Augusto Rojas Martínez

Impact of NGS in the medical sciences: Genetic syndromes with an increased risk of developing cancer as an example of the use of new technologies

The increased speed and decreasing cost of sequencing, along with an understanding of the clinical relevance of emerging information for patient management, has led to an explosion of potential applications in healthcare. Currently, SNP arrays and Next-Generation Sequencing (NGS) technologies are relatively new techniques used to scan genomes for gains and losses, losses of heterozygosity (LOH), SNPs, and indel variants as well as to perform complete sequencing of a panel of candidate genes, the entire exome (whole exome sequencing) or even the whole genome. As a result, these new high-throughput technologies have facilitated progress in the understanding and diagnosis of genetic syndromes and cancers, two disorders traditionally considered to be separate diseases but that can share causal genetic alterations in a group of developmental disorders associated with congenital malformations and cancer risk. The purpose of this work is to review these syndromes as an example of a group of disorders that has been included in a panel of genes for NGS analysis. We also highlight the relationship between development and cancer and underline the connections between these syndromes.

Genética y medicina molecular en cardiología

Los descubrimientos de los aspectos moleculares del funcionamiento celular estan cambiando los conceptos de salud y enfermedad. Todas las areas de la medicina, incluyendo la cardiologia, se enriquecen con pruebas diagnosticas para determinar la predisposicion y realizar la deteccion de alteraciones moleculares. Esta revision acerca de la genetica y de los aspectos moleculares en cardiologia se escribe en el centenario del redescubrimiento de los principios de Mendel y en el momento en que se anuncia la secuenciacion del genoma humano. El articulo comienza con consideraciones acerca de la constitucion pluricelular del cuerpo humano y de los principios de la genetica y sus bases moleculares, incluyendo una breve descripcion de los metodos de mapeo genetico. A continuacion, se hace una resena historica sobre la genetica medica, la medicina molecular y el Proyecto del Genoma Humano. Finalmente se realiza una exposicion sobre el espectro de enfermedades geneticas, utilizando ejemplos de afecciones cardiovasculares.

Comparison of specific expression profile in two in vitro hypoxia models

The microenvironment plays a fundamental role in carcinogenesis: Acidity and hypoxia are actively involved in this process. It is important to have in vitro models to study these mechanisms. The models that are most commonly referred to are the hypoxia chamber and the chemical induction [Cobalt (II) chloride]. It is not yet defined if these models are interchangeable if the metabolic effect is the same, and if the results may be compared in these models. In the present study, the response to the effect of stress (hypoxia and acidity) in both models was evaluated. The results indicated that in the chemical model, the effect of hypoxia appeared in an early form at 6 h; whereas in the gas chamber the effect was slow and gradual and at 72 h there was an overexpression of erythropoietin (EPO), vascular endothelial growth factor (VEGF), carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1α (HIF1α). In addition to the genes analyzed by reverse transcription-quantitative polymerase chain reaction, the global expression analysis between both models revealed the 9 most affected genes in common. The present study additionally identified 3 potential genes (lysyl oxidase, ankyrin repeat domain 37, B-cell lymphoma 2 interacting protein 3 like) previously identified in other studies, which may be considered as universal hypoxia genes along with HIF1α, EPO, VEGF, glucose transporter 1 (GLUT1), CA9, and LDH. To the best of the authors knowledge, this is the first time that both hypoxia models have been compared, and it was demonstrated that the effect of hypoxia induction was time sensitive in each model. These observations must be considered prior to selecting one of these models to identify selective hypoxia genes and their effects in cancer.