Publication
Ancestry of the α-MRE Associated with the 3.7kb α-Thalassemia Deletion in the Portuguese Population
| 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 | 2024-01-04T13:49:14Z | |
| dc.date.available | 2024-01-04T13:49:14Z | |
| dc.date.issued | 2022-11-17 | |
| dc.description | Abstract publicado em: Medicine (Baltimore). 2023 Mar 31; 102(13): e33154. Published online 2023 Mar 31. doi: 10.1097/MD.0000000000033154 | pt_PT |
| dc.description.abstract | 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. It is genetically polymorphic and six haplotypes (A to F) have been identified in different populations. The D haplotype was primary described in African populations and is nearly absent in other populations. The aims of this study were to identify the α-MRE haplotype associated with the common 3.7kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and to investigate its ancestry. We searched for the -α3.7del in 111 selected Portuguese individuals by Gap-PCR. In addition, a DNA fragment containing the α-MRE was amplified by PCR and Sanger sequenced. Statistical analysis was performed using R software. Fifty individuals have the wild-type α-globin genotype (group I), 34 are heterozygous for the -α3.7del (group II) and 27 are homozygous (group III). Regarding the α-MRE, four haplotypes were found (A to D). The ancestral A haplotype is predominant in all groups. The B haplotype is the second most frequent in groups I and II, whereas in group III haplotype D is the second most prevalent. Concerning genotypes, the α-MRE AA and AB are the most common in group I, while genotype AD is more prevalent in group III. In fact, 71.4% of AD individuals are homozygous for the -α3.7del. Moreover, the distribution of α-MRE haplotypes and genotypes are significantly different between groups with and without the -α3.7del (p<0.001). Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are split from these and found to be more closely related to the African population. This study revealed for the first time an association of a specific α-MRE haplotype with the common -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as the D haplotype has an alteration in the consensus sequence for the AP-1/NF-E2 binding site and in vitro experiments showed a decrease in its enhancer activity on α-globin genes. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/8842 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.subject | Doenças Genéticas | pt_PT |
| dc.subject | alfa-talassémia | pt_PT |
| dc.subject | Regulação Génica | pt_PT |
| dc.subject | HS-40 | pt_PT |
| dc.subject | Deleção | pt_PT |
| dc.subject | Portugal | pt_PT |
| dc.title | Ancestry of the α-MRE Associated with the 3.7kb α-Thalassemia Deletion in the Portuguese Population | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Coimbra, Portugal | pt_PT |
| oaire.citation.title | 26th Annual Meeting of the Portuguese Society of Human Genetics, 17-19 November 2022 | pt_PT |
| person.familyName | Faustino | |
| person.givenName | Paula | |
| person.identifier.ciencia-id | F01A-353A-433E | |
| person.identifier.orcid | 0000-0002-6269-4867 | |
| person.identifier.rid | M-3519-2014 | |
| person.identifier.scopus-author-id | 8158641100 | |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |
| relation.isAuthorOfPublication | 94303e78-8b7d-4e24-811d-3af3b1a4e330 | |
| relation.isAuthorOfPublication.latestForDiscovery | 94303e78-8b7d-4e24-811d-3af3b1a4e330 |