Search

Your search keyword '"Schuler-Faccini, L"' showing total 195 results
Start Over Author "Schuler-Faccini, L"
195 results on '"Schuler-Faccini, L"'

1. Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies

Author

Bromley, R. L., primary, Bickle Graz, M., additional, Bluett-Duncan, M., additional, Chambers, C., additional, Damkier, P., additional, Dietrich, K., additional, Dolk, H., additional, Grant, K., additional, Mattson, S., additional, Meador, K. J., additional, Nordeng, H., additional, Oberlander, T. F., additional, Ornoy, A., additional, Revet, A., additional, Richardson, J., additional, Rovet, J., additional, Schuler-Faccini, L., additional, Smearman, E., additional, Simms, V., additional, Vorhees, C., additional, Wide, K., additional, Wood, A., additional, Yates, L., additional, Ystrom, E., additional, Supraja, T. A., additional, and Adams, J., additional

Published
2023
Full Text
View/download PDF

2. Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies

Author

Bromley, R L, Bickle Graz, M, Bluett-Duncan, M, Damkier, P, Dietrich, K, Dolk, H, Mattson, S, Meador, K J, Nordeng, H, Oberlander, T F, Ornoy, A, Revet, A, Rovet, J, Schuler-Faccini, L, Smearman, E, Simms, V, Vorhees, C, Wide, K, Ystrom, E, and Supraja, T A

Abstract

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance.

Published
2023

3. Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide

Author

Moorthie, Sowmiya, Blencowe, Hannah, Darlison, Matthew W., Lawn, Joy, Morris, Joan K., Modell, Bernadette, Congenital Disorders Expert Group, Bittles, A. H., Blencowe, H., Christianson, A., Cousens, S., Darlison, M. W., Gibbons, S., Hamamy, H., Khoshnood, B., Howson, C. P., Lawn, J., Mastroiacovo, P., Modell, B., Moorthie, S., Morris, J. K., Mossey, P. A., Neville, A. J., Petrou, M., Povey, S., Rankin, J., Schuler-Faccini, L., Wren, C., and Yunnis, K. A.

Published
2018
Full Text
View/download PDF

4. Disentangling Signatures of Selection Before and After European Colonization in Latin Americans

Author

Kim, Y, Mendoza-Revilla, J, Chacon-Duque, JC, Fuentes-Guajardo, M, Ormond, L, Wang, K, Hurtado, M, Villegas, V, Granja, V, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Barquera, R, Gomez-Valdes, J, Villamil-Ramirez, H, de Cerqueira, CCS, Rivera, KMB, Nieves-Colon, MA, Gignoux, CR, Wojcik, GL, Moreno-Estrada, A, Hunemeier, T, Ramallo, V, Schuler-Faccini, L, Gonzalez-Jose, R, Bortolini, M-C, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Balding, D, Fumagalli, M, Adhikari, K, Ruiz-Linares, A, Hellenthal, G, Kim, Y, Mendoza-Revilla, J, Chacon-Duque, JC, Fuentes-Guajardo, M, Ormond, L, Wang, K, Hurtado, M, Villegas, V, Granja, V, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Barquera, R, Gomez-Valdes, J, Villamil-Ramirez, H, de Cerqueira, CCS, Rivera, KMB, Nieves-Colon, MA, Gignoux, CR, Wojcik, GL, Moreno-Estrada, A, Hunemeier, T, Ramallo, V, Schuler-Faccini, L, Gonzalez-Jose, R, Bortolini, M-C, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Balding, D, Fumagalli, M, Adhikari, K, Ruiz-Linares, A, and Hellenthal, G

Abstract

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.

Published
2022

7. Prediction of eye, hair and skin colour in Latin Americans

Author

Palmal, S, Adhikari, K, Mendoza-Revilla, J, Fuentes-Guajardo, M, de Cerqueira, CCS, Bonfante, B, Chacon-Duque, JC, Sohail, A, Hurtado, M, Villegas, V, Granja, V, Jaramillo, C, Arias, W, Barquera Lozano, R, Everardo-Martinez, P, Gomez-Valdes, J, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Parolin, M-L, Gonzalez-Jose, R, Schuler-Faccini, L, Bortolini, M-C, Acuna-Alonzo, V, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Balding, D, Faux, P, Ruiz-Linares, A, Palmal, S, Adhikari, K, Mendoza-Revilla, J, Fuentes-Guajardo, M, de Cerqueira, CCS, Bonfante, B, Chacon-Duque, JC, Sohail, A, Hurtado, M, Villegas, V, Granja, V, Jaramillo, C, Arias, W, Barquera Lozano, R, Everardo-Martinez, P, Gomez-Valdes, J, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Parolin, M-L, Gonzalez-Jose, R, Schuler-Faccini, L, Bortolini, M-C, Acuna-Alonzo, V, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Balding, D, Faux, P, and Ruiz-Linares, A

Abstract

Here we evaluate the accuracy of prediction for eye, hair and skin pigmentation in a dataset of > 6500 individuals from Mexico, Colombia, Peru, Chile and Brazil (including genome-wide SNP data and quantitative/categorical pigmentation phenotypes - the CANDELA dataset CAN). We evaluated accuracy in relation to different analytical methods and various phenotypic predictors. As expected from statistical principles, we observe that quantitative traits are more sensitive to changes in the prediction models than categorical traits. We find that Random Forest or Linear Regression are generally the best performing methods. We also compare the prediction accuracy of SNP sets defined in the CAN dataset (including 56, 101 and 120 SNPs for eye, hair and skin colour prediction, respectively) to the well-established HIrisPlex-S SNP set (including 6, 22 and 36 SNPs for eye, hair and skin colour prediction respectively). When training prediction models on the CAN data, we observe remarkably similar performances for HIrisPlex-S and the larger CAN SNP sets for the prediction of hair (categorical) and eye (both categorical and quantitative), while the CAN sets outperform HIrisPlex-S for quantitative, but not for categorical skin pigmentation prediction. The performance of HIrisPlex-S, when models are trained in a world-wide sample (although consisting of 80% Europeans, https://hirisplex.erasmusmc.nl), is lower relative to training in the CAN data (particularly for hair and skin colour). Altogether, our observations are consistent with common variation of eye and hair colour having a relatively simple genetic architecture, which is well captured by HIrisPlex-S, even in admixed Latin Americans (with partial European ancestry). By contrast, since skin pigmentation is a more polygenic trait, accuracy is more sensitive to prediction SNP set size, although here this effect was only apparent for a quantitative measure of skin pigmentation. Our results support the use of HIrisPlex-S in the pr

Published
2021

8. A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation

Author

Bonfante, B, Faux, P, Navarro, N, Mendoza-Revilla, J, Dubied, M, Montillot, C, Wentworth, E, Poloni, L, Varon-Gonzalez, C, Jones, P, Xiong, Z, Fuentes-Guajardo, M, Palmal, S, Chacon-Duque, JC, Hurtado, M, Villegas, V, Granja, V, Jaramillo, C, Arias, W, Barquera, R, Everardo-Martinez, P, Sanchez-Quinto, M, Gomez-Valdes, J, Villamil-Ramirez, H, de Cerqueira, CCS, Hunemeier, T, Ramallo, V, Liu, F, Weinber, SM, Shaffer, JR, Stergiakouli, E, Howe, LJ, Hysi, PG, Spector, TD, Gonzalez-Jose, R, Schuler-Faccini, L, Bortolini, R-C, Acuna-Alonzo, V, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Thauvin-Robinet, C, Faivre, L, Costedoat, C, Balding, D, Cox, T, Kayser, M, Duplomb, L, Yalcin, B, Cotney, J, Adhikari, K, Ruiz-Linares, A, Bonfante, B, Faux, P, Navarro, N, Mendoza-Revilla, J, Dubied, M, Montillot, C, Wentworth, E, Poloni, L, Varon-Gonzalez, C, Jones, P, Xiong, Z, Fuentes-Guajardo, M, Palmal, S, Chacon-Duque, JC, Hurtado, M, Villegas, V, Granja, V, Jaramillo, C, Arias, W, Barquera, R, Everardo-Martinez, P, Sanchez-Quinto, M, Gomez-Valdes, J, Villamil-Ramirez, H, de Cerqueira, CCS, Hunemeier, T, Ramallo, V, Liu, F, Weinber, SM, Shaffer, JR, Stergiakouli, E, Howe, LJ, Hysi, PG, Spector, TD, Gonzalez-Jose, R, Schuler-Faccini, L, Bortolini, R-C, Acuna-Alonzo, V, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Thauvin-Robinet, C, Faivre, L, Costedoat, C, Balding, D, Cox, T, Kayser, M, Duplomb, L, Yalcin, B, Cotney, J, Adhikari, K, and Ruiz-Linares, A

Abstract

To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.

Published
2021

9. A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans

Author

Chen, Y, Andre, M, Adhikari, K, Blin, M, Bonfante, B, Mendoza-Revilla, J, Fuentes-Guajardo, M, Palmal, S, Chacon-Duque, JC, Hurtado, M, Villegas, V, Granja, V, Jaramillo, C, Arias, W, Lozano, RB, Everardo-Martinez, P, Gomez-Valdes, J, Villamil-Ramirez, H, de Cerqueira, CCS, Hunemeier, T, Ramallo, V, Gonzalez-Jose, R, Schuler-Faccini, L, Bortolini, M-C, Acuna-Alonzo, V, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Balding, D, Tobin, DJ, Wang, S, Faux, P, Ruiz-Linares, A, Chen, Y, Andre, M, Adhikari, K, Blin, M, Bonfante, B, Mendoza-Revilla, J, Fuentes-Guajardo, M, Palmal, S, Chacon-Duque, JC, Hurtado, M, Villegas, V, Granja, V, Jaramillo, C, Arias, W, Lozano, RB, Everardo-Martinez, P, Gomez-Valdes, J, Villamil-Ramirez, H, de Cerqueira, CCS, Hunemeier, T, Ramallo, V, Gonzalez-Jose, R, Schuler-Faccini, L, Bortolini, M-C, Acuna-Alonzo, V, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Balding, D, Tobin, DJ, Wang, S, Faux, P, and Ruiz-Linares, A

Abstract

BACKGROUND: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVES: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. METHODS: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. RESULTS: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.

Published
2021

11. A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia

Author

Adhikari, K, Mendoza-Revilla, J, Sohail, A, Fuentes-Guajardo, M, Lampert, J, Chacon-Duque, JC, Hurtado, M, Villegas, V, Granja, V, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Barquera Lozano, R, Everardo, P, Gomez-Valdes, J, Villamil-Ramirez, H, Silva de Cerqueira, CC, Hunemeier, T, Ramallo, V, Schuler-Faccini, L, Salzano, FM, Gonzalez-Jose, R, Bortolini, M-C, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Tobin, DJ, Fumagalli, M, Balding, D, Ruiz-Linares, A, Adhikari, K, Mendoza-Revilla, J, Sohail, A, Fuentes-Guajardo, M, Lampert, J, Chacon-Duque, JC, Hurtado, M, Villegas, V, Granja, V, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Barquera Lozano, R, Everardo, P, Gomez-Valdes, J, Villamil-Ramirez, H, Silva de Cerqueira, CC, Hunemeier, T, Ramallo, V, Schuler-Faccini, L, Salzano, FM, Gonzalez-Jose, R, Bortolini, M-C, Canizales-Quinteros, S, Gallo, C, Poletti, G, Bedoya, G, Rothhammer, F, Tobin, DJ, Fumagalli, M, Balding, D, and Ruiz-Linares, A

Abstract

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.

Published
2019

12. Latin Americans show wide-spread Converso ancestry and the imprint of local Native ancestry on physical appearance

Author

Chacon-Duque, J., Adhikari, K., Fuentes-Guajardo, M., Mendoza-Revilla, J., Acuna-Alonzo, V., Barquera Lozano, R., Quinto-Sanchez, M., Gomez-Valdes, J., Everardo Martinez, P., Villamil-Ramirez, H., Hunemeier, T., Ramallo, V., Silva de Cerqueira, C., Hurtado, M., Villegas, V., Granja, V., Villena, M., Vasquez, R., Llop, E., Sandoval, J., Salazar-Granara, A., Parolin, M., Sandoval, K., Penaloza-Espinosa, R., Rangel-Villalobos, H., Winkler, C., Klitz, W., Bravi, C., Molina, J., Corach, D., Barrantes, R., Gomes, V., Resende, C., Gusmao, L., Amorim, A., Xue, Y., Dugoujon, J., Moral, P., Gonzalez-Jose, R., Schuler-Faccini, L., Salzano, F., Bortolini, M., Canizales-Quinteros, S., Poletti, G., Gallo, C., Bedoya, G., Rothhammer, F., Balding, D., Hellenthal, G., and Ruiz-Linares, A.

Subjects
parasitic diseases
Abstract

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the admixture of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods here we infer the sub-populations involved in admixture for over 6,500 Latin Americans and evaluate the impact of sub-continental ancestry on the physical appearance of these individuals. We find that pre-Columbian Native genetic structure is mirrored in Latin Americans and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that Central Andean ancestry impacts on variation of facial features in Latin Americans, particularly nose morphology, possibly relating to environmental adaptation during the evolution of Native Americans.

Published
2018

13. Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans

Author

Wu, S. (Sijie), Zhang, M. (Manfei), Yang, X. (Xinzhou), Peng, F. (Fuduan), Zhang, J. (Juan), Tan, J. (Jingze), Yang, Y. (Yajun), Wang, L. (Lina), Hu, Y. (Yanan), Peng, Q. (Qianqian), Li, J. (Jinxi), Liu, Y. (Yu), Guan, Y. (Yaqun), Chen, C. (Chen), Hamer, M.A. (Merel), Nijsten, T.E.C. (Tamar), Zeng, C. (Changqing), Adhikari, K. (Kaustubh), Gallo, C. (Carla), Poletti, G. (Giovanni), Schuler-Faccini, L. (Lavinia), Bortolini, M.-C. (Maria-Cátira), Canizales-Quinteros, S. (Samuel), Rothhammer, F. (Francisco), Bedoya, E.G. (Elsie), González-José, R. (Rolando), Li, H. (Hui), Krutmann, J. (Jean), Liu, F. (Fan), Kayser, M.H. (Manfred), Ruiz-Linares, A. (Andres), Tang, K. (Kun), Xu, S. (Shuhua), Zhang, L. (Liang), Jin, L. (Li), Wang, S. (Sijia), Wu, S. (Sijie), Zhang, M. (Manfei), Yang, X. (Xinzhou), Peng, F. (Fuduan), Zhang, J. (Juan), Tan, J. (Jingze), Yang, Y. (Yajun), Wang, L. (Lina), Hu, Y. (Yanan), Peng, Q. (Qianqian), Li, J. (Jinxi), Liu, Y. (Yu), Guan, Y. (Yaqun), Chen, C. (Chen), Hamer, M.A. (Merel), Nijsten, T.E.C. (Tamar), Zeng, C. (Changqing), Adhikari, K. (Kaustubh), Gallo, C. (Carla), Poletti, G. (Giovanni), Schuler-Faccini, L. (Lavinia), Bortolini, M.-C. (Maria-Cátira), Canizales-Quinteros, S. (Samuel), Rothhammer, F. (Francisco), Bedoya, E.G. (Elsie), González-José, R. (Rolando), Li, H. (Hui), Krutmann, J. (Jean), Liu, F. (Fan), Kayser, M.H. (Manfred), Ruiz-Linares, A. (Andres), Tang, K. (Kun), Xu, S. (Shuhua), Zhang, L. (Liang), Jin, L. (Li), and Wang, S. (Sijia)

Abstract

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10−10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10−8). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10−11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the pop

Published
2018
Full Text
View/download PDF

14. Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance

Author

Chacon-Duque, J-C, Adhikari, K, Fuentes-Guajardo, M, Mendoza-Revilla, J, Acuna-Alonzo, V, Barquera, R, Quinto-Sanchez, M, Gomez-Valdes, J, Everardo Martinez, P, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Villena, M, Vasquez, R, Llop, E, Sandoval, JR, Salazar-Granara, AA, Parolin, M-L, Sandoval, K, Penaloza-Espinosa, RI, Rangel-Villalobos, H, Winkler, CA, Klitz, W, Bravi, C, Molina, J, Corach, D, Barrantes, R, Gomes, V, Resende, C, Gusmao, L, Amorim, A, Xue, Y, Dugoujon, J-M, Moral, P, Gonzalez-Jose, R, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Poletti, G, Gallo, C, Bedoya, G, Rothhammer, F, Balding, D, Hellenthal, G, Ruiz-Linares, A, Chacon-Duque, J-C, Adhikari, K, Fuentes-Guajardo, M, Mendoza-Revilla, J, Acuna-Alonzo, V, Barquera, R, Quinto-Sanchez, M, Gomez-Valdes, J, Everardo Martinez, P, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Villena, M, Vasquez, R, Llop, E, Sandoval, JR, Salazar-Granara, AA, Parolin, M-L, Sandoval, K, Penaloza-Espinosa, RI, Rangel-Villalobos, H, Winkler, CA, Klitz, W, Bravi, C, Molina, J, Corach, D, Barrantes, R, Gomes, V, Resende, C, Gusmao, L, Amorim, A, Xue, Y, Dugoujon, J-M, Moral, P, Gonzalez-Jose, R, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Poletti, G, Gallo, C, Bedoya, G, Rothhammer, F, Balding, D, Hellenthal, G, and Ruiz-Linares, A

Abstract

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.

Published
2018

15. Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans

Author

Wu, SJ, Zhang, MF, Yang, XZ, Peng, FD, Zhang, J, Tan, JZ, Yang, YJ, Wang, LN (Lina), Hu, YN, Peng, QQ, Li, JX, Liu, Y, Guan, YQ, Chen, C, Hamer, Merel, Nijsten, Tamar, Zeng, CQ, Adhikari, K, Gallo, C, Poletti, G, Schuler-Faccini, L, Bortolini, MC, Canizales-Quinteros, S, Rothhammer, F, Bedoya, G, Gonzalez-Jose, R, Li, H, Krutmann, J, Liu, Fan, Kayser, Manfred, Ruiz-Linares, A, Tang, K, Xu, SH, Zhang, Lei, Jin, L, Wang, SJ, Wu, SJ, Zhang, MF, Yang, XZ, Peng, FD, Zhang, J, Tan, JZ, Yang, YJ, Wang, LN (Lina), Hu, YN, Peng, QQ, Li, JX, Liu, Y, Guan, YQ, Chen, C, Hamer, Merel, Nijsten, Tamar, Zeng, CQ, Adhikari, K, Gallo, C, Poletti, G, Schuler-Faccini, L, Bortolini, MC, Canizales-Quinteros, S, Rothhammer, F, Bedoya, G, Gonzalez-Jose, R, Li, H, Krutmann, J, Liu, Fan, Kayser, Manfred, Ruiz-Linares, A, Tang, K, Xu, SH, Zhang, Lei, Jin, L, and Wang, SJ

Published
2018

16. The phenotypic spectrum of congenital Zika syndrome

Author

Del Campo M, Feitosa IM, Ribeiro EM, Horovitz DD, Pessoa AL, França GV, García-Alix A, Doriqui MJ, Wanderley HY, Sanseverino MV, Neri JI, Pina-Neto JM, Santos ES, Verçosa I, Cernach MC, Medeiros PF, Kerbage SC, Silva AA, van der Linden V, Martelli CM, Cordeiro MT, Dhalia R, Vianna FS, Victora CG, Cavalcanti DP, Schuler-Faccini L, and Zika Embryopathy Task Force-Brazilian Society of Medical Genetics ZETF-SBGM

Subjects
disruptive sequence, congenital Zika syndrome, teratogen, congenital Zika infection, dysmorphology, congenital Zika sequence, fetal brain disruption sequence, disruption, Zika virus, teratology
Abstract

In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.

Published
2017

17. Prevalence of ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms in Brazilian breast cancer-unaffected women

Author

Giacomazzi, J., Aguiar, E., Palmero, E.I., Schmidt, A.V., Skonieski, G., Filho, D.D., Bock, H., Saraiva-Pereira, M.L., Ewald, I.P., Schuler-Faccini, L., Camey, S.A., Caleffi, M., Giugliani, R., and Ashton-Prolla, P.

Subjects
Progesterone receptor gene, lcsh:R5-920, Breast cancer susceptibility, lcsh:Biology (General), Estrogen receptor gene, Genetic polymorphisms, lcsh:Medicine (General), lcsh:QH301-705.5
Abstract

Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease.

Published
2012

18. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features

Author

Adhikari, K, Fontanil, T, Cal, S, Mendoza-Revilla, J, Fuentes-Guajardo, M, Chacon-Duque, J-C, Al-Saadi, F, Johansson, JA, Quinto-Sanchez, M, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Barquera Lozano, R, Macin Perez, G, Gomez-Valdes, J, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Gallo, C, Poletti, G, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Rothhammer, F, Bedoya, G, Gonzalez-Jose, R, Headon, D, Lopez-Otin, C, Tobin, DJ, Balding, D, Ruiz-Linares, A, Adhikari, K, Fontanil, T, Cal, S, Mendoza-Revilla, J, Fuentes-Guajardo, M, Chacon-Duque, J-C, Al-Saadi, F, Johansson, JA, Quinto-Sanchez, M, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Barquera Lozano, R, Macin Perez, G, Gomez-Valdes, J, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Gallo, C, Poletti, G, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Rothhammer, F, Bedoya, G, Gonzalez-Jose, R, Headon, D, Lopez-Otin, C, Tobin, DJ, Balding, D, and Ruiz-Linares, A

Abstract

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.

Published
2016

19. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation

Author

Adhikari, K, Fuentes-Guajardo, M, Quinto-Sanchez, M, Mendoza-Revilla, J, Chacon-Duque, JC, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Barquera Lozano, R, Macin Perez, G, Gomez-Valdes, J, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Gallo, C, Poletti, G, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Cheeseman, M, Rosique, J, Bedoya, G, Rothhammer, F, Headon, D, Gonzalez-Jose, R, Balding, D, Ruiz-Linares, A, Adhikari, K, Fuentes-Guajardo, M, Quinto-Sanchez, M, Mendoza-Revilla, J, Chacon-Duque, JC, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Barquera Lozano, R, Macin Perez, G, Gomez-Valdes, J, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Gallo, C, Poletti, G, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Cheeseman, M, Rosique, J, Bedoya, G, Rothhammer, F, Headon, D, Gonzalez-Jose, R, Balding, D, and Ruiz-Linares, A

Abstract

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

Published
2016

21. Spinocerebellar ataxia type 3/Machado-Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions

Author

Souza, G.N., primary, Kersting, N., additional, Krum-Santos, A.C., additional, Santos, A.S.P., additional, Furtado, G.V., additional, Pacheco, D., additional, Gonçalves, T.A., additional, Saute, J.A., additional, Schuler-Faccini, L., additional, Mattos, E.P., additional, Saraiva-Pereira, M.L., additional, and Jardim, L.B., additional

Published
2016
Full Text
View/download PDF

22. A genome-wide association study identifies multiple loci for variation in human ear morphology

Author

Adhikari, K, Reales, G, Smith, AJP, Konka, E, Palmen, J, Quinto-Sanchez, M, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Fuentes, M, Pizarro, M, Barquera Lozano, R, Macin Perez, G, Gomez-Valdes, J, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Gallo, C, Poletti, G, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Rothhammer, F, Bedoya, G, Calderon, R, Rosique, J, Cheeseman, M, Bhutta, MF, Humphries, SE, Gonzalez-Jose, R, Headon, D, Balding, D, Ruiz-Linares, A, Adhikari, K, Reales, G, Smith, AJP, Konka, E, Palmen, J, Quinto-Sanchez, M, Acuna-Alonzo, V, Jaramillo, C, Arias, W, Fuentes, M, Pizarro, M, Barquera Lozano, R, Macin Perez, G, Gomez-Valdes, J, Villamil-Ramirez, H, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Hurtado, M, Villegas, V, Granja, V, Gallo, C, Poletti, G, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Rothhammer, F, Bedoya, G, Calderon, R, Rosique, J, Cheeseman, M, Bhutta, MF, Humphries, SE, Gonzalez-Jose, R, Headon, D, Balding, D, and Ruiz-Linares, A

Abstract

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10(-8) to 3 × 10(-14)). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.

Published
2015

23. Warfarin: A retrospective analysis of consultations to a Brazilian Teratology Information Service

Author

Silva, A.A., primary, Leopoldino, M.A.A., additional, Rocha, A.G., additional, Goldani, B.F., additional, Gomes, D.R.C., additional, Santos, D.S., additional, Vianna, F.S.L., additional, Matuella, G.F., additional, Metzdorf, L., additional, Bellaver, P., additional, Abeche, A.M., additional, Sanseverino, M.T.V., additional, and Schuler-Faccini, L., additional

Published
2015
Full Text
View/download PDF

24. Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

Author

Di Rienzo, A, Ruiz-Linares, A, Adhikari, K, Acuna-Alonzo, V, Quinto-Sanchez, M, Jaramillo, C, Arias, W, Fuentess, M, Pizarro, M, Everardo, P, de Avila, F, Gomez-Valdes, J, Leon-Mimila, P, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Burley, M-W, Konca, E, de Oliveira, MZ, Veronez, MR, Rubio-Codina, M, Attanasio, O, Gibbon, S, Ray, N, Gallo, C, Poletti, G, Rosique, J, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Rothhammers, F, Bedoya, G, Balding, D, Gonzalez-Jose, R, Di Rienzo, A, Ruiz-Linares, A, Adhikari, K, Acuna-Alonzo, V, Quinto-Sanchez, M, Jaramillo, C, Arias, W, Fuentess, M, Pizarro, M, Everardo, P, de Avila, F, Gomez-Valdes, J, Leon-Mimila, P, Hunemeier, T, Ramallo, V, Silva de Cerqueira, CC, Burley, M-W, Konca, E, de Oliveira, MZ, Veronez, MR, Rubio-Codina, M, Attanasio, O, Gibbon, S, Ray, N, Gallo, C, Poletti, G, Rosique, J, Schuler-Faccini, L, Salzano, FM, Bortolini, M-C, Canizales-Quinteros, S, Rothhammers, F, Bedoya, G, Balding, D, and Gonzalez-Jose, R

Abstract

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.

Published
2014

25. Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia

Author

Fernandes‐Lima, Z.S., primary, Paixão‐Côrtes, V.R., additional, de Andrade, A.K.M., additional, Fernandes, A.S., additional, Coronado, B.N.L., additional, Monte Filho, H.P., additional, Santos, M.J., additional, de Omena Filho, R.L., additional, Biondi, F.C., additional, Ruiz‐Linares, A., additional, Ramallo, V., additional, Hünemeier, T., additional, Schuler‐Faccini, L., additional, and Monlleó, I.L., additional

Published
2014
Full Text
View/download PDF

27. Prevalence of the STK15 F31I polymorphism and its relationship with mammographic density

Author

Giacomazzi, J., primary, Aguiar, E., additional, Palmero, E.I., additional, Schmidt, A.V., additional, Skonieski, G., additional, Duarte Filho, D., additional, Bock, H., additional, Saraiva-Pereira, M.L., additional, Schuler-Faccini, L., additional, Camey, S.A., additional, Caleffi, M., additional, Giugliani, R., additional, and Ashton-Prolla, P., additional

Published
2011
Full Text
View/download PDF

34. Prenatal exposure to misoprostol and vascular disruption defects: A case-control study

Author

Vargas, F.R., primary, Schuler-Faccini, L., additional, Brunoni, D., additional, Kim, C., additional, Meloni, V.F.A., additional, Sugayama, S.M.M., additional, Albano, L., additional, Llerena, J.C., additional, Almeida, J.C.C., additional, Duarte, A., additional, Cavalcanti, D.P., additional, Goloni-Bertollo, E., additional, Conte, A., additional, Koren, G., additional, and Addis, A., additional

Published
2000
Full Text
View/download PDF

38. Exploring the relationship between genetic instability and health outcomes in acute and chronic post-COVID syndrome.

Author

Martins BAA, Garcia ALH, Borges MS, Picinini J, Serpa ET, Nobles DDR, Silva LL, Dalberto D, Hansen AW, Spilki FR, Schuler-Faccini L, Rampelotto PH, and Da Silva J

Subjects
Humans, Male, Female, Middle Aged, Adult, DNA Damage genetics, Chronic Disease, Aged, Sex Factors, Surveys and Questionnaires, COVID-19 genetics, COVID-19 psychology, COVID-19 complications, COVID-19 epidemiology, Post-Acute COVID-19 Syndrome, Genomic Instability, SARS-CoV-2
Abstract

The COVID-19 pandemic has led to the emergence of acute and chronic post-COVID syndromes, which present diverse clinical manifestations. The underlying pathophysiology of these conditions is not yet fully understood, but genetic instability has been proposed as a potential contributing factor. This study aimed to explore the differential impact of physical and psychological health factors on genetic instability in individuals with acute and chronic post-COVID syndromes. In this study, three groups of subjects were analyzed: a control group, an acute post-COVID group, and a chronic post-COVID group, with a total of 231 participants. The participants were assessed using a questionnaire for long-COVID-19COVID, and female participants reported more symptoms than male participants in areas related to fatigue, memory, mental health, and well-being during the chronic phase. Genetic instability was assessed using the comet assay, and participants' physical and psychological profiles were evaluated. The overall results showed no significant differences in DNA damage, as measured by the comet assay, among the three groups, suggesting that genetic instability, as assessed by this method, may not be a primary driver of the distinct clinical presentations observed in post-COVID syndromes. However, when gender was considered, male participants in the acute long COVID group exhibited higher levels of genetic instability compared to females. Multiple linear regression analysis revealed that gender, age, and waist circumference were significant predictors of DNA damage. Among females in the acute group, sexual health, and eye-related symptoms significantly influenced the increase in DNA damage. These findings indicate the need for further investigation on the gender-specific differences in genetic instability and their potential implications for the pathophysiology of post-COVID syndromes. Exploring alternative markers of genetic instability and the interplay between genetic, inflammatory, and cellular processes could provide valuable insights for the management of these debilitating post-viral sequelae., (© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
Full Text
View/download PDF

39. Newborns with microcephaly in Brazil and potential vertical transmission of Oropouche virus: a case series.

Author

das Neves Martins FE, Chiang JO, Nunes BTD, Ribeiro BFR, Martins LC, Casseb LMN, Henriques DF, de Oliveira CS, Maciel ELN, Azevedo RDS, Cravo LCC, Barreto ARF, Pessoa ALS, Filho AJM, de Sousa JR, Schuler-Faccini L, Quaresma JAS, da Costa Vasconcelos PF, and da Silva Azevedo RDS

Abstract

Background: Oropouche fever, an orthobunyavirus disease endemic in Brazilian Amazon, has caused many febrile epidemics. In 2024, an epidemic of Oropouche fever spread in Brazil, with more than 7930 cases reported between Jan 1 and Aug 31. Infections in pregnant people have suggested the possibility of negative fetal consequences, therefore we tested newborns with microcephaly for known congenital pathogens and Oropouche virus (OROV)., Methods: In this case series, we assessed historical cases of infants born with microcephaly, arthrogryposis, and other congenital malformations without a confirmed cause and their mothers for potential OROV congenital infections. The study population consisted of infants born in Brazil with samples from 2015-21 and 2024. Serum and cerebrospinal fluid (CSF) from this case series were analysed for: syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex, HIV, Zika, dengue, and chikungunya. Individuals that were negative for these pathogens were then tested for OROV. Pathogen testing included ELISA and haemagglutination inhibition testing for antibodies and RT-PCR for virus RNA., Findings: We tested 68 samples from 65 historical cases of congential malformations and three cases from 2024. All cases were from ten states in Brazil. Three historical cases tested positive for OROV and 62 historical cases tested negative. The three cases from 2024 all tested positive for OROV. Of the positive cases, five were female and one was male. Not all pathogens were tested for each case, and some did not have maternal samples available. One of the newborns (case 6) died aged 47 days and tissue samples were tested by real-time RT-PCR, histopathology, and immunohistochemistry assays. One other newborn died in 2016 but no post-mortem samples were available. OROV IgM was detected in five of five newborn CSF samples, and five of five newborn serum samples. Four of five maternal serum samples were positive for OROV IgM. One of four newborn CSF samples (case 6 at age 44 days) was OROV positive by real-time RT-quantitative PCR and 0 of four newborn serum samples were positive, as were 0 of three maternal serum samples. Case 6 had major tissue changes of the brain macroscopically and microscopically, including necrotic and apoptotic changes of neurons, microglia and astrocytes, vacuolisation, and tissue atrophy. OROV RNA was detected in brain, lungs, kidney, CSF, and pleural fluid; OROV antigens were found in CNS, liver, kidney, heart, and lung, mainly in neurons and microglia and also in endothelial cells, suggesting vasculitis., Interpretation: We detected OROV IgM in six of 68 newborns with microcephaly of unknown cause. One infant who died had OROV RNA and antigen in several tissues, including the brain. The possibility of OROV vertical transmission and potential fetal harm must be investigated with urgency. The evidence presented here does not completely confirm vertical transmission or congenital malformations due to OROV, but thorough case finding and detailed investigation of maternal or fetal OROV infection is a priority., Funding: Evandro Chagas Institute, Secretaria de Vigilância em Saúde e Ambiente, and Ministry of Health and National Institute of Science and Technology for Emerging and Reemerging Viruses., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Published
2024
Full Text
View/download PDF

40. The importance of geographic and sociodemographic aspects in the characterization of mucopolysaccharidoses: a case series from Ceará state (Northeast Brazil).

Author

Cardoso-Dos-Santos AC, Mariath LM, Trapp F, Facchin ACB, Leistner S, Kubaski F, Giugliani R, Schuler-Faccini L, and Ribeiro EM

Abstract

Geographic and sociodemographic aspects may influence the natural history and epidemiology of mucopolysaccharidoses (MPS). The main objective in this work was to evaluate the clinical, molecular, and geographic profile of MPS in a population from Ceará (Northeast Brazil). For this, we have performed a descriptive cross-sectional study based on clinical evaluation, interviews with patients and/or family members, and review of medical records of 76 MPS patients. MPS II was the most common type, with the most affected individuals presenting missense pathogenic variants. Patients with MPS I proved to be the most severe clinical phenotype, presenting the first symptoms (mean: 7.1 months; SD = 4.5) and being diagnosed earlier (2.2 years; SD = 2.1) in comparison with the other types. In addition, we have shown that 13 individuals with MPS VI were born of consanguineous marriages in small, nearby cities, in a place where geographical isolation, consanguinity, and clusters of genetic diseases were previously reported. Ten of these individuals (at least, seven different families) presented a rare pathogenic variant in the ARSB gene, c.1143-8T > G in homozygosity, previously reported only among Iberian and South American patients. The results presented here provide a comprehensive picture of MPS in an important state of the Brazilian Northeast, a region that concentrates many risk factors for rare genetic diseases, such as endogamy, inbreeding, and reproductive isolation. We discuss the possible evolutionary processes and biosocial dynamics that can help to explain this finding in terms of population medical genetics and public health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
Full Text
View/download PDF

41. From bench to in silico and backwards: What have we done on genetics of recurrent pregnancy loss and implantation failure and where should we go next?

Author

Gomes FG, Boquett JA, Kowalski TW, Bremm JM, Michels MS, Pretto L, Rockenbach MK, Vianna FSL, Schuler-Faccini L, Sanseverino MTV, and Fraga LR

Abstract

Human reproduction goes through many challenges to its success and in many cases it fails. Cases of pregnancy loss are common outcomes for pregnancies, and implantation failures (IF) are common in assisted reproduction attempts. Although several risk factors have already been linked to adverse outcomes in reproduction, many cases remain without a definitive cause. Genetics of female reproduction is a field that may bring some pieces of this puzzle; however, there are no well-defined genes that might be related to the risk for recurrent pregnancy loss (RPL) and IF. Here, we present a literature review of the studies of genetic association in RPL and IF carried out in the Brazilian population and complemented with a database search to explore genes previously related to RPL and IF, where a search for genes previously involved in these conditions was performed in OMIM, HuGE, and CTD databases. Finally, we present the next steps for reproductive genetics investigation, through genomic sequencing analyses and discuss future plans in the study of RPL genetics. The combined strategy of looking for literature and databases is useful to raise hypotheses and to identify underexplored genes related to RPL and IF.

Published
2024
Full Text
View/download PDF

42. Congenital anomalies in Santa Catarina, Southern Brazil: macroregional and temporal birth prevalence for the period 2011-2020.

Author

Krieck LK, Barbian MH, Schuler-Faccini L, and Pinto Moehlecke Iser B

Abstract

Congenital anomalies (CAs) are an important cause of infant mortality and efficient surveillance is necessary for their prevention. Therefore, the objective of this study is to establish baselines of prevalence at birth of priority CAs for surveillance in the state of Santa Catarina, using data from the Live Birth Information System considering the period 2011-2019 (baseline) and 2020 (pandemic year). The analyses were carried out based on the mother's residence health macroregion. The CAs were selected following the ICD-10 coding for chapter XVII. Birth prevalence was calculated per 10,000 live births and the confidence interval was established at 95%. 2011-2019 recorded 88.8/10,000 births with CAs (total). For 2011-2019, limb defects (without polydactyly) were the most prevalent (14.1/10,000), followed by congenital heart defects (8.9), oral clefts (8.2), polydactyly (7.9), Down syndrome (5.6), hypospadias (5.4), neural tube defects (4.7), gastroschisis (3.3), undefined sex (1.2), microcephaly (0.8) and omphalocele (0.3). There were no significant differences in temporal and spatial distribution. However, unusual fluctuations were observed in 2020, which may reflect the pandemic in CAs notifications. In the base period, Santa Catarina recorded CAs below the expected level of being identified at birth. With this, we conclude that the training and awareness of teams are essential for the surveillance of CAs in Santa Catarina., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
Full Text
View/download PDF

43. Medication Use Among Pregnant Women With SARS-CoV-2 Infection and Risk of Hospitalization-A Study in Two Brazilian Hospitals.

Author

Rohweder R, Pereira NG, Micheletti BH, Mosello J, Campos JRM, Pereira MG, Santos CN, Simões NL, Matielo RLB, Bernardes LS, Oppermann MLR, Wender MCO, Lupattelli A, Nordeng H, and Schuler-Faccini L

Subjects
Humans, Pregnancy, Female, Brazil epidemiology, Adult, Retrospective Studies, Risk Factors, COVID-19 Drug Treatment, Young Adult, Anti-Bacterial Agents therapeutic use, Hospitalization statistics & numerical data, Pregnancy Complications, Infectious epidemiology, Pregnancy Complications, Infectious drug therapy, COVID-19 epidemiology, SARS-CoV-2
Abstract

There is limited evidence about the use of medications among pregnant women with COVID-19, as well as risk factors for hospitalization due to COVID-19 in pregnancy. We aimed to describe the use of medications among SARS-CoV-2-positive pregnant women at the time around infection and identify predictors for hospitalization due to COVID-19 in two hospitals in Brazil. This is a hospital record-based study among pregnant women with positive SARS-CoV-2 tests between March 2020 and August 2022 from two Brazilian hospitals. Characteristics of sociodemographic, obstetrical, and COVID-19 symptoms were extracted retrospectively. The prevalence use of medications was based on self-reported use, and this was administered at the hospital. Logistic regression was used to estimate predictors of hospitalization due to COVID-19. There were 278 pregnant women included in the study, of which 41 (14.7%) required hospitalization due to COVID-19. The remaining 237 (85.3%) had mild symptoms or were asymptomatic. Most of the women had the infection in the third trimester ( n = 149; 53.6%). The most prevalent medications used across all trimesters were analgesics (2.4% to 20.0%), antibacterials (15.0% to 23.1%), and corticosteroids (7.2% to 10.4%). Pre- or gestational hypertensive disorder (odds ratio (OR) 4.94, 95% confidence interval (CI) 1.65, 14.87) and having at least one dose of vaccine against SARS-CoV-2 (OR 0.13, 95% CI 0.04, 0.39) were associated with hospitalization due to COVID-19. Analgesics, antibacterials, and corticosteroids were the most frequently used medications among pregnant women with COVID-19. Women with hypertensive disorders have almost a five-fold increased risk of hospitalization due to COVID-19. Vaccination was the strongest protective factor for severe COVID-19. The COVID-19 vaccination among pregnant women should be promoted, and pregnant women diagnosed with COVID-19 who have hypertensive disorders should be closely monitored., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Ricardo Rohweder et al.)

Published
2024
Full Text
View/download PDF

44. Possible New Candidates Involved to Thalidomide-Related Limbs and Cardiac Defects: A Systems Biology Approach.

Author

Rengel BD, Schuler-Faccini L, Fraga LR, Vianna FSL, and Kowalski TW

Abstract

Thalidomide is a known teratogen that causes malformations especially in heart and limbs. Its mechanism of teratogenicity is still not fully elucidated. Recently, a new target of thalidomide was described, TBX5, and was observed a new interaction between HAND2 and TBX5 that is disrupted in the presence of thalidomide. Therefore, our study aimed to raise potential candidates for thalidomide teratogenesis, through systems biology, evaluating HAND2 and TBX5 interaction and heart and limbs malformations of thalidomide. Genes and proteins related to TBX5 and HAND2 were selected through TF2DNA, REACTOME, Human Phenotype Ontology, and InterPro databases. Networks were assembled using STRING © database. Network analysis were performed in Cytoscape © and R v3.6.2. Differential gene expression (DGE) analysis was performed through gene expression omnibus. We constructed a network for HAND2 and TBX5 interaction; a network for heart and limbs malformations of TE; and the two joined networks. We observed that EP300 protein seemed to be important in all networks. We also looked for proteins containing C2H2 domain in the assembled networks. ZIC3, GLI1, GLI3, ZNF148, and PRDM16 were the ones present in both heart and limbs malformations of TE networks. Furthermore, in the DGE analysis after treatment with thalidomide, we observed that FANCB, ESCO2, and XRCC2 were downregulated and present both in heart and limbs networks. Through systems biology, we were able to point to different new proteins and genes, and selected specially EP300, which was important in all the analyzed networks, to be further evaluated in the TE teratogenicity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
Full Text
View/download PDF

45. Microcephaly in South Brazil: Are cases of Congenital Zika Syndrome increasing in recent years?

Author

Terra AP, Rohweder R, Herber S, Friedrich L, Sanseverino MTV, Favreto C, Maria FS, Athayde EJ, Cardoso-Júnior LM, Marinho ACP, Marinho AP, Zarpelon T, and Schuler-Faccini L

Abstract

Northeast Brazil was the first region to detect a significant increase in babies born with microcephaly associated with prenatal zika virus infection in 2015. Rio Grande do Sul (RS) state was less impacted due to the temperate climate preventing the spread of the vector. This study investigated the prevalence and etiology of congenital microcephaly in RS in two different periods. This cross-sectional descriptive study included all live births with congenital microcephaly in RS from 2015 to 2022. Cases were divided into two groups: P1 "outbreak" (2015-16); and P2 "endemic" (2017-22). There were 58 cases of microcephaly (3.8/10,000) in P1 and 148 (1.97/10,000) in P2. Congenital Zika Virus infection was the etiology in 5.2% (n=3) in P1 and 6.7% (n=10) in P2. In conclusion, although the ZIKV outbreak in Brazil has receded, RS remains an area of concern, with a possible slight increase of live births with microcephaly secondary to ZIKV prenatal infection relative to the number of cases due to congenital infections. The broader distribution of the vector Aedes aegypti with warmer temperatures in our state might be linked to the increase in recent years. This study can be an alert to other regions of temperate or subtropical climates.

Published
2024
Full Text
View/download PDF

46. Caffeine intake during pregnancy and adverse outcomes: An integrative review.

Author

Rohweder R, de Oliveira Schmalfuss T, Dos Santos Borniger D, Ferreira CZ, Zanardini MK, Lopes GPTF, Barbosa CP, Moreira TD, Schuler-Faccini L, Sanseverino MTV, da Silva AA, Abeche AM, Vianna FSL, and Fraga LR

Subjects
Pregnancy, Infant, Newborn, Female, Humans, Coffee adverse effects, Infant, Low Birth Weight, Gestational Age, Caffeine adverse effects, Abortion, Spontaneous
Abstract

Caffeine intake during pregnancy is common. Caffeine crosses the placenta, raising concerns about its possible deleterious effects on the developing embryo/fetus. Studies on this subject show conflicting results, and still there is no consensus on the recommended dose of caffeine during pregnancy. We performed an integrative review with studies from six databases, using broad MESH terms to allow the identification of publications that addressed the outcomes of caffeine use during pregnancy, with no date limit for publications, in English and Portuguese language. The research returned 16,192 articles. After removing duplicates, screening by title, abstract and full-text, we evaluated 257 and included 59 articles. We found association between caffeine intake and pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. The effects were often dose dependent. No association with prematurity has been demonstrated, but one study showed a small reduction in gestational age with increasing doses of caffeine intake. Defining a safe dose for caffeine intake during pregnancy is a challenging task due to the heterogeneity in study designs and results, as well as the difficulty of reliably assessing the amount of caffeine consumed. In some studies, exposures below the recommended level of caffeine intake during pregnancy (200 mg/day), as suggested by the guidelines, were associated with pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. Well-designed studies with reliable quantification of caffeine intake are needed to assess the safety of low doses during pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2024
Full Text
View/download PDF

47. Clusters of oculocutaneous albinism in isolated populations in Brazil: A community genetics challenge.

Author

Moura P, Cardoso-Dos-Santos AC, and Schuler-Faccini L

Abstract

Oculocutaneous albinism (OCA) is a heterogeneous group of genetic disorders involving deficiencies in melanin biosynthesis, with consequent skin, hair, and eye hypopigmentation. The world prevalence is estimated at 1/17,000, but there is high variability among populations. The affected individuals, besides clinical complications, can suffer from discrimination. The Brazilian population is highly admixed, with isolated and inbred communities. Previous reports indicated the presence of diverse isolated communities with a high prevalence of OCA in Brazil. The present work sought to review and characterize clusters of albinism in this country based on scientific literature search, newspapers, and websites. We identified and characterized 18 clusters, 13 confirmed by scientific studies. Seven clusters are in the Northeast region, with predominant African ancestry, and seven others in indigenous communities, particularly among the Kaingaing in South Brazil. Isolation and inbreeding associated with founder effects seem to be the most plausible explanation. Molecular studies and clinical classification are still limited. Their localization in deprived regions with poor infrastructure makes them particularly vulnerable to the social and clinical consequences of lacking melanin. We reinforce the need for a tailored approach to these communities, including appropriate medical care, social support, and genetic counselling.

Published
2023
Full Text
View/download PDF

48. HLA haplotypes and differential regional mortality caused by COVID-19 in Brazil: an ecological study based on a large bone marrow donor bank dataset.

Author

Boquett JA, Vianna FSL, Fagundes NJR, Schroeder L, Barbian M, Zagonel-Oliveira M, Andreis TF, Pôrto LCMS, Chies JAB, Schuler-Faccini L, Ashton-Prolla P, and Rosset C

Subjects
Humans, Haplotypes, Brazil epidemiology, Gene Frequency, HLA-B Antigens genetics, HLA-DRB1 Chains genetics, Alleles, HLA Antigens genetics, HLA-A Antigens genetics, Bone Marrow, COVID-19 genetics
Abstract

The coronavirus disease 2019 (COVID-19) mortality rates varied among the states of Brazil during the course of the pandemics. The human leukocyte antigen (HLA) is a critical component of the antigen presentation pathway. Individuals with different HLA genotypes may trigger different immune responses against pathogens, which could culminate in different COVID-19 responses. HLA genotypes are variable, especially in the highly admixed Brazilian population. In this ecological study, we aimed to investigate the correlation between HLA haplotypes and the different regional distribution of COVID-19 mortality in Brazil. HLA data was obtained from 4,148,713 individuals registered in The Brazilian Voluntary Bone Marrow Donors Registry. COVID-19 data was retrieved from epidemiological bulletins issued by State Health Secretariats via Brazil's Ministry of Health from February/2020 to July/2022. We found a positive significant correlation between the HLA-A*01~B*08~DRB1*03 haplotype and COVID-19 mortality rates when we analyzed data from 26 states and the Federal District. This result indicates that the HLA-A*01~B*08~DRB1*03 haplotype may represent an additional risk factor for dying due to COVID-19. This haplotype should be further studied in other populations for a better understanding of the variation in COVID-19 outcomes across the world.

Published
2023
Full Text
View/download PDF

49. The role of glial cells in Zika virus-induced neurodegeneration.

Author

Quincozes-Santos A, Bobermin LD, Costa NLF, Thomaz NK, Almeida RRS, Beys-da-Silva WO, Santi L, Rosa RL, Capra D, Coelho-Aguiar JM, DosSantos MF, Heringer M, Cirne-Lima EO, Guimarães JA, Schuler-Faccini L, Gonçalves CA, Moura-Neto V, and Souza DO

Subjects
Humans, Neuroglia metabolism, Central Nervous System metabolism, Brain metabolism, Zika Virus physiology, Zika Virus Infection complications, Zika Virus Infection drug therapy, Zika Virus Infection pathology
Abstract

Zika virus (ZIKV) is a strongly neurotropic flavivirus whose infection has been associated with microcephaly in neonates. However, clinical and experimental evidence indicate that ZIKV also affects the adult nervous system. In this regard, in vitro and in vivo studies have shown the ability of ZIKV to infect glial cells. In the central nervous system (CNS), glial cells are represented by astrocytes, microglia, and oligodendrocytes. In contrast, the peripheral nervous system (PNS) constitutes a highly heterogeneous group of cells (Schwann cells, satellite glial cells, and enteric glial cells) spread through the body. These cells are critical in both physiological and pathological conditions; as such, ZIKV-induced glial dysfunctions can be associated with the development and progression of neurological complications, including those related to the adult and aging brain. This review will address the effects of ZIKV infection on CNS and PNS glial cells, focusing on cellular and molecular mechanisms, including changes in the inflammatory response, oxidative stress, mitochondrial dysfunction, Ca 2+ and glutamate homeostasis, neural metabolism, and neuron-glia communication. Of note, preventive and therapeutic strategies that focus on glial cells may emerge to delay and/or prevent the development of ZIKV-induced neurodegeneration and its consequences., (© 2023 Wiley Periodicals LLC.)

Published
2023
Full Text
View/download PDF

50. Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci.

Author

Li Y, Xiong Z, Zhang M, Hysi PG, Qian Y, Adhikari K, Weng J, Wu S, Du S, Gonzalez-Jose R, Schuler-Faccini L, Bortolini MC, Acuna-Alonzo V, Canizales-Quinteros S, Gallo C, Poletti G, Bedoya G, Rothhammer F, Wang J, Tan J, Yuan Z, Jin L, Uitterlinden AG, Ghanbari M, Ikram MA, Nijsten T, Zhu X, Lei Z, Jia P, Ruiz-Linares A, Spector TD, Wang S, Kayser M, and Liu F

Subjects
Humans, Male, Animals, Mice, Phenotype, Asia, Polymorphism, Single Nucleotide genetics, Genome-Wide Association Study methods, Genetic Loci
Abstract

Human ear morphology, a complex anatomical structure represented by a multidimensional set of correlated and heritable phenotypes, has a poorly understood genetic architecture. In this study, we quantitatively assessed 136 ear morphology traits using deep learning analysis of digital face images in 14,921 individuals from five different cohorts in Europe, Asia, and Latin America. Through GWAS meta-analysis and C-GWASs, a recently introduced method to effectively combine GWASs of many traits, we identified 16 genetic loci involved in various ear phenotypes, eight of which have not been previously associated with human ear features. Our findings suggest that ear morphology shares genetic determinants with other surface ectoderm-derived traits such as facial variation, mono eyebrow, and male pattern baldness. Our results enhance the genetic understanding of human ear morphology and shed light on the shared genetic contributors of different surface ectoderm-derived phenotypes. Additionally, gene editing experiments in mice have demonstrated that knocking out the newly ear-associated gene (Intu) and a previously ear-associated gene (Tbx15) causes deviating mouse ear morphology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results