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Using Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human health

2024-04Journal article Open access
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dc.contributor.authorAndaluz, Stephanie
dc.contributor.authorZhao, Bojin
dc.contributor.authorSinha, Siddharth
dc.contributor.authorLagniton, Philip Naderev Panuringan
dc.contributor.authorCosta, Diogo Alpuim
dc.contributor.authorDing, Xiaofan
dc.contributor.authorBrito, Miguel
dc.contributor.authorWang, San Ming
dc.date.accessioned2024-04-29T11:46:48Z
dc.date.available2024-04-29T11:46:48Z
dc.date.issued2024-04
dc.descriptionThis study was supported by grants from the Macau Science and Technology Development Fund (085/2017/A2, 0077/2019/AMJ) (SMW), 0032/2022/A1 (SMW, XD), the University of Macau (SRG2017-00097-FHS, MYRG2019-00018-FHS, MYRG2020-00094-FHS) (SMW), SRG2023-00007-FHS (XD), the Faculty of Health Sciences, University of Macau (FHSIG/SW/0007/2020P, MOE Frontiers Science Center for Precision Oncology pilot grant, and a startup fund) (SMW); Lisbon Polytechnic Institute research grant (MB). Stephanie Andaluz is supported by a fellowship from the International Affairs Office of the University of Macau.pt_PT
dc.description.abstractBackground: Admixture occurs between different ethnic human populations. The global colonization in recent centuries by Europeans led to the most significant admixture in human history. While admixture may enhance genetic diversity for better fitness, it may also impact on human health by transmitting genetic variants for disease susceptibility in the admixture population. The admixture by Portuguese global exploration initiated in the 15th century has reached over 20 million of Portuguese-heritage population worldwide. It provides a valuable model to study the impact of admixture on human health. BRCA1 and BRCA2 (BRCA) are two of the important tumor suppressor genes. The pathogenic variation (PV) in BRCA is well determined to cause a high risk of hereditary breast and ovarian cancer. Tracing the distribution of Portuguese BRCA PV in the Portuguese-heritage population will help to understand the impact of admixture on cancer susceptibility in modern humans. In this study, we analyzed the distribution of the Portuguese-originated BRCA variation in the Brazilian population, which has a high degree of Portuguese heritage. Methods: By comprehensive data mining, standardization, and annotation, we generated a Portuguese-derived BRCA variation dataset and a Brazilian-derived BRCA variation dataset. We compared the two BRCA variation datasets to identify the BRCA variants shared between the two populations. Results: The Portuguese-derived BRCA variation dataset consists of 220 BRCA variants including 78 PVs from 11,482 Portuguese cancer patients, 93 (42.2%) in BRCA1 and 127 (57.7%) in BRCA2. Of the 556 Portuguese BRCA PV carriers carrying the 78 PVs, 331 (59.5%) carried the three Portuguese-BRCA founder PVs of BRCA1 c.2037delinsCC, BRCA1 c.3331_3334del and BRCA2 c.156_157insAlu. The Brazilian-derived BRCA variation dataset consists of 255 BRCA PVs from 7,711 cancer patients, 136 (53.3%) in BRCA1 and 119 (46.6%) in BRCA2. We developed an open database named dbBRCA-Portuguese (https://genemutation.fhs.um.edu.mo/dbbrca-portuguese/) and an open database named dbBRCA-Brazilian (https://genemutation.fhs.um.edu.mo/dbbrca-brazilian) to host the BRCA variation data from Portuguese and Brazilian populations. We compared the BRCA PV datasets between Portuguese and Brazilian populations and identified 29 Portuguese-specific BRCA PVs shared between Portuguese and Brazilian populations, 14 in BRCA1 including the Portuguese founder BRCA1 c.3331_3334del and BRCA1 c.2037delinsCC, and 15 in BRCA2 including the Portuguese founder BRCA2 c.156_157insAlu. Searching the 78 Portuguese BRCA PVs in over 5,000 ancient human genomes identified evolution origin for only 8 PVs in Europeans dated between 37,470 and 3,818 years before the present, confirming the Portuguese-specificity of Portuguese BRCA PVs; comparing the 78 Portuguese BRCA PVs Portuguese, 255 Brazilian BRCA PVs, and 134 African BRCA PVs showed little overlapping, ruling out the possibility that the BRCA PVs shared between Portuguese and Brazilian may also be contributed by African. Conclusion: Our study provides evidence that the admixture in recent human history contributed to cancer susceptibility in modern humans.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAndaluz S, Zhao B, Sinha S, Kagniton PN, Costa DA, Brito M, et al. Using Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human health. BMC Genomics. 2024;25:416.pt_PT
dc.identifier.doi10.1186/s12864-024-10311-4pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/17401
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringer Naturept_PT
dc.relation.publisherversionhttps://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-024-10311-4pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAdmixturept_PT
dc.subjectBRCA1pt_PT
dc.subjectBRCA2pt_PT
dc.subjectPathogenic variantspt_PT
dc.subjectCancer riskpt_PT
dc.subjectPortugalpt_PT
dc.subjectBrasilpt_PT
dc.titleUsing Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human healthpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage416pt_PT
oaire.citation.titleBMC Genomicspt_PT
oaire.citation.volume25pt_PT
person.familyNameBrito
person.givenNameMiguel
person.identifier.ciencia-id231F-F341-7E93
person.identifier.orcid0000-0001-6394-658X
person.identifier.ridA-7970-2016
person.identifier.scopus-author-id35224551000
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication4252d8e0-800c-4d67-8b13-0b711d860669
relation.isAuthorOfPublication.latestForDiscovery4252d8e0-800c-4d67-8b13-0b711d860669

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