Browsing by Author "Almeida, T."
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- Convergent evolution of IL-6 in two leporids (Oryctolagus and Pentalagus) originated an extended proteinPublication . Neves, F.; Abrantes, J.; Pinheiro, A.; Almeida, T.; Pinho-Costa, P.; Esteves, P.J.Interleukin 6 (IL-6) is a class-I helical cytokinewith a broad spectrum of biological activities and a gene structure conserved throughout vertebrates, with five coding exons. IL-6 from European rabbits belonging to the subspecies Oryctolagus cuniculus cuniculus was previously shown to differ from other mammals by extending an additional 27 amino acids. However, in other leporids (Sylvilagus spp and Lepus spp) that diverged from the European rabbit ~12 million years ago this mutation was not present. In this study, we extended the study of IL-6 for the Oryctolagus cuniculus algirus subspecies and five additional lagomorphs’ genera(Brachylagus, Bunolagus, Pentalagus, Romerolagus, and Ochotona). We confirmed the presence of the mutated stop codon in both O. c. cuniculus and O. c. algirus.We found that the typical stop codon is present in Sylvilagus bachmani and Lepus europaeus, in agreement with previous reports, but also in Bunolagus, Brachylagus, and Ochotona. Remarkably, in Pentalagus we detected a deletion of the stop codon causing an extension of IL-6 for 17 extra residues. Our results indicate that the IL-6 extension in those species occurred by two independent events: one occurred between 2 and 8 million years ago in the ancestral of the Oryctolagus subspecies, and the other occurred in a Pentalagus ancestral at a maximum of 9 million years ago. The absence of this IL-6 extension in Bunolagus, sister genus of Oryctolagus, shows that this evolutionary event happened by convergence suggesting some functional relevance.
- Genetic characterization of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18) with relevant biological roles in lagomorphsPublication . Neves, F.; Abrantes, J.; Almeida, T.; de Matos, A.L.; Costa, Paulo; Esteves, P.J.ILs, as essential innate immune modulators, are involved in an array of biological processes. In the European rabbit (Oryctolagus cuniculus) IL-1α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12A, IL-12B, IL-15 and IL-18 have been implicated in inflammatory processes and in the immune response against rabbit hemorrhagic disease virus and myxoma virus infections. In this study we characterized these ILs in six Lagomorpha species (European rabbit, pygmy rabbit, two cottontail rabbit species, European brown hare and American pika). Overall, these ILs are conserved between lagomorphs, including in their exon/intron structure. Most differences were observed between leporids and American pika. Indeed, when comparing both, some relevant differences were observed in American pika, such as the location of the stop codon in IL-1α and IL-2, the existence of a different transcript in IL8 and the number of cysteine residues in IL-1β. Changes at N-glycosylation motifs were also detected in IL-1, IL-10, IL-12B and IL-15. IL-1α is the protein that presents the highest evolutionary distances, which is in contrast to IL-12A where the distances between lagomorphs are the lowest. For all these ILs, sequences of human and European rabbit are more closely related than between human and mouse or European rabbit and mouse.
- Wide spectrum of F9 variants in hemophilia B families from the Portuguese populationPublication . Moreira, Isabel; Diniz, Maria João; Tavares, Alice; Morais, Sara; Freitas, B.; Araújo, F.; Gago, T.; Antunes, EM; Catarino, C.; Campos, M.; Almeida, T.; Santos, S.B.; Maria, R.; Kjollerstrom, P.; Lavinha, João; David, DezsoIntroduction: Hemophilia B is an X-linked bleeding disorder caused by molecular defects in the Factor IX gene (F9), leading to either deficiency or functional abnormality of Factor IX. Actual data indicate a high heterogeneity of variants in F9. Over 1000 different variants have been reported, including pathogenic single nucleotide variants (SNPs), indels and complex variants. Materials and Methods: 86 index patients and 313 relatives were studied. F9 variant analysis was performed from total genomic DNA by PCR followed either by SSCP and DNA sequencing or direct DNA sequencing. When no variant was detected by sequencing, F9 analysis by MLPA was performed. Segregation studies were performed in each family. Results: Overall, 52 different F9 variants have been identified, including 49 SNPs or small indels, a gross duplication (exons 2-6) and two deletions of the entire gene. Ten of the variants had been firstly reported by us and three are novel: c.391+5G>T; c.432T>G, p.(Phe144Leu) and c.749C>A, p.(Ala250Glu). This approach allowed establishing the carrier state of over 300 women and 12 prenatal diagnoses were performed. Conclusions: The spectrum of F9 variants identified in the Portuguese population significantly overlaps that observed in other populations. Identification of F9 gene variants in patients allows genotype-phenotype correlations and carrier detection, as well as prenatal diagnosis. Sanger sequencing of the coding region and adjacent intronic sequences of F9 still remains a valid and effective tool for the molecular study of hemophila B, providing information for appropriate genetic counseling and new insights regarding the molecular basis of the pathology.