket, Gignoux, Christopher R, Boorgula, Meher Preethi, Wojcik, Genevieve, Campbell, Monica, Vergara, Candelaria, Torgerson, Dara G, Ortega, Victor E, Doumatey, Ayo, Johnston, Henry Richard, Acevedo, Nathalie, Araujo, Maria Ilma, Avila, Pedro C, Belbin, Gillian, Bleecker, Eugene, Bustamante, Carlos, Caraballo, Luis, Cruz, Alvaro, Dunston, Georgia M, Eng, Celeste, Faruque, Mezbah U, Ferguson, Trevor S, Figueiredo, Camila, Ford, Jean G, Gan, Weiniu, Gourraud, Pierre-Antoine, Hansel, Nadia N, Hernandez, Ryan D, Herrera-Paz, Edwin Francisco, Jiménez, Silvia, Kenny, Eimear E, Knight-Madden, Jennifer, Kumar, Rajesh, Lange, Leslie A, Lange, Ethan M, Lizee, Antoine, Maul, Pissamai, Maul, Trevor, Mayorga, Alvaro, Meyers, Deborah, Nicolae, Dan L, O'Connor, Timothy D, Oliveira, Ricardo Riccio, Olopade, Christopher O, Olopade, Olufunmilayo, Qin, Zhaohui S, Rotimi, Charles, Vince, Nicolas, Watson, Harold, Wilks, Rainford J, Wilson, James G, Salzberg, Steven, Ober, Carole, Burchard, Esteban G, Williams, L Keoki, Beaty, Terri H, Taub, Margaret A, Ruczinski, Ingo, Mathias, Rasika A, Barnes, Kathleen C, and CAAPA

Subjects
CAAPA
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

7. Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus

Author

Vergara, Candelaria, Thio, Chloe L, Johnson, Eric, Kral, Alex H, O'Brien, Thomas R, Goedert, James J, Mangia, Alessandra, Piazzolla, Valeria, Mehta, Shruti H, Kirk, Gregory D, Kim, Arthur Y, Lauer, Georg M, Chung, Raymond T, Cox, Andrea L, Peters, Marion G, Khakoo, Salim I, Alric, Laurent, Cramp, Matthew E, Donfield, Sharyne M, Edlin, Brian R, Busch, Michael P, Alexander, Graeme, Rosen, Hugo R, Murphy, Edward L, Latanich, Rachel, Wojcik, Genevieve L, Taub, Margaret A, Valencia, Ana, Thomas, David L, and Duggal, Priya

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Nutrition and Dietetics, Hepatitis - C, Emerging Infectious Diseases, Hepatitis, Infectious Diseases, Genetics, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Human Genome, Liver Disease, Infection, Good Health and Well Being, Black People, Female, Genome-Wide Association Study, Hepacivirus, Hepatitis C, Hispanic or Latino, Host-Pathogen Interactions, Humans, Interferons, Interleukins, Major Histocompatibility Complex, Male, Receptors, G-Protein-Coupled, Remission, Spontaneous, United States, Viral Load, White People, GWAS, SNP, Risk, Cytokine, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsSpontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance, but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry.MethodsWe performed genotype analyses of 4423 people from 3 ancestry groups: 2201 persons of African ancestry (445 with HCV clearance and 1756 with HCV persistence), 1739 persons of European ancestry (701 with HCV clearance and 1036 with HCV persistence), and 486 multi-ancestry Hispanic persons (173 with HCV clearance and 313 with HCV persistence). Samples were genotyped using Illumina (San Diego, CA) arrays and statistically imputed to the 1000 Genomes Project. For each ancestry group, the association of single-nucleotide polymorphisms with HCV clearance was tested by log-additive analysis, and then a meta-analysis was performed.ResultsIn the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P = 5.99 × 10-50) and the MHC locus 6p21.32 (P = 1.15 × 10-21). We also associated HCV clearance with polymorphisms in the G-protein-coupled receptor 158 gene (GPR158) at 10p12.1 (P = 1.80 × 10-07). These 3 loci had independent, additive effects of HCV clearance, and account for 6.8% and 5.9% of the variance of HCV clearance in persons of European and African ancestry, respectively. Persons of African or European ancestry carrying all 6 variants were 24-fold and 11-fold, respectively, more likely to clear HCV infection compared with individuals carrying none or 1 of the clearance-associated variants.ConclusionsIn a meta-analysis of data from 3 studies, we found variants in MHC genes, IFNL4-IFNL3, and GPR158 to increase odds of HCV clearance in patients of European and African ancestry. These findings could increase our understanding of immune response to and clearance of HCV infection.

Published
2019

8. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.

Author

Daya, Michelle, Rafaels, Nicholas, Brunetti, Tonya M, Chavan, Sameer, Levin, Albert M, Shetty, Aniket, Gignoux, Christopher R, Boorgula, Meher Preethi, Wojcik, Genevieve, Campbell, Monica, Vergara, Candelaria, Torgerson, Dara G, Ortega, Victor E, Doumatey, Ayo, Johnston, Henry Richard, Acevedo, Nathalie, Araujo, Maria Ilma, Avila, Pedro C, Belbin, Gillian, Bleecker, Eugene, Bustamante, Carlos, Caraballo, Luis, Cruz, Alvaro, Dunston, Georgia M, Eng, Celeste, Faruque, Mezbah U, Ferguson, Trevor S, Figueiredo, Camila, Ford, Jean G, Gan, Weiniu, Gourraud, Pierre-Antoine, Hansel, Nadia N, Hernandez, Ryan D, Herrera-Paz, Edwin Francisco, Jiménez, Silvia, Kenny, Eimear E, Knight-Madden, Jennifer, Kumar, Rajesh, Lange, Leslie A, Lange, Ethan M, Lizee, Antoine, Maul, Pissamai, Maul, Trevor, Mayorga, Alvaro, Meyers, Deborah, Nicolae, Dan L, O'Connor, Timothy D, Oliveira, Ricardo Riccio, Olopade, Christopher O, Olopade, Olufunmilayo, Qin, Zhaohui S, Rotimi, Charles, Vince, Nicolas, Watson, Harold, Wilks, Rainford J, Wilson, James G, Salzberg, Steven, Ober, Carole, Burchard, Esteban G, Williams, L Keoki, Beaty, Terri H, Taub, Margaret A, Ruczinski, Ingo, Mathias, Rasika A, Barnes, Kathleen C, and CAAPA

Subjects
CAAPA, Chromosomes, Human, Pair 8, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 17, Humans, Asthma, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, African Americans, Hispanic Americans, United States, Genome-Wide Association Study, Genetic Loci, Chromosomes, Human, Pair 12, Pair 17, Pair 8, Polymorphism, Single Nucleotide
Abstract

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.

Published
2019

12. Association of HLA-DRB1∗09:01 with tIgE levels among African-ancestry individuals with asthma

Author

Vince, Nicolas, Limou, Sophie, Daya, Michelle, Morii, Wataru, Rafaels, Nicholas, Geffard, Estelle, Douillard, Venceslas, Walencik, Alexandre, Boorgula, Meher Preethi, Chavan, Sameer, Vergara, Candelaria, Ortega, Victor E., Wilson, James G., Lange, Leslie A., Watson, Harold, Nicolae, Dan L., Meyers, Deborah A., Hansel, Nadia N., Ford, Jean G., Faruque, Mezbah U., Bleecker, Eugene R., Campbell, Monica, Beaty, Terri H., Ruczinski, Ingo, Mathias, Rasika A., Taub, Margaret A., Ober, Carole, Noguchi, Emiko, Barnes, Kathleen C., Torgerson, Dara, and Gourraud, Pierre-Antoine

Published
2020
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13. Assembly of a pan-genome from deep sequencing of 910 humans of African descent

Author

Sherman, Rachel M., Forman, Juliet, Antonescu, Valentin, Puiu, Daniela, Daya, Michelle, Rafaels, Nicholas, Boorgula, Meher Preethi, Chavan, Sameer, Vergara, Candelaria, Ortega, Victor E., Levin, Albert M., Eng, Celeste, Yazdanbakhsh, Maria, Wilson, James G., Marrugo, Javier, Lange, Leslie A., Williams, L. Keoki, Watson, Harold, Ware, Lorraine B., Olopade, Christopher O., Olopade, Olufunmilayo, Oliveira, Ricardo R., Ober, Carole, Nicolae, Dan L., Meyers, Deborah A., Mayorga, Alvaro, Knight-Madden, Jennifer, Hartert, Tina, Hansel, Nadia N., Foreman, Marilyn G., Ford, Jean G., Faruque, Mezbah U., Dunston, Georgia M., Caraballo, Luis, Burchard, Esteban G., Bleecker, Eugene R., Araujo, Maria I., Herrera-Paz, Edwin F., Campbell, Monica, Foster, Cassandra, Taub, Margaret A., Beaty, Terri H., Ruczinski, Ingo, Mathias, Rasika A., Barnes, Kathleen C., and Salzberg, Steven L.

Published
2019
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20. Characterizing SARS-CoV-2 Transcription of Subgenomic and Genomic RNAs During Early Human Infection Using Multiplexed Droplet Digital Polymerase Chain Reaction

Author

Hwang, Hyon S, primary, Lo, Che-Min, additional, Murphy, Michael, additional, Grudda, Tanner, additional, Gallagher, Nicholas, additional, Luo, Chun Huai, additional, Robinson, Matthew L, additional, Mirza, Agha, additional, Conte, Madison, additional, Conte, Abigail, additional, Zhou, Ruifeng, additional, Vergara, Candelaria, additional, Brooke, Christopher B, additional, Pekosz, Andrew, additional, Mostafa, Heba H, additional, Manabe, Yukari C, additional, Thio, Chloe L, additional, and Balagopal, Ashwin, additional

Published
2022
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21. Correction: Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection

Author

Vergara, Candelaria, Duggal, Priya, Thio, Chloe L., Valencia, Ana, O’Brien, Thomas R., Latanich, Rachel, Timp, Winston, Johnson, Eric O., Kral, Alex H., Mangia, Alessandra, Goedert, James J., Piazzola, Valeria, Mehta, Shruti H., Kirk, Gregory D., Peters, Marion G., Donfield, Sharyne M., Edlin, Brian R., Busch, Michael P., Alexander, Graeme, Murphy, Edward L., Kim, Arthur Y., Lauer, Georg M., Chung, Raymond T., Cramp, Matthew E., Cox, Andrea L., Khakoo, Salim I., Rosen, Hugo R., Alric, Laurent, Wheelan, Sarah J., Wojcik, Genevieve L., Thomas, David L., and Taub, Margaret A.

Published
2020
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23. Characterizing SARS-CoV-2 transcription of subgenomic and genomic RNAs during early human infection using multiplexed droplet digital PCR.

Author

Hwang, Hyon S, Lo, Che-Min, Murphy, Michael, Grudda, Tanner, Gallagher, Nicholas, Luo, Chun Huai, Robinson, Matthew L, Mirza, Agha, Conte, Madison, Conte, Abigail, Zhou, Ruifeng, Vergara, Candelaria, Brooke, Christopher B, Pekosz, Andrew, Mostafa, Heba H, Manabe, Yukari C, Thio, Chloe L, and Balagopal, Ashwin

Subjects
SARS-CoV-2, POLYMERASE chain reaction
Abstract

Background: Control of SARS-CoV-2 (SCV-2) transmission requires understanding SCV-2 replication dynamics.Methods: We developed a multiplexed droplet digital PCR (ddPCR) assay to quantify SCV-2 subgenomic RNAs (sgRNAs), which are only produced during active viral replication, and discriminate them from genomic RNAs (gRNAs). We applied the assay to specimens from 144 people with single nasopharyngeal samples and 27 people with >1 sample. Results were compared to qPCR and viral culture.Results: sgRNAs were quantifiable across a range of qPCR cycle threshold (Ct) values and correlated with Ct values. The ratio of sgRNA:gRNA was stable across a wide range of Ct values, whereas adjusted amounts of N sgRNA to a human housekeeping gene declined with higher Ct values. Adjusted sgRNA and gRNA amounts were quantifiable in culture-negative samples, although levels were significantly lower than in culture-positive samples. Daily testing of 6 persons revealed that sgRNA is concordant with culture results during the first week of infection but may be discordant with culture later in infection. Further, sgRNA:gRNA is constant during infection despite changes in viral culture.Conclusions: Ct values from qPCR correlate with active viral replication. More work is needed to understand why some cultures are negative despite presence of sgRNA. [ABSTRACT FROM AUTHOR]

Published
2023
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24. Author Correction: Assembly of a pan-genome from deep sequencing of 910 humans of African descent

Author

Sherman, Rachel M., Forman, Juliet, Antonescu, Valentin, Puiu, Daniela, Daya, Michelle, Rafaels, Nicholas, Boorgula, Meher Preethi, Chavan, Sameer, Vergara, Candelaria, Ortega, Victor E., Levin, Albert M., Eng, Celeste, Yazdanbakhsh, Maria, Wilson, James G., Marrugo, Javier, Lange, Leslie A., Williams, L. Keoki, Watson, Harold, Ware, Lorraine B., Olopade, Christopher O., Olopade, Olufunmilayo, Oliveira, Ricardo R., Ober, Carole, Nicolae, Dan L., Meyers, Deborah A., Mayorga, Alvaro, Knight-Madden, Jennifer, Hartert, Tina, Hansel, Nadia N., Foreman, Marilyn G., Ford, Jean G., Faruque, Mezbah U., Dunston, Georgia M., Caraballo, Luis, Burchard, Esteban G., Bleecker, Eugene R., Araujo, Maria I., Herrera-Paz, Edwin F., Campbell, Monica, Foster, Cassandra, Taub, Margaret A., Beaty, Terri H., Ruczinski, Ingo, Mathias, Rasika A., Barnes, Kathleen C., and Salzberg, Steven L.

Published
2019
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26. Post‐sequelae symptoms and comorbidities after COVID‐19

Author

Duggal, Priya, primary, Penson, Tristan, additional, Manley, Hannah N., additional, Vergara, Candelaria, additional, Munday, Rebecca M., additional, Duchen, Dylan, additional, Linton, Elizabeth A., additional, Zurn, Amber, additional, Keruly, Jeanne C., additional, Mehta, Shruti H., additional, and Thomas, David L., additional

Published
2022
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29. A genome-wide association study on African-ancestry populations for asthma

Author

Mathias, Rasika A., Grant, Audrey V., Rafaels, Nicholas, Hand, Tracey, Gao, Li, Vergara, Candelaria, Tsai, Yuhjung J., Yang, Mao, Campbell, Monica, Foster, Cassandra, Gao, Peisong, Togias, A., Hansel, Nadia N., Diette, Gregory, Adkinson, N. Franklin, Liu, Mark C., Faruque, Mezbah, Dunston, Georgia M., Watson, Harold R., Bracken, Michael B., Hoh, Josephine, Maul, Pissamai, Maul, Trevor, Jedlicka, Anne E., Murray, Tanda, Hetmanski, Jacqueline B., Ashworth, Roxann, Ongaco, Chrissie M., Hetrick, Kurt N., Doheny, Kimberly F., Pugh, Elizabeth W., Rotimi, Charles N., Ford, Jean, Eng, Celeste, Burchard, Esteban G., Sleiman, Patrick M.A., Hakonarson, Hakon, Forno, Erick, Raby, Benjamin A., Weiss, Scott T., Scott, Alan F., Kabesch, Michael, Liang, Liming, Abecasis, Gonçalo, Moffatt, Miriam F., Cookson, William O.C., Ruczinski, Ingo, Beaty, Terri H., and Barnes, Kathleen C.

Published
2010
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32. Genome-Wide Association Study Identification of Novel Loci Associated with Airway Responsiveness in Chronic Obstructive Pulmonary Disease

Author

Hansel, Nadia N., Paré, Peter D., Rafaels, Nicholas, Sin, Don D., Sandford, Andrew, Daley, Denise, Vergara, Candelaria, Huang, Lili, Elliott, Mark W., Pascoe, Chris D., Arsenault, Bryna A., Postma, Dirkje S., Boezen, Marike H., Bossé, Yohan, van den Berge, Maarten, Hiemstra, Pieter S., Cho, Michael H., Litonjua, Augusto A., Sparrow, David, Ober, Carole, Wise, Robert A., Connett, John, Neptune, Enid R., Beaty, Terri H., Ruczinski, Ingo, Mathias, Rasika A., and Barnes, Kathleen C.

Published
2015
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33. Genome-wide study identifies two loci associated with lung function decline in mild to moderate COPD

Author

Hansel, Nadia N., Ruczinski, Ingo, Rafaels, Nicholas, Sin, Don D., Daley, Denise, Malinina, Alla, Huang, Lili, Sandford, Andrew, Murray, Tanda, Kim, Yoonhee, Vergara, Candelaria, Heckbert, Susan R., Psaty, Bruce M., Li, Guo, Elliott, W. Mark, Aminuddin, Farzian, Dupuis, Josée, O’Connor, George T., Doheny, Kimberly, Scott, Alan F., Boezen, H. Marike, Postma, Dirkje S., Smolonska, Joanna, Zanen, Pieter, Mohamed Hoesein, Firdaus A., de Koning, Harry J., Crystal, Ronald G., Tanaka, Toshiko, Ferrucci, Luigi, Silverman, Edwin, Wan, Emily, Vestbo, Jorgen, Lomas, David A., Connett, John, Wise, Robert A., Neptune, Enid R., Mathias, Rasika A., Paré, Peter D., Beaty, Terri H., and Barnes, Kathleen C.

Published
2013
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34. Genetic make up and structure of Colombian populations by means of uniparental and biparental DNA markers

Author

Rojas, Winston, Parra, Maria Victoria, Campo, Omer, Caro, Maria Antonieta, Lopera, Juan Guillermo, Arias, William, Duque, Constanza, Naranjo, Andres, Garcia, Jharley, Vergara, Candelaria, Lopera, Jaime, Hernandez, Erick, Valencia, Ana, Caicedo, Yuri, Cuartas, Mauricio, Gutierrez, Javier, Lopez, Sergio, Ruiz-Linares, Andres, and Bedoya, Gabriel

Subjects
Genetic markers -- Research, Human population genetics -- Research, Anthropology/archeology/folklore
Abstract

Colombia is a country with great geographic heterogeneity and marked regional differences in pre-Columbian native population density and in the extent of past African and European immigration. As a result, Colombia has one of the most diverse populations in Latin America. Here we evaluated ancestry in over 1,700 individuals from 24 Colombian populations using biparental (autosomal and X-Chromosome), maternal (mtDNA), and paternal (Y-chromosome) markers. Autosomal ancestry varies markedly both within and between regions, confirming the great genetic diversity of the Colombian population. The X-chromosome, mtDNA, and Y-chromosome data indicate that there is a pattern across regions indicative of admixture involving predominantly Native American women and European and African men. Am J Phys Anthropol 143:13-20, 2010. KEY WORDS Colombia; mestizo; genetic markers; admixture DOI 10.1002/ajpa.21270

Published
2010

36. Coassociations between IL10 polymorphisms, IL-10 production, helminth infection, and asthma/wheeze in an urban tropical population in Brazil

Author

Figueiredo, Camila Alexandrina, Barreto, Maurício Lima, Alcantara-Neves, Neuza Maria, Rodrigues, Laura Cunha, Cooper, Philip John, Cruz, Alvaro A., Pontes-de-Carvalho, Lain Carlos, Lemaire, Denise C., dos Santos Costa, Ryan, Amorim, Leila D., Vergara, Candelaria, Rafaels, Nicholas, Gao, Li, Foster, Cassandra, Campbell, Monica, Mathias, Rasika A., and Barnes, Kathleen C.

Published
2013
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37. A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus

Author

Vergara, Candelaria, primary, Valencia, Ana, additional, Thio, Chloe L, additional, Goedert, James J, additional, Mangia, Alessandra, additional, Piazzolla, Valeria, additional, Johnson, Eric, additional, Kral, Alex H, additional, O’Brien, Thomas R, additional, Mehta, Shruti H, additional, Kirk, Gregory D, additional, Kim, Arthur Y, additional, Lauer, Georg M, additional, Chung, Raymond T, additional, Cox, Andrea L, additional, Peters, Marion G, additional, Khakoo, Salim I, additional, Alric, Laurent, additional, Cramp, Matthew E, additional, Donfield, Sharyne M, additional, Edlin, Brian R, additional, Busch, Michael P, additional, Alexander, Graeme, additional, Rosen, Hugo R, additional, Murphy, Edward L, additional, Wojcik, Genevieve L, additional, Taub, Margaret A, additional, Thomas, David L, additional, and Duggal, Priya, additional

Published
2020
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38. Gene Encoding Duffy Antigen/Receptor for Chemokines Is Associated with Asthma and IgE in Three Populations

Author

Vergara, Candelaria, Tsai, Yuhjung J., Grant, Audrey V., Rafaels, Nicholas, Gao, Li, Hand, Tracey, Stockton, Maria, Campbell, Monica, Mercado, Dilia, Faruque, Mezbah, Dunston, Georgia, Beaty, Terri H., Oliveira, Ricardo Riccio, Ponte, Eduardo V., Cruz, Alvaro A., Carvalho, Edgar, Araujo, Maria Ilma, Watson, Harold, Schleimer, Robert P., Caraballo, Luis, Nickel, Renate G., Mathias, Rasika A., and Barnes, Kathleen C.

Published
2008
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40. Decreased Activated CD4+ T Cell Repertoire Diversity After Antiretroviral Therapy in HIV-1/HCV Coinfection Correlates with CD4+ T Cell Recovery.

Author

Skinner, Nicole E., Vergara, Candelaria, El-Diwany, Ramy, Paul, Harry, Skaist, Alyza, Wheelan, Sarah J., Thomas, David L., Ray, Stuart C., Balagopal, Ashwin, and Bailey, Justin R.

Subjects
*T cells, *T cell receptors, *ANTIRETROVIRAL agents, *MIXED infections, *HEPATITIS C virus, *VIRUS diseases, *CELL populations
Abstract

Dysfunctional immune activation accumulates during chronic viral infection and contributes to disease pathogenesis. In HIV-1, immune activation is exacerbated by concurrent infection with hepatitis C virus (HCV), accelerating depletion of CD4+ T cells. HIV-1 suppression with antiretroviral therapy (ART) generally reconstitutes CD4+ T cell counts, while also reducing the proportion that is activated. Whether this immune reconstitution also reduces the complexity of the CD4+ T cell population is unknown. We sought to characterize the relationship between activated CD4+ T cell repertoire diversity and immune reconstitution following ART in HIV-1/HCV coinfection. We extracted T cell receptor (TCR) sequences from RNA sequencing data obtained from activated CD4+ T cells of HIV-1/HCV coinfected individuals before and after treatment with ART (clinical trial NCT01285050). There was notable heterogeneity in both the extent of CD4+ T cell reconstitution and in the change in activated CD4+ TCR repertoire diversity following ART. Decreases in activated CD4+ TCR repertoire diversity following ART were predictive of the degree of CD4+ T cell reconstitution. The association of decreased activated CD4+ TCR repertoire diversity and improved CD4+ T cell reconstitution may represent loss of nonspecifically activated TCR clonotypes, and possibly selective expansion of specifically activated CD4+ clones. These results provide insight into the dynamic relationship between activated CD4+ TCR diversity and CD4+ T cell recovery of HIV-1/HCV coinfected individuals after suppression of HIV-1 viremia. [ABSTRACT FROM AUTHOR]

Published
2021
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41. Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations

Author

Daya, Michelle, primary, Rafaels, Nicholas M., additional, Brunetti, Tonya M., additional, Chavan, Sameer, additional, Levin, Albert M., additional, Shetty, Aniket, additional, Gignoux, Cristopher R., additional, Boorgula, Meher Preethi, additional, Wojcik, Genevieve, additional, Campbell, Monica, additional, Vergara, Candelaria I., additional, Torgerson, Dara G., additional, Ortega, Victor E., additional, Doumatey, Ayo, additional, Johnston, Henry R., additional, Acevedo, Nathalie, additional, Araujo, Maria A., additional, Avila, Pedro C., additional, Belbin, Gillian, additional, Bleecker, Eugene R., additional, Bustamante, Carlos, additional, Caraballo, Luis, additional, Cruz, Alvaro A., additional, Dunston, Georgia M., additional, Eng, Celeste, additional, Faruque, Mezbah U., additional, Ferguson, Trevor S., additional, Figueiredo, Camila, additional, Ford, Jean G., additional, Gan, Weiniu, additional, Gourraud, Pierre-Antoine, additional, Hansel, Nadia, additional, Hernandez, Ryan D., additional, Herrera-Paz, Edwin P., additional, Jimenez, Silvia, additional, Kenny, Eimear E., additional, Knight-Madden, Jennifer, additional, Kumar, Rajesh, additional, Lange, Leslie E., additional, Lange, Ethan M., additional, Lizee, Antoine, additional, Maul, Pissamai, additional, Maul, Trevor, additional, Mayorga Sirera, Alvaro J., additional, Meyers, Deborah A., additional, Nicolae, Dan L., additional, D O'Connor, Timothy, additional, Oliveira, Ricardo R., additional, Olopade, Christopher O., additional, Olopade, Olufunmilayo, additional, Qin, Zhaohui S., additional, Rotimi, Charles, additional, Vince, Nicolas, additional, Watson, Harold, additional, Wilks, Rainford J., additional, Wilson, James G., additional, Salzberg, Steven, additional, Ober, Carole, additional, Burchard, Esteban G., additional, Williams, L. Keoki, additional, Beaty, Terri H., additional, Taub, Margaret A., additional, Ruczinski, Ingo, additional, Mathias, Rasika A., additional, and Barnes, Kathleen C., additional

Published
2019
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42. Assembly of a pan-genome from deep sequencing of 910 humans of African descent

Author

Sherman, Rachel M., primary, Forman, Juliet, additional, Antonescu, Valentin, additional, Puiu, Daniela, additional, Daya, Michelle, additional, Rafaels, Nicholas, additional, Boorgula, Meher Preethi, additional, Chavan, Sameer, additional, Vergara, Candelaria, additional, Ortega, Victor E., additional, Levin, Albert M., additional, Eng, Celeste, additional, Yazdanbakhsh, Maria, additional, Wilson, James G., additional, Marrugo, Javier, additional, Lange, Leslie A., additional, Williams, L. Keoki, additional, Watson, Harold, additional, Ware, Lorraine B., additional, Olopade, Christopher O., additional, Olopade, Olufunmilayo, additional, Oliveira, Ricardo R., additional, Ober, Carole, additional, Nicolae, Dan L., additional, Meyers, Deborah A., additional, Mayorga, Alvaro, additional, Knight-Madden, Jennifer, additional, Hartert, Tina, additional, Hansel, Nadia N., additional, Foreman, Marilyn G., additional, Ford, Jean G., additional, Faruque, Mezbah U., additional, Dunston, Georgia M., additional, Caraballo, Luis, additional, Burchard, Esteban G., additional, Bleecker, Eugene R., additional, Araujo, Maria I., additional, Herrera-Paz, Edwin F., additional, Campbell, Monica, additional, Foster, Cassandra, additional, Taub, Margaret A., additional, Beaty, Terri H., additional, Ruczinski, Ingo, additional, Mathias, Rasika A., additional, Barnes, Kathleen C., additional, and Salzberg, Steven L., additional

Published
2018
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45. Genome-wide association study of asthma in individuals of African ancestry reveals novel asthma susceptibility loci

Author

Daya, Michelle, primary, Rafaels, Nicholas, additional, Chavan, Sameer, additional, Johnston, Henry Richard, additional, Shetty, Aniket, additional, Gignoux, Christopher R., additional, Boorgula, Meher Preethi, additional, Campbell, Monica, additional, Maul, Pissamai, additional, Maul, Trevor, additional, Vergara, Candelaria, additional, Levin, Albert M., additional, Wojcik, Genevieve, additional, Torgerson, Dara G., additional, Ortega, Victor E., additional, Doumatey, Ayo, additional, Araujo, Maria Ilma, additional, Avila, Pedro C., additional, Bleecker, Eugene, additional, Bustamante, Carlos, additional, Caraballo, Luis, additional, Dunston, Georgia M., additional, Faruque, Mezbah U., additional, Ferguson, Trevor S., additional, Figueiredo, Camila, additional, Ford, Jean G., additional, Gourraud, Pierre-Antoine, additional, Hansel, Nadia N., additional, Hernandez, Ryan D., additional, Herrera-Paz, Edwin Francisco, additional, Kenny, Eimear E., additional, Knight-Madden, Jennifer, additional, Kumar, Rajesh, additional, Lange, Lesli A., additional, Lange, Ethan M., additional, Lizee, Antoine, additional, Mayorga, Alvaro, additional, Meyers, Deborah, additional, Nicolae, Dan L., additional, O’Connor, Timothy D., additional, Oliveira, Ricardo Riccio, additional, Olopade, Christopher O., additional, Olopade, Olufunmilayo, additional, Qin, Zhaohui S., additional, Rotimi, Charles, additional, Watson, Harold, additional, Wilks, Rainford J., additional, Williams, L. Keoki, additional, Wilson, James G., additional, Ober, Carole, additional, Burchard, Esteban G., additional, Beaty, Terri H., additional, Taub, Margaret A., additional, Ruczinski, Ingo, additional, Mathias, Rasika Ann, additional, Barnes, Kathleen C., additional, Adegnika, Ayola Akim, additional, Arinola, Ganiyu, additional, Ateba-Ngoa, Ulysse, additional, Ayestas, Gerardo, additional, Correa, Adolfo, additional, De La Vega, Francisco M., additional, Eng, Celeste, additional, Erazo, Said Omar Leiva, additional, Foreman, Marilyn G., additional, Foster, Cassandra, additional, Gao, Li, additional, Gao, Jingjing, additional, Gietzen, Kimberly, additional, Grammer, Leslie, additional, Gutierrez, Linda, additional, Hansen, Mark, additional, Hartert, Tina, additional, Hu, Yijuan, additional, Kim, Kwang-Youn A., additional, Landaverde-Torres, Pamela, additional, Marrugo, Javier, additional, Martinez, Beatriz, additional, Martinez, Rosella, additional, Mayorga, Luis F., additional, Mejia-Mejia, Delmy-Aracely, additional, Meza, Catherine, additional, Musani, Solomon, additional, Musharoff, Shaila, additional, Oluwole, Oluwafemi, additional, Pino-Yanes, Maria, additional, Ramos, Hector, additional, Saenz, Allan, additional, Salzberg, Steven, additional, Samms-Vaughan, Maureen, additional, Schleimer, Robert, additional, Scott, Alan F., additional, Shringarpure, Suyash S., additional, Song, Wei, additional, Szpiech, Zachary A., additional, Torres, Raul, additional, Varela, Gloria, additional, Vasquez, Olga Marina, additional, Ware, Lorraine B., additional, and Yazdanbakhsh, Maria, additional

Published
2017
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46. Transforming Growth Factor-Beta 1 (TGF-Beta 1) Gene Polymorphisms are Associated with Atopic Asthma and Helminth Infections in an Admixed Population

Author

Costa, Ryan Santos, primary, Figueiredo, Camila Alexandrina, additional, Barreto, Mauricio Lima, additional, Alcântara-Neves, Neuza Maria, additional, Rodrigues, Laura, additional, Cruz, Álvaro, additional, Pontes-de-Carvalho, Lain, additional, Vergara, Candelaria, additional, Rafaels, Nicholas M., additional, Foster, Cassandra, additional, Potee, Joseph, additional, Campbell, Monica, additional, Mathias, Rasika A., additional, and Barnes, Kathleen C., additional

Published
2017
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47. African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations

Author

Vergara, Candelaria, Murray, Tanda, Rafaels, Nicholas M., Lewis, Rachel, Campbell, Monica, Foster, Cassandra, Gao, Li, Faruque, Mezbah, Oliveira, Ricardo Riccio, Carvalho Filho, Edgar Marcelino de, Araujo, Maria Ilma Andrade Santos, Cruz Filho, Álvaro Augusto Souza da, Watson, Harold, Mercado, Dilia, Ruczinski, Ingo, Dunston, Georgia, Ford, Jean, Caraballo, Luis, Beaty, Terri H., Mathias, Rasika A., Barnes, Kathleen C., and Knight-Madden, Jennifer

Subjects
Ancestry, African, Asthma
Abstract

Texto completo: acesso restrito. p. 393–401 Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-11-19T11:41:52Z No. of bitstreams: 1 Candelaria Vergara.pdf: 683776 bytes, checksum: 3f244a5ee46560431d06949a67843bd9 (MD5) Approved for entry into archive by Delba Rosa (delba@ufba.br) on 2015-05-05T16:06:05Z (GMT) No. of bitstreams: 1 Candelaria Vergara.pdf: 683776 bytes, checksum: 3f244a5ee46560431d06949a67843bd9 (MD5) Made available in DSpace on 2015-05-05T16:06:05Z (GMT). No. of bitstreams: 1 Candelaria Vergara.pdf: 683776 bytes, checksum: 3f244a5ee46560431d06949a67843bd9 (MD5) Previous issue date: 2013 Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels.

Published
2013
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48. Relación entre estilos de aprendizaje y rendimiento académico en los estudiantes de tercer semestre de Psicología y Derecho de la Fundación Universitaria Tecnológico Comfenalco

Author

Atencia Vergara, Candelaria, Franco Anaya, Naury Milena, Rodríguez Barrios, Katia Stella, and Herrera Peña, María del Pilar

Subjects
Aprendizaje, Estudiantes de psicología, Métodos de enseñanza, Rendimiento académico, Estilos de aprendizaje, Estudiantes de Derecho
Abstract

En la actualidad se percibe diversidad de factores relacionados al estudio del aprendizaje en este sentido el presenta trabajo busca ampliar información frente al tema y revisar algunos modelos empleados actualmente, para contribuir al fortalecimiento de las bases teóricas sobre dicho concepto. Es importante realizar una caracterización de los perfiles de estilos de aprendizaje y a partir de su diagnóstico establecer estrategias didácticas y pedagógicas que favorezcan el estilo particular de los estudiantes y por ende contribuyan a mejorar los niveles de rendimiento académico. En la universidad contemporánea constituye una necesidad, reconocer las diferencias culturales y modos de aprender individuales que los estudiantes poseen, lo que permite asumir una práctica pedagógica que propicie la reflexión para un cambio didáctico donde se integren los procesos de enseñanza-aprendizaje.

Published
2013

49. Journal of Allergy and Clinical Immunology

Author

Masuko, Hironori, Gao, Li, Rafaels, Nicholas M., Vergara, Candelaria I., Huang, Lili, Campbell, Monica, Ruczinski, Ingo, Beaty, Terri H., Oliveira, Ricardo, Cruz Filho, Álvaro Augusto Souza da, Carvalho Filho, Edgar Marcelino de, Mathias, Rasika A., Araujo, Maria Ilma Andrade Santos, and Barnes, Kathleen C.

Abstract

Texto completo. Acesso restrito. p. 138 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-07-03T17:34:31Z No. of bitstreams: 1 444444444444.pdf: 42451 bytes, checksum: 90361afada296c71b1347ca98d96948e (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2013-10-31T18:04:28Z (GMT) No. of bitstreams: 1 444444444444.pdf: 42451 bytes, checksum: 90361afada296c71b1347ca98d96948e (MD5) Made available in DSpace on 2013-10-31T18:04:28Z (GMT). No. of bitstreams: 1 444444444444.pdf: 42451 bytes, checksum: 90361afada296c71b1347ca98d96948e (MD5) Previous issue date: 2013 Rationale IL33 is one of the most consistently associated candidate genes for asthma identified by GWAS in diverse ethnic groups. We previously demonstrated GWAS SNPs associated with asthma were also associated with asthma and schistosomiasis in African-ancestry Brazilians (356 nuclear families) living in Conde, Bahia, a region endemic for Schistosoma mansoni. We expanded these studies to include an additional set of variants selected from a recently completed deep-resequencing study in an African American asthma cohort. Methods Targeted resequencing in 77 kb around the IL33 gene in 183 asthmatic cases and 192 controls yielded 9 SNPs associated with asthma, these were genotyped in 772 Brazilian samples using TaqMan. Hardy-Weinberg testing was performed using PLINK and pairwise linkage disequilibrium was estimated using Haploview. Genetic association tests were performed using generalized estimating equation under a dominant model on the soluble adult worm antigen (SWAP)-specific IgE:IgG4 ratio (a measure of S. mansoniresistance) adjusting for age, gender, water contact index, and African admixture. Results Three SNPs were associated with higher SWAP-specific IgE:IgG4 (P=0.001, 0.004, 0.020, respectively). The most significant SNP mapped to intron 1, and the allele conferring asthma risk in the African American cohort also conferred protection against schistosomiasis. This intronic variant is independent from the previously reported GWAS co-associations (R2=0.133). Conclusions Additional genotyping of IL33 variants identified by targeted sequencing demonstrated a novel locus that co-associates with both asthma and schistosomiasis in populations of African ancestry. Salvador

Published
2013
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50. Journal of Allergy and Clinical Immunology

Author

Huang, Lili, Gao, Li, Figueiredo, Camila, Rafaels, Nicholas M., Vergara, Candelaria I., Ruczinski, Ingo, Beaty, Terri H., Barnes, Kathleen C., and Mathias, Rasika A.

Abstract

Texto completo. Acesso restrito. p. 53 Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-07-03T16:50:09Z No. of bitstreams: 1 3333333333333.pdf: 44766 bytes, checksum: 9c12787c8508e70b11e35307361711c2 (MD5) Made available in DSpace on 2013-07-03T16:50:09Z (GMT). No. of bitstreams: 1 3333333333333.pdf: 44766 bytes, checksum: 9c12787c8508e70b11e35307361711c2 (MD5) Previous issue date: 2013 Rationale ST2 (IL1RL1), is an IL1 family receptor that mediates important effectors of Th2 functions. Its soluble form (sST2) neutralizes its ligand, IL-33, by acting as a decoy receptor. Serum sST2 has been used as a biomarker for disease severity and outcome for multiple inflammatory and lung diseases, including atopic asthma. We undertook a targeted deep resequencing of ST2 gene in 241 samples of African ancestry to identify ST2variants controlling serum sST2 levels. Methods Serum sST2 concentration was measured by ELISA, and resequencing of ∼50kb (chr2:102922962-102973497) encompassing the ST2gene was performed using Illumina's HiSeq2000. Single-variant tests for all common variants (MAF≥5%) were performed using linear regression assuming an additive model on log serum total ST2 considering age, gender and the first two principal components on a pre-existing genome-wide association panel of ancestry informative markers to adjust for admixture. Results A total of 565 ST2 variants were identified, 192 of which had a MAF≥5% including 3 coding synonymous and 6 missense variants. In the sST2 level analysis, ten SNPs in strong linkage disequilibrium yielded p-value less than 10-3; a single common haplotype (frequency=65%) across all 10 SNPs yielded an overall p-value = 0.0002 and was negatively associated with sST2 levels (β = -0.09). Conclusions Sequencing ST2 gene revealed a novel haplotype influencing sST2 levels in individuals of African ancestry, including 5 variants mapping to intron 1 and 5 mapping to the 5’ region of ST2. Further work is ongoing to fully explore this association in an additional 400 subjects of African ancestry. Salvador

Published
2013
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