Publication
Ancestry of the major long-range regulatory site of the α-globin genes in the Portuguese population with the common 3.7 kb α-thalassemia deletion
| dc.contributor.author | Pena, Rita | |
| dc.contributor.author | Lopes, Pedro | |
| dc.contributor.author | Gaspar, Gisela | |
| dc.contributor.author | Miranda, Armandina | |
| dc.contributor.author | Faustino, Paula | |
| dc.date.accessioned | 2025-02-21T11:28:55Z | |
| dc.date.available | 2025-02-21T11:28:55Z | |
| dc.date.issued | 2024-05-05 | |
| dc.description.abstract | Background: The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of the α-globin gene expression. This enhancer is polymorphic and several haplotypes were identified in different populations, with haplotype D almost exclusively found in African populations. The purpose of this research was to identify the HS-40 haplotype associated with the 3.7 kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and determine its ancestry and influence on patients' hematological phenotype. Methods and results: We selected 111 Portuguese individuals previously analyzed by Gap-PCR to detect the presence of the -α3.7del: 50 without the -α3.7del, 34 heterozygous and 27 homozygous for the -α3.7del. The HS-40 region was amplified by PCR followed by Sanger sequencing. Four HS-40 haplotypes were found (A to D). The distribution of HS-40 haplotypes and genotypes are significantly different between individuals with and without the -α3.7del, being haplotype D and genotype AD the most prevalent in patients with this deletion in homozygosity. Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are separated from these and found more closely related to the African population. Conclusion: This study revealed for the first time an association of the HS-40 haplotype D with the -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as in vitro analysis of haplotype D showed a decrease in its enhancer activity on α-globin gene. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Mol Biol Rep. 2024 May 5;51(1):612. doi: 10.1007/s11033-024-09530-5 | |
| dc.identifier.doi | 10.1007/s11033-024-09530-5 | pt_PT |
| dc.identifier.issn | 0301-4851 | |
| dc.identifier.pmid | 38704770 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/10376 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Springer | |
| dc.relation.hasversion | https://link.springer.com/article/10.1007/s11033-024-09530-5 | |
| dc.relation.publisherversion | https://doi.org/10.1007/s11033-024-09530-5 | pt_PT |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject | HS-40 | pt_PT |
| dc.subject | Major Regulatory Elements | pt_PT |
| dc.subject | Alpha-thalassemia | pt_PT |
| dc.subject | 3.7 Kb Deletion | |
| dc.subject | Portuguese Population | |
| dc.subject | Hemoglobinopatias | pt_PT |
| dc.subject | Talassémia | pt_PT |
| dc.subject | Hemoglobina | pt_PT |
| dc.subject | Doenças Genéticas | pt_PT |
| dc.subject | Doenças Raras | pt_PT |
| dc.title | Ancestry of the major long-range regulatory site of the α-globin genes in the Portuguese population with the common 3.7 kb α-thalassemia deletion | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.startPage | 612 | |
| oaire.citation.title | Molecular Biology Reports | |
| oaire.citation.volume | 51 | pt_PT |
| oaire.version | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |
| person.familyName | Faustino | |
| person.givenName | Paula | |
| person.identifier.orcid | 0000-0002-8028-2567 | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isAuthorOfPublication | 7c5811e8-76f9-45fb-aa1f-1a7a857cd5ec | |
| relation.isAuthorOfPublication.latestForDiscovery | 7c5811e8-76f9-45fb-aa1f-1a7a857cd5ec |