The landscape of expression and alternative splicing variation across human traits

Understanding the consequences of individual transcriptome variation is fundamental to deciphering human biology and disease. We implement a statistical framework to quantify the contributions of 21 individual traits as drivers of gene expression and alternative splicing variation across 46 human tissues and 781 individuals from the Genotype-Tissue Expression project. We demonstrate that ancestry, sex, age, and BMI make additive and tissue-specific contributions to expression variability, whereas interactions are rare. Variation in splicing is dominated by ancestry and is under genetic control in most tissues, with ribosomal proteins showing a strong enrichment of tissue-shared splicing events. Our analyses reveal a systemic contribution of types 1 and 2 diabetes to tissue transcriptome variation with the strongest signal in the nerve, where histopathology image analysis identifies novel genes related to diabetic neuropathy. Our multi-tissue and multi-trait approach provides an extensive characterization of the main drivers of human transcriptome variation in health and disease.This study was funded by the HumTranscriptom project with reference PID2019-107937GA-I00. R.G.-P. was supported by a Juan de la Cierva fellowship (FJC2020-044119-I) funded by MCIN/AEI/10.13039/501100011033 and ‘‘European Union NextGenerationEU/PRTR.’’ J.M.R. was supported by a predoctoral fellowship from ‘‘la Caixa’’ Foundation (ID 100010434) with code LCF/BQ/DR22/11950022. A.R.-C. was supported by a Formación Personal Investigador (FPI) fellowship (PRE2019-090193) funded by MCIN/AEI. R.C.-G. was supported by an FPI fellowship (PRE2020-092510) funded by MCIN/AEI. M.M. was supported by a Ramon y Cajal fellowship (RYC-2017-22249).Peer ReviewedPostprint (published version

Caracterización de procesos implicados en la longevidad de la semilla mediante análisis de variedades naturales de Arabidopsis thaliana

[ES] La longevidad de la semilla es un rasgo adaptativo de importancia ecológica y económica. Las semillas pierden su viabilidad durante el almacenamiento, y en este proceso intervienen factores tanto ambientales como genéticos. Para profundizar en los procesos biológicos que controlan este rasgo, en este trabajo se han identificado accesiones naturales de la planta modelo Arabidopsis thaliana que presentan longevidades muy altas o muy bajas. Para esto se han realizado ensayos de germinación tras un almacenamiento de 30 meses, y tras un tratamiento de envejecimiento acelerado. Las accesiones seleccionadas han sido sometidas a ensayos de permeabilidad de la testa, de grosor de la capa de suberina del integumento externo, así como del contenido en glutatión, para determinar si alguna de estas propiedades correlaciona con la longevidad de la semilla. Finalmente, utilizando datos de genotipado, se han identificado polimorfismos asociados a este rasgo agronómico y resaltado aquellos genes con variantes polimórficas sesgadas entre accesiones muy longevas y poco longevas.[EN] Seed longevity is an adaptative trait of economic and ecologic importance. Seeds lose their viability during storage, and in this process both genetic and environmental factors intervene. To deepen in the biological processes that control this trait, natural accessions of the model plant Arabidopsis thaliana that have very high or very low longevity have been identified. For this, germination tests have been carried out after storage for 30 months, and after an accelerated aging. The selected accessions have been subjected to tests of patency of the seed coat, thickness of the suberin layer of the external integument, as well as the content of glutathione, to determine if any of these properties correlates with the longevity of the seed. Finally, using genotyping data, polymorphisms associated with this agronomic trait have been identified and those genes with polymorphic variants biased between very long-lived accessions and few long-lived ones have been highlighted.Chazarra Gil, R. (2018). Caracterización de procesos implicados en la longevidad de la semilla mediante análisis de variedades naturales de Arabidopsis thaliana. http://hdl.handle.net/10251/109107TFG