Browsing by Subject "Genetics"
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- PublicationOpen AccessA BreakoutEDU for understanding gene expression in high school. A case study: design, implementation, and evaluation of the emotions of its implementation(Wiley, 2024-10-08) Manuel Fernández Díaz; Martínez Carmona, Marina; Ayuso Fernández, Gabriel Enrique; Fernández Díaz, Manuel; Serrano García, Francisco José; Plaza Griñan, Antonia; Didáctica de las Ciencias Experimentales; Facultad de EducaciónKnowledge about genetics is essential to build a society capable of participating in socioscientific and ethical debates. However, this subject remains difficult for students, making it necessary to develop new educational strategies, such as gamification. Thus, two main objectives are established in this work: (a) to design and evaluate BreakoutEDU, a gamified activity to improve understanding of the content of gene expression; and (b) to study the emotions triggered by this activity among students. Using questionnaires and observation templates, the implementation of BreakoutEDU is evaluated in two groups of first-year high school students (15 and 10 students). The results are analyzed qualitatively and quantitatively. Bearing in mind the limitations of this study, it is concluded that the designed BreakoutEDU could support gamification as a good strategy to contextualize and approach the abstract content of gene expression. Moreover, the activity could maintain a balance between time, difficulty and students' skills, encourage teamwork and trigger mainly positive emotions.
- PublicationEmbargoAntithrombin p.Thr147Ala: The First Founder Mutation in People of African Origin Responsible for Inherited Antithrombin Deficiency(Thieme Gruppe, 2021) Orlando, Christelle; Morena-Barrio, Belén de la; Pareyn, Inge; Vanhoorelbeke, Karen; Martínez-Martínez, Irene; Vicente, Vicente; Corral, Javier; Jochmans, Kristin; Morena-Barrio, María Eugenia de la; MedicinaBackground: Hereditary antithrombin deficiency is a rare autosomal-dominant disorder predisposing to recurrent venous thromboembolism (VTE). To date, only two founder mutations have been described. Objectives: We investigated the antithrombin p.Thr147Ala variant, found in 12 patients of African origin. This variant is known as rs2227606 with minor allele frequency of 0.5% in Africans and absent in Europeans. A possible founder effect was investigated. Methods: Phenotypical characterization was established through immunological and functional methods, both under basal and stress conditions. Recombinant antithrombin molecules were constructed by site-directed mutagenesis and expressed in HEK-293T cells. Secreted antithrombin was purified and functionally characterized. Structural modeling was performed to predict the impact of the mutation on protein structure. A novel nanopore sequencing approach was used for haplotype investigation. Results: Ten patients experienced VTE, stroke, or obstetric complications. Antithrombin antigen levels and anti-IIa activity were normal or slightly reduced while anti-Xa activity was reduced with only one commercial assay. On crossed immunoelectrophoresis, an increase of antithrombin fractions with reduced heparin affinity was observed under high ionic strength conditions but not under physiological conditions. The recombinant p.Thr147Ala protein displayed a reduced anti-Xa activity. Structural modeling revealed that residue Thr147 forms three hydrogen bonds that are abolished when mutated to alanine. The investigated patients shared a common haplotype involving 13 SERPINC1 intragenic single nucleotide polymorphisms. Conclusion: Antithrombin p.Thr147Ala, responsible for antithrombin type II heparin binding site deficiency, is the first founder mutation reported in people of African ancestry. This study further emphasizes the limitations of commercial methods to diagnose this specific subtype.
- PublicationOpen AccessBRAF mutation: Current and future clinical pathological applications in colorectal carcinoma(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Yan Seen Ng, Jessica; Tai Lu, Cu; King yin Lam, AlfredThe aims are to review the relevance of the BRAF mutations in the clinical settings of colorectal carcinoma. All the literature concerning BRAF mutations and colorectal carcinoma published in PubMed from 2010 to 2018 was reviewed. Multiple variants of BRAF mutations exist in colorectal cancer, the most common type being V600E. The mutation is found in 5 to 15% of colorectal carcinomas and is less common in Asian populations. BRAF mutations are linked with older age, female gender, cigarette smoking and are more common in the right (proximal) portion of the large intestine. BRAF mutations are associated with carcinomas of high histological grade and advanced cancer stages. Often BRAF mutated carcinomas demonstrate adverse histological features such as lymphovascular invasion, perineural invasion, tumour budding and lymph node metastases. BRAF mutations are found in serrated polyposis syndrome and have a negative correlation with hereditary nonpolyposis colorectal cancer (HNPCC). An array of methods of detection of BRAF mutation in colorectal carcinoma are available, such as immunohistochemistry and next generation sequencing, etc. Combinatorial approaches involving anti-BRAF therapies targeting both MAPK signalling as well as the PI3K/mTOR pathway could be a new approach for treatment of metastatic colorectal carcinoma. To conclude, BRAF mutation is important in the pathogenesis of colorectal cancer. Further research on the detection method as well as its role in target therapy will help to improve the management of patients with colorectal cancer
- PublicationOpen AccessDefinición de conceptos jurídicos vs. Listado de enfermedades susceptibles como soluciones respecto al uso del diagnóstico genético preimplantacional(2018-03-08) Jiménez González, JoaquínLa Ley española 14/2006, de 26 de mayo, sobre técnicas de reproducción humana asistida, acepta la realización de un diagnóstico genético preimplantacional (DGP) cuando se trata de evitar una enfermedad genética grave, de aparición precoz y sin curación postnatal actual, aparte de los supuestos con informe favorable de la Comisión Nacional de Reproducción Humana Asistida (CNRHA). Sin embargo, estos conceptos no han sido definidos. Ello ha originado diferencias en la interpretación de la Ley por parte de las clínicas y unidades de reproducción humana asistida que practican la prueba, repercutiendo en las posibilidades de las personas para acceder a un DGP. La definición de estos criterios parece esencial para garantizar el principio de justicia, aunque también cabe la posibilidad de crear un listado de enfermedades susceptibles por parte de a CNRHA, deber legal que aún no se ha realizado
- PublicationOpen AccessEl enfoque de una salud (One health) en la investigación oncológica.(Universidad de Murcia, Servicio de Publicaciones., 2025) Reyes Villarreal, Mariangela; Fuente Cortéz, Beatriz Elizabeth de la; Vidal Gutiérrez , Oscar; Sin departamento asociadoEl enfoque para abordar los desafíos de salud global esbozado en el proyecto One Health (Una Salud) ha contribuido a la comprensión de la etiopatogenia de las enfermedades oncológicas y a la prevención de los factores asociados susceptibles de ser modificados. La colaboración interdisciplinaria es fundamental en la lucha contra la creciente incidencia de cáncer a nivel mundial y debe ser fomentada por la comunidad científica, por los organismos promotores de la salud y por los Estados.
- PublicationOpen AccessFactores psicosociales que influyen en la relación médico paciente en la consulta de genética clínica(Universidad de Murcia. Servicio de Publicaciones, 2023) Ortiz Quiroga, Diana Marcela; Jalisi, Stephan; Castro Sardi, Ximena; Ariza Araújo, Yoseth; Pachajoa, HarryIntroducción: la genética clínica ha sido reconocida como una práctica dedicada al diagnóstico y al manejo de los trastornos genéticos por parte del médico genetista. Sin embargo, los datos sobre la forma como funciona la consulta de genética clínica en Colombia, son inexistentes y, sin información acerca de los retos en la atención a la población con enfermedad genética. El objetivo de este estudio fue la caracterización psicosocial de la consulta de genética clínica en un hospital,privado, de alta complejidad, de la ciudad de Cali, Colombia. Métodos: este estudio se llevó a caboc ombinando la observación y la entrevista semi-estructurada a dos médicos genetistas de una institución de salud, privada, en Cali, con catorce observaciones y dos entrevistas. Resultados: se identificaron factores, internos y externos a la consulta, que influyeron en su dinámica: las barreras en el sistema de salud, la tipología de la consulta y los factores personales del médico genetista.Conclusión: la atención integral de las personas con condiciones genéticas debe trascender elabordaje biológico, en la deficiencia, a un abordaje que también considere aspectos psicológicos ysociales
- PublicationOpen AccessGenetic aberrations as the targets of oncology research: Involvement of paraffin-embedded tissues(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Dobashi, Yoh; Goto, Akiteru; Endo, Tetsuya; Ooi, AkishiCancer is a complex and heterogeneous group of diseases which have been generally classified by their clinical and histopathological features. The genomes of cancer cells are altered by diverse mechanisms and these genetic aberrations lead to a variety of pathological changes. A number of technological advances have allowed us to analyze the cancer genome by various ‘-omics’ techniques, and have accelerated the exploration for the primary genetic aberrations that drive cancer. The state-of-the-art technologies that have developed over the past few decades have enabled researchers to catalogue these genetic aberrations in detail. These aberrations include changes in gene structure and the copy number, mutation, and modification of DNA. Simultaneously, there have been significant achievements in the translation of the genomic discoveries “from the bench to the bed”, which have provided valuable contributions to the progress in cancer therapy. One technology that has been central to these research efforts has been the histopathology of cancer specimens, particularly the use of formalin-fixed, paraffin-embedded tissues. In this overview, we consider the development of oncology research from the past to current efforts, and highlight the roles of histopathology and paraffin-embedded tissues in these efforts.
- PublicationOpen AccessGenetics of hypertrophic cardiomyopathy: A review of current state.(Wiley, 2017-03-21) Sabater Molina, María; Pérez Sánchez, Inmaculada; Gimeno, Juan Ramón; Hernández del Rincón, Juan Pedro; Ciencias SociosanitariasHypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. HCM is a highly complex and heterogeneous disease regarding not only the number of associated mutations but also the severity of phenotype, symptom burden, and the risk of complications, such as heart failure and sudden death. The penetrance is incomplete and it is age and gender dependent. It is accepted as a disease of the sarcomere. Sixty percent of HCM cases carry mutations in 1 of 8 sarcomere protein genes, mainly non-sense MYBPC3 and missense MYH7 variants. Young patients with severe phenotype and other clinical features are included in proposed scores for prediction of high positive genetic result. The number of genes reported as disease-causing has increased in the last few years, in some cases without robust evidence. Currently available in silico tools are not always useful for differentiation between benign and deleterious variants. There is enough information on genotypephenotype correlations to start understanding the mechanisms of the disease. Genetic and environmental modifiers have been explored with some interesting insights from miRNA studies with potential as biomarkers and therapeutic agents. There is an additional value of genetic testing in HCM for prognosis. Knowledge about genetics and functional studies are the basis of near future therapies.
- PublicationRestrictedHypertrophic cardiomyopathy or storage cardiomyopathy? Role of genetics to predict outcome(Elsevier, 2011-06-25) Oliva Sandoval, María José; Muñoz Esparza, Carmen; García Molina, Esperanza; Sabater Molina, María; Ciencias Sociosanitarias
- PublicationOpen AccessIr(III) Compounds Containing a Terdentate Ligand Are Potent Inhibitors of Proliferation and Effective Antimetastatic Agents in Aggressive Triple-Negative Breast Cancer Cells(American Chemical Society, 2023-06-06) Cutillas Aullo, Natalia; Ruiz López, José; Novohradsky, Vojtech; Marco Calero, Alicia; Markova, Lenka; Brabec, Viktor; Química InorgánicaHerein, we report a series of new octahedral iridium(III) complexes Ir1–Ir9 of the type [Ir(N^N^N)(C^N)Cl]PF6 (N^N^N = 4′-(p-tolyl)-2,2′:6′,2″-terpyridine; C^N = deprotonated 2-arylbenzimidazole backbone) to introduce new metal-based compounds for effective inhibition of metastatic processes in triple-negative breast cancer (TNBC). The results show that the structural modifications within the C^N scaffold strongly impact the antimetastatic properties of these complexes in TNBC cells. Furthermore, testing the antimetastatic effects of the investigated Ir complexes revealed that the highest antimetastatic activity in TNBC cells is exhibited by complex Ir1. This result was in contrast to the effects of the clinically used drug doxorubicin used in conventional chemotherapy of TNBC, which conversely promoted metastatic properties of TNBC cells. Thus, the latter result suggests that doxorubicin chemotherapy may increase the risk of metastasis of breast cancer cells, so the search for new drugs to treat breast cancer that would show better antitumor effects than doxorubicin is justified.
- PublicationOpen AccessLimitar a manipulação genética eugênica e manter respeito à vida: intersecções entre Direito e Ética como reguladores da biociência criativa(2018-03-08) Freitas, Ramiro Ferreira deA engenharia genetica converteu-se, nos últimos anos, em preocupação geral da opinião pública e, principalmente, dos governos mais poderosos do mundo. Também movimenta a agenda científica, que se vê às voltas com polêmicos assuntos: patenteamento de genes, clonagem, testes pré-implantatórios, retorno dos preconceitos étnicos, enfim, a “crise” suposta do gênero humano.
- PublicationOpen AccessMatrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Diniz Fernandes, Tulio; Godoy Santos, Alexandre Leme; Santos, Maria Cristina; Pontin, Pedro; Alves Pereira, Caio Augusto; Justi Jardim, Yuri; Pereira Velosa, Ana Paula; Maffulli, Nicola; Teodoro, Walcy Rosolia; Capelozzi, Vera LuizaPosterior tibial tendinopathy (PTT) can lead to acquired flatfoot in adults. Many patients develop PTT without any identifiable risk factors. Molecular changes in extracellular matrix (ECM) and matrix metalloproteinase (MMP) polymorphism may influence the risk of developing PTT. We aim to investigate the association between matrix metalloproteinase-1 (MMP1) and (MMP-8) gene polymorphisms with changes in collagen I, III and V in PTT. A case-control study with 22 patients and 5 controls was performed. The MMP-1 (2G/2G) and MMP-8 (T/T) genotypes were determined by PCR-restriction fragment length polymorphism. Tendon specimens were evaluated by a histologic semiquantitative score, immunofluorescence and histomorphometry for collagen I, III and V. Tendon specimens from PTT demonstrated marked distortion of the architecture with necrosis, large basophilic areas with disruption of the normal linear orientation of collagen bundles, infiltration of inflammatory cells, dystrophic calcification and ossification. Under immunofluorescence, PTT tendon specimens showed weak green fluorescence and diffuse distribution of collagen I fibers, but strong fluorescence of collagen III and V. The collagen I fibers were significantly decreased whereas an increase of collagen III and V were found in PTT compared to control groups. In addition, PTT group presented a significant association with MMP-1 and MMP-8 gene polymorphisms. Patients with PTT matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms presented an increase of the collagen III and V ratio, suggesting that the higher proportion in degenerated tendons could contribute to a decrease in the mechanical resistance of the tissue. Still, functional and association studies are needed to elucidate evident roles of MMPs in PTT.
- PublicationRestrictedProbing the channel-bound shaker B inactivating peptide by stereoisomeric substitution at a strategic tyrosine residue(American Chemical Society, 2003-07-01) Encinar Hidalgo, José Antonio; Fernández Carvajal, Asia María; Poveda Larrosa, José Antonio; Molina Gallego, María Luisa; Albar, J.P.; Gavilanes Franco, Francisco; González Ros, José Manuel; Bioquímica y Biología Molecular B e InmunologíaA synthetic peptide patterned after the sequence of the inactivating ball domain of the Shaker B K+ channel, the ShB peptide, fully restores fast inactivation in the deletion Shaker BΔ6−46 K+ channel, which lacks the constitutive ball domains. On the contrary, a similar peptide in which tyrosine 8 is substituted by the secondary structure-disrupting d-tyrosine stereoisomer does not. This suggests that the stereoisomeric substitution prevents the peptide from adopting a structured conformation when bound to the channel during inactivation. Moreover, characteristic in vitro features of the wild-type ShB peptide such as the marked propensity to adopt an intramolecular β-hairpin structure when challenged by anionic phospholipid vesicles, a model target mimicking features of the inactivation site in the channel protein, or to insert into their hydrophobic bilayers, are lost in the d-tyrosine-containing peptide, whose behavior is practically identical to that of noninactivating peptide mutants. In the absence of high resolution crystallographic data on the inactivated channel/peptide complex, these latter findings suggest that the structured conformation required for the peptide to promote channel inactivation, as referred to above, is likely to be β-hairpin.
- PublicationOpen AccessRegional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease(Oxford Univeristy Press, 2021-03-11) Thomas, George E.C.; Zarkali, Angeliki; Ryten, Mina; Shmueli, Karin; Gil Martínez, Ana Luisa; Leyland, Louis-Ann; McColgan, Peter; Acosta-Cabronero, Julio; Lees, Andrew J.; Weil, Rimona S.; Ingeniería de la Información y las ComunicacionesThe mechanisms responsible for the selective vulnerability of specific neuronal populations in Parkinson’s disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions of 96 patients with Parkinson’s disease and 35 control subjects using quantitative susceptibility mapping. We estimated the expression of 15 745 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. Using partial least squares regression, we then identified the profile of gene transcription in the healthy brain that underlies increased cortical iron in patients with Parkinson’s disease relative to controls. Applying gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile and identified the sets of genes with spatial expression profiles in control brains that correlated significantly with the spatial pattern of cortical iron deposition in Parkinson’s disease. Gene ontological analyses revealed that these genes were enriched for biological processes relating to heavy metal detoxification, synaptic function and nervous system development and were predominantly expressed in astrocytes and glutamatergic neurons. Furthermore, we demonstrated that the genes differentially expressed in Parkinson’s disease are associated with the pattern of cortical expression identified in this study. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson’s disease, particularly the processes involving iron accumulation.
- PublicationRestrictedTyrosine phosphorylation of the inactivating peptide of the Shaker B potassium channel: a structural-functional correlate(American Chemical Society, 2002-09-12) Encinar Hidalgo, José Antonio; Fernández Carvajal, Asia María; Molina Gallego, María Luisa; Molina, A.; Poveda Larrosa, José Antonio; Albar, J.P.; López Barneo, José; Gavilanes Franco, Francisco; Ferrer Montiel, Antonio Vicente; González Ros, José Manuel; Bioquímica y Biología Molecular B e InmunologíaA synthetic peptide patterned after the sequence of the inactivating “ball” domain of the Shaker B K+ channel restores fast (N-type) inactivation in mutant deletion channels lacking their constitutive ball domains, as well as in K+ channels that do not normally inactivate. We now report on the effect of phosphorylation at a single tyrosine in position 8 of the inactivating peptide both on its ability to restore fast channel inactivation in deletion mutant channels and on the conformation adopted by the phosphorylated peptide when challenged by anionic lipid vesicles, a model target mimicking features of the inactivation site in the channel protein. We find that the inactivating peptide phosphorylated at Y8 behaves functionally as well as structurally as the noninactivating mutant carrying the mutation L7E. Moreover, it is observed that the inactivating peptide can be phosphorylated by the Src tyrosine kinase either as a free peptide in solution or when forming part of the membrane-bound protein channel as the constitutive inactivating domain. These findings suggest that tyrosine phosphorylation−dephosphorylation of this inactivating ball domain could be of physiological relevance to rapidly interconvert fast-inactivating channels into delayed rectifiers and vice versa.