Aspectos éticos de los bancos de datos de DNA de interés policial

El primer banco de datos policial basado en perfiles genéticos de DNA se introdujo en el Reino Unido en 1995. La identificación de posibles sospechosos se realiza por la comparación directa de un perfil genético recuperado del lugar de los hechos con otro almacenado en un banco dedatos. Desde un principio se ha demostrado que dichos bancos de DNA son una herramienta de investigación policial poderosa, pero que presenta diversos problemas éticos. Posteriormente se fue más allá buscando coincidencias parciales, que podrían indicar un vínculo familiar entre un perfil genético almacenado y otro obtenido en el lugar de los hechos. Este procedimiento genera un elevado número de sospechosos potenciales entre personas ajenas al caso que se investiga. Recientemente la búsqueda policial basada en el DNA ha penetrado en bancos de datos de interés no criminal, sino destinados a estimar el origen étnico de personas o descubrir familiares lejanos. Este tipo de búsquedas ha suscitado la posibilidad de generar un banco de datos universal de DNA, donde toda la población estuviese incluida. Estos y otros aspectos bioéticos respecto a la información basada en el DNA y a su acceso son tratados en el presente artículo

Long Non-Coding RNAs As Potential Novel Prognostic Biomarkers in Colorectal Cancer

Colorectal cancer (CRC) is the fourth most common cause of death worldwide. Surgery is usually the first line of treatment for patients with CRC but many tumors with similar histopathological features show significantly different clinical outcomes. The discovery of robust prognostic biomarkers in patients with CRC is imperative to achieve more effective treatment strategies and improve patient's care. Recent progress in next generation sequencing methods and transcriptome analysis has revealed that a much larger part of the genome is transcribed into RNA than previously assumed. Collectively referred to as non-coding RNAs (ncRNAs), some of these RNA molecules such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been shown to be altered and to play critical roles in tumor biology. This discovery leads to exciting possibilities for personalized cancer diagnosis, and therapy. Many lncRNAs are tissue and cancer-type specific and have already revealed to be useful as prognostic markers. In this review, we focus on recent findings concerning aberrant expression of lncRNAs in CRC tumors and emphasize their prognostic potential in CRC. Further studies focused on the mechanisms of action of lncRNAs will contribute to the development of novel biomarkers for diagnosis and disease progression

Determining population structure among Argentinian jaguars (Panthera onca)

The jaguar (Panthera onca) is the largest felid in America and the most emblematic South American predator. This carnivore species holds a high environmental importance in all ecosystems it inhabits for its apex predator role. Jaguar populations have suffered an important decline over the last century and today this species is considered as critically endangered in Argentina. Ensuring the sustainability of theremaining jaguar populations demands a high degree of knowledge about the current state of their genetic variability levels and a description of population structure is essential, especially to allow rational translocation and reintroduction actions. The first jaguar reference genome was released in2017 (Figueiro et al. 2017) by the Jaguar Genome Project, a consortium we integrate.With the aim of generating useful resources and information for the jaguar genetics and conservation from the genomic perspective, we carried out the whole genome sequencing of 9 jaguar samples using Illumina 2500 NSG technology. Here we present the first results obtained from these 9 genomescompared to the reference. We performed a population structure analysis in order to estimate the optimal number of populations present in our data and a Multiple Correspondece Analysis (MCA) clustering of our samples based on over 280.000 homozygous variable positions in their genomes. Theestimation of the optimal number of populations present among our samples resulted in 6, according to the Structure analysis. However, the MCA clustering analysis only revealed 5 groups of individuals. The main genetic cluster of animal obtained is integrated by captive animals from zoos and natural reserves and surprisingly a Paraguayan male. Apart from this central group, a wild Argentinian sample from Misiones (a province in the north-east of the country) was located. Also, an animal of Uruguayan origin and the reference, built from a Brazilian animal, located in individual clusters.More work including heterozygous variable position analysis will be performed to better describe the genetic variability among the sequenced jaguar genomes and accurately describe the current genetic situation and population structure of this species in Argentinian territory.Fil: Pisciottano, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Tarifa Reischle, Inti Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pegueroles Queralt, Cinta. Centro de Regulación Genómica; España. Universitat Pompeu Fabra; EspañaFil: Willis, Jesse R.. Centro de Regulación Genómica; EspañaFil: Julca Chavez, Irene Consuelo. Centro de Regulación Genómica; España. Universitat Pompeu Fabra; EspañaFil: Gabaldón, Toni. Centro de Regulación Genómica; España. Institució Catalana de Recerca i Estudis Avançats ; EspañaFil: Saragueta, Patricia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaExploring Genomic Landscapes EMBO WorkshopSan Pedro de AtacamaChileEMBOCenter for Genomic Regulatio

The era of reference genomes in conservation genomics

Progress in genome sequencing now enables the large-scale generation of reference genomes. Various international initiatives aim to generate reference genomes representing global biodiversity. These genomes provide unique insights into genomic diversity and architecture, thereby enabling comprehensive analyses of population and functional genomics, and are expected to revolutionize conservation genomics

Analysis of the P. lividus sea urchin genome highlights contrasting trends of genomic and regulatory evolution in deuterostomes

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle's lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement

Estudi de la recombinació en D. suboscura a nivell genòmic

[cat] La recombinació és un mecanisme universal que permet augmentar la variabilitat genètica dels organismes. Una major variabilitat es tradueix en una major capacitat d'adaptació a diferents ambients. De fet, l'estudi de la variabilitat genètica és un dels paràmetres claus a tenir en compte en la gestió d'espècies amenaçades. Un dels factors naturals que poden regular la taxa de recombinació al llarg d'un cromosoma és la presència d'inversions cromosòmiques. Les inversions, que són aberracions cromosòmiques en les que un fragment de DNA presenta una orientació invertida, redueixen la taxa de recombinació. Tot i que algunes d'aquestes inversions poden ser deletèries, en nombrosos casos s'ha observat que són adaptatives, mantenint combinacions d'al·lels favorables a un determinat ambient. Que les inversions cromosòmiques juguen un paper important en l'evolució dels organismes també s'observa pel fet que s'han descrit nombroses inversions específiques d'espècie. En la present tesi doctoral s'ha estudiat la recombinació al cromosoma O de "D. subobscura" a diferents nivells. Per una banda, s'han obtingut mapes genètics d'aquest cromosoma per dos ordenaments diferents. S'ha observat que la taxa recombinació a nivell global és força uniforme, tot i que es detecten hot i coldspots regionals. Un cop caracteritzada la recombinació en absència d'inversions, es van genotipar individus heterocariotípics per tal de determinar com les inversions modulen la recombinació. D'aquesta manera es va observar que la recombinació es troba gairebé inhibida a l'interior d'aquestes, i a més que fora d'elles la reducció és asimètrica. Per altra banda, l'anàlisi de gens nuclears candidats a estar involucrats en l'adaptació termal en individus provinents de diferents poblacions mostra que no hi ha diferències significatives, suggerint que hi ha un elevat flux gènic entre poblacions. En canvi, sí que es detecten diferències significatives en el contingut genètic de diferents ordenaments, analitzant gens localitzats dintre de les inversions. Per tant, el flux gènic es troba restringit a causa de les inversions, tot i que les estimes de recombinació mostren que aquesta no es troba totalment inhibida.[eng] Recombination is a universal mechanism that increases genetic variability of organisms. High levels of genetic diversity confer a higher capacity to adapt to different environments. For this reason, the levels of genetic variability constitute one of the key factors to take into account in the management of endangered species. Recombination rate across the chromosome is modulated by different factors, such as inversions. Chromosomal inversions, i.e. aberrations in which a chromosomal fragment is reversed, decrease the rate of genetic exchange. It is known that some inversions can be deleterious but in most of the cases, it has been shown that they are adaptive since they permit the maintenance of adaptive combination of alleles. Moreover, they play an important role in the evolution of species, since numerous inversions species-specific have been described. The main goal of this PhD thesis is to study the recombination in the O chromosome of "D. subobscura" at different levels. Genetic maps from two different types of arrangements were obtained. It was observed that at a global level, the recombination rate across the chromosome is uniform, despite some cold- and hotspots can be detected at the regional level. Furthermore, in order to determine how inversions modulate recombination rate, an analysis of heterokaryotypic lines differing by chromosomal inversions was carried out. From there, it was observed that recombination is inhibited inside inversions but also outside them, the reduction being asymmetrical in the two inversions breakpoints. On the other hand, the analysis of candidate genes to be involved in thermal adaptation in individuals from different populations presenting the same arrangement showed no significant differences, suggesting a high gene flow between arrangements. However, significant genetic differences were detected when comparing the genetic content of different arrangements. Thus, gene flux is restricted by chromosomal inversions although recombination is not totally prevented

Secondary structure impacts patterns of selection in human IncRNAs

Background: Metazoans transcribe many long non-coding RNAs (lncRNAs) that are poorly conserved and whose function remains unknown. This has raised the questions of what fraction of the predicted lncRNAs is actually functional, and whether selection can effectively constrain lncRNAs in species with small effective population sizes such as human populations. Results: Here we evaluate signatures of selection in human lncRNAs using inter-specific data and intra-specific comparisons from five major populations, as well as by assessing relationships between sequence variation and predictions of secondary structure. In all analyses we included a reference of functionally characterized lncRNAs. Altogether, our results show compelling evidence of recent purifying selection acting on both characterized and predicted lncRNAs. We found that RNA secondary structure constrains sequence variation in lncRNAs, so that polymorphisms are depleted in paired regions with low accessibility and tend to be neutral with respect to structural stability. Conclusions: Important implications of our results are that secondary structure plays a role in the functionality of lncRNAs, and that the set of predicted lncRNAs contains a large fraction of functional ones that may play key roles that remain to be discovered.Toni Gabaldon's (TG’s) group acknowledges support from the Spanish Ministry of Economy and Competitiveness grants “Centro de Excelencia Severo Ochoa 2013-2017” SEV-2012-0208 and BFU2015-67107, cofounded by the European Regional Development Fund (ERDF); from the European Union and ERC Seventh Framework Programme (FP7/2007-2013) under grant agreements FP7-PEOPLE-2013-ITN-606786 and ERC-2012-StG-310325; and a grant from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement number H2020-MSCA-ITN-2014-642095

La utilización forense del ADN de animales y plantas: aspectos jurídicos y sociales

La genética de animales y plantas puede ser útil para resolver ciertos casos criminales donde el estudio del ADN humano no haya aportado suficientemente información. También pueden investigarse situaciones en las que los animales son los agresores o las víctimas. La genética forense aplicada a plantas puede servir para relacionar un agresor con la escena del crimen o deducir una localización previa donde estuvo un cadáver. Otro aspecto destacado de la genética forense es el poder detectar los delitos contra especies animales y vegetales protegidas. Los avances en genética y genómica han abierto nuevas aproximaciones analíticas para resolver este último tipo de casos

Target enrichment enables the discovery of lncRNAs with somatic mutations or altered expression in paraffin-embedded colorectal cancer samples

Long non-coding RNAs (lncRNAs) play important roles in cancer and are potential new biomarkers or targets for therapy. However, given the low and tissue-specific expression of lncRNAs, linking these molecules to particular cancer types and processes through transcriptional profiling is challenging. Formalin-fixed, paraffin-embedded (FFPE) tissues are abundant resources for research but are prone to nucleic acid degradation, thereby complicating the study of lncRNAs. Here, we designed and validated a probe-based enrichment strategy to efficiently profile lncRNA expression in FFPE samples, and we applied it for the detection of lncRNAs associated with colorectal cancer (CRC). Our approach efficiently enriched targeted lncRNAs from FFPE samples, while preserving their relative abundance, and enabled the detection of tumor-specific mutations. We identified 379 lncRNAs differentially expressed between CRC tumors and matched healthy tissues and found tumor-specific lncRNA variants. Our results show that numerous lncRNAs are differentially expressed and/or accumulate variants in CRC tumors, thereby suggesting a role in CRC progression. More generally, our approach unlocks the study of lncRNAs in FFPE samples, thus enabling the retrospective use of abundant, well documented material available in hospital biobanks

Genomic basis for early-life mortality in sharpsnout seabream

Mortality at early life stages of fishes is common in nature and can be shaped by stochastic and selective processes. Selective mortality has rarely been assessed in natural conditions but can now be studied by combining genomic data with information on different life stages that realates to fitness. Here we investigate selective mortality between settlers and six‑month survivors of the sharpsnout seabream by genotype‑phenotype/environmental association studies in three localities along a geographic gradient. We gathered information on 105 individuals at 85,031 SNPs, obtained from individual based 2b‑RAD libraries, as well as 9 phenotypic and environmental variables derived from individual otolith readings. We found common signals across localities for potential selection, such as lower survival rates for individuals hatching earlier, growing faster and experiencing higher temperatures during their planktonic phase. We identified 122 loci with parallel significant association to phenotypic and environmental variables. Importantly, one of these loci mapped to the exonic region of the il20rb, a gene involved in immune response, in the hylogenetically closest reference genome, showing parallel frequency changes in non‑synonymous mutations in the three studied populations. Further temporal assessments are needed to understand how polymorphisms that are key to selective mortality are maintained