Perfil transcriptómico en el músculo longisimus dorsi: Una comparación entre líneas de cerdo ibérico

[ES] La deposición de altos niveles de grasa intramuscular, particularmente rica en ácido oleico, es característica del cerdo ibérico. Estos dos parámetros, que definen en gran parte la alta calidad de sus productos curados, presentan gran variabilidad entre las estirpes que componen la población de cerdo ibérico. En un experimento previó se realizó́ un cruce dialélico completo entre las estirpes Retinto y Torbiscal, reconocidas en el libro genealógico de la raza gestionado por la Asociación Española de Cerdo Ibérico (AECERIBER). En este experimento, se vio la existencia de diferencias entre estas líneas y sus cruces para grasa intramuscular y composición de ácidos grasos en el músculo Longissimus dorsi. El objetivo de este trabajo es estudiar estas diferencias de tejido muscular entre líneas a nivel trascriptómico utilizando secuenciación masiva del transcriptoma.[EN] The deposition of intramuscular fat and the content of oleic fatty acid is characteristic in the Iberian pig. These two parameters present great variability among the strains that make up the Iberian pig population. In a previous experiment a complete diallelic cross generated using Retinto and Torbiscal strains was carried out. In this experiment, differences between lines for Intramuscular fat and fatty acids profile in Longissimus dorsi were found. The aim of this work is to study the muscle tissue differences between lines at transcriptomic level using whole transcriptome shotgun sequencing.Villaplana Velasco, A. (2018). Perfil transcriptómico en el músculo longisimus dorsi: Una comparación entre líneas de cerdo ibérico. http://hdl.handle.net/10251/107615TFG

Integrative investigation of retinal vascular complexity and its application for cardiovascular disease

The early detection of cardiovascular events is a key strategy for controlling and reducing their leading and increasing morbidity and mortality worldwide. The integration of novel technological and scientific advances has been central for early identifying the pathogenesis of these multifactorial diseases, and this is certainly the case of the retina. The retina is the innermost layer of the eye unique in allowing the observation of the vascular system in vivo using non-invasive imaging modalities. By implementing semi-automated scoring, retinal images can provide phenotypes that capture the structure of the vascular network, such as the branching pattern. The branching pattern, also named retinal vascular complexity, is an unexplored trait of the retinal vasculature that captures the degree of intricacy and branching complexity of the entire plexus. This trait then can quantify subtle variations within the network, making it an optimal phenotype for investigating morphological variation within the retinal plexus. There is increasing evidence that retinal vascular complexity could offer earlier insight into the progression of major cardiovascular diseases than established risk factors. Thus, retinal vascular complexity could be a promising noninvasive biomarker for fatal cardiovascular events, such as myocardial infarction and stroke. Multiple efforts have integrated this phenotype into cardiovascular predictive models but have not translated so far into a substantial prediction improvement when compared to established models based on demographic and clinical variables. Population-based studies demonstrated that retinal vascular phenotypes different from vascular complexity have a genetic basis, where associated loci also contribute to cardiovascular physiology and pathology. This suggests a shared genetic basis between the retinal and global vascular systems during early ischaemic stages, contributing to similar pathophysiological variations. However, there is little information about the genetic component that underlies the retinal vascular complexity and little is known about the additional predictive value of this trait for predicting fatal vascular events. Elucidating its genetic architecture and its predictive value are then of great importance, as it could lead to a better understanding of the regulation of retinal and major vascular systems and, consequently, substantiate the future application of retinal vascular complexity as a biomarker of systemic vascular health. This thesis aims to comprehensively analyse retinal vascular complexity by integrating epidemiological, genetic, and translational disciplines. To this end, we obtained retinal vascular complexity from retinal fundus images and demographic, clinical, and genotyping information from approximately 38,800 participants with white-British ancestry in the UK Biobank. Exploratory analyses revealed that retinal vascular complexity is associated with image quality, age, sex, ocular, and cardiovascular traits and conditions. We found that decreased vascular complexity is associated with a higher risk of myocardial infarction and stroke, independently of established risk factors. Furthermore, we found nine independent loci after finemapping (rs73175105 in chromosome 3; rs16891982 in chromosome 5; rs12203592, and rs9375805 in chromosome 6; rs6018400 in chromosome 12; rs12913832, rs72714116, and rs58843292 in chromosome 15; and rs73226964 in chromosome 21) located near EIF2B5, SLC45A2, IRF4, RDH5, HERC2, OCA2, and AGPAT3 genes contributing to retinal vascular complexity that were previously reported in genetic studies of ocular and cardiovascular disease. Functional and enrichment analyses indicated that three of these loci (rs16891982, rs12203592, and rs12913832) regulate NOTCH and VEGF transcriptional signalling activity, which are central mechanisms to the development and physiology of the retinal vasculature and influence global vascular pathology. Finally, we characterised the predictive value of retinal vascular complexity in ischaemic risk through the development of separate predictive strategies for coronary artery disease, myocardial infarction, and stroke. We observed that our predictive models including retinal vascular complexity and a disease-specific polygenic risk score achieved a greater perfomance when compared with a reproduction of established baseline models (AUCMI = 0.770±0.0013 vs AUCMI−Baseline = 0.711±0.0021, AUCCAD = 0.763±0.0018 vs AUCCAD−Baseline = 0.713±0.0021, and AUCSTR = 0.690±0.0015 vs AUCSTR−Baseline = 0.639±0.0025). Further analyses on our proposed models revealed that Df and the polygenic risk score captured an early predictive value for these conditions not fully reflected in clinical variables, resulting in a more accurate and earlier risk stratification. Overall, this study was the first to date to delve into the genetic component of retinal vascular complexity, describing part of its genetic mechanisms and its association with global vascular genetics, and exploring its application in the stratification of ischaemic risk. Our findings are consistent with previous reports, suggesting that retinal vascular complexity has an intricate shared genetic basis with cardiovascular conditions. Furthermore, our observations indicate that predictive models that leverage retinal vascular complexity could be clinical opportune systems to early identify individuals at high risk of major ischaemic events. This thesis ultimately sheds new light on the value of highly accessible vascular imaging phenotypes and their promising application in personalised medicine

Comparative Transcriptome Profile between Iberian Pig Varieties Provides New Insights into Their Distinct Fat Deposition and Fatty Acids Content

[EN] Iberian pigs are meat quality models due to their high fat content, high intramuscular fat, and oleic fatty acid composition. These parameters present great variability and are differentiated among the lines that make up the Iberian pig population. However, there is little information on how the genetic expression influences quality across Iberian varieties. This study aimed to compare the muscle expression profile between two varieties of Iberian pig (Torbiscal and Retinto) and their reciprocal crosses, differentiated by fatness. Our results suggest that the Retinto variety, which has the greatest fat content amongst the studied Iberian varieties, showed a higher expression of genes related to adiposity. Likewise, a higher expression of genes related to lipolysis was found in the Torbiscal variety, described as having less fat content than Retinto. Further genetic variation analysis in these Iberian varieties showed relevant associations for SNP (Single Nucleotide Polymorphism), related to these differentially expressed genes, with the meat quality traits. Thus, our findings evidence that differences in the genetic architecture and expression of Iberian varieties might explain the variability in their fat content and composition and hence, their meat quality. The high deposition of intramuscular fat and the content of oleic fatty acid are characteristic of the Iberian pig. These two parameters present great variability and are differentiated amongst the varieties that make up the Iberian pig population. Although previous studies generated evidence for causal genes and polymorphisms associated to the adipogenic potential of the Iberian pig, there is little information about how genetic expression influences this trait's variability. The aim of this study was to analyses the expression profile between two varieties of Iberian pig (Torbiscal and Retinto) and their reciprocal crosses differentiated in their intramuscular fat (IMF) content and fatty acid (FA) composition in the Longissimus thoracis muscle using an RNA-seq approach. Our results corroborate that the Retinto variety is the fattiest amongst all studied varieties as its upregulated genes, such as FABP3 and FABP5, SLC27A1 and VEGFA among others, contribute to increasing adiposity. In its turn, Torbiscal pigs showed an upregulation of genes associated with the inhibition of fat deposition such as ADIPOQ and CPT1A. Further genetic variation analysis in these Iberian varieties showed relevant associations for SNP located within the differentially expressed genes with IMF and FA content. Thus, the differences found in the genetic architecture and the muscle transcriptome of these Iberian varieties might explain the variability in their fat content and composition and hence, their meat quality.This study was funded by the INIA grant RTA 2012-0054-C02-01* and the Centre for the Development of Industrial Technology grant IDI-20140447.Villaplana-Velasco, A.; Noguera, JL.; Pena, RN.; Ballester, M.; Muñoz, L.; González, E.; Tejeda, JF.... (2021). Comparative Transcriptome Profile between Iberian Pig Varieties Provides New Insights into Their Distinct Fat Deposition and Fatty Acids Content. Animals. 11(3):1-14. https://doi.org/10.3390/ani1103062711411

Retinal vascular complexity in UK Biobank

The early detection of cardiovascular events is a key strategy for controlling and reducing its leading and increasing morbidity and mortality worldwide. The integration of novel technological and scientific advances has been central for early identifying the pathogenesis of this multifactorial disease, and this is certainly the case of the retina. The retina is the innermost layer of the eye unique in allowing the observation of the vascular system in vivo using noninvasive imaging modalities. By implementing semi-automated software, retinal images can provide phenotypes that capture the structure of the vascular network, such as the branching pattern. There is increasing evidence that the retinal branching pattern, also named retinal vascular complexity, might offer earlier insights into the progression of major cardiovascular diseases than established risk factors. Thus, retinal vascular complexity could be a promising noninvasive biomarker for fatal cardiovascular events, such as myocardial infarction and stroke. Population-based studies demonstrated that retinal vascular phenotypes have a genetic basis, where associated loci also contribute to cardiovascular physiology and pathology. Evidence points towards a shared genetic basis plausibly influencing the equivalent pathophysiological variations in the retinal and global vascular system at early ischaemic stages. However, there is little information about the genetic component that underlies the retinal vascular complexity and its associated mechanisms common to general vascular health. Elucidating these genetic mechanisms is of great importance, as it could lead to a better understanding of the regulation of retinal and major vascular systems and, consequently, substantiate the future application of retinal vascular complexity as an intermediary of systemic vascular health. This study comprehensively analysed retinal vascular complexity by integrating epidemiological, genetic, and translational disciplines. To this end, we obtained retinal vascular complexity from retinal fundus images and demographic, clinical, and genotyping information from approximately 38,800 individuals with white-British ancestry, 5,000 individuals with white European ancestry, 500 individuals with Asian ancestry and 500 individuals with African ancestry from the UK Biobank. We found nine loci contributing to retinal vascular complexity that were previously reported in genetic studies of ocular and cardiovascular disease. Functional and enrichment analyses indicated that these loci regulate transcriptional mechanisms central to the development and physiology of the retinal vasculature and influence global vascular pathology. Overall, this study delved into the genetic component of retinal vascular complexity, describing part of its genetic mechanisms and its association with global vascular genetics. Our findings are consistent with previous reports, suggesting that retinal vascular complexity has an intricate shared genetic basis with cardiovascular conditions. This study ultimately sheds new light on the value of highly accessible vascular imaging phenotypes and their promising application in personalised medicine