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1. An epistatic interaction between pre-natal smoke exposure and socioeconomic status has a significant impact on bronchodilator drug response in African American youth with asthma

Author

Magaña, J, Contreras, MG, Keys, KL, Risse-Adams, O, Goddard, PC, Zeiger, AM, Mak, ACY, Elhawary, JR, Samedy-Bates, LA, Lee, E, Thakur, N, Hu, D, Eng, C, Salazar, S, Huntsman, S, Hu, T, Burchard, EG, and White, MJ

Subjects
Data Management and Data Science, Information and Computing Sciences, Biological Sciences, Bioinformatics and Computational Biology, Asthma, Lung, Health Disparities, Pediatric, Social Determinants of Health, Minority Health, 2.1 Biological and endogenous factors, Respiratory, Good Health and Well Being, Epistatic interactions, Non-parametric methods, Asthma drug response, Health disparities, Pediatric asthma, Epistatic interactions, Non-parametric methods, Asthma drug response, Health disparities, Pediatric asthma, Artificial Intelligence and Image Processing, Medical Biochemistry and Metabolomics, Specialist Studies in Education, Bioinformatics and computational biology, Data management and data science
Abstract

BackgroundAsthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables.ResultsWe evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 233 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to quantify interaction effects using an information-theory metric known as Information Gain (IG). We performed analyses in the full dataset and in sex-stratified subsets. Our analyses identified several interaction models significantly, and suggestively, associated with BDR. The strongest interaction significantly associated with BDR was a pairwise interaction between pre-natal smoke exposure and socioeconomic status (full dataset IG: 2.78%, p = 0.001; female IG: 7.27%, p = 0.004)). Sex-stratified analyses yielded divergent results for females and males, indicating the presence of sex-specific effects.ConclusionsOur study identified novel interaction effects significantly, and suggestively, associated with BDR in African American children with asthma. Notably, we found that all of the interactions identified by ViSEN were "pure" interaction effects, in that they were not the result of strong main effects on BDR, highlighting the complexity of the network of biological and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods, thus emphasizing the importance of employing statistical methods optimized to detect both additive and non-additive interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.

Published
2020

2. Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes (PRIMERO): Design and Baseline Characteristics for Puerto Rico's Inaugural Asthma Birth Cohort Study

Author

Witonsky, J.I., primary, Borrell, L.N., additional, Burchard, E.G., additional, Chang, C.-H., additional, Collard, H.R., additional, Contreras, M.G., additional, Elhawary, J.R., additional, Eng, C., additional, Everman, J.L., additional, Fairbanks-Mahnke, A., additional, Guerrero, T.R., additional, Hu, D., additional, Huntsman, S., additional, Jackson, N., additional, Li, Y., additional, Lopez, N., additional, Medina, V., additional, Montanez-Lopez, C.A., additional, Moore, C.M., additional, Morin, A., additional, Nieves, N., additional, Oh, S., additional, Otero, R.A., additional, Pruesse, E., additional, Rios, C., additional, Rivera, R.C., additional, Rodriguez, L., additional, Sajuthi, S., additional, Salazar, S., additional, Secor, E.A., additional, Serrano, G., additional, Vazquez, G., additional, Williams, B.J.M., additional, Zhang, P., additional, Ziv, E., additional, Rodriguez-Santana, J.R., additional, Seibold, M.A., additional, and Sheppard, D., additional

Published
2024
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3. PAI‐1 gain‐of‐function genotype, factors increasing PAI‐1 levels, and airway obstruction: The GALA II Cohort

Author

Sherenian, MG, Cho, SH, Levin, A, Min, J‐Y, Oh, SS, Hu, D, Galanter, J, Sen, S, Huntsman, S, Eng, C, Rodriguez‐Santana, JR, Serebrisky, D, Avila, PC, Kalhan, R, Smith, LJ, Borrell, LN, Seibold, MA, Williams, L Keoki, Burchard, EG, and Kumar, R

Subjects
Biomedical and Clinical Sciences, Immunology, Lung, Genetics, Prevention, Clinical Research, Asthma, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adolescent, Adult, Airway Obstruction, Alleles, Asthma, Occupational, Child, Cohort Studies, Ethnicity, Female, Gain of Function Mutation, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Male, Odds Ratio, Plasminogen Activator Inhibitor 1, Polymorphism, Single Nucleotide, Respiratory Function Tests, Young Adult, asthma, epidemiology, PAI-1, pediatrics, Nutrition and Dietetics, Public Health and Health Services, Allergy
Abstract

BackgroundPAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma.ObjectiveWe sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level.MethodsWe studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function.ResultsThere was an interaction between asthma status and the PAI-1 polymorphism on FEV1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV1 /FVC (P

Published
2017

4. Maternal age and asthma in Latino populations

Author

Abid, Z, Oh, SS, Hu, D, Sen, S, Huntsman, S, Eng, C, Farber, HJ, Rodriguez‐Cintron, W, Rodriguez‐Santana, JR, Serebrisky, D, Avila, PC, Thyne, SM, Kim, K‐Y A, Borrell, LN, Williams, LK, Seibold, MA, Burchard, EG, and Kumar, R

Subjects
Biomedical and Clinical Sciences, Immunology, Pediatric, Clinical Research, Lung, Asthma, Reproductive health and childbirth, Adolescent, Case-Control Studies, Child, Female, Hispanic or Latino, Humans, Male, Maternal Age, Population Surveillance, Risk Factors, United States, Young Adult, prenatal exposures, asthma, Nutrition and Dietetics, Public Health and Health Services, Allergy
Abstract

BackgroundYounger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations.ObjectivesWe sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children.MethodsWe included 3473 Latino children aged 8-21 years (1696 subjects with physician-diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship.ResultsMaternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors (OR = 0.73, 95% CI: 0.57-0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans (OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma (OR = 0.65, 95% CI: 0.44-0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings (OR = 0.44, 95% CI: 0.23-0.81).Conclusion and clinical relevanceIn contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability.

Published
2016

5. Adapt-Mix: Learning local genetic correlation structure improves summary statistics-based analyses

Author

Burchard, Esteban, Zaitlen, Noah, Park, DS, Brown, B, Eng, C, Huntsman, S, Hu, D, Torgerson, DG, and Burchard, EG

Abstract

© The Author 2015. Published by Oxford University Press.Motivation: Approaches to identifying new risk loci, training risk prediction models, imputing untyped variants and fine-mapping causal variants from summary statistics of genome-wide association stud

Published
2015

6. High mammographic density in women of Ashkenazi Jewish descent

Author

Ziv, Elad, Cummings, Steven, Kerlikowske, Karla, Caswell, JL, Shepherd, JA, Cummings, SR, Hu, D, and Huntsman, S

Abstract

Introduction: Percent mammographic density (PMD) adjusted for age and body mass index is one of the strongest risk factors for breast cancer and is known to be approximately 60% heritable. Here we report a finding of an association between genetic ancestry

Published
2013

7. NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity

Author

Moecking, J., Masters, S.L., Harapas, C.R., Eng, C., Davidson, S., Laohamonthonkul, P., Hu, D., Hansbro, P.M., Horvat, J.C., Chalker, K., O'Donoghue, R.J.J., Huntsman, S., Ting, J.P., Burchard, E.G., White, M.J., Hrovat-Schaale, K., Geyer, M., Gerlic, M., Yu, C.-H., and Calleja, D.J.

Abstract

Background: NLRP1 is an innate immune sensor that can form cytoplasmic inflammasome complexes. Polymorphisms in NLRP1 are linked to asthma; however, there is currently no functional or mechanistic explanation for this. Objective: We sought to clarify the role of NLRP1 in asthma pathogenesis. Methods: Results from the GALA II cohort study were used to identify a link between NLRP1 and asthma in Mexican Americans. In vitro and in vivo models for NLRP1 activation were applied to investigate the role of this inflammasome in asthma at the molecular level. Results: We document the association of an NLRP1 haplotype with asthma for which the single nucleotide polymorphism rs11651270 (M1184V) individually is the most significant. Surprisingly, M1184V increases NLRP1 activation in the context of N-terminal destabilization, but decreases NLRP1 activation on dipeptidyl peptidase 9 inhibition. In vitro studies demonstrate that M1184V increases binding to dipeptidyl peptidase 9, which can account for its inhibitory role in this context. In addition, in vivo data from a mouse model of airway inflammation reveal a protective role for NLRP1 inflammasome activation reducing eosinophilia in this setting. Conclusions: Linking our in vitro and in vivo results, we found that the NLRP1 variant M1184V reduces inflammasome activation in the context of dipeptidyl peptidase 9 inhibition and could thereby increase asthma severity. Our studies may have implications for the treatment of asthma in patients carrying this variant of NLRP1.

Published
2021
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8. NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity

Author

Moecking, J, Laohamonthonkul, P, Chalker, K, White, MJ, Harapas, CR, Yu, C-H, Davidson, S, Hrovat-Schaale, K, Hu, D, Eng, C, Huntsman, S, Calleja, DJ, Horvat, JC, Hansbro, PM, O'Donoghue, RJJ, Ting, JP, Burchard, EG, Geyer, M, Gerlic, M, Masters, SL, Moecking, J, Laohamonthonkul, P, Chalker, K, White, MJ, Harapas, CR, Yu, C-H, Davidson, S, Hrovat-Schaale, K, Hu, D, Eng, C, Huntsman, S, Calleja, DJ, Horvat, JC, Hansbro, PM, O'Donoghue, RJJ, Ting, JP, Burchard, EG, Geyer, M, Gerlic, M, and Masters, SL

Abstract

BACKGROUND: NLRP1 is an innate immune sensor that can form cytoplasmic inflammasome complexes. Polymorphisms in NLRP1 are linked to asthma; however, there is currently no functional or mechanistic explanation for this. OBJECTIVE: We sought to clarify the role of NLRP1 in asthma pathogenesis. METHODS: Results from the GALA II cohort study were used to identify a link between NLRP1 and asthma in Mexican Americans. In vitro and in vivo models for NLRP1 activation were applied to investigate the role of this inflammasome in asthma at the molecular level. RESULTS: We document the association of an NLRP1 haplotype with asthma for which the single nucleotide polymorphism rs11651270 (M1184V) individually is the most significant. Surprisingly, M1184V increases NLRP1 activation in the context of N-terminal destabilization, but decreases NLRP1 activation on dipeptidyl peptidase 9 inhibition. In vitro studies demonstrate that M1184V increases binding to dipeptidyl peptidase 9, which can account for its inhibitory role in this context. In addition, in vivo data from a mouse model of airway inflammation reveal a protective role for NLRP1 inflammasome activation reducing eosinophilia in this setting. CONCLUSIONS: Linking our in vitro and in vivo results, we found that the NLRP1 variant M1184V reduces inflammasome activation in the context of dipeptidyl peptidase 9 inhibition and could thereby increase asthma severity. Our studies may have implications for the treatment of asthma in patients carrying this variant of NLRP1.

Published
2021

9. Genome-Wide Association Study of Bronchodilator Drug Response (BDR) in Minority Children with Asthma Provides Insights into Its Genetic Risk Factors

Author

Joo, J., primary, Mak, A.C.Y., additional, Xiao, S., additional, Sleiman, P., additional, Hu, D., additional, Huntsman, S., additional, Eng, C., additional, Kan, M., additional, Diwadkar, A., additional, Hakonarson, H., additional, Williams, L.K., additional, Burchard, E.G., additional, and Himes, B.E., additional

Published
2021
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10. NLRP1 variant M1184V decreases inflammasome activation in the context of DPP9 inhibition and asthma severity.

Author

Moecking J, Laohamonthonkul P, Chalker K, White MJ, Harapas CR, Yu C-H, Davidson S, Hrovat-Schaale K, Hu D, Eng C, Huntsman S, Calleja DJ, Horvat JC, Hansbro PM, O'Donoghue RJJ, Ting JP, Burchard EG, Geyer M, Gerlic M, Masters SL, Moecking J, Laohamonthonkul P, Chalker K, White MJ, Harapas CR, Yu C-H, Davidson S, Hrovat-Schaale K, Hu D, Eng C, Huntsman S, Calleja DJ, Horvat JC, Hansbro PM, O'Donoghue RJJ, Ting JP, Burchard EG, Geyer M, Gerlic M, and Masters SL

Abstract

Background

NLRP1 is an innate immune sensor that can form cytoplasmic inflammasome complexes. Polymorphisms in NLRP1 are linked to asthma; however, there is currently no functional or mechanistic explanation for this.

Objective

We sought to clarify the role of NLRP1 in asthma pathogenesis.

Methods

Results from the GALA II cohort study were used to identify a link between NLRP1 and asthma in Mexican Americans. In vitro and in vivo models for NLRP1 activation were applied to investigate the role of this inflammasome in asthma at the molecular level.

Results

We document the association of an NLRP1 haplotype with asthma for which the single nucleotide polymorphism rs11651270 (M1184V) individually is the most significant. Surprisingly, M1184V increases NLRP1 activation in the context of N-terminal destabilization, but decreases NLRP1 activation on dipeptidyl peptidase 9 inhibition. In vitro studies demonstrate that M1184V increases binding to dipeptidyl peptidase 9, which can account for its inhibitory role in this context. In addition, in vivo data from a mouse model of airway inflammation reveal a protective role for NLRP1 inflammasome activation reducing eosinophilia in this setting.

Conclusions

Linking our in vitro and in vivo results, we found that the NLRP1 variant M1184V reduces inflammasome activation in the context of dipeptidyl peptidase 9 inhibition and could thereby increase asthma severity. Our studies may have implications for the treatment of asthma in patients carrying this variant of NLRP1.

Published
2020

11. An antioxidant function for DMSP and DMS in marine algae

Author

Sunda, W., Kieber, D. J., Kiene, R. P., and Huntsman, S.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): W. Sunda (corresponding author) [1]; D. J. Kieber [2]; R. P. Kiene [3]; S. Huntsman [1] The algal osmolyte dimethylsulphoniopropionate (DMSP) and its enzymatic cleavage product dimethylsulphide (DMS) contribute [...]

Published
2002
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12. Abstract PR05: A genetic variant at 6q25 associated with estrogen receptor-negative breast cancer subtypes in Peruvian breast cancer patients

Author

Marker, K.M., primary, Vidaurre, T., additional, Tamayo, L.I., additional, Vásquez, J.N., additional, Florez, R. Meza, additional, Casavilca, S., additional, Calderon, M., additional, Abugattas, J.E., additional, Gómez, H.L., additional, Fuentes, H.A., additional, Pimentel, C.L. Monge, additional, Song, S., additional, Cherry, D., additional, Huntsman, S., additional, Hu, D., additional, Ziv, E., additional, and Fejerman, L., additional

Published
2020
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13. Whole Genome Sequencing Association and Gene-by-Air-Pollution Interaction Analyses Identified KITLG as a Novel Baseline Lung Function Gene Candidate Among African American Children with Asthma

Author

Mak, A.C.Y., primary, Sajuthi, S., additional, Saef, B., additional, Hu, D., additional, Xiao, S., additional, Sleiman, P., additional, Joo, J., additional, Lee, E.Y., additional, Huntsman, S., additional, Eng, C., additional, LeNoir, M.A., additional, Brigino-Buenaventura, E., additional, Salazar, S., additional, Oh, S.S., additional, Himes, B.E., additional, Hakonarson, H., additional, Williams, L.K., additional, White, M.J., additional, Seibold, M.A., additional, and Burchard, E.G., additional

Published
2020
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14. Pairwise and Higher-Order Epistatic Interactions Have a Significant Impact on Bronchodilator Drug Response in African American Youth with Asthma

Author

Magaña, J, primary, Contreras, MG, additional, Keys, KL, additional, Risse-Adams, O, additional, Goddard, PC, additional, Zeiger, AM, additional, Mak, ACY, additional, Elhawary, JR, additional, Samedy-Bates, LA, additional, Lee, E, additional, Thakur, N, additional, Hu, D, additional, Eng, C, additional, Salazar, S, additional, Huntsman, S, additional, Hu, T, additional, Burchard, EG, additional, and White, MJ, additional

Published
2020
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17. PRKCH and Severe Asthma Exacerbations in Latino Children

Author

Forno, E., primary, Yan, Q., additional, Herrera-Luis, E., additional, Pino-Yanes, M., additional, Rios, R., additional, Han, Y.-Y., additional, Oh, S., additional, Acosta-Perez, E., additional, Zhang, R., additional, Hu, D., additional, Eng, C., additional, Huntsman, S., additional, Avila, L., additional, Boutaoui, N., additional, Cloutier, M.M., additional, Soto-Quiros, M.E., additional, Weiss, S.T., additional, Lasky-Su, J.A., additional, Figueiredo, C.A., additional, Barreto, M., additional, Canino, G., additional, Chen, W., additional, Burchard, E.G., additional, and Celedon, J.C., additional

Published
2019
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19. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Author

Paternoster, L, Standl, M, Waage, J, Baurecht, H, Hotze, M, Strachan, DP, Curtin, JA, Bonnelykke, K, Tian, C, Takahashi, A, Esparza-Gordillo, J, Alves, AC, Thyssen, JP, den Dekker, HT, Ferreira, MA, Altmaier, E, Sleiman, PMA, Xiao, FL, Gonzalez, JR, Marenholz, I, Kalb, B, Pino-Yanes, M, Xu, C-J, Carstensen, L, Groen-Blokhuis, MM, Venturini, C, Pennell, CE, Barton, SJ, Levin, AM, Curjuric, I, Bustamante, M, Kreiner-Moller, E, Lockett, GA, Bacelis, J, Bunyavanich, S, Myers, RA, Matanovic, A, Kumar, A, Tung, JY, Hirota, T, Kubo, M, McArdle, WL, Henderson, AJ, Kemp, JP, Zheng, J, Smith, GD, Rueschendorf, F, Bauerfeind, A, Lee-Kirsch, MA, Arnold, A, Homuth, G, Schmidt, CO, Mangold, E, Cichon, S, Keil, T, Rodriguez, E, Peters, A, Franke, A, Lieb, W, Novak, N, Foelster-Holst, R, Horikoshi, M, Pekkanen, J, Sebert, S, Husemoen, LL, Grarup, N, De Jongste, JC, Rivadeneira, F, Hofman, A, Jaddoe, VWV, Pasmans, SGMA, Elbert, NJ, Uitterlinden, AG, Marks, GB, Thompson, PJ, Matheson, MC, Robertson, CF, Ried, JS, Li, J, Zuo, XB, Zheng, XD, Yin, XY, Sun, LD, McAleer, MA, O'Regan, GM, Fahy, CMR, Campbell, LE, Macek, M, Kurek, M, Hu, D, Eng, C, Postma, DS, Feenstra, B, Geller, F, Hottenga, JJ, Middeldorp, CM, Hysi, P, Bataille, V, Spector, T, Tiesler, CMT, Thiering, E, Pahukasahasram, B, Yang, JJ, Imboden, M, Huntsman, S, Vilor-Tejedor, N, Relton, CL, Myhre, R, Nystad, W, Custovic, A, Weiss, ST, Meyers, DA, Soederhaell, C, Melen, E, Ober, C, Raby, BA, Simpson, A, Jacobsson, B, Holloway, JW, Bisgaard, H, Sunyer, J, Probst-Hensch, NM, Williams, LK, Godfrey, KM, Wang, CA, Boomsma, DI, Melbye, M, Koppelman, GH, Jarvis, D, McLean, WHI, Irvine, AD, Zhang, XJ, Hakonarson, H, Gieger-, C, Burchard, EG, Martin, NG, Duijts, L, Linneberg, A, Jarvelin, M-R, Noethen, MM, Lau, S, Huebner, N, Lee, Y-A, Tamari, M, Hinds, DA, Glass, D, Brown, SJ, Heinrich, J, Evans, DM, Weidinger, S, AAGC, AAGC, and Epidemio, EGL

Abstract

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.

Published
2015

20. Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits

Author

Moreno-Estrada A, Gignoux CR, Fernández-López JC, Zakharia F, Sikora M, Contreras AV, Acuña-Alonzo V, Sandoval K, Eng C, Romero-Hidalgo S, Ortiz-Tello P, Robles V, Kenny EE, Nuño-Arana I, Barquera-Lozano R, Macín-Pérez G, Granados-Arriola J, Huntsman S, Galanter JM, Via M, Ford JG, Chapela R, Rodriguez-Cintron W, Rodríguez-Santana JR, Romieu I, Sienra-Monge JJ, del Rio Navarro B, London SJ, Ruiz-Linares A, Garcia-Herrera R, Estrada K, Hidalgo-Miranda A, Jimenez-Sanchez G, Carnevale A, Soberón X, Canizales-Quinteros S, Rangel-Villalobos H, Silva-Zolezzi I, Burchard EG, and Bustamante CD

Subjects
Genome, Human, Mexican Americans, Population, Indians, North American, Black People, Genetic Variation, Humans, Mexico, White People
Abstract

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.

Published
2014

21. The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity

Author

Chan, P. Y., primary, Silva, E. A. C., additional, De Kouchkovsky, D., additional, Joannas, L. D., additional, Hao, L., additional, Hu, D., additional, Huntsman, S., additional, Eng, C., additional, Licona-Limon, P., additional, Weinstein, J. S., additional, Herbert, D. R., additional, Craft, J. E., additional, Flavell, R. A., additional, Repetto, S., additional, Correale, J., additional, Burchard, E. G., additional, Torgerson, D. G., additional, Ghosh, S., additional, and Rothlin, C. V., additional

Published
2016
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23. Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas

Author

Fejerman L, Chen GK, Eng C, Huntsman S, Hu D, Williams A, Pasaniuc B, John EM, Via M, Gignoux C, Ingles S, Monroe KR, Kolonel LN, Torres-Mejía G, Pérez-Stable EJ, Burchard EG, Henderson BE, Haiman CA, and Ziv E

Abstract

Among US Latinas and Mexican women, those with higher European ancestry have increased risk of breast cancer. We combined an admixture mapping and genome-wide association mapping approach to search for genomic regions that may explain this observation. Latina women with breast cancer (n= 1497) and Latina controls (n= 1272) were genotyped using Affymetrix and Illumina arrays. We inferred locus-specific genetic ancestry and compared the ancestry between cases and controls. We also performed single nucleotide polymorphism (SNP) association analyses in regions of interest. Correction for multiple-hypothesis testing was conducted using permutations (P(corrected)). We identified one region where genetic ancestry was significantly associated with breast cancer risk: 6q25 [odds ratio (OR) per Indigenous American chromosome 0.75, 95% confidence interval (CI): 0.65-0.85, P= 1.1 × 10(-5), P(corrected)= 0.02]. A second region on 11p15 showed a trend towards association (OR per Indigenous American chromosome 0.77, 95% CI: 0.68-0.87, P= 4.3 × 10(-5), P(corrected)= 0.08). In both regions, breast cancer risk decreased with higher Indigenous American ancestry in concordance with observations made on global ancestry. The peak of the 6q25 signal includes the estrogen receptor 1 (ESR1) gene and 5' region, a locus previously implicated in breast cancer. Genome-wide association analysis found that a multi-SNP model explained the admixture signal in both regions. Our results confirm that the association between genetic ancestry and breast cancer risk in US Latinas is partly due to genetic differences between populations of European and Indigenous Americans origin. Fine-mapping within the 6q25 and possibly the 11p15 loci will lead to the discovery of the biologically functional variant/s behind this association.

Published
2012

24. Integration of Mouse and Human Genome-Wide Association Data Identifies KCNIP4 as an Asthma Gene

Author

Himes, BE, Sheppard, K, Berndt, A, Leme, AS, Myers, RA, Gignoux, CR, Levin, AM, Gauderman, WJ, Yang, JJ, Mathias, RA, Romieu, I, Torgerson, DG, Roth, LA, Huntsman, S, Eng, C, Klanderman, B, Ziniti, J, Senter-Sylvia, J, Szefler, SJ, Lemanske, RF, Zeiger, RS, Strunk, RC, Martinez, FD, Boushey, H, Chinchilli, VM, Israel, E, Mauger, D, Koppelman, GH, Postma, DS, Nieuwenhuis, MAE, Vonk, JM, Lima, JJ, Irvin, CG, Peters, SP, Kubo, M, Tamari, M, Nakamura, Y, Litonjua, AA, Tantisira, KG, Raby, BA, Bleecker, ER, Meyers, DA, London, SJ, Barnes, KC, Gilliland, FD, Williams, LK, Burchard, EG, Nicolae, DL, Ober, C, DeMeo, DL, Silverman, EK, Paigen, B, Churchill, G, Shapiro, SD, Weiss, ST, Himes, BE, Sheppard, K, Berndt, A, Leme, AS, Myers, RA, Gignoux, CR, Levin, AM, Gauderman, WJ, Yang, JJ, Mathias, RA, Romieu, I, Torgerson, DG, Roth, LA, Huntsman, S, Eng, C, Klanderman, B, Ziniti, J, Senter-Sylvia, J, Szefler, SJ, Lemanske, RF, Zeiger, RS, Strunk, RC, Martinez, FD, Boushey, H, Chinchilli, VM, Israel, E, Mauger, D, Koppelman, GH, Postma, DS, Nieuwenhuis, MAE, Vonk, JM, Lima, JJ, Irvin, CG, Peters, SP, Kubo, M, Tamari, M, Nakamura, Y, Litonjua, AA, Tantisira, KG, Raby, BA, Bleecker, ER, Meyers, DA, London, SJ, Barnes, KC, Gilliland, FD, Williams, LK, Burchard, EG, Nicolae, DL, Ober, C, DeMeo, DL, Silverman, EK, Paigen, B, Churchill, G, Shapiro, SD, and Weiss, ST

Abstract

Asthma is a common chronic respiratory disease characterized by airway hyperresponsiveness (AHR). The genetics of asthma have been widely studied in mouse and human, and homologous genomic regions have been associated with mouse AHR and human asthma-related phenotypes. Our goal was to identify asthma-related genes by integrating AHR associations in mouse with human genome-wide association study (GWAS) data. We used Efficient Mixed Model Association (EMMA) analysis to conduct a GWAS of baseline AHR measures from males and females of 31 mouse strains. Genes near or containing SNPs with EMMA p-values <0.001 were selected for further study in human GWAS. The results of the previously reported EVE consortium asthma GWAS meta-analysis consisting of 12,958 diverse North American subjects from 9 study centers were used to select a subset of homologous genes with evidence of association with asthma in humans. Following validation attempts in three human asthma GWAS (i.e., Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG) and two human AHR GWAS (i.e., SHARP, DAG), the Kv channel interacting protein 4 (KCNIP4) gene was identified as nominally associated with both asthma and AHR at a gene- and SNP-level. In EVE, the smallest KCNIP4 association was at rs6833065 (P-value 2.9e-04), while the strongest associations for Sepracor/LOCCS/LODO/Illumina, GABRIEL, DAG were 1.5e-03, 1.0e-03, 3.1e-03 at rs7664617, rs4697177, rs4696975, respectively. At a SNP level, the strongest association across all asthma GWAS was at rs4697177 (P-value 1.1e-04). The smallest P-values for association with AHR were 2.3e-03 at rs11947661 in SHARP and 2.1e-03 at rs402802 in DAG. Functional studies are required to validate the potential involvement of KCNIP4 in modulating asthma susceptibility and/or AHR. Our results suggest that a useful approach to identify genes associated with human asthma is to leverage mouse AHR association data. © 2013 Himes et al.

Published
2013

26. Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease

Author

Scherer, M. L., primary, Nalls, M. A., additional, Pawlikowska, L., additional, Ziv, E., additional, Mitchell, G., additional, Huntsman, S., additional, Hu, D., additional, Sutton-Tyrrell, K., additional, Lakatta, E. G., additional, Hsueh, W.-C., additional, Newman, A. B., additional, Tandon, A., additional, Kim, L., additional, Kwok, P.-Y., additional, Sung, A., additional, Li, R., additional, Psaty, B., additional, Reiner, A. P., additional, and Harris, T., additional

Published
2009
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29. The Role of Circulation and Stability in Controlling the Relative Abundance of Dinoflagellates and Diatoms Over the Peru Shelf

Author

Huntsman, S. A., Brink, Kenneth H., Barber, Richard T., Blasco, Dolors, Huntsman, S. A., Brink, Kenneth H., Barber, Richard T., and Blasco, Dolors

Abstract

During a six-week study, the dinoflagellate abundance at C-3, a mid-shelf station off the Peruvian coast, fluctuated widely. At times of maximum cell density (400 cells/ml) dinoflagellates comprised up to 80% of the combined dinoflagellate-diatom population. Our data suggest that after their initial advection into the study site, the dinoflagellates persisted because of stability in the euphotic zone and reseeding by the subsurface poleward undercurrent. The increased stability that favored dinoflagellates did not exclude diatoms at C-3. Diatoms could utilize the available silica and regenerated nitrogen to maintain growth rates adequate to counteract losses from sinking and grazing

Published
1981

30. Germline genetic contribution to the immune landscape of cancer

Author

Denise M. Wolf, Scott Huntsman, Farshad Farshidfar, Younes Mokrab, Cynthia Stretch, Rebecca E. Graff, Francesco M. Marincola, Laszlo Radvanyi, Rosalyn W. Sayaman, Vesteinn Thorsson, Wouter Hendrickx, Michele Ceccarelli, Eduard Porta-Pardo, Randy F. Sweis, Simon Shelley, Jérôme Galon, Jessica Roelands, Donglei Hu, Carolina Heimann, Michael J. Campbell, Mohamad Saad, Davide Bedognetti, Tomas Kirchhoff, Elad Ziv, Najeeb Syed, Oliver F. Bathe, Barcelona Supercomputing Center, Sayaman, R. W., Saad, M., Thorsson, V., Hu, D., Hendrickx, W., Roelands, J., Porta-Pardo, E., Mokrab, Y., Farshidfar, F., Kirchhoff, T., Sweis, R. F., Bathe, O. F., Heimann, C., Campbell, M. J., Stretch, C., Huntsman, S., Graff, R. E., Syed, N., Radvanyi, L., Shelley, S., Wolf, D., Marincola, F. M., Ceccarelli, M., Galon, J., Ziv, E., and Bedognetti, D.

Subjects
0301 basic medicine, Male, medicine.medical_treatment, T-Lymphocytes, Genes, BRCA1, Genome-wide association study, Retinoblastoma-Like Protein p107, Cancer immunotherapy, heritability, Germline, 0302 clinical medicine, Interferon, iATLAS, Neoplasms, Databases, Genetic, Immunology and Allergy, Killer Cells, GWAS, 2.1 Biological and endogenous factors, Lymphocytes, Aetiology, Càncer -- Aspectes genètics, germline genetic, beta Catenin, Cancer, Immune subtype, Genetics, Middle Aged, Gene Expression Regulation, Neoplastic, Killer Cells, Natural, Infectious Diseases, 030220 oncology & carcinogenesis, Natural, Female, Immunotherapy, medicine.drug, Signal Transduction, Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Immune subtypes, Immunology, rare variant analysi, Biology, Article, 03 medical and health sciences, Quantitative Trait, Databases, Lymphocytes, Tumor-Infiltrating, Quantitative Trait, Heritable, Immune system, Tumors--Immunological aspects, Genetic, cancer immunity, germline genetics, rare variant analysis, medicine, Humans, Genetic Predisposition to Disease, Tumor-Infiltrating, cancer immune landscape, Gene, Heritable, Germ-Line Mutation, Neoplastic, Human Genome, TCGA, medicine.disease, BRCA1, Wnt Proteins, 030104 developmental biology, Good Health and Well Being, Gene Expression Regulation, Genes, Interferons, Genome-Wide Association Study
Abstract

Understanding the contribution of the host’s genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139 well-defined immune traits in ∼9000 cancer patients enrolled in TCGA. High heritability was observed for estimates of NK cell and T cell subset infiltration and for interferon signaling. Common variants of IFIH1, TMEM173 (STING1), and TMEM108 were associated with differential interferon signaling and variants mapping to RBL1 correlated with T cell subset abundance. Pathogenic or likely pathogenic variants in BRCA1 and in genes involved in telomere stabilization and Wnt-β-catenin also acted as immune modulators. Our findings provide evidence for the impact of germline genetics on the composition and functional orientation of the tumor immune microenvironment. The curated datasets, variants, and genes identified provide a resource toward further understanding of tumor-immune interactions. We are grateful to the Society for Immunotherapy of Cancer (SITC) for the logistical support of the investigator meeting within the SITC Cancer Immune Responsiveness Workshop (San Francisco CA, US, April 2018; Houston, TX, US, May 2019). We are also grateful to Noah Zaitlen and Andy Dahl for useful discussions on heritability interaction analyses. This work was funded in part by the National Institutes of Health R01CA227466 and K24CA169004 to EZ and T32CA221709 postdoctoral fellowship to RWS, Qatar National Research Fund (QNRF) NPRP11S-0121-180351 grant and the Sidra Precision Medicine Program internal grant (SDR100035 and SDR400023) to DB, Associazione Italiana per la Ricerca sul cancro (AIRC) grant IG2018-21846 to MC, the Cancer Research Institute funding to VT, and the Fundació Bancaria La Caixa, a La Caixa Junior Leader Fellowship (LCF/BQ/PI18/11630003) to EP-P.

Published
2021

32. Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients

Author

Paige M. Bracci, Celine M. Vachon, Thomas Martin, Shaji Kumar, Daniel J. Serie, Alexandra J. Greenberg, Laura Fejerman, Djordje Atanackovic, Brandt Jones, Federico Canzian, Robert B. Diasio, Vincent Rajkumar, Jeffrey L. Wolf, Blake T. Aftab, Alessandro Martino, Susan L. Slager, Herlander Marques, Donglei Hu, Eric Dean, Marek Dudziński, Martha Glenn, Yi Zhao, Marzena Wątek, Nicola J. Camp, Elad Ziv, Karen Curtin, Adam M. Lee, Juan Sainz, Joaquin Martinez-Lopez, Artur Jurczyszyn, Lisa A. Cannon-Albright, Charles Dumontet, Scott Huntsman, Jennifer L. Caswell-Jin, Annette Juul Vangsted, Daniele Campa, Gabriele Buda, Krzysztof Jamroziak, [Ziv,E, Hu,D, Caswell.Jin,J,H, Fejerman,L, Huntsman,S] Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California USA. [Dean,E] Sutter Medical Center of Santa Rosa, Santa Rosa, California USA. [Martino,A, Campa,D, Canzian,F] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Serie,D] Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida USA. [Curtin,K, Zhao,Y, Atanackovic,D, Glenn,M, Cannon-Albright,L, Jones,B, Camp,NJ] Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, USA. [Aftalb,B, Martin,T, Wolf,J]Division of Hematology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California USA. [Bracci,P] Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California , USA. [Buda,G] Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University Hospital, Pisa, Italy. [Diasio,R, Lee,A] Department of Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Mayo Clinic, Rochester, Minnesota USA. [Dumontet,C] INSERM UMR 1052/CNRS 5286, Laboratoire de Cytologie Analytique, Faculte´ de Me´decine Rockefeller, Universite´ Claude Bernard Lyon I, Lyon, France. [Dudzinski,M] Department of Hematology, Rzeszow Regional Hospital, Rzeszow 35-301, Poland. [Greenberg,A] Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905, USA. [Greenberg,A, Vachon, C] Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [Jamroziak,K] Department of Hematology, Medical University of Lodz, Lodz, Poland. [Jurczyszyn,A] Department of Hematology, Cracow University Hospital, Cracow, Poland. [Kumar,S, Rajkumar,V] Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA. [Marques,H] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga , Portugal. [Martinez-Lopez,J] Hematology Service, CRIS facility for Hematological research, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain. [Sainz,J] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. Department of Hematology, Virgen de las Nieves University Hospital, Granada, Spain. [Vangsted,AJ] Department of Hematology, Righospitalet and Roskilde Hospital, Copenhagen University, Copenhagen, Denmark. [Watek,M] Department of Hematology, Holycross Cancer Center, Kielce, Poland. [Slager,S] Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota USA., and This work was supported by the Steve and Nancy Grand Multiple Myeloma Translational Initiative and a grant from Expression Analysis and a grant from the National Cancer Institute (R21CA191896). E.Z. is supported in part by a mid-career award in patient research from the National Cancer Institute (K24169004). Collection of blood samples from Polish patients and controls from Łodz area, and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. NN402178334). DNA extraction from Danish healthy controls was supported by The Research Fund at Region Sjælland, Denmark. The Utah study was supported by LLS 6067–09, CA152336 and CA134674, with data collection made possible, in part, by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data sets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the NCI SEER Program with additional support from the Utah State Department of Health and the University of Utah.

Subjects
Oncology, medicine.medical_specialty, tumor, Ciências da Saúde [Ciências Médicas], General Physics and Astronomy, Genome-wide association study, Single-nucleotide polymorphism, Kaplan-Meier Estimate, Biology, Bioinformatics, Polymorphism, Single Nucleotide, survival, Article, General Biochemistry, Genetics and Molecular Biology, gene expression, genome, health risk, meta-analysis, polymorphism, social theory, Internal medicine, medicine, Humans, Allele, Gene, Multiple myeloma, Science & Technology, Multidisciplinary, General Chemistry, medicine.disease, Minor allele frequency, Meta-analysis, Cohort, Multiple Myeloma, Chromosomes, Human, Pair 16, Genome-Wide Association Study
Abstract

A corrigendum to this article was published on 09 December 2015: https://doi.org/10.1038/ncomms10203. The corrigendum is also available at: http://hdl.handle.net/1822/62281 This work was supported by the Steve and Nancy Grand Multiple Myeloma Translational Initiative and a grant from Expression Analysis and a grant from the National Cancer Institute (R21CA191896). E.Z. is supported in part by a mid-career award in patient research from the National Cancer Institute (K24169004). Collection of blood samples from Polish patients and controls from Łodz area, and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. NN402178334).DNA extraction from Danish healthy controls was supported by The Research Fund at Region Sjælland, Denmark. The Utah study was supported by LLS 6067–09, CA152336and CA134674, with data collection made possible, in part, by the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data sets within the UPDB is provided by the Huntsman Cancer Institute (HCI) and the HCICancer Center Support grant, P30 CA42014. The UCR is supported in part by NIH contract HHSN261201000026C from the NCI SEER Program with additional support from the Utah State Department of Health and the University of Utah. In Utah, we thank Jathine Wong for support in formatting files and advice on R programming. Several authors (E.Z., N.C., F.C., C.V.) are members of the International Multiple Myeloma Consortium. We are grateful to the leadership and other members of the International Multiple Myeloma Consortium for facilitating this collaborative study.

Published
2015

33. Sequence, 'subtle' alternative splicing and expression of the CYYR1 (cysteine/tyrosine-rich 1) mRNA in human neuroendocrine tumors

Author

Silvia Canaider, Federica Facchin, Flavia Frabetti, Paolo Carinci, Shane Huntsman, Raffaella Casadei, Maria Zannotti, Domenico Coppola, Pierluigi Strippoli, Lorenza Vitale, Luca Lenzi, Vitale L., Frabetti F., Huntsman S. A., Canaider S., Casadei R., Lenzi L., Facchin F., Carinci P., Zannotti M., Coppola D., and Strippoli P.

Subjects
Adult, Male, Cancer Research, Pan troglodytes, Molecular Sequence Data, Sequence Homology, Sequence alignment, Biology, Digestive System Neoplasms, Polymorphism, Single Nucleotide, lcsh:RC254-282, Evolution, Molecular, Species Specificity, Neoplasms, Genetics, Animals, Humans, Point Mutation, Protein Isoforms, Amino Acid Sequence, RNA, Messenger, RNA, Neoplasm, Codon, Gene, Peptide sequence, Aged, Expressed sequence tag, Messenger RNA, Alanine, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Alternative splicing, HUMAN, Membrane Proteins, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Molecular biology, Gene Expression Regulation, Neoplastic, Alternative Splicing, Neuroendocrine Tumors, Oncology, RNA splicing, Female, Chromosome 21, GENOMICS, Sequence Alignment, Research Article
Abstract

Background CYYR1 is a recently identified gene located on human chromosome 21 whose product has no similarity to any known protein and is of unknown function. Analysis of expressed sequence tags (ESTs) have revealed high human CYYR1 expression in cells belonging to the diffuse neuroendocrine system (DNES). These cells may be the origin of neuroendocrine (NE) tumors. The aim of this study was to conduct an initial analysis of sequence, splicing and expression of the CYYR1 mRNA in human NE tumors. Methods The CYYR1 mRNA coding sequence (CDS) was studied in 32 NE tumors by RT-PCR and sequence analysis. A subtle alternative splicing was identified generating two isoforms of CYYR1 mRNA differing in terms of the absence (CAG- isoform, the first described mRNA for CYYR1 locus) or the presence (CAG+ isoform) of a CAG codon. When present, this specific codon determines the presence of an alanine residue, at the exon 3/exon 4 junction of the CYYR1 mRNA. The two mRNA isoform amounts were determined by quantitative relative RT-PCR in 29 NE tumors, 2 non-neuroendocrine tumors and 10 normal tissues. A bioinformatic analysis was performed to search for the existence of the two CYYR1 isoforms in other species. Results The CYYR1 CDS did not show differences compared to the reference sequence in any of the samples, with the exception of an NE tumor arising in the neck region. Sequence analysis of this tumor identified a change in the CDS 333 position (T instead of C), leading to the amino acid mutation P111S. NE tumor samples showed no significant difference in either CYYR1 CAG- or CAG+ isoform expression compared to control tissues. CYYR1 CAG- isoform was significantly more expressed than CAG+ isoform in NE tumors as well as in control samples investigated. Bioinformatic analysis revealed that only the genomic sequence of Pan troglodytes CYYR1 is consistent with the possible existence of the two described mRNA isoforms. Conclusion A new "subtle" splicing isoform (CAG+) of CYYR1 mRNA, the sequence and the expression of this gene were defined in a large series of NE tumors.

Published
2007

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