| Autor: |
Serena Capasso, Giovanna Cardiero, Gennaro Musollino, Romeo Prezioso, Rosario Testa, Sabrina Dembech, Giulio Piluso, Vincenzo Nigro, F. Anna Digilio, Giuseppina Lacerra |
| Přispěvatelé: |
Capasso, Serena, Cardiero, Giovanna, Musollino, Gennaro, Prezioso, Romeo, Testa, Rosario, Dembech, Sabrina, Piluso, Giulio, Nigro, Vincenzo, Digilio, F Anna, Lacerra, Giuseppina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
PLOS Genetics. 19:e1010727 |
| ISSN: |
1553-7404 |
| DOI: |
10.1371/journal.pgen.1010727 |
| Popis: |
We report three novel deletions involving the Multispecies Conserved Sequences (MCS) R2, also known as the Major Regulative Element (MRE), in patients showing the α-thalassemia phenotype. The three new rearrangements showed peculiar positions of the breakpoints. 1) The (αα)ES is a telomeric 110 kb deletion ending inside the MCS-R3 element. 2) The (αα)FG, 984 bp-long, ends 51 bp upstream to MCS-R2; both are associated with a severe α-thalassemia phenotype. 3) The (αα)CT, 5058 bp-long starts at position +93 of MCS-R2 and is the only one associated to a mild α-thalassemia phenotype. To understand the specific role of different segments of the MCS-R2 element and of its boundary regions we carried out transcriptional and expression analysis. Transcriptional analysis of patients’ reticulocytes showed that (αα)ES was unable to produce α2-globin mRNA, while a high level of expression of the α2-globin genes (56%) was detected in (αα)CT deletion, characterized by the presence of the first 93 bp of MCS-R2. Expression analysis of constructs containing breakpoints and boundary regions of the deletions (αα)CT and (αα)FG, showed comparable activity both for MCS-R2 and the boundary region (-682/-8). Considering that the (αα)CT deletion, almost entirely removing MCS-R2, has a less severe phenotype than the (αα)FG α0thalassemia deletion, removing both MCS-R2 almost entirely and an upstream 679 bp, we infer for the first time that an enhancer element must exist in this region that helps to increase the expression of the α-globin genes. The genotype-phenotype relationship of other previously published MCS-R2 deletions strengthened our hypothesis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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